1. 全球毒品流行的现状与趋势
1.1 主要毒品类型的全球分布与流行特征
全球毒品流行呈现出复杂的区域差异性和主导类型多样性。阿片类药物、兴奋剂和合成毒品是当前全球毒品市场上的主要类别。
芬太尼及其类似物作为强效合成阿片类药物，其非法生产和贩运已成为全球性问题，特别是在北美地区。芬太尼的药效是海洛因的50倍，生产成本低廉，易于通过邮件等渠道分销，导致其在美国的非法阿片类市场中泛滥成灾1。根据对暗网市场数据的分析，芬太尼及芬太尼类似物在全球范围内的供应持续存在，其中超过44.7%的合成阿片类药物广告涉及芬太尼（包括药用和非药用）或其类似物2。加拿大是合成海洛因（一种新型合成阿片类药物）的主要发货地，而其他新型合成阿片类药物（如U-47,700、AP-237）则主要从中国发货2。
甲基苯丙胺（冰毒）是全球滥用第二广泛的毒品，仅次于大麻，全球约有3500万使用者3。在美国，甲基苯丙胺的使用率和相关死亡率在过去十年中翻了一番，预示其可能成为继阿片类药物之后的下一个物质滥用危机，并可能在全球范围内蔓延4。在亚洲，特别是中国，合成毒品（包括甲基苯丙胺）的使用在2003年至2010年间呈现出惊人的增长，新吸毒者中海洛因的比例下降了52.3%，而合成毒品的比例激增了860.7%5。
可卡因是全球范围内第二大被滥用和贩运的非法药物，尤其在15-34岁的男性群体中，其终生使用率、去年使用率和上月使用率都较高6。
合成卡西酮类药物，通常被称为“浴盐”，是另一类日益受到关注的合成兴奋剂。这类物质并非真正的浴盐，而是含有甲氧基去氧麻黄酮（MDPV）和甲卡西酮等兴奋剂成分7。在波兰，随着有害物质被列入违禁品清单，新的设计师药物（如“dopalacze”）迅速出现在市场上，其中合成大麻素和卡西酮衍生物占大多数8。匈牙利东南部的研究显示，在2008年至2015年间，甲基苯丙胺等经典兴奋剂的使用保持稳定，但设计师兴奋剂（SDDs）在2012-2013年达到高峰，甚至超过了经典兴奋剂的流行率，其中戊酮、3-MMC、αPVP、αPHP和4-CMC是常见的SDDs9。
澳大利亚则面临处方阿片类药物滥用的挑战。自1990年代以来，澳大利亚的阿片类药物处方量显著增加，特别是在2015年前的20年里，处方量增长了15倍，其中羟考酮的使用量急剧上升10。虽然鸦片类药物处方数量持续增长，但人均口服吗啡当量（OME）衡量使用量自2014年以来可能已趋于平稳10。可待因仍然是最普遍获得的阿片类药物，其次是羟考酮和曲马多10。此外，苯二氮卓类药物在澳大利亚老年人群中的使用虽然在2010年至2016年间略有下降，但仍然处于不适当的高水平，特别是85岁以上的老年人11。
1.2 时间维度的流行变化：2015-2025年关键数据
在2015年至2025年期间，全球毒品流行呈现出显著且令人担忧的变化趋势，尤其在甲基苯丙胺使用量、阿片类过量死亡数以及物质使用障碍（SUD）患病率方面。
甲基苯丙胺使用量与浓度：美国国家健康和营养检查调查（NHANES）数据显示，2005年至2018年间，美国可卡因或甲基苯丙胺的使用率和使用频率均有所增加，而首次使用年龄相对稳定，约为20岁 12。更值得关注的是，对美国49个州和哥伦比亚特区尿液毒品检测（UDT）样本的分析显示，从2013年到2023年，尿液样本中甲基苯丙胺的调整后浓度显著上升，从2013年的665.27 ng/mg肌酐增加到2023年的3461.59 ng/mg肌酐 13。这表明，不仅使用人数增加，个体暴露于甲基苯丙胺的量也在显著上升。
阿片类过量死亡数的激增：阿片类药物过量死亡是全球面临的严峻挑战，尤其在美国。在COVID-19大流行期间，美国多个州报告了阿片类药物过量死亡率的显著增长。阿拉斯加、科罗拉多、印第安纳、内华达、北卡罗来纳、罗德岛和弗吉尼亚州的阿片类过量死亡率均出现大幅增长，例如阿拉斯加增加了55.3%，科罗拉多增加了80.2% 14。芬太尼及其合成阿片类药物是导致这些死亡激增的主要原因 1415。对Reddit物质使用论坛的趋势分析也印证了这一点，2013年至2021年间，芬太尼相关内容在所有毒品相关子版块中增长了1292%，其中多药物滥用和兴奋剂子版块的增长最为迅速 16。此外，从2013年到2023年，尿液样本中芬太尼的调整后浓度从4.61 ng/mg肌酐显著增加到38.23 ng/mg肌酐，而海洛因的浓度同期有所下降 13。这表明芬太尼已逐渐取代传统阿片类药物，成为过量死亡的主要驱动因素。值得注意的是，美沙酮相关的过量死亡在2020年3月之后也呈现上升趋势，无论是否涉及其他合成阿片类药物，这尤其影响了西班牙裔和非西班牙裔黑人个体 17。
全球青少年群体的感染率变化：青少年群体对毒品的易感性令人担忧。根据对全球47个国家12-15岁学龄青少年（2009-2018年数据）的调查，大麻使用率为7.02%，甲基苯丙胺使用率为4.05% 18。大麻使用在美洲地区最为普遍（11.31%），而非洲地区则有最高的甲基苯丙胺使用率（4.34%） 18。高收入国家的大麻使用率最高（9.45%），而低收入国家最低（3.46%） 18。此外，在法国，普瑞巴林（pregabalin）的娱乐性使用在青少年中急剧增加，特别是在2018年之后，这些使用者多为男性，中位年龄15岁，且大部分无家可归或居住在移民收容所 19。这表明青少年群体在不同地区和不同毒品类型上都面临着严重的滥用风险。
综上所述，2015年以来，全球毒品流行呈现出阿片类（特别是芬太尼）和甲基苯丙胺滥用及其相关危害的持续上升趋势，并且在青少年群体中，新兴合成毒品和传统毒品的滥用率也居高不下，这无疑对全球公共卫生构成了重大威胁。
2. 毒品滥用的健康危害：生理与心理双重影响
2.1 直接生理损害与并发症
毒品滥用对人体造成广泛而深远的生理损害，这些损害不仅涉及特定器官系统，还表现为多种并发症，严重影响滥用者的健康和生命质量。
口腔健康问题：物质滥用与口腔健康状况恶化密切相关。滥用者普遍存在更高的龋齿（龋坏、缺失和充填牙齿，DMFT指数）和牙周疾病发生率 20。一项针对非法毒品（如大麻和可卡因/可待因）使用者的研究发现，这些人群的口腔黏膜病变发生率显著增加，唾液流速降低 21。另一项研究则具体指出，吸烟/无烟烟草的滥用与更高的龋齿患病率相关（平均DMFT指数为4.73±4.32），且口腔卫生指数显著更差，烟草使用持续时间和频率与中度及重度龋齿水平呈正相关 22。毒品滥用者通常较少接受牙科护理，导致龋齿情况更严重，但修复体更少 20。
肝脏疾病：肝脏是物质代谢的主要器官，因此毒品滥用极易导致肝脏损伤。酒精滥用是肝脏疾病的常见原因，可导致酒精相关性肝病（ALD），包括脂肪肝、酒精性肝炎和肝硬化 23。年龄增长会加剧急慢性酒精引起的肝损伤，其机制可能与中性粒细胞中Sirtuin 1 (SIRT1) -C/EBPα-miRNA-223轴的下调有关 23。除了酒精，多种药物和毒品也会引起药物性肝损伤（DILI）24。自噬在酒精和药物性肝损伤中发挥保护作用，通过清除受损的线粒体、脂滴、蛋白质聚集体及肝细胞中的加合物来减轻损伤 24。
感染性疾病：注射吸毒是多种感染性疾病传播的主要途径，包括人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）25。全球约有7110万人慢性感染HCV，其中注射吸毒是主要的传播途径之一 26。在2015年，全球约有175万新增HCV感染病例 26。HIV感染者也常伴有HCV和HBV（乙型肝炎病毒）共感染，这些病毒具有相似的传播途径，包括静脉吸毒、输血和性接触 2728。缅甸的一项研究显示，HIV阳性渔民中HCV共感染率更高，且注射吸毒行为更为普遍，国际移民渔民的注射吸毒率高达23.0% 29。
心脏疾病：注射吸毒还与感染性心内膜炎（IE）特别是右侧感染性心内膜炎（RSIE）显著相关 25。RSIE约占所有感染性心内膜炎病例的5%至10%，主要发生在注射吸毒人群中，且常伴有HIV和HCV共感染 3031。从2010年到2015年，与注射吸毒相关的感染性心内膜炎住院率增加了12倍 25。金黄色葡萄球菌是最常见的致病菌 31。右侧感染性心内膜炎通常表现为持续发热和呼吸道症状，而左侧感染性心内膜炎常见的全身栓塞体征则不明显 31。及时诊断需要高度怀疑。预计在未来十年内，仅注射吸毒相关感染性心内膜炎导致的死亡将造成超过726万年的潜在寿命损失 25。此外，2012年，美国因阿片类使用障碍（OUD）相关的住院治疗达53万例，其中7亿美元的费用与OUD相关的感染有关 25。
这些生理损害和并发症的广泛存在，凸显了毒品滥用对个体健康的严重威胁，并对全球公共卫生系统构成了巨大挑战。
2.2 心理与精神健康风险
毒品滥用对心理和精神健康的损害是深远且复杂的，常常导致物质使用障碍（SUDs）与其他精神疾病的共病，并涉及复杂的神经生物学机制。
物质使用障碍（SUDs）的发展路径：物质使用障碍，例如甲基苯丙胺使用障碍（MUD）和阿片类使用障碍（OUD），其发展是一个渐进的过程，个体在接触毒品后，逐渐形成依赖，并最终演变为慢性复发性疾病。神经影像学研究揭示，慢性兴奋剂和阿片类药物使用会导致大脑过程和回路的缺陷，这些缺陷与对毒品线索的反应性增强以及目标导向决策能力的下降有关 32。大脑犒赏回路（特别是伏隔核、腹侧被盖区）和认知控制回路（前额叶皮层）的功能失调在SUDs的发生发展中扮演关键角色。此外，研究表明，情感性精神障碍和物质滥用障碍可能存在共同的生物学机制，涉及多巴胺、GABA和谷氨酸等神经递质及其受体，以及促肾上腺皮质激素释放激素和下丘脑-垂体-肾上腺轴的激活，氧化应激和炎症反应也参与其中 33。
与抑郁症、焦虑症的共病关联：
- 兴奋剂与抑郁症：兴奋剂依赖个体患抑郁症的比例远高于普通人群。抑郁症状被认为是兴奋剂戒断的主要组成部分。这两种疾病的共病可能反映了血清素、多巴胺和肽系统（如促肾上腺皮质激素释放因子CRF和神经肽Y NPY）功能的共同神经化学改变 34。这些改变在患者以及抑郁症和兴奋剂依赖的动物模型中均有观察到，特别是在边缘脑结构中 34。尽管两者之间似乎没有显著的共享遗传或基因关联，但兴奋剂可能会诱导与抑郁症相似的神经生物学变化，这些变化可能成为治疗靶点 34。例如，甲基苯丙胺会作为多巴胺能神经毒素，导致精神病患者出现更多的锥体外系副作用（EPSE），尤其是那些长期使用甲基苯丙胺的患者，随着抗精神病药物剂量的增加，EPSE的发生可能性更高 35。
- 甲基苯丙胺与精神障碍：甲基苯丙胺使用障碍（MUD）常始于青春期，并常伴有其他精神或心理障碍。普遍存在的共病包括烟草使用障碍、品行障碍、创伤后应激障碍、焦虑症和注意缺陷障碍 36。这些共病机制复杂，可能包括：预先存在的障碍促使个体通过甲基苯丙胺进行自我治疗；慢性甲基苯丙胺使用诱发精神障碍；以及MUD与精神障碍共享风险因素 36。甲基苯丙胺和阿片类药物的滥用流行会导致严重的心理、身体和精神健康成本，反复复发以及过早死亡的风险增高 32。
- 大麻与精神病：大量证据表明，滥用非法药物，特别是大麻和甲基苯丙胺，在精神病和精神分裂症的病理生理学中具有病因学作用 3738。吸烟和精神分裂症之间存在高度共病，且尼古丁成瘾与精神分裂症之间的神经机制复杂，可能涉及血清素、大麻素和谷氨酸的空间分布改变 39。
自杀倾向与死亡风险：物质使用障碍与自杀风险显著相关。患有SUDs的个体，尤其是在伴有抑郁症、焦虑症等共病的情况下，自杀念头和自杀行为的风险会大幅增加。COVID-19大流行期间，焦虑、恐惧、悲伤、适应困难、创伤后应激障碍症状和自杀倾向在普通人群和特定亚群中均有所增加，而这种精神病理学的存在会增加物质滥用和酒精使用的风险，作为一种适应不良的应对策略 40。此外，有物质使用障碍的人群面临更高的COVID-19感染和重症风险，特别是阿片类使用障碍和烟草使用障碍患者，其住院和死亡结果也更差 40。这凸显了SUDs在多重风险因素叠加下对个体生存的严重威胁。
神经生物学基础：毒品对大脑的影响是其导致精神健康问题的基础。奖赏和动机的神经回路被认为是毒品成瘾的神经基础 41。药物使用会募集室旁丘脑核（PVT）中的神经元，该区域被认为是控制目标导向行为的关键节点，并与边缘系统有相互联系 41。长期酒精暴露后谷氨酸能神经适应显著增强，特别是GluN2B-NMDA受体表达和功能的上调，这可能反映了活动依赖性适应性稳态可塑性 42。这些神经生物学改变解释了毒品滥用为何会改变情绪调节、认知功能和冲动控制，进而导致或加剧精神疾病的发生。
总而言之，毒品滥用与多种心理和精神健康风险紧密相连，形成恶性循环。深入理解其发展路径、共病关联及神经生物学基础，对于开发有效的干预和治疗策略至关重要。
3. 毒品问题的社会经济负担评估
毒品问题不仅对个体健康造成严重危害，也给社会带来了沉重的经济负担。这种负担体现在医疗、司法、生产力损失以及社会福利等多个方面。
3.1 医疗与司法系统的直接成本
毒品滥用对医疗和司法系统造成的直接成本是巨大的。这些成本主要来源于对物质使用障碍的治疗、过量死亡的紧急响应、以及与毒品相关的犯罪活动和感染性疾病的处置。
阿片类使用障碍及过量死亡的经济负担：阿片类危机尤其凸显了毒品问题的经济影响。在美国，2017年阿片类使用障碍和致命性阿片类药物过量的社会成本估计高达1.02万亿美元43。这一庞大数字主要由阿片类使用障碍导致的生命质量下降以及致命性阿片类过量导致的生命损失价值构成43。在更早的评估中，2001年美国处方阿片类药物滥用的总成本约为86亿美元，医疗费用方面，阿片类滥用者的人均医疗费用为15,884美元，而非滥用者为1,830美元44。到2015年，有强力证据表明，美国处方阿片类药物滥用的社会成本已超过每年500亿美元44。加拿大和美国是全球人均阿片类药物使用量最高的国家之一，也因此面临着阿片类危机的毁灭性后果。最新的数据显示，阿片类危机在美国造成的经济负担为785亿美元，在加拿大为35亿美元45。
具体到医疗系统，阿片类相关急诊科就诊的费用是显著的。2016年至2017年间，美国急诊科因阿片类相关诊断和过量就诊的病例总计288万次（占所有成人急诊就诊的1.23%），产生了95.7亿美元的急诊费用，即每年约47.8亿美元46。其中，医疗补助（Medicaid）和医疗保险（Medicare）承担了总费用的66%46。对于州级医疗补助计划而言，阿片类使用障碍带来的财政压力也在持续增长。1999年至2013年间，美国17个州的医疗补助计划中，被诊断为阿片类使用障碍的患者数量增加了378%，从39,109人增至186,979人。同期，医疗补助与阿片类使用障碍相关的总成本增长了两倍多，从1999年的9.19亿美元增至2013年的30多亿美元47。将这一数据推算至全美范围，医疗补助与阿片类使用障碍相关的成本从1999年的20多亿美元增至2013年的80多亿美元，15年间累计总成本超过724亿美元47。
注射吸毒相关感染的医疗支出与司法干预成本：注射吸毒是多种感染性疾病传播的主要途径，这些疾病的治疗也带来了巨大的医疗负担。例如，丙型肝炎病毒（HCV）感染是全球公共卫生面临的严峻挑战，约有80%的HCV感染负担集中在低收入和中等收入国家48。在中国天津，虽然政府通过创新的融资模式显著减轻了患者治疗HCV的经济负担（退休人员和在职员工的自付费用分别为其月工资的0.7和1.0倍），但HCV治疗本身仍是一项昂贵的支出，需要强大的战略性价格谈判和集中采购来降低成本49。
注射吸毒者（PWID）常常经历严重的注射相关感染（IRIs），这也给医疗系统带来了高昂的成本。例如，在美国佛罗里达州，对住院的PWID人群进行评估显示，注射相关感染导致了显著的医疗系统成本50。此外，酒精使用障碍也是全球最普遍的精神疾病之一，其社会成本极高，但治疗却往往不足51。虽然酒精使用障碍的成本与毒品滥用有所不同，但两者共同构成了物质滥用在医疗和司法系统中的沉重负担。全球疾病负担研究（GBD 2019）显示，酒精使用导致的死亡中，有6.8%（95%不确定区间：5.2-8.5%）归因于损伤52，这其中包含大量的急诊和住院医疗费用以及司法干预成本。
综合来看，毒品问题，特别是阿片类药物滥用和注射吸毒相关感染，给医疗和司法系统带来了万亿美元级别的经济负担，这不仅消耗了大量公共资源，也使得社会在应对其他公共卫生挑战时面临更大的压力。
3.2 间接社会影响与长期损失
除了直接的医疗和司法成本，毒品问题还带来了广泛的间接社会影响和长期损失，这些影响往往难以量化，但对社会结构和发展造成了深远破坏。
生产力损失：物质滥用导致的生产力损失是毒品问题最显著的间接成本之一。这主要体现在因过早死亡、失能、疾病以及缺勤和工作表现不佳等因素造成的劳动参与率下降。酒精和药物滥用是导致生产力损失的关键因素，通过提高医疗保健成本、增加犯罪行为、造成失业和降低工作效率来产生经济影响 53。例如，在挪威，尽管酒精相关的缺勤和出勤不足的发生率相对较低，但少数或单一员工的酒精问题仍可能对工作场所产生重大的、深远的负面影响，包括经济和实际问题，以及对更广泛的社会心理环境和工作场所安全造成的担忧 54。可卡因滥用对年轻成年毒品使用者影响尤为严重，导致生产力下降和过早的发病率增加 55。此外，脑损伤幸存者，特别是在生命早期受伤的个体，更可能在后期滥用药物和酒精 56。创伤性脑损伤（TBI）后的酒精滥用与较差的康复结果以及未来再次遭受头部创伤的可能性大大增加相关，从而降低了积极的长期结果并大幅增加了社会成本 56。
家庭破裂与代际传递：毒品滥用对家庭结构和成员关系造成严重冲击，并可能导致问题代际传递。胎儿酒精谱系障碍（FASD）是其中一个典型的例子，它是由孕期酒精暴露引起的，可导致儿童出现一系列神经行为缺陷，包括认知障碍、执行功能受损、语言发育迟缓、学习记忆困难以及适应功能和学业表现不佳等 57 58。FASD患儿通常存在智力或行为障碍，虽然无法治愈，但早期干预和终身支持有助于管理这些困难 59。孕期饮酒不仅损害胎儿发育，还会导致家庭内部冲突、忽视儿童以及经济困难，进一步加剧了家庭破裂的风险。
社区安全威胁与犯罪率上升：毒品滥用与犯罪活动之间存在密切关联，严重威胁社区安全。毒品交易、毒驾以及因获取毒品而实施的盗窃、抢劫等犯罪行为，都会导致社会治安恶化和犯罪率上升。此外，法律和政策对非法药物使用的刑事化，尤其对注射吸毒者（PWID）而言，对艾滋病毒（HIV）的预防和治疗产生了负面影响 60。研究表明，80%的毒品刑事化研究结果表明，这种刑事化对艾滋病毒的预防和治疗产生了负面影响，最常见的刑事化指标是监禁和街头警务，最常见的艾滋病毒预防和治疗指标是注射器共用和艾滋病毒感染率 60。这不仅加剧了疾病传播，也使得边缘化群体更难获得医疗和社会服务，从而形成恶性循环。
总而言之，毒品问题的间接社会经济负担是巨大的，它通过侵蚀劳动生产力、破坏家庭结构和代际健康、以及威胁社区安全等方式，对社会造成了广泛而持久的负面影响。有效解决毒品问题，需要综合考虑这些间接成本，并采取多部门协作的策略。
4. 高风险人群的流行特征与脆弱性分析
4.1 青少年与青年群体的易感性
青少年和青年时期（15-24岁）是物质使用障碍（SUDs）发展的关键窗口期，这一群体的生理、心理和社会特点使其对毒品滥用表现出更高的易感性。全球疾病负担（GBD）研究2019年的数据显示，在全球范围内，15-24岁年龄组的SUD患病率显著，突显了这一问题的普遍性61。
物质使用障碍患病率：
2019年，全球范围内5至24岁人群中，有3100万人患有物质使用障碍。全球在2019年，SUDs的平均患病率为1.22%61。物质使用障碍造成的伤残调整生命年（YLDs）中，有2.80%归因于SUDs，且在25岁之前发生的精神障碍YLDs占所有精神障碍YLDs的24.85%，这其中SUDs占据了相当一部分比重61。在美国，毒品使用障碍的负担沉重且不断扩大，男性、年轻人口以及阿片类药物使用障碍亚型是尤其需要关注的群体62。
驱动因素的作用机制：
- 同伴压力：同伴影响是青少年和青年物质滥用的一个关键因素。研究表明，同伴压力对新兴成年人（18-29岁）的物质使用行为具有显著影响63。负面同伴压力（例如，同伴怂恿饮酒或吸食大麻）会增加狂饮、终生饮酒和终生吸食大麻的可能性63。在男性青少年中，同伴饮酒行为与个体酒精使用之间存在正相关64。此外，与偏差同伴的交往与物质使用的发生率密切相关，特别是当这种交往与交感神经系统反应迟钝相结合时65。这种同伴影响在青春期尤其强烈，因为青少年大脑中奖励系统的高度敏感性和前额叶控制系统的不成熟使其更易受外界刺激和风险行为的影响66。
- 心理健康问题：心理健康问题是青少年和青年物质滥用的另一个重要驱动因素。许多青少年可能会通过物质使用来“自我治疗”潜在的心理困扰。例如，美国2015-2019年国家药物使用和健康调查数据显示，出于非自我治疗动机（如追求快感、试验）滥用处方阿片类药物的青少年和青年，其物质使用障碍和心理健康问题的患病率最高67。即使是出于缓解疼痛等自我治疗动机，也需要对这些个体进行物质使用和心理健康筛查67。
- 社交媒体影响：社交媒体在青少年和青年群体的生活中扮演着日益重要的角色，但同时也带来了一定的风险。系统回顾和荟萃分析显示，社交媒体使用与青少年冒险行为之间存在积极的、小到中度的关联，包括物质使用（r = 0.19）和冒险性行为（r = 0.21）68。花费更多时间在社交媒体上与青少年内化问题（如抑郁、焦虑）和共病性内化/外化问题（如攻击性行为）的风险增加有关，尤其是每天使用社交媒体超过3小时的青少年69。对加州高中生的调查研究进一步指出，青少年接触电子烟和/或大麻相关的社交媒体内容，包括朋友、微影响者甚至品牌发布的帖子，与电子烟、大麻使用以及两者共同使用的风险增加相关70。这表明社交媒体平台上的内容传播可能潜移默化地影响青少年的物质使用观念和行为。
- 大脑发育与风险决策：青少年时期大脑仍在发育，尤其是前额叶皮层，该区域负责执行功能、冲动控制和风险评估。这种“不成熟”的大脑结构使得青少年更容易寻求刺激和冒险行为，且对延迟奖赏的评估能力较低6671。行为经济学理论认为，青少年和青年对毒品的使用决策与毒品的可获得性、价格以及对非物质替代活动的价值判断有关71。研究还发现，与延迟奖赏决策相关的脑状态可以预测青少年戒毒干预的反应72。
综合来看，青少年和青年群体在生理、心理和社会层面存在多重脆弱性，使其成为毒品滥用及其SUDs的高风险人群。理解这些驱动因素的作用机制对于制定有针对性的预防和干预策略至关重要。
4.2 注射吸毒者与边缘群体的特殊风险
注射吸毒者（People Who Inject Drugs, PWID）及其所处的边缘群体面临着特殊的健康风险和脆弱性，这些风险主要源于注射行为本身导致的感染传播，以及低收入、无保险、住房不稳定等社会经济因素造成的健康结局恶化。
注射相关感染（HIV/HCV）的传播模式：
注射吸毒是艾滋病毒（HIV）和丙型肝炎病毒（HCV）在全球范围内传播的主要途径之一 737475。共用针具和注射设备使得病毒能够直接进入血液循环，导致这些高危感染在PWID群体中迅速蔓延。
- HCV传播：HCV感染在PWID中极为普遍，全球注射吸毒者中抗HCV阳性率高达65%-90% 76。HCV感染者中约有80%发展为慢性感染，这些慢性感染者可能将病毒传播给他人 76。研究显示，即使在同一城市的不同PWID群体中，HCV的流行率也可能存在显著差异，例如，对居住在旧金山街头和无家可归的PWID进行的分析发现，HCV抗体阳性率高达90.1%，这远高于当地其他研究中报告的约70%的HCV感染率。这表明无家可归等社会经济因素进一步加剧了感染风险。此外，PWID的社会网络在疾病传播中也扮演着重要角色，了解这些网络的结构有助于设计更有效的干预措施，例如，纽约市的研究发现，认识29岁以上的阿片类药物使用者与HCV阳性检测结果相关 77。在台湾，自2005年以来，注射吸毒者已成为HIV/AIDS流行的主要贡献者，由于注射吸毒者中HCV感染率高，导致HIV/HCV共感染显著增加 73。
- HIV传播：HIV和HCV感染具有相同的传播途径和共同的风险因素，因此HIV/HCV共感染在注射吸毒者中非常普遍 75。研究表明，在亚洲国家，注射吸毒人群中HIV感染率从中国的6.3%到马来西亚的19%不等，HCV感染率从印度和台湾的41%到越南的74%不等 74。监狱和封闭设施为HIV和病毒性肝炎在拘留期间和释放后的传播创造了机会 78。全球范围内，注射吸毒者（PWID）的HIV感染率是其他囚犯的6倍，HCV感染率是8倍 78。
社会经济因素对健康结局的叠加恶化效应：
低收入、无保险、住房不稳定、种族歧视以及司法系统介入等社会经济因素，在注射吸毒者和其他边缘群体中相互作用，显著加剧了其健康脆弱性，导致更差的健康结局。
- 住房不稳定与无家可归：住房不稳定或无家可归的个体面临更高的HIV和HCV感染风险 79。例如，费城在2018年发现注射吸毒者中HIV感染爆发，发现露营地被拆除和缺乏针具获取是HIV持续传播的促进因素 79。无家可归不仅增加了感染风险，还严重阻碍了健康服务的可及性，使得预防和治疗措施难以有效实施。研究表明，居住环境（如孤立饲养）可以影响行为敏感性的发展和持续性，即环境因素能改变药物滥用引起的成瘾行为 80818283。社会冲突等压力情境也会通过改变社会环境而影响乙醇诱导的行为敏感性 80。
- 低收入与无保险：贫困是健康差异的重要驱动因素 8485。低收入群体往往无法负担医疗费用，即使有保险，也可能因社会歧视和污名化而在获取医疗服务时遭遇障碍。一项针对使用毒品的女性的研究发现，社会稳定性（包括住房稳定和人身安全）与心理健康服务和医疗护理的可及性呈正相关，稳定性高的女性未满足的医疗需求显著降低 86。这表明改善社会因素有助于提升医疗可及性。
- 司法系统介入与刑事化：司法系统对药物使用的刑事化，特别是对注射吸毒者的刑事化，对HIV预防和治疗产生了负面影响 8788。逮捕、监禁和街头警务等刑事化措施不仅导致PWID中断治疗，还可能增加其在狱中感染疾病的风险 78。监狱中的药物使用和针具共用行为是HIV/HCV传播的重要原因，且预防服务（如美沙酮治疗、针具交换项目）在监狱中的可及性往往非常有限 78。对毒品检测中存在的种族差异性分析显示，少数族裔，特别是黑人和西班牙裔美国人，在毒品检测中被不成比例地作为目标，尽管不同种族间的毒品使用率相似 89。这种偏见影响了就业机会、法律结果和治疗可及性，反映了更广泛的社会偏见，导致歧视和边缘化的循环 89。
- 种族歧视与边缘化：种族和民族不平等广泛存在于医疗保健体系中，即使在以人为本的减害项目中也未能幸免 90。结构性健康决定因素框架必须体现反种族主义才能有效，否则将加剧边缘化群体的健康不平等 90。毒品使用中的种族化历史模式需要得到承认，以促进公平、反种族主义的护理 90。
综上所述，注射吸毒者和边缘群体面临的健康挑战是多因素叠加的结果。病毒感染风险、不良社会经济条件与结构性不平等共同作用，导致这些群体在健康、社会融合和生活质量方面处于极其脆弱的境地。有效的干预措施必须超越单纯的疾病治疗，涵盖社会支持、住房保障、反歧视政策和司法改革等多个层面。
5. 毒品干预与治疗的进展及挑战
5.1 现有药物与行为治疗的效果与局限
毒品干预与治疗是应对全球毒品流行及其危害的关键环节。目前，针对不同物质使用障碍，药物治疗和行为疗法均取得了不同程度的进展，但也面临各自的局限性。
5.1.1 药物治疗：阿片类激动剂治疗（OAT）的效果与苯丙胺类药物治疗的困境
阿片类激动剂治疗（OAT）：
阿片类使用障碍（OUD）的治疗中，药物辅助治疗（Medication-Assisted Treatment, MAT）被认为是“金标准” 91。其中，美沙酮（Methadone）和丁丙诺啡（Buprenorphine）是主要的阿片类激动剂治疗（Opioid Agonist Therapy, OAT）药物，通过作为阿片受体激动剂来减少对阿片类药物的渴求和戒断症状 9293。
大量研究证实了OAT的有效性。美沙酮和丁丙诺啡治疗能够显著降低非法阿片类药物的使用率和过量死亡风险 9495。一项针对美国数据的回顾性分析显示，与未接受丁丙诺啡治疗的OUD患者相比，接受丁丙诺啡-纳洛酮治疗的患者在一年内的死亡率降低了34%（2.6% vs 4.0%；相对风险0.661），且缓解率提高了约1.9倍（18.8% vs 10.1%） 96。这强调了丁丙诺啡-纳洛酮作为OUD主要治疗手段的重要性 96。对于怀孕女性的OUD治疗，阿片类激动剂治疗（OAT）也是标准的护理方案 9497。此外，纳曲酮（Naltrexone）作为阿片受体拮抗剂，也用于OUD的治疗，尽管其在随机对照试验的荟萃分析中显示能减少非法阿片类药物使用，但对死亡率的影响证据尚不明确 95。
OAT的益处不仅体现在个体层面，也对社会具有显著的成本效益。一项基于模型的成本效益分析表明，与不治疗相比，使用美沙酮治疗每获得一个质量调整生命年（QALY）的成本为16,000美元，而结合纳洛酮分发的美沙酮治疗为22,000美元/QALY。当纳入刑事司法成本时，所有形式的MAT（包括丁丙诺啡、美沙酮和纳曲酮）都比不治疗更具成本效益，每人一生可节省25,000至105,000美元，其中美沙酮联合应急管理（CM）的成本节约最大 91。这表明扩大OAT的可及性不仅能挽救生命，还能带来显著的社会经济效益。然而，OAT的广泛应用仍然受限于可及性，尤其是在初级保健环境中，部分地区仍存在法规障碍 95。苯丙胺类使用障碍（ATS）治疗的困境：
与阿片类药物不同，苯丙胺类兴奋剂（包括甲基苯丙胺）使用障碍（ATS）的药物治疗进展缓慢，至今仍无获批的药理学疗法 9899。ATS成瘾是一个严重的全球公共卫生问题，带来重大的医疗、精神和经济后果 98。尽管研究人员在单胺、谷氨酸、内源性阿片肽和γ-氨基丁酸（GABA）系统等神经生物学机制方面进行了探索，并尝试了如安非他酮（Bupropion）、纳曲酮（Naltrexone）和米氮平（Mirtazapine）等药物，但目前尚未有充分证据表明其具有显著疗效 9899。药物研发面临的主要挑战包括开发新的临床前动物模型、设计严格的大规模临床试验以及考虑患者的遗传多态性 98。因此，针对ATS的药物治疗仍然是一个未被满足的巨大需求，需要更多的研究投入。
5.1.2 行为疗法：认知行为疗法（CBT）与动机访谈（MI）
行为疗法在物质使用障碍的治疗中占据重要地位，常与药物治疗结合使用。
认知行为疗法（CBT）：
认知行为疗法是一种广泛应用于精神障碍治疗的心理疗法，也被认为是物质使用障碍的一线干预措施 100101。CBT通过帮助患者识别并改变导致物质滥用的思维模式和行为习惯来发挥作用 101。系统回顾和荟萃分析表明，CBT联合药物治疗在酒精或物质使用障碍（SUDs）患者中具有显著疗效 100。与常规护理结合药物治疗相比，CBT联合药物治疗具有益处（效应值g范围0.18-0.28） 100。CBT在青少年物质滥用治疗中也显示出积极效果，通常作为家庭疗法或多组分疗法的一部分 101102。
然而，CBT并非没有局限。研究发现，CBT在与药理治疗结合时，其效果不一定优于其他特定疗法（如动机增强疗法、应急管理） 100。此外，作为常规护理和药物治疗的附加疗法时，CBT的证据结果好坏参半 100。这表明，虽然CBT是有效的，但其在不同情境下的相对优势可能需要进一步明确，并且可能需要根据具体药物类型和患者特征进行调整 100。对于同时患有精神健康和物质使用障碍（即双重诊断）的个体，CBT也被探索作为一种治疗方法，尽管现有证据在疗效上仍有局限性，但CBT在改善精神健康或物质使用症状方面显示出一定程度的改善 103。动机访谈（MI）：
动机访谈（MI）是一种以患者为中心、指导性的咨询方法，旨在通过探索和解决矛盾心理来增强个体改变行为的内在动机和承诺 104105。MI被广泛应用于物质使用障碍的治疗中，尤其是在初期阶段，以提高患者的治疗依从性和改变意愿。
与不干预相比，MI可能在短期内（直至短期随访期）减少物质使用 104。在与评估和反馈相比时，MI在中期和长期随访中可能轻微减少物质使用 104。然而，与常规治疗（treatment as usual）或其他积极干预措施相比，MI对物质使用的影响可能很小或没有差异 104。对于改变意愿和治疗保留率，MI的作用尚不明确 104。尽管MI在全球范围内广泛应用，但研究的异质性（包括参与者特征、所用物质和干预措施）以及对干预实施质量报告的不足，使得对其长期有效性的评估面临挑战 104106。此外，现有研究缺乏对MI强度更高或结合疗法的有效性评估 105。这意味着MI可能在启动改变动机方面非常有用，但在维持长期戒断方面可能需要与其他更全面的干预措施结合使用。
综合来看，现有药物和行为疗法在毒品干预中都发挥着重要作用。OAT在降低阿片类药物使用者的死亡率和改善预后方面效果显著，但仍需提高可及性。针对苯丙胺类药物的药物治疗仍是研究空白。行为疗法如CBT和MI在不同程度上帮助患者改变行为，但其长期疗效和在复杂共病情况下的应用仍有待深入研究和优化。
5.2 新型疗法与公共卫生策略的探索
面对传统疗法的局限和日益复杂的毒品流行态势，科学界和公共卫生领域正积极探索新型疗法和更具创新性的公共卫生策略，以期提高治疗效果、扩大服务可及性并降低成瘾风险。
5.2.1 非致幻迷幻剂类似物（如tabernanthalog）的抗成瘾潜力
迷幻剂（Psychedelics）因其在治疗抑郁症、创伤后应激障碍等神经精神疾病方面的潜力而重新受到关注 107108。然而，其致幻作用限制了临床应用的可扩展性，尤其是在需要广泛监测和患者脆弱性的情境下 109。为克服这一挑战，研究人员正在积极开发非致幻性迷幻剂类似物（Non-hallucinogenic Psychedelics, NHPs）。
其中，tabernanthalog (TBG) 是从迷幻生物碱伊博加因（ibogaine）中衍生出的一种水溶性、非致幻、无毒的类似物 110。伊博加因在人类和动物中都表现出抗成瘾特性，其长效作用可能通过激活神经营养因子信号传导来修改与成瘾相关的神经网络 110。然而，伊博加因的毒性、致幻潜力和诱发心律失常的倾向阻碍了其临床开发 110。TBG的出现旨在规避这些安全问题，通过功能导向合成原则，识别并保留伊博加因的治疗药效团关键结构元素 110。
在啮齿动物模型中，TBG已被证明能促进结构性神经可塑性、减少酒精和海洛因寻求行为，并产生抗抑郁样效应 110。此外，TBG还能通过调节神经炎症和小胶质细胞激活，减轻癌症引起的认知功能障碍，这进一步凸显了其在神经精神疾病治疗中的潜力 111。与传统的致幻剂相比，TBG在不引起致幻作用的前提下展现出神经可塑性效应，为治疗物质使用障碍提供了一条潜在的新途径 107112。目前，针对NHPs在情绪和焦虑障碍中的应用，已有动物研究显示出抗抑郁样效果，且未观察到致幻反应，这为未来在人体研究中探索其抗成瘾作用提供了有力支持 109。
5.2.2 远程医疗对可及性的提升
COVID-19大流行加速了远程医疗在物质使用障碍治疗中的应用，特别是对阿片类药物使用障碍（OUD）的治疗。远程医疗模式通过消除地理障碍、降低交通成本和提高便利性，显著提升了治疗的可及性。
- 阿片类激动剂治疗（OAT）的可及性改善：疫情期间，美国联邦政府对丁丙诺啡（buprenorphine）的处方规定进行了多项放宽，以增加OUD患者获得该药物的机会，包括放宽X-waiver限制和允许远程医疗服务 113。一些研究案例表明，远程医疗结合未经观察的丁丙诺啡-纳洛酮居家诱导治疗克拉托姆（Kratom）使用障碍是成功的，为传统治疗可及性受限的地区提供了替代方案 114。此外，远程医疗与面对面治疗在丁丙诺啡治疗OUD患者的保留率上没有显著差异，但远程医疗在成本效益方面更具优势，为每增加1%的治疗保留率节省了3750美元的额外成本 115。这表明远程医疗不仅能维持治疗效果，还能降低总治疗成本，具有推广价值 115。
- 挑战与机遇：尽管远程医疗带来了诸多益处，但也面临挑战。例如，罗德岛州的数据显示，虽然处方CII-CV类物质的医生数量有所增加，且处方丁丙诺啡的医生比例翻倍，但丁丙诺啡的初始治疗人数仍远低于疫情前的水平 113。这提示，尽管政策有所放宽，但仍存在其他障碍限制了治疗的普及。未来的研究应进一步探讨长期治疗结果、治疗依从性的性别差异，以及如何将远程医疗更好地整合到标准实践中，以优化资源分配和提高治疗可及性 115。
5.2.3 疫苗等前沿技术的研究进展
疫苗和免疫疗法作为一种创新策略，通过阻止毒品进入大脑或加速其在体内的清除，从而减弱甚至消除毒品的奖赏效应和毒性作用，为药物成瘾的预防和治疗提供了新的前景 116117。
- 抗毒品疫苗：针对尼古丁、可卡因、甲基苯丙胺、苯环利定（PCP）和吗啡等多种毒品的疫苗正在高级开发阶段 116。疫苗的作用机制主要是在血液中结合毒品，从而阻止或减缓毒品进入中枢神经系统 116118。这种药代动力学拮抗剂的作用可以减少毒品的欣快感和毒性效应，预防成瘾，并降低复发率 118。例如，可卡因是全球最古老、使用最广泛的非法药物之一，但目前尚无批准的药理学疗法来对抗可卡因依赖。抗可卡因疫苗的研发旨在解决这一问题，尽管挑战重重，但已取得一定进展 119。
- 抗体疗法：除了疫苗，治疗性抗体也是免疫疗法的重要组成部分。抗体疗法的主要优势在于其能提供即时效果 117。通过开发高效、长半衰期的人源化抗体，可以靶向毒品分子，促进其在体内的清除，从而减轻毒品的生理和心理作用 117。抗体疗法在癌症治疗中已取得巨大成功，为药物成瘾领域提供了借鉴 117。
这些新型疗法和公共卫生策略的探索，为解决全球毒品流行带来的严峻挑战提供了新的希望。非致幻迷幻剂类似物有望提供更安全的治疗选择，远程医疗显著提高了服务的可及性，而疫苗和抗体等免疫疗法则从根本上改变了成瘾的生物学基础，未来有望成为物质使用障碍防治的重要工具。
5.3 政策与预防措施的优化方向
有效的毒品政策与预防措施是控制全球毒品流行、减轻其健康与社会危害的关键。优化这些策略需要综合考虑毒品的危害性、高风险人群的脆弱性以及现有干预措施的有效性，并倡导以科学证据为基础的、以人为本的综合性策略。
5.3.1 基于危害的毒品分类体系的应用价值
传统的毒品分类体系往往侧重于法律管制，而较少关注毒品对个体和社会的实际危害。《柳叶刀》（Lancet）杂志提出的评估矩阵提供了一个更具科学性和透明度的框架，用于评估各种毒品的危害，从而为制定更合理的毒品政策提供依据 120。
- 评估框架：该矩阵从九个维度评估毒品的危害，包括三个与个体健康相关的维度（例如，急性死亡率、慢性死亡率、依赖性）和六个与社会危害相关的维度（例如，相关犯罪、环境损害、经济成本） 120。通过专家评估和量化打分，该体系能够对不同毒品（包括非法药物和酒精、烟草等合法药物）的综合危害进行排名 120。这种方法弥补了传统分类的不足，使得政策制定者能够更全面地理解毒品带来的问题，并将其危害与现有的法律管制级别进行比较 120。
- 政策启示：基于危害的分类体系能够揭示一些传统认知误区，例如，酒精和烟草等合法药物在某些危害维度上的得分可能可能高于一些非法药物 120。这意味着政策制定者应超越仅仅基于合法性的考量，转向更侧重于公共健康危害的策略。例如，可以根据毒品的危害程度调整税收、限制广告、实施更严格的销售管制，甚至对危害极大的合法物质采取更严格的管制措施，同时对危害相对较低的非法物质考虑去刑事化或减刑，以将司法资源集中于更严重的犯罪行为。
- 提高公众意识：一个透明且基于证据的危害评估体系有助于提高公众对不同物质危害的认识，从而促进更健康的决策。它还能为健康教育信息提供科学支持，增强其说服力。
5.3.2 针对高风险人群的早期筛查与综合干预
早期发现和综合干预对于预防毒品滥用向物质使用障碍发展以及减轻其危害至关重要，特别是在青少年、注射吸毒者和边缘群体等高风险人群中。
- 早期筛查：
- 青少年群体：青少年时期是物质滥用高发期，早期筛查能够及时识别有风险的个体。例如，在学校和社区环境中推广物质使用障碍的普遍筛查，结合问卷调查和简短的访谈，可以帮助识别那些早期开始使用毒品或有滥用倾向的青少年。针对青少年心理健康问题的筛查也至关重要，因为心理健康问题往往是物质滥用的驱动因素之一。
- 医疗保健机构：在初级保健、急诊室和其他医疗环境中，对患者进行物质使用障碍的常规筛查、简短干预和转诊治疗（SBIRT）被认为是有效的策略。对于阿片类药物使用者，筛查和早期识别可以预防阿片类使用障碍（OUD）的发生 121。
- 综合干预策略：
- 心理干预与社会支持结合：毒品问题通常是生理、心理和社会多重因素交织的复杂问题，因此，单一的干预措施往往效果有限。综合干预强调将药物治疗（如OAT）与行为疗法（如CBT、动机访谈）结合，同时辅以强大的社会支持系统。例如，针对物质使用障碍患者的康复计划应包括职业培训、住房援助、家庭支持和再社会化服务，以帮助他们重新融入社会。
- 针对特定高风险群体：
- 青少年：针对青少年的干预应侧重于技能训练（例如，应对同伴压力的能力、情绪调节策略）、家庭支持（例如，改善亲子沟通、提供家庭治疗）以及学校环境中的预防教育。同时，应解决青少年普遍存在的心理健康问题，如抑郁、焦虑和注意力缺陷多动障碍（ADHD），因为这些问题是物质滥用的重要危险因素 122。
- 注射吸毒者（PWID）：针对PWID的干预措施应包括减害策略，如针具交换项目（NSP）和安全注射点（SIS），以减少HIV/HCV等感染性疾病的传播 123。同时，确保其获得全面医疗服务，并解决住房不稳定、贫困等社会经济障碍。
- 边缘群体：对于面临多种社会经济劣势的边缘群体，干预措施必须考虑到他们的特殊需求，例如提供文化敏感的治疗服务、消除歧视、提供法律援助，并确保其在就业、住房和医疗方面的平等机会。
- 多部门协作：政策与预防措施的优化需要政府、医疗卫生系统、教育机构、司法部门、社区组织和家庭的多部门协作。例如，司法系统应考虑将毒品犯罪者转介至治疗而非单纯监禁，因为有研究显示，药物滥用治疗的后续护理对于预防复发至关重要 124。公共卫生部门应主导减害策略的推广和实施，并加强对毒品趋势的监测和研究。
通过采纳基于危害的毒品分类体系来指导政策制定，并实施针对高风险人群的早期筛查和综合性、多部门协作的干预措施，全球可以更有效地应对毒品流行带来的挑战，并减轻其对人类健康和社会的危害。
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参考文献
1Fentanyl: A Whole New World?PubMed
Rachel L Rothberg, Kate Stith
J Law Med Ethics. 2018 Jun;46(2):314-324. doi: 10.1177/1073110518782937.
This article seeks to document the latest danger in the opioid crisis: fentanyl and related synthetic opioids. Fifty times more potent than pure heroin, cheaper to manufacture in laboratories worldwide, and easily distributed by mail and couriers, fentanyl is flooding the illicit opioid markets throughout the country.
2Listed for sale: Analyzing data on fentanyl, fentanyl analogs and other novel synthetic opioids on one cryptomarket.PubMed
Francois R Lamy, Raminta Daniulaityte, Monica J Barratt, et al.
Drug Alcohol Depend. 2020 Aug 1;213:108115. doi: 10.1016/j.drugalcdep.2020.108115. Epub 2020 Jun 12.
BACKGROUND: The United States is facing a "triple wave" epidemic fueled by novel synthetic opioids. Cryptomarkets, anonymous marketplaces located on the deep web, play an increasingly important role in the distribution of illicit substances. This article presents the data collected and processed by the eDarkTrends platform concerning the availability trends of novel synthetic opioids listed on one cryptomarket. METHODS: Listings from the DreamMarket cryptomarket "Opioids" and "Research Chemicals" sections were collected between March 2018 and January 2019. Collected data were processed using eDarkTrends Named Entity Recognition algorithm to identify opioid drugs, and to analyze their availability trends in terms of frequency of listings, available average weights, average prices, and geographic indicators of shipment origin and destination information. RESULTS: 95,011 opioid-related listings were collected through 26 crawling sessions. 33 novel synthetic opioids were identified in 3.3 % of the collected listings. 44.7 % of these listings advertised fentanyl (pharmaceutical and non-pharmaceutical) or fentanyl analogs for an average of 2.8 kgs per crawl. "Synthetic heroin" accounted for 33.2 % of novel synthetic opioid listings for an average 1.1 kgs per crawl with 97.7 % of listings advertised as shipped from Canada. Other novel synthetic opioids (e.g., U-47,700, AP-237) represented 22 % of these listings for an average of 6.1 kgs per crawl with 97.2 % of listings advertised as shipped from China. CONCLUSIONS: Our data indicate consistent availability of a wide variety of novel synthetic opioids both in retail and wholesale-level amounts. Identification of new substances highlights the value of cryptomarket data for early warning systems of emerging substance use trends.
3DARK Classics in Chemical Neuroscience: Methamphetamine.PubMed
Thomas J Abbruscato, Paul C Trippier
ACS Chem Neurosci. 2018 Oct 17;9(10):2373-2378. doi: 10.1021/acschemneuro.8b00123. Epub 2018 Apr 6.
Methamphetamine has the second highest prevalence of drug abuse after cannabis, with estimates of 35 million users worldwide. The ( S)-(+)-enantiomer is the illicit drug, active neurostimulant, and eutomer, while the ( R)-(-)-enantiomer is contained in over the counter decongestants. While designated a schedule II drug in 1970, ( S)-(+)-methamphetamine is available by prescription for the treatment of attention-deficit disorder and obesity. The illicit use of ( S)-(+)-methamphetamine results in the sudden "rush" of stimulation to the motivation, movement, pleasure, and reward centers in the brain, caused by rapid release of dopamine. In this review, we will provide an overview of the synthesis, pharmacology, adverse effects, and drug metabolism of this widely abused psychostimulant that distinguish it as a DARK classic in Chemical Neuroscience.
4Neurobiology, Clinical Presentation, and Treatment of Methamphetamine Use Disorder: A Review.PubMed
Martin P Paulus, Jennifer L Stewart
JAMA Psychiatry. 2020 Sep 1;77(9):959-966. doi: 10.1001/jamapsychiatry.2020.0246.
IMPORTANCE: The prevalence of and mortality associated with methamphetamine use has doubled during the past 10 years. There is evidence suggesting that methamphetamine use disorder could be the next substance use crisis in the United States and possibly worldwide. OBSERVATION: The neurobiology of methamphetamine use disorder extends beyond the acute effect of the drug as a monoaminergic modulator and includes intracellular pathways focused on oxidative stress, neurotoxic and excitotoxic effects, and neuroinflammation. Similarly, the clinical picture extends beyond the acute psychostimulatory symptoms to include complex cardiovascular and cerebrovascular signs and symptoms that need to be identified by the clinician. Although there are no pharmacologic treatments for methamphetamine use disorder, cognitive behavioral therapy, behavioral activation, and contingency management show modest effectiveness. CONCLUSIONS AND RELEVANCE: There is a need to better understand the complex neurobiology of methamphetamine use disorder and to develop interventions aimed at novel biological targets. Parsing the disorder into different processes (eg, craving or mood-associated alterations) and targeting the neural systems and biological pathways underlying these processes may lead to greater success in identifying disease-modifying interventions. Finally, mental health professionals need to be trained in recognizing early cardiovascular and cerebrovascular warning signs to mitigate the mortality associated with methamphetamine use disorder.
5Tracking the evolution of drug abuse in China, 2003-10: a retrospective, self-controlled study.PubMed
Zhongwei Jia, Zhiming Liu, Ping Chu, et al.
Addiction. 2015 Jan;110 Suppl 1:4-10. doi: 10.1111/add.12769.
AIM: To characterize trends in drug abuse in China before and after the 2005 initiation of the 'People's War on Drugs'. DESIGN: Retrospective self-controlled study. SETTING: Annual, nation-wide surveillance from 2003 to 2010 of all registered drug users in China's National Surveillance System on Drug Abuse (NSSDA). PARTICIPANTS: A total of 1,184,124 drug users registered in NSSDA were involved in this study and were classified into three groups based on registered dates-pre-war group (n=230,278) registered 2003-04, phase I group (n=518,651) registered 2005-07 and phase II group (n=435,195) registered 2008-10. MEASUREMENTS: Indicators included proportions of:(i) new and relapsed drug users, (ii) heroin and synthetic drug users among new users, (iii) people aged 35 years or younger and (iv) women. Comparisons were made across groups using annual data to describe temporal trends. FINDINGS: Between 2003 and 2010 the proportion of heroin users decreased by 52.3% and synthetic drugs use increased 860.7% among new users, while a 12.8% decrease in the proportion of heroin users and a 918.8% increase in synthetic drug use in all users was detected. Compared with the pre-war group, the proportion of relapsed users decreased 2.6% and 29.1% in the phase I and phase II groups, respectively, but a significant increase in the proportion of new users was found in phase I (OR=1.24, CI=1.15-1.35, p<0.0001), followed by an apparent decrease in phase II compared with phase I (OR=0.75, CI=0.70-0.80, p<0.0001). Similarly, the proportion of heroin users decreased 15.1 and 24.2% among new drug users in phase I and phase II in comparison with the pre-war group. CONCLUSION: The decrease in proportions of drug users in China between 2003/4 and 2008/10 may suggest some positive influence of the 'People's War on Drugs', especially in the decreased proportion of relapsed users. In contrast, there was a rapid increase in new synthetic drug use over the same period.
6Diagnosis and consequences of cocaine addiction.PubMed
L Karila, A Petit, W Lowenstein, et al.
Curr Med Chem. 2012;19(33):5612-8. doi: 10.2174/092986712803988839.
Cocaine remains the second most commonly used and trafficked illicit drug in the world after cannabis. This psychostimulant drug has become an essential part of the world drug scene with a different use among countries. Prevalence of cocaine use (lifetime, last year, last month use) is particulary high among males aged between 15 and 34 years. Five per cent of cocaine users will develop a substance- dependence during the first year of use, and 20% of these will become long-term cocaine-dependent patients. The number of patients entering drug treatment for primary cocaine use has been increasing in Europe for several years. Cocaine addiction is a worldwide public health problem, which has somatic, psychological, psychiatric, socio-economic and judicial complications. This article aims to provide the clinician with a detailed description of the clinical aspects, the adverse effects and the complications of cocaine addiction. Literature searches were conducted for the period from January 1985 to February 2012 using PubMed, EMBASE, PsycInfo, and Google Scholar.
7Substituted cathinone products: a new trend in "bath salts" and other designer stimulant drug use.PubMed
Erik W Gunderson, Matthew G Kirkpatrick, Laura M Willing, et al.
J Addict Med. 2013 May-Jun;7(3):153-62. doi: 10.1097/ADM.0b013e31829084b7.
There is a growing concern about the availability of a new generation of "designer drug" stimulants that are marketed as "bath salts" and other household products. The products are not true bath salts and contain substituted cathinone stimulant substances, such as methylenedioxypyrovalerone (MDPV) and mephedrone. Calls to the American Association of Poison Control Centers regarding "bath salts" consumption began in 2010 and have continued since that time. Few reports of systematic epidemiologic surveillance or definitive clinical effects of toxicity specifically associated with "bath salts" consumption have been reported in the medical literature. The current narrative review describes the growing trend of designer substituted cathinone use, pharmacology, clinical effects, and recent regulatory changes. It is hoped that a greater understanding of the clinical effects and use patterns will help inform policy and practice.
8Designer drugs – still a threat?PubMed
Emil Bartosz Rozenek, Karolina Wilczyńska, Monika Górska, et al.
Przegl Epidemiol. 2019;73(3):337-347. doi: 10.32394/pe.73.23.
INTRODUCTION: In Poland, an increasing number of psychoactive substances are becoming prohibited by law as psychotropic or narcotic substances, or as new psychoactive substances (NPSs). Owing to the enormous technological possibilities offered by today’s science, synthesis of new derivatives of prohibited compounds is no longer a problem. The moment a dangerous substance is outlawed, new designer drugs (in Poland known as ‘dopalacze’) appear on the market. STATE OF KNOWLEDGE: An amendment to the Act on Counteracting Drug Addiction issued in July 2018 made it possible for the NPS to be considered drugs by law. Synthetic cannabinoids and cathinone derivatives make up the majority of NPSs identified by the authorities in Poland. Synthetic cannabinoids which can, unlike cannabinoid receptor agonists of plant origin, cause death by somatic toxicity, are particularly dangerous. The ability to quickly recognize poisoning with synthetic opioids is crucial, since an antidote reversing the depressive effect of opioids on the respiratory center can be administered. SUMMARY: This work collects the most important and up-to-date information on designer drugs, based on reports and articles published between 2015 and 2019. The covered aspects include: the current definition of designer drugs in relation to the Polish law, their exact division due to the clinical effects they cause and the description of the threats they pose. Emphasis was given to the current situation of the designer drug market in Poland.
9Changes in illicit, licit and stimulant designer drug use patterns in South-East Hungary between 2008 and 2015.PubMed
Zsófia Árok, Tamás Csesztregi, Éva Sija, et al.
Leg Med (Tokyo). 2017 Sep;28:37-44. doi: 10.1016/j.legalmed.2017.07.001. Epub 2017 Jul 8.
The aim of this work is to present the changes in classical illicit and licit drug, as well as stimulant designer drug (SDD) consumption of suspected drug users in South-East Hungary between 2008 and 2015. Urine and/or blood samples of 2976 subjects were analyzed for these groups of substances of which 1777 (59.7%) were tested positive. THC was the most frequent (32.2%) substance, followed by classical stimulants (amphetamine, metamphetamine, MDMA, cocain) (21.4%), SDDs (17.0%), benzodiazepines (15.5%), medical opiates (codeine without morphine, methadone, tramadol) (4.03%), and morphine with or without 6-acethyl-morphine (1.98%). The annual rate of cannabis consumption continuously decreased after 2010. The use of classical stimulants was constant, except for a significant increase in 2015. Benzodiazepine incidence increased and remained steady after 2011. Medical opiate and morphine frequency was variable. SDDs were found in the highest number in 2012-13, exceeding the frequency of classical stimulants. The most prevalent SDDs were as follows: 2010 - mephedrone, 2011 - 4-MEC, methylone, MDPV, 4-FMC, and 4-FA, and 2012-2015 - pentedrone. Beside pentedrone, 3-MMC, αPVP, αPHP, and 4-CMC were detected with a notable number in this period. Multi-drug use was found in 30-43% of suspects tested positive between 2008 and 2014, which elevated to 52% in 2015. The frequency of substances in the biological samples corresponded to their seizure rate. When SDDs were included on the NPS list, their frequency in biological samples and in seized materials slightly decreased or did not change. However, a marked decrease was observed following classification as illicit drugs.
10Trends in opioid prescribing in Australia: a systematic review.PubMed
Peter J Donovan, David Arroyo, Champika Pattullo, et al.
Aust Health Rev. 2020 Apr;44(2):277-287. doi: 10.1071/AH18245.
Objective This review systematically identified studies that estimated the prevalence of prescription opioid use in Australia, assessed the prevalence estimates for bias and identified areas for future research. Methods Literature published after 2000 containing a potentially representative estimate of prescription opioid use in adults, in the community setting, in Australia was included in this review. Studies that solely assessed opioid replacement, illicit opioid usage or acute hospital in-patient use were excluded. Databases searched included PubMed, EMBASE, Web of Science and the grey literature. Results The search identified 2253 peer-reviewed publications, with 34 requiring full-text review. Of these, 20 were included in the final qualitative analysis, in addition to four publications from the grey literature. Most studies included analysed prescription claims data for medicines dispensed via Australia's national medicines subsidy scheme (the Pharmaceutical Benefits Scheme). Although data sources were good quality, all prevalence estimates were at least at moderate risk of bias, predominantly due to incompleteness of data or potential confounding. Included publications demonstrated a significant rise in opioid use up to 2017 (including a 15-fold increase in prescriptions dispensed over the 20 years to 2015), predominantly driven by a sharp rise in oxycodone use. Although opioid prescription numbers continue to escalate, usage, as measured by oral morphine equivalent per capita, may have plateaued since 2014. Codeine remains the most prevalently obtained opioid, followed by oxycodone and tramadol. There was a substantial delay (median 30 months; interquartile range 20-37 months) to publication of opioid usage data from time of availability. Conclusions Australia has experienced a marked increase in opioid prescribing since the 1990s. Current published literature is restricted to incomplete, delayed and historical data, limiting the ability of clinicians and policy makers to intervene appropriately. What is known about the topic? Opioid prescriptions in Australia have continued to increase since the 1990s and may be mirroring the epidemic being seen in the US. What does this paper add? This paper systematically identifies all publications that have examined the prevalence of prescription opioid use in Australia since 2000, and only identified prevalence estimates that were at moderate or high risk of bias, and found significant delays to publication of these estimates. What are the implications for practitioners? Because published literature on the prevalence of prescription opioid consumption is restricted to incomplete, delayed and historical data, the ability of clinicians and policy makers to appropriately intervene to curb prescription opioid use is limited. A national policy of real-time monitoring and reporting of opioid prescribing may support improvements in practice.
11Benzodiazepine Use in Older Adults in the United States, Ontario, and Australia from 2010 to 2016.PubMed
Jonathan Brett, Donovan T Maust, Zach Bouck, et al.
J Am Geriatr Soc. 2018 Jul;66(6):1180-1185. doi: 10.1111/jgs.15292. Epub 2018 Feb 12.
OBJECTIVES: To detail annual trends in benzodiazepine incidence and prevalence in older adults between 2010 and 2016 in three countries. DESIGN: Observational multicountry cohort study with harmonized study protocol. SETTING: The United States (veteran population); Ontario, Canada; and Australia. PARTICIPANTS: All people aged 65 and older (8,270,000 people). MEASUREMENTS: Annual incidence and prevalence of benzodiazepine use stratified according to age group (65-74, 75-84, ≥85) and sex. We performed multiple regression analyses to assess whether rates of incident and prevalent use changed significantly over time. RESULTS: Over the study period, we observed a significant decrease in incident benzodiazepine use in the United States (2.6% to 1.7%) and Ontario (6.0% to 4.4%) but not Australia (7.0% to 6.7%). We found significant declines in prevalent use in all countries (United States: 9.2% to 7.3%; Ontario: 18.2% to 13.4%; Australia: 20.2% to 16.8%). Although incidence and prevalence increased with age in Ontario and Australia, they decreased with age in the United States. Incidence and prevalence were higher in women in all countries. CONCLUSION: Consistent with other international studies, there have been small but significant reductions in the incidence and prevalence of benzodiazepine use in older adults in all three countries, with the exception of incidence in Australia, although use remains inappropriately high-particularly in those aged 85 and older-which warrants further attention from clinicians and policy-makers.
12Age of Onset and Its Related Factors in Cocaine or Methamphetamine Use in Adults from the United States: Results from NHANES 2005-2018.PubMed
Alexandre Arthur Guerin, Jee Hyun Kim
Int J Environ Res Public Health. 2021 Nov 22;18(22):12259. doi: 10.3390/ijerph182212259.
Cocaine and methamphetamine are widely used illicit psychostimulants worldwide, with steadily increasing global markets that may impact on the frequency of use. Importantly, their use typically begins in youth. This is a particular concern because there is a link between the early age of first substance use and severity of substance use disorder later in life. The aim of the present study was therefore to investigate trends in prevalence, frequency, and age of onset of cocaine or methamphetamine use between 2005 and 2018 in the United States, using the nationally representative NHANES datasets. Factors associated with the ages of cocaine or methamphetamine use onset were also identified. From 2005 to 2018, prevalence and frequencies of cocaine or methamphetamine use increased, while age of onset remained relatively stable (~20 years of age). Annual household income, use of other substances, and intravenous drug use were identified as factors associated with early onset cocaine or methamphetamine use. These factors have important implications toward developing new prevention programs to reduce psychostimulant use.
13Fentanyl, Heroin, Methamphetamine, and Cocaine Analyte Concentrations in Urine Drug Testing Specimens.PubMed
Andrew S Huhn, Penn Whitley, B Levi Bolin, et al.
JAMA Netw Open. 2024 Oct 1;7(10):e2441063. doi: 10.1001/jamanetworkopen.2024.41063.
IMPORTANCE: The US is experiencing a protracted drug overdose crisis primarily associated with exposure to illicitly manufactured fentanyl (IMF), methamphetamine, and cocaine. Overdose risk and treatment responses may be directly affected by absolute drug exposure concentrations and drug use prevalence. OBJECTIVE: To quantify changes in absolute drug exposure concentrations from 2013 to 2023. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed urine drug testing (UDT) results from urine specimens collected between January 1, 2013, and August 22, 2023, in 49 states and the District of Columbia. Urine specimens were obtained from patients aged 18 years or older who presented to substance use disorder treatment clinics. The UDT was ordered by clinicians based on medical necessity. EXPOSURES: Urine specimens were analyzed for the following drugs or metabolites (analytes tested in parentheses): fentanyl (fentanyl), heroin (6-monoacetylmorphine), cocaine (benzoylecgonine), and methamphetamine (methamphetamine) using liquid chromatography with tandem mass spectrometry. MAIN OUTCOMES AND MEASURES: Relative concentrations of fentanyl, heroin, cocaine, and methamphetamine. Creatinine-normalized drug concentration values were log-transformed prior to visualization and statistical analyses. The Mann-Kendall trend test was performed to examine trends over time. To estimate the geospatial and temporal patterns of drug concentration, a second series of models (1 for each drug) with an interaction effect for clinic location and collection year were fit. RESULTS: A total of 921 931 unique UDT samples were collected from patients (549 042 males [59.6%]; median [IQR] age, 34 [27-44] years). The adjusted fentanyl concentration in urine specimens was 38.23 (95% CI, 35.93-40.67) ng/mg creatinine in 2023 and 4.61 (95% CI, 3.59-5.91) ng/mg creatinine in 2013. The adjusted methamphetamine concentration was 3461.59 (95% CI, 3271.88-3662.30) ng/mg creatinine in 2023 and 665.27 (95% CI, 608.51-727.32) ng/mg creatinine in 2013. The adjusted cocaine concentration was 1122.23 (95% CI, 1032.41-1219.87) ng/mg creatinine in 2023 and 559.71 (95% CI, 524.69-597.06) ng/mg creatinine in 2013. The adjusted heroin concentration was 58.36 (95% CI, 48.26-70.58) ng/mg creatinine in 2023 and 146.59 (95% CI, 136.06-157.92) ng/mg creatinine in 2013. Drug concentrations varied across US Census divisions. CONCLUSIONS AND RELEVANCE: This cross-sectional study found that absolute concentrations of fentanyl, methamphetamine, and cocaine in urine specimens increased from 2013 to 2023, with a decrease in heroin concentration during that period. The findings suggest that exposure to these substances, as well as the illicit drug supply, has fundamentally changed in many parts of the US, highlighting the need to reinforce surveillance initiatives and accelerate efforts to treat individuals with IMF and/or stimulant exposure.
14Opioid overdose decedent characteristics during COVID-19.PubMed
Gian-Gabriel P Garcia, Erin J Stringfellow, Catherine DiGennaro, et al.
Ann Med. 2022 Dec;54(1):1081-1088. doi: 10.1080/07853890.2022.2067350.
INTRODUCTION: Alongside the emergence of COVID-19 in the United States, several reports highlighted increasing rates of opioid overdose from preliminary data. Yet, little is known about how state-level opioid overdose death trends and decedent characteristics have evolved using official death records. METHODS: We requested vital statistics data from 2018-2020 from all 50 states and the District of Columbia, receiving data from 14 states. Accounting for COVID-19, we excluded states without data past March 2020, leaving 11 states for analysis. We defined state-specific analysis periods from March 13 until the latest reliable date in each state's data, then conducted retrospective year-over-year analyses comparing opioid-related overdose death rates, the presence of specific opioids and other psychoactive substances, and decedents' sex, race, and age from 2020 to 2019 and 2019 to 2018 within each state's analysis period. We assessed whether significant changes in 2020 vs. 2019 in opioid overdose deaths were new or continuing trends using joinpoint regression. RESULTS: We found significant increases in opioid-related overdose death rates in Alaska (55.3%), Colorado (80.2%), Indiana (40.1%), Nevada (50.0%), North Carolina (30.5%), Rhode Island (29.6%), and Virginia (66.4%) - all continuing previous trends. Increases in synthetic opioid-involved overdose deaths were new in Alaska (136.5%), Indiana (27.6%), and Virginia (16.5%), whilst continuing in Colorado (44.4%), Connecticut (3.6%), Nevada (75.0%), and North Carolina (14.6%). We found new increases in male decedents in Indiana (12.0%), and continuing increases in Colorado (15.2%). We also found continuing increases in Black non-Hispanic decedents in Massachusetts (43.9%) and Virginia (33.7%). CONCLUSION: This research analyzes vital statistics data from 11 states, highlighting new trends in opioid overdose deaths and decedent characteristics across 10 of these states. These findings can inform state-specific public health interventions and highlight the need for timely and comprehensive fatal opioid overdose data, especially amidst concurrent crises such as COVID-19. Key messages:Our results highlight shifts in opioid overdose trends during the COVID-19 pandemic that cannot otherwise be extracted from aggregated or provisional opioid overdose death data such as those published by the Centres for Disease Control and Prevention.Fentanyl and other synthetic opioids continue to drive increases in fatal overdoses, making it difficult to separate these trends from any possible COVID-19-related factors.Black non-Hispanic people are making up an increasing proportion of opioid overdose deaths in some states.State-specific limitations and variations in data-reporting for vital statistics make it challenging to acquire and analyse up-to-date data on opioid-related overdose deaths. More timely and comprehensive data are needed to generate broader insights on the nature of the intersecting opioid and COVID-19 crises.
15Abuse of fentanyl: An emerging problem to face.PubMed
Katarzyna Kuczyńska, Piotr Grzonkowski, Łukasz Kacprzak, et al.
Forensic Sci Int. 2018 Aug;289:207-214. doi: 10.1016/j.forsciint.2018.05.042. Epub 2018 Jun 2.
Fentanyl is a potent synthetic opioid used as a narcotic analgesic supplement in general and regional anesthesia as well as in management of persistent, severe chronic pain. Alarming epidemiological and forensic medicine reports, accumulated mainly during the last two decades, point to a growing increase in illicit use of fentanyl, mainly in North America and Europe. Toxicological data indicates that fentanyl use is inextricably linked with polydrug use. There are two main sources of fentanyl on the "recreational" drug market. First, the most common, combines illicitly manufactured fentanyl from clandestine sources. The drug is often mixed up with heroin ("fake heroin") to increase its potency at a little cost, or included in cocaine products. It can also be mixed into and sold as oxycodone-, hydrocodone- or alprazolam-containing tablets. The other way to gain fentanyl is through the diversion of fentanyl-containing medicines, especially transdermal patches (FTPs). Fentanyl extracted from FTP can be administered intravenously, insufflated or inhaled after volatilization. The drug can also be delivered by oral or transmucosal application of the whole patch, or by rectal insertion. The most common overdose symptoms are coma, lethargy, respiratory depression and arrest. Although naloxone, an opioid receptor antagonist, is the standard drug for fentanyl overdose rescue, attempts to revive patients with naloxone could be unsuccessful, due to the rapid onset of fentanyl's action. As the fentanyl problem is constantly growing, there is an urgent need for new, effective harm-reduction strategies and technologies, as well as overdose maintenance.
16Trends in Fentanyl Content on Reddit Substance Use Forums, 2013-2021.PubMed
Amanda M Bunting, Noa Krawczyk, Thomas Lippincott, et al.
J Gen Intern Med. 2023 Nov;38(15):3283-3287. doi: 10.1007/s11606-023-08256-7. Epub 2023 Jun 9.
BACKGROUND: Fentanyl is a pressing concern in the current drug supply. Social media data can provide access to near real-time understanding of drug trends that may complement official mortality data. DESIGN: The total number of fentanyl-related posts and the total number of posts for eight drug subreddit categories (alcohol, cannabis, hallucinogens, multi-drug, opioids, over the counter, sedatives, stimulants) were collected from 2013 to 2021 using the Pushshift Reddit dataset. The proportion of fentanyl-related posts as a fragment of total subreddit posts was examined. Linear regressions described the rate of change in post volume over time. RESULTS: Overall, fentanyl-related content increased across drug-related subreddits from 2013 to 2021 (1292% increase, linear trend p ≤ 0.001). Opioid subreddits (30.62 per 1000 posts, linear trend p ≤ 0.001) had the most fentanyl-related content during the examined time period. Multi-drug (5.95 per 1000; p ≤ 0.01), sedative (3.23 per 1000, p ≤ 0.01), and stimulant (1.60 per 1000, p ≤ 0.01) subreddits also had substantial increases in fentanyl-related content. The greatest increases occurred in the multi-drug (1067% 2013:2021) and stimulant (1862% 2014:2021) subreddits. CONCLUSION: Fentanyl-related posts on Reddit trended upward, with the fastest rate of change for multi-substance and stimulant subreddits. Beyond opioids, harm reduction and public health messaging should ensure inclusion of individuals who use other drugs.
17Methadone-involved overdose deaths in the United States before and during the COVID-19 pandemic.PubMed
Robert A Kleinman, Marcos Sanches
Drug Alcohol Depend. 2023 Jan 1;242:109703. doi: 10.1016/j.drugalcdep.2022.109703. Epub 2022 Nov 19.
BACKGROUND: Few studies have characterized methadone-involved overdose deaths in the US since 2014 despite changing patterns of opioid use, the onset of the COVID-19 pandemic, and changes to take-home dose guidance in opioid treatment programs (OTPs) in March 2020. METHODS: Data on monthly overdose deaths in the US from January 1, 2007 to March 31, 2021 were obtained through CDC WONDER. Interrupted time series models were used to assess for changes in series levels starting in April 2020. Analyses were stratified by involvement of synthetic opioids in overdose deaths. RESULTS: An increase in methadone-involved overdoses of 105.4 deaths per month (95 % CI: 73.8-137.0) occurred starting in April 2020 compared with prior trends (p < 0.001). Trends in methadone-involved overdose deaths showed a step increase starting in April 2020 both with (54.2 deaths per month; 95 % CI: 39.4-68.9) and without (51.7 deaths per month; 95 % CI: 23.4-78.0) synthetic opioid involvement (p < 0.001 for both). Among overdose deaths without synthetic opioids, the increase in methadone-involved overdose deaths accounted for 26.5 % of the increase between the 12-month periods before and after March 2020. The relative percentage increase in methadone-involved overdose deaths, both with and without synthetic opioid co-involvement, was highest among Hispanic and non-Hispanic Black individuals. CONCLUSIONS: Methadone-involved overdose deaths, both with and without other synthetic opioid co-involvement, increased during the 12-month period after March 2020, compared with prior trends. These results provide a cautionary addition to previous findings of no or limited methadone-related harms after the US regulatory changes during the COVID-19 pandemic.
18Global prevalence of cannabis and amphetamine/methamphetamine use among adolescents in 47 countries: a population-based study from WHO database.PubMed
Yejun Son, Seohyun Hong, Yesol Yim, et al.
World J Pediatr. 2025 Mar;21(3):291-305. doi: 10.1007/s12519-025-00883-w. Epub 2025 Mar 20.
BACKGROUND: Adolescent drug use poses significant public health challenges worldwide, with detrimental effects on mental and physical health. Most existing research focuses on Western countries, holding a gap in understanding drug use in low- and middle-income countries. Thus, we aimed to assess the prevalence of cannabis and amphetamine or methamphetamine use among school-going adolescents aged 12-15 years across 47 countries globally. METHODS: We used data from the Global School-based Student Health Survey from 47 countries (2009-2018) to analyze cannabis and amphetamine/methamphetamine use and age at first drug use among adolescents (n = 220,362). A meta-analysis utilizing random-effects models estimated prevalence rates and weighted linear regression analyzed trends. Student's t tests were used to compare two-subgroup categories, while one-way ANOVA was employed for analyses involving the four-subgroup category. Stratification analysis by sex, World Bank income category, region, and country-specific characteristics based on World Health Organization data were also performed. RESULTS: The study included a total of 220,362 school-going adolescents aged 12-15 years (49.96% girls) from 47 countries. The overall prevalence of cannabis use was 7.02% [95% confidence interval (CI) 6.16-7.89], with higher usage among boys [9.20% (95% CI 8.05-10.36)] compared to girls [4.20% (95% CI 3.68-4.72)]. Amphetamine/methamphetamine use prevalence was 4.05% (95% CI 3.51-4.60), also higher among boys [5.14% (95% CI 4.45-5.84)] than girls [2.34% (95% CI 2.00-2.69)]. The region of the Americas exhibited the highest prevalence of cannabis use [11.31% (95% CI 8.44-14.17)], while the African region showed the highest prevalence of amphetamine use [4.34% (95% CI 3.14-5.53)]. High-income countries reported the highest prevalence of cannabis use [9.45% (95% CI, 6.06 to 12.84)], whereas low-income countries had the lowest [3.46% (95% CI 2.01-4.91)]. Higher prevalence rates were associated with countries having higher homicide rates, better sanitation services, and higher health expenditures. CONCLUSIONS: Cannabis use among adolescents is more prevalent than amphetamine or methamphetamine use, with significant sex differences showing higher prevalence among boys. The highest prevalence of cannabis use was observed in Latin America, while Africa exhibited the highest rates of amphetamine use. Findings from the present study indicate a need for public policies and programs targeting adolescents to effectively reduce adolescent drug use.
19Increase in pregabalin recreational use in adolescents in France.PubMed
Laurene Dufayet, Weniko Care, Sylvie Deheul, et al.
Clin Toxicol (Phila). 2021 Nov;59(11):1027-1030. doi: 10.1080/15563650.2021.1892719. Epub 2021 Mar 18.
INTRODUCTION: Misuse/abuse of pregabalin is increasing worldwide. French Poison Control Centers (PCCs) recently received several unusual calls regarding the recreational use of pregabalin in adolescents. This study aims to describe this new and specific population of pregabalin misusers. METHODS: We extracted all cases of pregabalin intentional exposures reported to the French National Database of Poisonings (FNDP) from 2004 to 2020. We compared the proportion of recreational exposure to pregabalin between adolescents (10-17 years) and adults (>18 years). We reviewed all cases of pregabalin recreational exposures in adolescent in order to describe the characteristics of this population. RESULTS: During the study period, 382 cases of acute intentional exposure to pregabalin were reported in adolescents and 1188 in adults, 94/382 (24.6%) and 43/1188 (3.6%) were pregabalin recreational use, respectively ( < .0001). Almost all cases of pregabalin recreational use in adolescent were reported from 2018 (86/94; 91%). Most of those adolescent patients were males (male/female ratio - 5.3:1) and the median age was 15 years (range: 11-17.8). They were homeless or living in migrant shelters in most of the cases (73/90, 81%). Two-third of these exposures (62/94; 66%) involved other toxicant(s) than pregabalin. Most of the patients remains asymptomatic (10/94; 11%), or developed minor to moderate neurological symptoms (76/94; 81%). Eight developed severe symptoms (8/94; 8%) including coma (5/8) or generalized seizures (2/8). Five patients (5/8) required oro-tracheal intubation. No fatality was reported. CONCLUSIONS: We observed a sharp increase in pregabalin recreational use in adolescents in France. It should lead to prevention campaigns, targeted at the population at risk described in this study.
20A systematic review and meta-analysis of the association between poor oral health and substance abuse.PubMed
Hooman Baghaie, Steve Kisely, Malcolm Forbes, et al.
Addiction. 2017 May;112(5):765-779. doi: 10.1111/add.13754. Epub 2017 Mar 16.
BACKGROUND AND AIMS: Substance use disorders are associated commonly with comorbid physical illness. There are fewer data on dental disease in these conditions, in spite of high rates of dry mouth (xerostomia), as well as the associated indirect or life-style effects such as poverty and lack of access to care. We compared the oral health of people with substance use disorders (SUDs) with non-using controls. METHOD: This was a systematic search for studies from the last 35 years of the oral health of people reporting SUDs. We used MEDLINE, PsycInfo, OVID, Google Scholar, EMBASE and article bibliographies. Results were compared with the general population. Oral health was assessed in terms of dental caries and periodontal disease using the following standardized measures: the mean number of decayed, missing and filled teeth (DMFT) or surfaces (DMFS) and probing pocket depth. Non-carious tooth loss was assessed clinically. RESULTS: We identified 28 studies that had sufficient data for a meta-analysis, comprising 4086 SU patients and 28 031 controls. People with SUD had significantly higher mean scores for DMFT [mean difference = 5.15, 95% confidence interval (CI) = 2.61-7.69 and DMFS (mean difference = 17.83, 95% CI = 6.85-28.8]. They had more decayed teeth but fewer restorations, indicating reduced access to dental care. Patients with SUD also exhibited greater tooth loss, non-carious tooth loss and destructive periodontal disease compared to controls. CONCLUSION: Patients with substance use disorders have greater and more severe dental caries and periodontal disease than the general population, but are less likely to have received dental care.
21Oral health assessment for users of marijuana and cocaine/crack substances.PubMed
Mariane Beatriz Sordi, Rachel Captzan Massochin, Alessandra Rodrigues de Camargo, et al.
Braz Oral Res. 2017 Dec 18;31:e102. doi: 10.1590/1807-3107BOR-2017.vol31.0102.
The objective of this study was to assess the oral health status of users of illicit drugs such as marijuana and cocaine/crack and compare it with individuals not using these chemical substances. Questionnaires were applied to 35 illicit drugs users to gather information on demographic status, general health, and use of drugs. Then, a clinical assessment of the oral health condition was performed to collect data on decayed, missing and filled teeth (DMFT) index, salivary flow rate (SFR), and mucosal lesions. The control group was composed of 35 non-illicit drug users. In the experimental group, 91.43% were males, 80% were smokers, and 42.85% were alcoholics. Cocaine was the most common drug used (77.15%), followed by marijuana (68.6%), and crack (51.4%). The average DMFT index was 9.8 and the SFR was reduced in 60% of subjects. Mucosal alterations were detected, but no potentially malignant disorders or oral cancer were diagnosed. Compared to control group, significantly higher values for gender (40%, p = 0.0001), smoking (22.86%) and heavy drinking (5.7%) habits (p = 0.0001), SFR (31.4%; p = 0.0308), and oral lesions (p = 0.0488) were found for the experimental group, although significantly higher values were found in the control group for DMFT index (p = 0.0148). It can be concluded that the use of illicit drugs contributed to an increased prevalence of oral mucosa lesions. In addition, a decline on SFR and a reduced DMFT index was observed for illicit drug users.
22Dental Caries and Oral Health Status of Psychoactive Substance Abusers.PubMed
Rashmi Bhavsar, Vandana Shah, Namratha A Ajith, et al.
Int J Environ Res Public Health. 2022 May 10;19(10):5818. doi: 10.3390/ijerph19105818.
UNLABELLED: Substance-abuse disorders are universally associated with comorbid illness. Tobacco is a widely abused substance across the globe and presents a critical public health problem. The precise correlation between tobacco use and dental caries remains unclear. Thus, the present study aimed to evaluate the correlation between tobacco use and dental caries. METHODOLOGY: Based on selection criteria, a total of 270 (age 20-50 years) participants were included in the study, and were categorized as group A (n = 135), consisting of tobacco users, and group B (n = 135), comprising healthy controls (non-users). The Decayed, Missing, and Filled index (DMFT) was used to measure caries status. The Simplified Oral Hygiene index was used to evaluate oral health. RESULTS: The tobacco group reported the use of cigarettes; smokeless tobacco in indigenous forms, such as gutka (areca nut, tobacco, and slaked lime), betel nut chewing; and a combination. Individuals with tobacco habits had a higher prevalence of dental caries (Mean DMFT 4.73 ± 4.32) compared to the non-habit group (Mean DMFT 3.17 ± 3.11 ( = 0.001). The Oral Hygiene index was significantly higher (indicating bad/poor oral hygiene) in tobacco abusers than those of non-users ( = 0.0001). Duration and frequency of tobacco use were correlated with the levels of moderate and severe caries ( = 0.001). CONCLUSION: Psychoactive substance abuse, such as smoking/smokeless tobacco consumption, is associated with higher prevalence of dental caries.
23Aging exaggerates acute-on-chronic alcohol-induced liver injury in mice and humans by inhibiting neutrophilic sirtuin 1-C/EBPα-miRNA-223 axis.PubMed
Ruixue Ren, Yong He, Dong Ding, et al.
Hepatology. 2022 Mar;75(3):646-660. doi: 10.1002/hep.32152. Epub 2021 Dec 5.
BACKGROUND AND AIMS: Aging exacerbates liver neutrophil infiltration and alcohol-associated liver disease (ALD) in mice and humans, but the underlying mechanisms remain obscure. This study aimed to examine the effect of aging and alcohol consumption on neutrophilic Sirtuin 1 (SIRT1) and microRNA-223 (miR-223), and their contribution to ALD pathogeneses. APPROACH AND RESULTS: Young and aged myeloid-specific Sirt1 knockout mice were subjected to chronic-plus-binge ethanol feeding. Blood samples from healthy controls and patients with chronic alcohol drinking who presented with acute intoxication were analyzed. Neutrophilic Sirt1 and miR-223 expression were down-regulated in aged mice compared with young mice. Deletion of the Sirt1 gene in myeloid cells including neutrophils exacerbated chronic-plus-binge ethanol-induced liver injury and inflammation and down-regulated neutrophilic miR-223 expression. Immunoprecipitation experiments revealed that SIRT1 promoted C/EBPα deacetylation by directly interacting with C/EBPα, a key transcription factor that controls miR-223 biogenesis, and subsequently elevated miR-223 expression in neutrophils. Importantly, down-regulation of SIRT1 and miR-223 expression was also observed in circulating neutrophils from middle-aged and elderly subjects compared with those from young individuals. Chronic alcohol users with acute intoxication had a reduction in neutrophilic SIRT1 expression in young and middle-aged patients, with a greater reduction in the latter group. The neutrophilic SIRT1 expression correlated with neutrophilic miR-223 and serum alanine transaminase levels in those patients. CONCLUSIONS: Aging increases the susceptibility of alcohol-induced liver injury in mice and humans through the down-regulation of the neutrophilic SIRT1-C/EBPα-miR-223 axis, which could be a therapeutic target for the prevention and/or treatment of ALD.
24Role of autophagy in alcohol and drug-induced liver injury.PubMed
Jessica A Williams, Wen-Xing Ding
Food Chem Toxicol. 2020 Feb;136:111075. doi: 10.1016/j.fct.2019.111075. Epub 2019 Dec 23.
Alcohol-related liver disease (ALD) and drug-induced liver injury (DILI) are common causes of severe liver disease, and successful treatments are lacking. Autophagy plays a protective role in both ALD and DILI by selectively removing damaged mitochondria (mitophagy), lipid droplets (lipophagy), protein aggregates and adducts in hepatocytes. Autophagy also protects against ALD by degrading interferon regulatory factor 1 (IRF1) and damaged mitochondria in hepatic macrophages. Specifically, we will discuss selective autophagy for removal of damaged mitochondria and lipid droplets in hepatocytes and autophagy-mediated degradation of IRF1 in hepatic macrophages as protective mechanisms against alcohol-induced liver injury and steatosis. In addition, selective autophagy for removal of damaged mitochondria and protein adducts for protection against DILI is discussed in this review. Development of new therapeutics for ALD and DILI is greatly needed, and selective autophagy pathways may provide promising targets. Drug and alcohol effects on autophagy regulation as well as protective mechanisms of autophagy against DILI and ALD are highlighted in this review.
25Infectious Complications of Injection Drug Use.PubMed
Laura R Marks, Nathanial S Nolan, Stephen Y Liang, et al.
Med Clin North Am. 2022 Jan;106(1):187-200. doi: 10.1016/j.mcna.2021.08.006.
The opioid overdose epidemic is one of the leading causes of death in adults. Its devastating effects have included not only a burgeoning overdose crisis but also multiple converging infectious diseases epidemics. The use of both opioids and other substances through intravenous (IV) administration places individuals at increased risks of infectious diseases ranging from invasive bacterial and fungal infections to human immunodeficiency virus (HIV) and viral hepatitis. In 2012, there were 530,000 opioid use disorder (OUD)-related hospitalizations in the United States (US), with $700 million in costs associated with OUD-related infections. The scale of the crisis has continued to increase since that time, with hospitalizations for injection drug use-related infective endocarditis (IDU-IE) increasing by as much as 12-fold from 2010 to 2015. Deaths from IDU-IE alone are estimated to result in over 7,260,000 years of potential life lost over the next 10 years. There have been high-profile injection-related HIV outbreaks, and injection drug use (IDU) is now the most common risk factor for hepatitis C virus (HCV). As this epidemic continues to grow, clinicians in all aspects of medical care are increasingly confronted with infectious complications of IDU. This review will describe the pathogenesis, clinical syndromes, epidemiology, and models of treatment for common infectious complications among persons who inject drugs (PWIDs).
26Epidemiology of hepatitis C virus infection.PubMed
Françoise Roudot-Thoraval
Clin Res Hepatol Gastroenterol. 2021 May;45(3):101596. doi: 10.1016/j.clinre.2020.101596. Epub 2021 Feb 17.
Hepatitis C is a global health problem, with an estimated 71·1 million individuals chronically infected worldwide, accounting for 1% (95% uncertainty interval: 0.8-1.1) of the population. HCV transmission is most commonly associated with direct exposure to blood, via blood transfusions, unsafe health-care-related injections and intravenous drug use. The global incidence of HCV was 23·7 cases per 100 000 population (95% uncertainty interval 21·3-28·7) in 2015, with an estimated 1·75 million new HCV infections diagnosed in 2015. An estimated 2.3 millions of people living with HIV have serological markers of past or current HCV infection. Globally, the most common infections are with HCV genotypes 1 (44% of cases), 3 (25% of cases), and 4 (15% of cases). Approximately 10-20% of individuals who are chronically infected with HCV develop complications, such as cirrhosis, end stage liver disease, and hepatocellular carcinoma over a period of 20-30 years. Direct-acting antiviral therapy is curative, dramatically reducing the mortality related to HCV and the need for liver transplantation, but it is estimated that only 20% of individuals with hepatitis C know their diagnosis, and only 15% of those with known hepatitis C have been treated. Increased diagnosis and linkage to care through universal access to affordable point-of-care diagnostics and pangenotypic direct-acting antiviral therapy is essential to achieve the WHO 2030 elimination targets.
27Hepatitis in AIDS patients.PubMed
Muhammad Imran Qadir
Rev Med Virol. 2018 Jan;28(1). doi: 10.1002/rmv.1956. Epub 2017 Oct 13.
The individuals with HIV infection are more susceptible to develop coinfections with infectious pathogens such as HCV and HBV. The routes of transmission of these pathogens are the same including sexual contact, injection drug use, or at birth from mother to an infant. The main reason of morbidity and mortality in HIV infected individuals is a liver disease in the context of antiretroviral therapy, and coinfection such as HCV and HBV complicates this condition. Nucleos(t)ide analogues are used for HBV infection management, and treatment of HCV infection is done by PegIFN and ribavirin combination and protease inhibitors. In this review, we focused on hepatitis B and C infections in HIV patients along with their therapies.
28Substance abuse, HIV-1 and hepatitis.PubMed
Nirzari Parikh, Michael R Nonnemacher, Vanessa Pirrone, et al.
Curr HIV Res. 2012 Oct;10(7):557-71. doi: 10.2174/157016212803306023.
During the course of human immunodeficiency virus type 1 (HIV-1) disease, the virus has been shown to effectively escape the immune response with the subsequent establishment of latent viral reservoirs in specific cell populations within the peripheral blood (PB) and associated lymphoid tissues, bone marrow (BM), brain, and potentially other end organs. HIV-1, along with hepatitis B and C viruses (HBV and HCV), are known to share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Substance abuse, including the use of opioids and cocaine, is a significant risk factor for exposure to HIV-1 and the development of acquired immune deficiency syndrome, as well as HBV and HCV exposure, infection, and disease. Thus, coinfection with HIV-1 and HBV or HCV is common and may be impacted by chronic substance abuse during the course of disease. HIV- 1 impacts the natural course of HBV and HCV infection by accelerating the progression of HBV/HCV-associated liver disease toward end-stage cirrhosis and quantitative depletion of the CD4+ T-cell compartment. HBV or HCV coinfection with HIV-1 is also associated with increased mortality when compared to either infection alone. This review focuses on the impact of substance abuse and coinfection with HBV and HCV in the PB, BM, and brain on the HIV-1 pathogenic process as it relates to viral pathogenesis, disease progression, and the associated immune response during the course of this complex interplay. The impact of HIV-1 and substance abuse on hepatitis virus-induced disease is also a focal point.
29Increased hepatitis C virus co-infection and injection drug use in HIV-infected fishermen in Myanmar.PubMed
Janet Ousley, Robin Nesbitt, Nang Thu Thu Kyaw, et al.
BMC Infect Dis. 2018 Dec 14;18(1):657. doi: 10.1186/s12879-018-3558-y.
BACKGROUND: In Southeast Asia, though fishermen are known to be a key population at high risk of HIV, little is known about their co-infection rates with Hepatitis C virus (HCV), or how illness and risk behaviors vary by occupation or type of fishermen. In Myanmar, this lack of knowledge is particularly acute, despite the fact that much of the country's border is coastline. METHODS: We conducted a retrospective analysis to assess clinical, demographic, and risk characteristics of HIV-infected, ≥15-year-old males under HIV care from 2004 to 2014. Subgroups of fishermen were categorized according to the location of fishing activities, boat ownership, and length of time at sea. Generalized linear models assessed odds of high risk behaviors, including MSM (men who have sex with men), transactional sex, injection drug use (IDU), and HCV co-infection among international, local subsistence, and national migrant fishermen. RESULTS: Of 2798 adult males who enrolled in HIV care between 2004 and 2014, 41.9% (n = 1172) were fishermen. Among these, migrants had the highest odds of engaging in risk behaviors such as sex work (Myanmar national migrants: OR 3.26 95% CI: 2.20 to 4.83), and injecting drugs (international migrants: OR 2.93, 95% CI: 1.22 to 3.87) when compared to the general male HIV clinic population. 15.9% of all fishermen reported past or current IDU (23.0% of international migrants). 22.8% of all fishermen were also co-infected with HCV, and though predictably injectors had the highest odds (OR 20.1, 95% CI: 13.7 to 29.5), even after controlling for other risk factors, fishermen retained higher odds (OR 2.37 95% CI: 1.70 to 3.32). CONCLUSIONS: HIV positive fishermen in Myanmar had higher odds of HCV co-infection. They also disproportionally injected drugs and engaged in transactional sex more than other patients. This is especially pronounced among international migrant fishermen. HIV-infected fishermen should be counseled on high risk activities, screened for HCV, and targeted by harm reduction programs.
30Right-Sided Infective Endocarditis 2020: Challenges and Updates in Diagnosis and Treatment.PubMed
Hezzy Shmueli, Felix Thomas, Nir Flint, et al.
J Am Heart Assoc. 2020 Aug 4;9(15):e017293. doi: 10.1161/JAHA.120.017293. Epub 2020 Jul 23.
Compared with the extensive data on left-sided infective endocarditis (IE), there is much less published information on the features and management of right-sided IE. Right-sided IE accounts for 5% to 10% of all IE cases, and compared with left-sided IE, it is more often associated with intravenous drug use, intracardiac devices, and central venous catheters, all of which has become more prevalent over the past 20 years. In this manuscript on right-sided IE we provide an up-to-date overview on the epidemiology, etiology, microbiology, potential locations of infection in the right heart, diagnosis, imaging, common complications, management, and prognosis. We present updated information on the treatment of pacemaker and device infections, infected fibrin sheaths that appear to be an easily missed source of infection after central line as well as pacemaker removal. We review current data on the AngioVac percutaneous aspiration device, which can obviate the need for surgery in patients with infected pacemaker leads and fibrin sheaths. We also focused on advanced diagnostic modalities, such as positron emission tomography/computed tomography. All of these are supported by specific case examples with detailed echocardiographic imaging from our experience.
31Native valve right sided infective endocarditis.PubMed
Karolina Akinosoglou, Efstratios Apostolakis, Markos Marangos, et al.
Eur J Intern Med. 2013 Sep;24(6):510-9. doi: 10.1016/j.ejim.2013.01.010. Epub 2013 Jan 28.
Right-sided infective endocarditis (RSIE) accounts for 5-10% of all cases of infective endocarditis (IE), and is predominantly encountered in the injecting drug user (IDU) population, where HIV and HCV coinfections often coexist. Staphylococcus aureus is the most common pathogen. The pathogenesis of RSIE is still not well understood. RSIE usually presents as a persistent fever with respiratory symptoms whilst signs of systemic embolisation as seen in left-sided IE are notably absent. The prompt diagnosis of RSIE thus requires a high index of suspicion. Transthoracic echocardiography (TTE) can detect the majority of RSIE, whilst transoesophageal echocardiography (TOE) can increase sensitivity. Virulence of the causative organism and vegetation size are the major determinants of prognosis. Most cases of RSIE resolve with appropriate antibiotic administration.
32Bouncing back: Brain rehabilitation amid opioid and stimulant epidemics.PubMed
Jennifer L Stewart, April C May, Martin P Paulus
Neuroimage Clin. 2019;24:102068. doi: 10.1016/j.nicl.2019.102068. Epub 2019 Nov 5.
Recent methamphetamine and opioid use epidemics are a major public health concern. Chronic stimulant and opioid use are characterized by significant psychosocial, physical and mental health costs, repeated relapse, and heightened risk of early death. Neuroimaging research highlights deficits in brain processes and circuitry that are linked to responsivity to drug cues over natural rewards as well as suboptimal goal-directed decision-making. Despite the need for interventions, little is known about (1) how the brain changes with prolonged abstinence or as a function of various treatments; and (2) how symptoms change as a result of neuromodulation. This review focuses on the question: What do we know about changes in brain function during recovery from opioids and stimulants such as methamphetamine and cocaine? We provide a detailed overview and critique of published research employing a wide array of neuroimaging methods - functional and structural magnetic resonance imaging, electroencephalography, event-related potentials, diffusion tensor imaging, and multiple brain stimulation technologies along with neurofeedback - to track or induce changes in drug craving, abstinence, and treatment success in stimulant and opioid users. Despite the surge of methamphetamine and opioid use in recent years, most of the research on neuroimaging techniques for recovery focuses on cocaine use. This review highlights two main findings: (1) interventions can lead to improvements in brain function, particularly in frontal regions implicated in goal-directed behavior and cognitive control, paired with reduced drug urges/craving; and (2) the targeting of striatal mechanisms implicated in drug reward may not be as cost-effective as prefrontal mechanisms, given that deep brain stimulation methods require surgery and months of intervention to produce effects. Overall, more studies are needed to replicate and confirm findings, particularly for individuals with opioid and methamphetamine use disorders.
33A review of the neurobiological underpinning of comorbid substance use and mood disorders.PubMed
Nieves Gómez-Coronado, Rickinder Sethi, Chiara Cristina Bortolasci, et al.
J Affect Disord. 2018 Dec 1;241:388-401. doi: 10.1016/j.jad.2018.08.041. Epub 2018 Aug 11.
BACKGROUND: There is evidence that substance use disorders and other mental disorders may have shared biological mechanisms. However, the neurobiological basis of this comorbidity remains only partially explained. This review describes the historical evolution of the dual disorders concept and approach, and reviews the existing literature on neurobiological findings specifically regarding comorbid substance use and mood disorders. METHODS: Searches were conducted using PubMed and Scopus in December 2017. A Boolean search was performed using combinations of "dual diagnosis" or "dual disorder" or "depression" or "bipolar" or "affective disorder" or "mood disorder" and "substance use" or "substance abuse" and "neurobiology" or "functional neuroimaging" or "genetics" or "neurotransmitters" or "neuroendocrinology" in the title or abstract, or as keywords, using no language restriction. RESULTS: 32 studies met the inclusion criteria. We found robust evidence for involvement of the neurotransmitters dopamine, GABA and glutamate and their receptors, as well as by the central corticotrophin-releasing hormone, hypothalamic-pituitary-adrenal axis activation, oxidative stress and inflammation. Recent studies focusing on neuroimaging and genetics have not shown consistent results. LIMITATIONS: Only two search tools were used; most identified studies excluded the population of interest (comorbid mood and substance abuse disorders). CONCLUSIONS: The neurobiological relevance for the occurrence of comorbid mood and substance abuse disorders has not been fully elucidated. Considering the high levels of individuals who experience comorbidity in these areas as well as the negative associated outcomes, this is clearly an area that requires further in-depth investigation. Furthermore, findings from this area can help to inform drug abuse prevention and intervention efforts, and especially how they relate to populations with psychiatric symptoms.
34Depression and stimulant dependence: neurobiology and pharmacotherapy.PubMed
T R Kosten, A Markou, G F Koob
J Nerv Ment Dis. 1998 Dec;186(12):737-45. doi: 10.1097/00005053-199812000-00001.
Depressive disorder rates in stimulant-dependent individuals are substantially higher than community rates. Further, depressive symptoms are considered a major component of stimulant withdrawal. The comorbidity of these disorders may reflect shared neurochemical alterations in the function of serotonin, dopamine, and peptide systems, such as corticotropin releasing factor (CRF) and neuropeptide Y (NPY). These alterations are observed in patients, and in animal models of depression and stimulant dependence, particularly in limbic brain structures. This shared neurobiology does not seem to result from significant shared heritability or genetic linkage; stimulants may induce changes in neurobiology that are similar to those found in depression, and these changes might provide a therapeutic target. Stimulant-dependent patients with a depressive disorder may be a specific subpopulation for antidepressant trials, and they might reduce their stimulant abuse when treated with antidepressants. Nevertheless, concomitant dependence on alcohol or opioids may influence this response, and antidepressants appear to be more effective for depression in combined stimulant and opioid dependence than in combined stimulant and alcohol dependence.
35Methamphetamine Use and Antipsychotic-related Extrapyramidal Side-effects in Patients with Psychotic Disorders.PubMed
Henk S Temmingh, Wim van den Brink, Fleur Howells, et al.
J Dual Diagn. 2020 Apr-Jun;16(2):208-217. doi: 10.1080/15504263.2020.1714099. Epub 2020 Jan 26.
Extrapyramidal side-effects (EPSE) are frequent in patients treated with antipsychotics and comorbid substance use disorders (SUDs). Methamphetamine has been shown to act as a dopaminergic neurotoxin. We aimed to determine whether EPSE occur more often in patients with psychotic disorders and co-occurring methamphetamine (MA) use disorders, and we examined the relationship between MA use, antipsychotic type, dose and EPSE. This study was a secondary analysis of data from three separate primary studies. Across all studies, psychiatric and SUD diagnoses were determined using the SCID-I for DSM-IV. EPSE were determined using the Simpson-Angus Scale (SAS) for Parkinsonism, the Barnes Akathisia Rating scale (BARS), and the Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia. Participants were classified as having any EPSE if they scored above the cutoff on any of the EPSE scales (SAS, BARS, AIMS). We analyzed data using multivariable logistic regression analysis. The sample included 102 patients with non-affective or affective psychotic disorders. Of the total sample, 65.7% were male, 54.9% had schizophrenia spectrum disorders, 20.5% bipolar type I disorder with psychotic features, 11.7% schizoaffective disorder and 12.7% had substance-induced psychosis. A diagnosis of a methamphetamine use disorder (abuse or dependence) was present in 25.5% of participants. EPSE occurred in 38.2% of patients and were significantly associated with MA use in the unadjusted and adjusted analysis, = 4.01, 95% CI [1.07, 14.98], = .039. Patients with MA dependence and MA use >3 years were significantly more likely to have EPSE. We found a significant interaction effect between MA use disorders and standardized antipsychotic dose on the occurrence of EPSE, = 1.01, 95% CI [1.00, 1.01], = .042, with MA users having a disproportionally higher likelihood of having EPSE compared to MA non-users as antipsychotic dosage increased. There were no significant associations of EPSE with comorbid alcohol, cannabis, or methaqualone use disorders. Patients with a MA use disorder were significantly more likely to have EPSE with evidence for a dose-response effect. Clinicians should carefully titrate antipsychotic dosage from lower to higher doses to avoid EPSE in patients with MA use disorders.
36Beyond the tip of the iceberg: A narrative review to identify research gaps on comorbid psychiatric disorders in adolescents with methamphetamine use disorder or chronic methamphetamine use.PubMed
Sören Kuitunen-Paul, Veit Roessner, Lukas A Basedow, et al.
Subst Abus. 2021;42(1):13-32. doi: 10.1080/08897077.2020.1806183. Epub 2020 Sep 1.
Methamphetamine use disorder (MUD) frequently begins in adolescence, often accompanied by other psychiatric or mental disorders. Up to now, no comprehensive review about MUD and comorbid disorders in adolescents is available. We thus aimed to review the literature on comorbid mental disorders and MUD in adolescents in order to identify future research topics. : A PubMed search was conducted in July 2019. Relevant comorbidities were defined as attention-deficit disorder with/without hyperactivity, anxiety disorders, depression, eating disorders, post-traumatic stress disorder, psychosis, borderline personality disorder, conduct disorder and antisocial personality disorder, as well as other substance use disorders. For each comorbidity, we summarized prevalence rates, findings on comorbidity mechanisms, and recommended treatment options, if applicable. : Few articles focused on MUD in adolescents. Prevalence rates differed largely between comorbid disorders, with tobacco use disorder, conduct disorder, post-traumatic stress disorder, anxiety disorders, and attention-deficit disorders being the most prevalent comorbidities while eating disorders were rare. Examined onset patterns and comorbidity mechanisms indicated three groups of comorbidities: preexisting disorders self-medicated with methamphetamine, disorders induced by chronic methamphetamine use, and disorders arising due to risk factors shared with MUD. Reviewed comorbidities were frequently associated with worse treatment outcomes. : The limited evidence is in stark contrast to the presumably high prevalence and relevance of comorbid mental disorders in adolescents with MUD. Suggestions for future research topics, informed by adult findings, include genetic vulnerabilities, biological changes, and consequences of different use patterns. Surprisingly few MUD treatment programs explicitly integrate comorbid mental disorder modules.
37Drugs of abuse and increased risk of psychosis development.PubMed
Anand Gururajan, Elizabeth E Manning, Maren Klug, et al.
Aust N Z J Psychiatry. 2012 Dec;46(12):1120-35. doi: 10.1177/0004867412455232. Epub 2012 Jul 25.
OBJECTIVE: There is considerable evidence to suggest that the abuse of illicit drugs, particularly cannabis and methamphetamine, has aetiological roles in the pathogenesis of psychosis and schizophrenia. Factors that may increase susceptibility to the propsychotic effects of these drugs include the age at which the abuse starts as well as family history of genetic polymorphisms relevant to the pathophysiology of this disorder. However, the neurobiological mechanisms involved in drug abuse-associated psychosis remain largely unclear. METHODS AND RESULTS: This paper presents an overview of the available evidence, including clinical, animal model, and molecular studies, with a focus on brain regions and neurotransmitters systems, such as dopamine and glutamate, previously implicated in psychosis. CONCLUSION: It is clear that further studies are urgently needed to provide a greater insight into the mechanisms that mediate the long-term and neurodevelopmental effects of cannabis and methamphetamine. A dialogue between basic science and clinical research may help to identify at-risk individuals and novel pathways for treatment and prevention.
38Interactions between cannabis and schizophrenia in humans and rodents.PubMed
Ahmed A Moustafa, Mohamed Salama, Roseanne Peak, et al.
Rev Neurosci. 2017 Oct 26;28(7):811-823. doi: 10.1515/revneuro-2016-0083.
In this review, we provide an overview of the relationship between cannabis use and the development of schizophrenia, using both animal and human studies. We further discuss the potential neural mechanism that may mediate the relationship between cannabis use and schizophrenia symptoms. We finally provide clinical implications and future studies that can further elucidate the relationship between cannabis and schizophrenia.
39Altered functional dynamics gradient in schizophrenia with cigarette smoking.PubMed
Yanchi Chen
Cereb Cortex. 2023 May 24;33(11):7185-7192. doi: 10.1093/cercor/bhad030.
Schizophrenia is associated with a high prevalence of cigarette smoking. Neural dynamics are spatially structured and shaped by both microscale molecular and macroscale functional architectures, which are disturbed in the diseased brain. The neural mechanism underlying the schizophrenia-nicotine dependence comorbidity remains unknown. In this study, we aimed to test whether there is an interaction between schizophrenia and smoking in brain neural dynamics, and how the main effect of the 2 factors related to the molecular architecture. Functional magnetic resonance imaging data were obtained from 4 groups: schizophrenia and healthy controls with/without smoking. We identified 2 dynamics gradients combined with over 5,000 statistical features of the brain region's time series. The interaction effect was found in the high-order functional network, and the main effect of schizophrenia was in the bilateral orbitofrontal cortices. Moreover, the disease- and smoking-related alteration in brain pattern was associated with spatial distribution of serotonin, cannabinoid, and glutamate. Collectively, these findings supported the self-medication hypothesis in schizophrenia-nicotine dependence with a neural intrinsic dynamics perspective.
40Substance use during the COVID-19 pandemic: What is really happening?PubMed
Eleftherios Mellos, Thomas Paparrigopoulos
Psychiatriki. 2022 Mar 28;33(1):17-20. doi: 10.22365/jpsych.2022.072. Epub 2022 Feb 21.
The COVID-19 pandemic is associated with increased levels of anxiety, fear, sadness, difficulty adjusting, symptoms of post-traumatic stress disorder and suicidality, both in the general population and specific subgroups. The presence of this type of psychopathology increases the risk of involvement with or worsens the use of addictive substances and alcohol as a maladaptive coping strategy.1 According to these data, people with substance use disorders are a population at high risk for COVID-19 infection and serious illness. Α large controlled retrospective case study in the US found that people with substance use disorders are significantly more vulnerable to COVID-19 and its complications (primarily those with opioid use disorder OR = 10.21 and with tobacco use disorder OR = 8.25), and that the course and outcome of the disease (hospitalization, death) was worse than in non-dependent individuals. The main culprits are increased physical co-morbidity (frequent respiratory and cardiovascular problems), poor health and living conditions, marginalization and difficulties in accessing health services. 2,3 Ιnternational epidemiological data during the first months of the pandemic regarding the use of addictive substances do not lead to safe conclusions. A cross-sectional online epidemiological study conducted on a sample of 36,538 adults from 21 European countries between April and July 2020 found an overall decrease in alcohol use, which was mainly attributed to the reduction of heavy episodic consumption, while at the same time an increase in alcohol consumption among people with severe alcohol use was recorded. Τhe use of cannabis and nicotine showed increasing trends, as well as the use of cocaine, but to a lesser extent, while the use of MDMA (ecstasy) showed a decrease.4 In a review of 45 cross-sectional studies conducted between December 2019 and November 2020, alcohol use was on the rise overall, despite geographical variations, as was the use of other addictive substances, cannabis in particular.5 It should be noted that those who increased alcohol use during quarantine were those exhibiting higher levels of negative emotionality mechanisms.6 In Greece, an online cross-sectional survey in April 2020 in the general population during the first lockdown showed a reduction in alcohol use (43.7% of alcohol users reduced or quit), a reduction in cannabis (67.3% quit), while 33.3% increased nicotine use. These changes were attributed to the limitation of alcohol availability, social distancing, changes in daily routine and income reduction.7,8 Also, wastewater samples from Athens, analyzed by the Laboratory of Analytical Chemistry of EKPA, showed a significant increase in the use of cocaine (67%), amphetamine (350%) and methamphetamine (37%), and a decrease in the use of MDMA (- 38%) during the first lockdown, compared to the corresponding period of the previous year.9 Analysis of wastewater samples from other European cities "suggest that levels of use of most drugs appear generally lower during the initial lockdowns, but then appear to bounce back once lockdown was lifted. A comparison with 2019 appears to suggest similar overall consumption of most drugs, and in several cities possibly even higher levels, based on this data source. Exceptions here appear to be MDMA and methamphetamine, two drugs for which the levels observed in 2020 appear lower in most of the participating cities".10,11 There were also changes in the locations of use of the substances, as with the periodic restrictions the use was transferred mainly at home and in open public spaces; in some cases, it was associated with increased intravenous use and cases of intoxication. Finally, intermittent difficulties in drug availability and trafficking have led users to search for other substances, increase experimentation and multidrug use, and make online purchases. In addition, there is concern about the increasing abuse of benzodiazepines, which are either diverted from therapeutic use or appear on the illicit market, often as new benzodiazepines.10,12 According to the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), "the drug market has been remarkably resilient to disruption caused by the pandemic" … Drug trafficking has adapted to the new conditions with changes in routes and methods of trafficking, and by further enhancing the digital presence of the drug market… "Any reductions in drug consumption seen during the initial lockdowns rapidly disappeared as social distancing measures were eased. In general terms, there appears to have been less consumer interest in drugs usually associated with recreational events, such as MDMA, and greater interest in drugs linked with home use. However, the easing of restrictions … during the summer was associated with a rebound in the levels of use". Also, "survey data suggest that those using drugs occasionally prior to COVID-19 may have reduced or even ceased their use during the pandemic, but more-regular users may have increased their drug consumption".10 Measures taken to control the pandemic have reduced and modified the mental health and addiction treatment services provided. Although services have been adequately restored, there has initially been a 60% reduction in the availability and provision of detoxification services in Europe.13 Live contact, mainly at group level, was significantly reduced or stopped altogether for a long period, as well as the frequency of individual appointments. Therapeutic programs sought to respond to the new conditions using technology and telemedicine, providing online group support and psychotherapy. Substitution treatment programs have become more flexible by providing long-term pharmaceutical substitutes (take home) to prevent users from moving. There have also been facilitations in prescribing by treating physicians. Thus, the addicts' contact with the treatment process was maintained, but it was insufficient to meet their increased needs during this period. In conclusion, it should be noted that substance use appears to have an autonomous dynamism in relation to the pandemic and the consequent psychopathology, being in a "loose" causal relationship with it. Therefore, hasty and untimely generalizations should be avoided, and easy conclusions should not be drawn through extrapolations from previous socio-economic crises of different types or through partial spatiotemporal understandings, which are usually presented by the media in the form of negative alarming information.
41The paraventricular thalamic nucleus: A key hub of neural circuits underlying drug addiction.PubMed
Kuikui Zhou, Yingjie Zhu
Pharmacol Res. 2019 Apr;142:70-76. doi: 10.1016/j.phrs.2019.02.014. Epub 2019 Feb 14.
Drug addiction is a chronic relapsing brain disease characterized by compulsive, out-of-control drug use and the appearance of negative somatic and emotional consequences when drug access is prevented. The limited efficacy of treatment urges researchers toward a deeper understanding of the neural mechanism of drug addiction. Brain circuits that regulate reward and motivation are considered to be the neural substrate of drug addiction. An increasing body of literature indicates that the paraventricular thalamic nucleus (PVT) could serve as a key node in the neurocircuits that control goal-directed behaviors. In this review, we summarize the anatomical and functional evidence that the PVT regulates drug-related behaviors. The PVT receives extensive inputs from the brainstem and hypothalamus, and is reciprocally connected with the limbic system. Neurons in the PVT are recruited by drug exposure as well as cues and context associated with drug taking. Pathway-specific perturbation studies have begun to decipher the precise role of PVT circuits in drug-related behaviors. We also highlight recent findings about the involvement of neural plasticity of the PVT pathways in drug addiction and provide perspectives on future studies.
42Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition.PubMed
Elizabeth J Burnett, L Judson Chandler, Heather Trantham-Davidson
Prog Neuropsychopharmacol Biol Psychiatry. 2016 Feb 4;65:309-20. doi: 10.1016/j.pnpbp.2015.08.012. Epub 2015 Sep 1.
INTRODUCTION: Alcohol dependence is characterized by a reduction in reward threshold, development of a negative affective state, and significant cognitive impairments. Dependence-induced glutamatergic neuroadaptations in the neurocircuitry mediating reward, affect and cognitive function are thought to underlie the neural mechanism for these alterations. These changes serve to promote increased craving for alcohol and facilitate the development of maladaptive behaviors that promote relapse to alcohol drinking during periods of abstinence. OBJECTIVE: To review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition. RESULTS: Evidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure. In particular, up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, this observation as well as other glutamatergic neuroadaptations are often circuit and cell-type specific. DISCUSSION: Dependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests that they play an important role in the development of behaviors that increase the probability for relapse. As our understanding of the complexity of the neurocircuitry involved in the addictive process has advanced, it has become increasingly clear that investigations of cell-type and circuit-specific effects are required to gain a more comprehensive understanding of the glutamatergic adaptations and their functional consequences in alcohol addiction. CONCLUSION: While pharmacological treatments for alcohol dependence and relapse targeting the glutamatergic system have shown great promise in preclinical models, more research is needed to uncover novel, possibly circuit-specific, therapeutic targets that exhibit improved efficacy and reduced side effects.
43The economic burden of opioid use disorder and fatal opioid overdose in the United States, 2017.PubMed
Curtis Florence, Feijun Luo, Ketra Rice
Drug Alcohol Depend. 2021 Jan 1;218:108350. doi: 10.1016/j.drugalcdep.2020.108350. Epub 2020 Oct 27.
BACKGROUND: The United States (U.S.) is experiencing an ongoing opioid crisis. Economic burden estimates that describe the impact of the crisis are needed when considering federal and state resources devoted to addressing overdoses. In this study, we estimate the societal costs for opioid use disorder and fatal overdose from all opioids in 2017. METHODS: We estimated costs of fatal overdose from all opioids and opioid use disorder based on the incidence of overdose deaths and the prevalence of past-year opioid use disorder for 2017. Incidence of fatal opioid overdose was obtained from the National Vital Statistics System; prevalence of past-year opioid use disorder was estimated from the National Survey of Drug Use and Health. Costs were estimated for health care, criminal justice and lost productivity. Costs for the reduced quality of life for opioid use disorder and life lost due to fatal opioid overdose were valued using U.S. Department of Health and Human Services guidelines for valuing reductions in morbidity and mortality. RESULTS: Costs for opioid use disorder and fatal opioid overdose in 2017 were estimated to be $1.02 trillion. The majority of the economic burden is due to reduced quality of life from opioid use disorder and the value of life lost due to fatal opioid overdose. CONCLUSIONS: These estimates can assist decision makers in understanding the magnitude of opioid use disorder and fatal overdose. Knowing the magnitude and distribution of the economic burden can inform public policy, clinical practice, research, and prevention and response activities.
44Economic Burden of Prescription Opioid Misuse and Abuse: A Systematic Review.PubMed
Gary M Oderda, Joanita Lake, Katja Rüdell, et al.
J Pain Palliat Care Pharmacother. 2015;29(4):388-400. doi: 10.3109/15360288.2015.1101641.
A 2009 systematic review found that the total cost of prescription opioid abuse in 2001 in the United States was approximately $8.6 billion and medical expenses were estimated to be $15,884 for opioid abusers and $1,830 for nonabusers. A search was conducted for English publications on the cost of prescription opioid abuse and misuse from 2009 to 2014. The initial literature search identified 5,412 citations. Title and abstract review selected 59 for further review. The final review process resulted in 16 publications for inclusion that examined cost from the payer perspective. Mean costs to the payer for abusers were $23,000-$25,000 per year and excess costs approximately $15,000 per patient. Three papers were identified that presented societal costs, including direct and indirect costs such as criminal justice costs and costs associated with lost productivity. The strongest evidence suggests that societal cost is in excess of $50 billion per year in the United States. Prescription opioid abuse and misuse is a common and important problem throughout the world that has significant associated societal costs and excess medical costs.
45Economic burden of opioid crisis and the role of pharmacist-led interventions.PubMed
Chiranjeev Sanyal
J Am Pharm Assoc (2003). 2021 May-Jun;61(3):e70-e74. doi: 10.1016/j.japh.2020.11.006. Epub 2020 Dec 2.
Opioids are often used to treat pain and improve function. Canada and the United States are one of the highest users of opioids per capita worldwide and are experiencing the devastating consequences of the opioid crisis. The objectives of this commentary are 2-fold: first, highlight the economic burden of the opioid crisis in the United States and Canada; second, define the role of pharmacists to address this crisis. A body of literature delineates the cost of this crisis to health care system, lost productivity, and law enforcement. Contemporary data indicate that the economic burden of the opioid crisis was $78.5 billion and $3.5 billion in the United States and Canada, respectively. Community pharmacists are often the first health care providers who identify issues with opioid prescriptions, signs of misuse, abuse, and diversion. Contemporary studies highlight their critical role to address this crisis by ensuring the safe and appropriate use of opioids, which can decrease morbidity, mortality, use of health services and societal resources, and costs. The expanding scope of practice and the amendment of existing regulations and legislations have the potential to maximize the contribution of pharmacists to address this crisis. Pharmacists should be reimbursed for the services they provide to be sustainable.
46Prevalence and charges of opioid-related visits to U.S. emergency departments.PubMed
James R Langabeer, Angela L Stotts, Bentley J Bobrow, et al.
Drug Alcohol Depend. 2021 Apr 1;221:108568. doi: 10.1016/j.drugalcdep.2021.108568. Epub 2021 Feb 3.
OBJECTIVE: An overwhelming responsibility for responding to the opioid epidemic falls on hospital emergency departments (ED). We sought to examine the overall prevalence rate and associated charges of opioid-related diagnoses and overdoses. Although charge data do not necessarily represent cost, they are proxy indicators of resource utilization and burden. METHODS: We conducted a retrospective study of the National Emergency Department Sample (NEDS) dataset, the largest all-payer ED database in the United States. We queried using specific relevant ICD-10 codes to estimate the number of adult ED visits for both opioid poisonings and other opioid-related diagnoses during 2016 and 2017, which was the most recent publicly available data. Prevalence rates and financial charges were calculated by year and odds ratios were used to examine differences. RESULTS: Of approximately 234 million adult visits to EDs across 2016 and 2017, 2.88 million (1.23%) were related to opioids, with overdoses comprising nearly 27.5% and visits for other opioid-related diagnoses totaling 72.5%. As the primary diagnosis, opioids were responsible for 37% of all ED visits across both years. Total opioid-related visits for the two years accounted for $9.57 billion in ED charges, or $4.78 billion annually, with Medicaid and Medicare responsible for 66% of all charges. CONCLUSION AND RELEVANCE: Approximately one of every 80 visits to the ED were opioid-related, leading to financial charges approaching $5 billion per year. Since both prevalence and the economic burden of opioid-related visits are high, targeted interventions to address this epidemic's impact on healthcare systems should be a national priority.
47The economic burden of the opioid epidemic on states: the case of Medicaid.PubMed
Douglas L Leslie, Djibril M Ba, Edeanya Agbese, et al.
Am J Manag Care. 2019 Jul;25(13 Suppl):S243-S249.
The societal burden of opioid use disorder (OUD) is considerable and contributes to increased healthcare costs and overdose deaths. However, the burden is not well understood. The purpose of this analysis is to estimate the state Medicaid programs' costs for treating OUD and how these costs have changed over time. We used data from the Medicaid Analytic eXtract files from 17 states between 1999 and 2013 to examine the healthcare costs associated with OUD. Inpatient, outpatient, and prescription medication costs related to the treatment of OUD were included, as were excess costs for other healthcare services (eg, general medical care) for individuals with OUD relative to a comparison group of individuals without OUD matched on age, sex, and state. We then extrapolated our results to the entire US Medicaid population using population-based sample weights. All costs were adjusted for inflation and are reported in 2017 US dollars. During our study period, the number of patients who were diagnosed with OUD increased 378%, from 39,109 (0.21% of total Medicaid enrollment) in 1999 to 186,979 (0.60% of total Medicaid enrollment) in 2013 in our 17-state sample. Even after adjusting for inflation, total Medicaid costs associated with OUD more than tripled during this time, reaching more than $3 billion in 2013, from $919 million in 1999. Most of this growth was due to excess non-OUD treatment costs for patients with OUD, which increased 363% over the period; the rate of growth is triple the expenditures for OUD treatment services. When the results were extrapolated to the entire United States, the Medicaid costs associated with OUD increased from more than $2 billion in 1999 to more than $8 billion in 2013. The total cumulative costs that were associated with OUD for this extrapolated 50-state sample over a 15-year time period amounts to more than $72.4 billion. OUD imposes considerable financial burden on state Medicaid programs, and the burden is increasing over time.
48A path to eradication of hepatitis C in low- and middle-income countries.PubMed
Camilla S Graham, Tracy Swan
Antiviral Res. 2015 Jul;119:89-96. doi: 10.1016/j.antiviral.2015.01.004. Epub 2015 Jan 20.
We are entering a new era in the treatment of hepatitis C virus (HCV) infection and almost all patient groups in high-income countries have the potential to be cured with all-oral, highly potent combinations of direct-acting antiviral drugs. Soon the main barrier to curing hepatitis C, even in wealthy countries, will be the high price of these all-oral regimens. The gulf between the advances in HCV drug development and access to treatment for individual patients will be even greater in low- and middle-income countries (LMIC) where 80% of the global burden of HCV infection and mortality exists. Ensuring that people in LMIC have access to regimens against HCV will require a similar level of advocacy and public-private partnerships as has transformed the control of other global diseases such as HIV. Numerous challenges will need to be overcome. These include improving low-cost diagnostic tests, especially in sub-Saharan Africa where the false-positive rate is unacceptably high, reducing iatrogenic spread of HCV, addressing transmission among people who inject drugs (PWID), and ensuring affordable access to antiviral treatment for all people living with HCV infection in LMIC. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication."
49Unblocking Barriers of Access to Hepatitis C Treatment in China: Lessons Learned from Tianjin.PubMed
Peiwen Zhang, Ran Guo, Jun Lian, et al.
Ann Glob Health. 2020 Apr 6;86(1):36. doi: 10.5334/aogh.2763.
BACKGROUND: The high price is a critical barrier of access to new direct-anting-antiviral (DAA) therapies for hepatitis C for both the patients and the society. Many countries continue to face the challenge of financing such expensive medicines. Such examples include both high-income and middle-income countries. Existing evidence about the efforts of China to address this challenge is limited. To our knowledge, this is the first detailed description of a novel financing model and comprehensive analysis of its impact on patient financial burden of hepatitis C treatment in China. OBJECTIVE: To examine the evolution of approaches to navigating patients' barriers of access to DAA-based treatment of hepatitis C in Tianjin City, China. METHODS: Review of publicly available literature, including published and grey literature. Conduct on-site data extraction and key informant interview. The patient financial burden of hepatitis C treatment was analyzed. The financial burden of hepatitis C patients with different treatment models and health insurance financing models was measured by calculating the number of annual income to cover patient out-of-pocket (OOP) expenditure for the standard treatment course accordingly. FINDINGS: Tianjin is the first area to pilot a capitated provider payment program for the treatment of hepatitis C. Through which, the retirees and employees spend 0.7 and 1.0 months of their salary, and residents spend 5.6-6.8 months of their salary for the treatment, the financial burden of patients were much relieved. By the end of March 2019, the first-year pilot program had 876 hepatitis C patients registered the new insurance coverage and treated in Tianjin. CONCLUSIONS: The study showed that the financial barriers of access to new hepatitis C treatment for patients could be unblocked with government commitment and novel financing models. International experiences demonstrated that centralized bulk procurement is a good leverage for price negotiation, primarily when using innovative payment approaches. To replicate the initial success of Tianjin, continued efforts are needed for stronger strategic price negotiation, preferably at central level. The case of Tianjin brings implications to the other areas of China and even other developing countries that government commitment, novel financing model and pooled procurement are critical elements of stronger purchasing power and a better secure of treatment.
50Hospital Costs of Injection Drug Use in Florida.PubMed
Austin E Coye, Kasha J Bornstein, Tyler S Bartholomew, et al.
Clin Infect Dis. 2021 Feb 1;72(3):499-502. doi: 10.1093/cid/ciaa823.
People who inject drugs (PWID) experience significant injection-related infections (IRIs) at significant healthcare system cost. This study used and validated an algorithm based on the International Classification of Diseases, Tenth Revision, to estimate hospitalized PWID populations, assess the total statewide morbidity for IRIs among PWID, and calculate associated costs of care.
51Alcohol use disorders.PubMed
Jürgen Rehm, Sawitri Assanangkornchai, Christian S Hendershot, et al.
Lancet. 2025 Nov 8;406(10516):2269-2281. doi: 10.1016/S0140-6736(25)01496-5. Epub 2025 Oct 9.
Alcohol use disorders consist of conditions characterised by compulsive heavy alcohol use and loss of control over alcohol intake. Alcohol use disorders are some of the most prevalent mental disorders globally, with higher prevalence in high-income countries and lower prevalence in low-income countries. The recent COVID-19 pandemic was associated with an increase in fully alcohol-attributable mortality, in part triggered by alcohol-specific interactions with stress. Despite their high prevalence, alcohol use disorders remain undertreated, even though there are scientifically established and cost-effective psychosocial, community, and pharmacological interventions available. In addition, promising new treatment modalities have been developed and are currently being tested. The two main barriers to better access to evidence-based alcohol use disorder treatment are low availability, due to the absence of government or public funding for such treatment, and stigma. The first barrier could be overcome by increasing alcohol excise taxation, which currently falls considerably short of covering the social costs of alcohol use. In addition to generating revenues, increasing excise taxation could reduce health-care costs by reducing hospitalisations for all alcohol-attributable conditions, including alcohol use disorders. Overall, integrated alcohol control policies could improve the prevention of alcohol use disorders, improve access to treatment, and reduce stigma.
52Global, regional, and national burden of injuries, and burden attributable to injuries risk factors, 1990 to 2019: results from the Global Burden of Disease study 2019.PubMed
Public Health. 2024 Dec;237:212-231. doi: 10.1016/j.puhe.2024.06.011. Epub 2024 Oct 24.
OBJECTIVES: In this study, the trends and current situation of the injury burden as well as attributable burden to injury risk factors at global, regional, and national levels based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 are presented. STUDY DESIGN: To assess the attributable burden of injury risk factors, the data of interest on data sources were retrieved from the Global Health Data Exchange (GHDx) and analyzed. METHODS: Cause-specific death from injuries was estimated using the Cause of Death Ensemble model in the GBD 2019. The burden attributable to each injury risk factor was incorporated in the population attributable fraction to estimate the total attributable deaths and disability-adjusted life years. The Socio-demographic Index (SDI) was used to evaluate countries' developmental status. RESULTS: Globally, there were 713.9 million (95% uncertainty interval [UI]: 663.8 to 766.9) injuries incidence and 4.3 million (UI: 3.9 to 4.6) deaths caused by injuries in 2019. There was an inverse relationship between age-standardized disability-adjusted life year rate and SDI quintiles in 2019. Overall, low bone mineral density was the leading risk factor of injury deaths in 2019, with a contribution of 10.5% (UI: 9.0 to 11.6) of total injuries and age-standardized deaths, followed by occupational risks (7.0% [UI: 6.3-7.9]) and alcohol use (6.8% [UI: 5.2 to 8.5]). CONCLUSION: Various risks were responsible for the imposed burden of injuries. This study highlighted the small but persistent share of injuries in the global burden of diseases and injuries to provide beneficial data to produce proper policies to reach an effective global injury prevention plan.
53Substance Abuse Screening and Treatment.PubMed
Johnny C Tenegra, Bobby Leebold
Prim Care. 2016 Jun;43(2):217-27. doi: 10.1016/j.pop.2016.01.008.
One of the more prevalent and often undiagnosed problems seen by primary care clinicians is substance misuse. Resulting in increased morbidity and mortality, loss of productivity, and increased health care costs, substance misuse in our society remains a significant public health issue. Primary care physicians are on the front lines of medical care, and as such, are in a distinctive position to recognize potential problems in this area and assist. This article outlines office-based screening approaches and strategies for managing and treating this complex issue confronting primary care.
54Alcohol-related absence and presenteeism: Beyond productivity loss.PubMed
Kristin Buvik, Inger Synnøve Moan, Torleif Halkjelsvik
Int J Drug Policy. 2018 Aug;58:71-77. doi: 10.1016/j.drugpo.2018.05.005. Epub 2018 Jun 1.
BACKGROUND: Alcohol use by employees is associated with negative consequences for the workplace in terms of absence and poor work performance. The aims of this study were to map the prevalence of alcohol-related absence and inefficiency using survey data from a broad sample of employees, and to explore how alcohol-related absence and presenteeism are experienced and handled using data from qualitative interviews. METHODS: The prevalence data stems from a web survey completed by 1940 Norwegian employees aged 20-74 years. The qualitative data consists of analyses of 24 interviews with managers, co-workers of heavy drinking employees, and heavy drinking employees, from various lines of businesses. RESULTS: 1-2% reported alcohol-related full day absence in the last 12 months, and 2% reported partial day absence; 11% reported inefficiency due to drinking the previous day. Analyses of interview data revealed that alcohol-related absence and presenteeism may cause a range of economic and practical problems. Managers reported spending a lot of resources and effort on single cases. In addition, the results showed how the presence of a heavy drinking employee may have a negative impact on the broader psychosocial environment, and cause concern for workplace safety. Due to consideration of the drinker's well-being and fear of negative reactions, problem cases can last for years. CONCLUSIONS: Despite the relatively low prevalence of alcohol-related absence and inefficiency, the study suggest that the alcohol-related problems of a few, or only one, employee may still have substantial and far-reaching negative consequences for the workplace.
55Cocaine and the heart.PubMed
M Egred, G K Davis
Postgrad Med J. 2005 Sep;81(959):568-71. doi: 10.1136/pgmj.2004.028571.
Cocaine is the second commonest illicit drug used and the most frequent cause of drug related deaths. Its use is associated with both acute and chronic complications that may involve any system, the most common being the cardiovascular system. Cocaine misuse has a major effect in young adult drug users with resulting loss of productivity and undue morbidity with cocaine related cardiac and cerebrovascular effects. Many cocaine users have little or no idea of the risks associated with its use. Patients, health care professionals, and the public should be educated about the dangers and the considerable risks of cocaine use. This review concentrates on the cardiovascular effects of cocaine and their management.
56Alcohol abuse after traumatic brain injury: Experimental and clinical evidence.PubMed
Zachary M Weil, John D Corrigan, Kate Karelina
Neurosci Biobehav Rev. 2016 Mar;62:89-99. doi: 10.1016/j.neubiorev.2016.01.005. Epub 2016 Jan 24.
Brain injury survivors, particularly those injured early in life are very likely to abuse drugs and alcohol later in life. Alcohol abuse following traumatic brain injury (TBI) is associated with poorer rehabilitation outcomes and a greatly increased chance of suffering future head trauma. Thus, substance abuse among persons with brain injury reduces the chances for positive long-term outcomes and greatly increases the societal costs. In this review, we discuss the evidence for modulation of drinking behavior after TBI and the costs of problem drinking after TBI from both a biomedical and economic perspective. Further, we review the existing animal models of drinking after brain injury and consider the potential underlying psychosocial and neurobiological mediators of this phenomenon. In particular, we highlight the potential interactions among TBI, neuroinflammation and alcohol abuse. Substance abuse is a major problem in this vulnerable patient population and a greater understanding of the underlying biology has the potential to greatly improve outcomes.
57Fetal Alcohol Spectrum Disorders: A Review of the Neurobehavioral Deficits Associated With Prenatal Alcohol Exposure.PubMed
Sarah N Mattson, Gemma A Bernes, Lauren R Doyle
Alcohol Clin Exp Res. 2019 Jun;43(6):1046-1062. doi: 10.1111/acer.14040. Epub 2019 May 2.
In utero alcohol exposure can disrupt the development of the fetal brain and result in a wide range of neurobehavioral outcomes collectively known as fetal alcohol spectrum disorders (FASD). This paper provides a comprehensive review of the cognitive and behavioral outcomes of prenatal alcohol exposure, including domains of general intelligence, executive functioning, language development, learning and memory, adaptive functioning, academic performance, and concurrent psychopathology. In addition, the current status of the neurobehavioral profile of FASD and its potential as a diagnostic tool will be discussed.
58Fetal Alcohol Spectrum Disorders.PubMed
Riley J Felicicchia, Christina R Veziris, Sarah N Mattson
Curr Top Behav Neurosci. 2025;75:99-116. doi: 10.1007/7854_2024_569.
Prenatal alcohol exposure (PAE) can cause a wide range of physical, neurobehavioral, and neurocognitive impairments that impact developmental trajectories throughout the lifespan. Clinically, individuals who have been exposed to alcohol prenatally and who show physical or neurobehavioral difficulties may be classified as having a condition included in fetal alcohol spectrum disorders (FASDs). The aim of this chapter is to summarize the current knowledge of FASD including diagnostic criteria, neurobehavioral outcomes, lifespan considerations, and interventions. Individuals with PAE exhibit challenges in the cognitive domains of executive functioning, general intelligence, motor function, learning, and memory. Aggression, trouble with the law, and oppositional behavior are also commonly associated with individuals with FASD. The effects of PAE can be attributed to altered neural development such as smaller total brain volume and structural abnormalities. Prenatal exposure to alcohol increases risk for co-occurring neurodevelopmental conditions and psychiatric disorders. This chapter will also review the current literature on pre- and postnatal interventions to target the effects of PAE.
59Fetal Alcohol Spectrum Disorders: Characteristics, Complications, and Treatment.PubMed
Lauren F Wilhoit, David A Scott, Brooke A Simecka
Community Ment Health J. 2017 Aug;53(6):711-718. doi: 10.1007/s10597-017-0104-0. Epub 2017 Feb 6.
Fetal Alcohol Spectrum Disorders (FASD) includes a continuum of disorders that occur in children as a result of their mothers' consumption of alcohol during pregnancy. The most severe of these disorders is Fetal Alcohol Syndrome (FAS). FASD presents differently in every child, but all children with FASD have intellectual and/or behavioral impairments. There is no cure for FASD, but research shows that early intervention and life-long support help those born with FASD to manage the difficulties that come with it. This paper examines the characteristics, complications, and treatment for FASD.
60HIV and the criminalisation of drug use among people who inject drugs: a systematic review.PubMed
Kora DeBeck, Tessa Cheng, Julio S Montaner, et al.
Lancet HIV. 2017 Aug;4(8):e357-e374. doi: 10.1016/S2352-3018(17)30073-5. Epub 2017 May 14.
BACKGROUND: Mounting evidence suggests that laws and policies prohibiting illegal drug use could have a central role in shaping health outcomes among people who inject drugs (PWID). To date, no systematic review has characterised the influence of laws and legal frameworks prohibiting drug use on HIV prevention and treatment. METHODS: Consistent with PRISMA guidelines, we did a systematic review of peer-reviewed scientific evidence describing the association between criminalisation of drug use and HIV prevention and treatment-related outcomes among PWID. We searched MEDLINE, Embase, SCOPUS, PsycINFO, Sociological Abstracts, CINAHL, Web of Science, and other sources. To be included in our review, a study had to meet the following eligibility criteria: be published in a peer-reviewed journal or presented as a peer-reviewed abstract at a scientific conference; examine, through any study design, the association between an a-priori set of indicators related to the criminalisation of drugs and HIV prevention or treatment among PWID; provide sufficient details on the methods followed to allow critical assessment of quality; be published or presented between Jan 1, 2006, and Dec 31, 2014; and be published in the English language. FINDINGS: We identified 106 eligible studies comprising 29 longitudinal, 49 cross-sectional, 22 qualitative, two mixed methods, four mathematical modelling studies, and no randomised controlled trials. 120 criminalisation indicators were identified (range 1-3 per study) and 150 HIV indicators were identified (1-5 per study). The most common criminalisation indicators were incarceration (n=38) and street-level policing (n=39), while the most frequent HIV prevention and treatment indicators were syringe sharing (n=35) and prevalence of HIV infection among PWID (n=28). Among the 106 studies included in this review, 85 (80%) suggested that drug criminalisation has a negative effect on HIV prevention and treatment, 10 (9%) suggested no association, five (5%) suggested a beneficial effect, one (1%) suggested both beneficial and negative effects, and five (5%) suggested both null and negative effects. INTERPRETATION: These data confirm that criminalisation of drug use has a negative effect on HIV prevention and treatment. Our results provide an objective evidence base to support numerous international policy initiatives to reform legal and policy frameworks criminalising drug use. FUNDING: Canadian Institutes of Health Research and US National Institutes of Health.
61Worldwide Prevalence and Disability From Mental Disorders Across Childhood and Adolescence: Evidence From the Global Burden of Disease Study.PubMed
Christian Kieling, Claudia Buchweitz, Arthur Caye, et al.
JAMA Psychiatry. 2024 Apr 1;81(4):347-356. doi: 10.1001/jamapsychiatry.2023.5051.
IMPORTANCE: The period from childhood to early adulthood involves increased susceptibility to the onset of mental disorders, with implications for policy making that may be better appreciated by disaggregated analyses of narrow age groups. OBJECTIVE: To estimate the global prevalence and years lived with disability (YLDs) associated with mental disorders and substance use disorders (SUDs) across 4 age groups using data from the 2019 Global Burden of Disease (GBD) study. DESIGN, SETTING, AND PARTICIPANTS: Data from the 2019 GBD study were used for analysis of mental disorders and SUDs. Results were stratified by age group (age 5 to 9, 10 to 14, 15 to 19, and 20 to 24 years) and sex. Data for the 2019 GBD study were collected up to 2018, and data were analyzed for this article from April 2022 to September 2023. EXPOSURE: Age 5 to 9 years, 10 to 14 years, 15 to 19 years, and 20 to 24 years. MAIN OUTCOMES AND MEASURES: Prevalence rates with 95% uncertainty intervals (95% UIs) and number of YLDs. RESULTS: Globally in 2019, 293 million of 2516 million individuals aged 5 to 24 years had at least 1 mental disorder, and 31 million had an SUD. The mean prevalence was 11.63% for mental disorders and 1.22% for SUDs. For the narrower age groups, the prevalence of mental disorders was 6.80% (95% UI, 5.58-8.03) for those aged 5 to 9 years, 12.40% (95% UI, 10.62-14.59) for those aged 10 to 14 years, 13.96% (95% UI, 12.36-15.78) for those aged 15 to 19 years, and 13.63% (95% UI, 11.90-15.53) for those aged 20 to 24 years. The prevalence of each individual disorder also varied by age groups; sex-specific patterns varied to some extent by age. Mental disorders accounted for 31.14 million of 153.59 million YLDs (20.27% of YLDs from all causes). SUDs accounted for 4.30 million YLDs (2.80% of YLDs from all causes). Over the entire life course, 24.85% of all YLDs attributable to mental disorders were recorded before age 25 years. CONCLUSIONS AND RELEVANCE: An analytical framework that relies on stratified age groups should be adopted for examination of mental disorders and SUDs from childhood to early adulthood. Given the implications of the early onset and lifetime burden of mental disorders and SUDs, age-disaggregated data are essential for the understanding of vulnerability and effective prevention and intervention initiatives.
62Burden of drug use disorders in the United States from 1990 to 2021 and its projection until 2035: results from the GBD study.PubMed
Tongchao Zhang, Lin Sun, Xiaolin Yin, et al.
BMC Public Health. 2024 Jun 19;24(1):1639. doi: 10.1186/s12889-024-19142-0.
BACKGROUND: Drug use disorders (DUDs) have emerged as one of the most significant public health crises, exerting a substantial influence on both community health and socio-economic progress. The United States (US) also suffers a heavy burden, it is necessary to figure out the situation from multiple perspectives and take effective measures to deal with it. Therefore, using the data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2021, we evaluated this topic. METHODS: Annual data on DUDs-related burden were collected from the GBD study 2021. We calculated the indicator of estimated annual percentage change (EAPC) to evaluate the changing trend of burden. The Bayesian model for age-period-cohort was introduced to forecast the burden. RESULTS: In 2021, the number and age-standardized rate of prevalence were particularly prominent, with 12,146.95 thousand and 3821.43 per 100,000, respectively. Higher burden was also observed in males, 15-45 years old populations, and opioid use disorders subtype. From 1990 to 2021, the DUDs-related burden increased in the US and all states, especially in West Virginia; and the national death-related burden with the highest increase (EAPC = 7.96). Other significant inverse associations were seen between EAPC, age-standardized rates, and socio-demographic index (SDI). Moreover, in the next 14 years, the projected DUDs burden remains exigent. CONCLUSIONS: The burden of DUDs in the US is heavy and has been enlarging. This study proposes that greater attention should be paid to the strategies in males, the younger population, opioid use disorders, and low-SDI states implemented by decision-makers to achieve goals such as reducing burden.
63Peer Pressure and Substance Use in Emerging Adulthood: A Latent Profile Analysis.PubMed
Angela Keyzers, Sun-Kyung Lee, Jodi Dworkin
Subst Use Misuse. 2020;55(10):1716-1723. doi: 10.1080/10826084.2020.1759642. Epub 2020 May 13.
Peers play an important role in influencing emerging adults' substance use behaviors, however, research on peer pressure has typically not been extended beyond adolescence to include emerging adulthood. Little research has examined the relationships between various peer pressure domains and emerging adult substance use. This study used quantitative data from 359 emerging adults (aged 18-29 years, = 25.46 years; 60.8% female; 74.2% White) to explore the associations between different types of peer pressure (e.g. peer pressure to socialize and peer pressure to use substances) and substance use among a diverse sample of emerging adults. Latent profile analysis and path analysis were used for analysis. Three unique profiles of perceived peer pressure emerged (negative peer pressure, positive peer pressure, and no perceived peer pressure). The negative peer pressure group was more likely to engage in binge drinking, lifetime alcohol use and lifetime marijuana use than the no peer pressure group. The positive peer pressure group was less likely to engage in lifetime alcohol or marijuana use compared to the no peer pressure group. Findings suggest that peer pressure is associated with emerging adult substance use, in both negative and positive ways. Results of the current study provide the critical groundwork for more sophisticated studies seeking to understand the pathways by which positive and negative peer pressure impact emerging adult behavior.
64Peer leaders and substance use among high-risk adolescents.PubMed
Patchareeya Pumpuang Kwan, Steve Sussman, Thomas W Valente
Subst Use Misuse. 2015 Feb;50(3):283-91. doi: 10.3109/10826084.2014.977395. Epub 2014 Nov 19.
OBJECTIVE: To examine the association between individual drug use and peer leaders use. METHOD: Analysis of drug use behaviors of 525 students randomized into three arms-control, standard, and networked where peers serve as group leaders. RESULTS: Among the combined male and female group, there was no association between peer leader and individual use. Among males, peer leader use at baseline was positively associated with individual alcohol use at post-test. Among females, peer leader use at post-test was negatively associated with marijuana and cigarette use. CONCLUSION: Having peer leaders in the network condition decreased the odds of marijuana and cigarette use among females. The opposite effect was found in males.
65Onset of substance use: Deviant peer, sex, and sympathetic nervous system predictors.PubMed
J Benjamin Hinnant, Brian T Gillis, Stephen A Erath, et al.
Dev Psychopathol. 2022 Oct;34(4):1506-1515. doi: 10.1017/S0954579421000158. Epub 2021 Jun 8.
We evaluated whether the association between deviant peer affiliation and onset of substance use is conditional upon sex and sympathetic nervous system (SNS) reactivity as measured by pre-ejection period (PEP). Community-sampled adolescents ( = 251; = 15.78 years; 53% female; 66% White, 34% Black) participated in three waves. PEP reactivity was collected during a mirror star-tracer stress task. Alcohol, marijuana, tobacco, or any substance use, as well as binge drinking and sexual activity involving substance use were outcomes predicted by affiliation with deviant peers and two- and three-way interactions with sex and PEP reactivity. Probability of substance use increased over time, but this was amplified for adolescents with greater deviant peer affiliation in conjunction with blunted PEP reactivity. The same pattern of results was also found for prediction of binge drinking and sexual activity involving substance use. Findings are discussed in the context of biosocial models of adolescent substance use and health risk behaviors.
66Neurobiology of Adolescent Substance Use Disorders.PubMed
Aditi Sharma, Jonathan D Morrow
Child Adolesc Psychiatr Clin N Am. 2016 Jul;25(3):367-75. doi: 10.1016/j.chc.2016.02.001. Epub 2016 Apr 9.
There are many facets of the neurobiology of substance use that are distinct in adolescence as compared with adulthood. The adolescent brain is subject to intense subcortical reward processes, but is left with an immature prefrontal control system that is often unable to resist the pull of potentially exciting activities like substance use, even when fully aware of the dangers involved. Peer influences serve only to magnify these effects and foster more sensation-seeking, risky behavior. The unique aspects of neurobiology should be taken into consideration when designing prevention programs and clinical interventions for adolescent substance use disorders.
67Heterogeneity in Prescription Opioid Misuse Motives by Age in Adolescents and Young Adults in the United States.PubMed
Ty S Schepis, Jason A Ford, Philip T Veliz, et al.
J Addict Med. 2025;19(4):381-389. doi: 10.1097/ADM.0000000000001428. Epub 2024 Dec 9.
OBJECTIVE: Adolescent (12-17 years) and young adult (18-25 years) prescription opioid misuse (POM) is linked to poor health outcomes. We investigated how POM motives vary across these ages and the potential links between motives and other substance use, mental health, and sociodemographic characteristics to help guide screening and prevention. METHODS: Pooled 2015-2019 US National Survey on Drug Use and Health data were used, with 137,858 participants. Cross-tabulations estimated prevalence of individual motives and motive category by age. Mutually exclusive motive categories were no past-year POM, pain relief only, pain/sleep/relax (ie, some combination of only these motives), and any non-self-treatment motives (eg, get high, experiment). Logistic regression models evaluated links between motive category and sociodemographic, mental health, and substance use (eg, alcohol, cannabis, nicotine, other prescription misuse) outcomes by age group, versus reference groups of no past-year POM or pain relief only. RESULTS: Pain relief was the most common POM motive (estimated at >50% at all ages), but POM for non-self-treatment motives was the most common category after 14 years. POM for non-self-treatment motives had the highest adjusted odds ratios (aORs) of all substance use and mental health characteristics (eg, past-year substance use disorder aORs of 6.11 in adolescents [95% confidence interval (CI), 4.23-8.85] and 4.81 [95% CI, 4.01-5.77] in young adults, versus the pain relief only reference). CONCLUSIONS: POM for any non-self-treatment motives is linked to the highest prevalence of other substance use and mental health concerns, whereas POM for pain relief also signals a need for substance use and mental health screening.
68Social media use and risky behaviors in adolescents: A meta-analysis.PubMed
Anna Vannucci, Emily G Simpson, Sonja Gagnon, et al.
J Adolesc. 2020 Feb;79:258-274. doi: 10.1016/j.adolescence.2020.01.014. Epub 2020 Feb 1.
INTRODUCTION: This systematic review and meta-analysis examined the associations between social media use and risky behaviors during adolescence, and evaluated study characteristics (e.g., sample age, type of social media platform assessed) that may moderate these relationships. METHODS: A comprehensive search strategy identified relevant studies from PsycInfo, PubMed, Google Scholar, and Proquest Dissertations and Theses Global. RESULTS: The final sample included 27 independent cross-sectional studies with a total of 67,407 adolescents (M = 15.5, range: 12.6-18.0 years; 51.7% girls; 57.2% White). Results from random effects models indicated that there were positive, small-to-medium correlations between social media use and engagement in risky behaviors generally (r = 0.21, 95% CI = 0.16-0.25), substance use (r = 0.19, 95% CI = 0.12-0.26), and risky sexual behaviors (r = 0.21, 95% CI = 0.15-0.28). There were an insufficient number of independent samples available to conduct a random effect models for violence-related behaviors (k = 3). Moderator analyses suggested that studies assessing solely early social media platforms (e.g., Facebook/MySpace only) in relation to substance use had smaller effect sizes than substance use studies assessing a broader range of contemporary social media platforms. In addition, younger samples had larger effect sizes for studies focused on social media use and risky sexual behaviors. CONCLUSIONS: The positive links identified between social media and risky behaviors during adolescence in this meta-analysis suggest that developmental theories of risk taking would benefit from incorporating the social media context. Longitudinal studies are needed to clarify directionality and make more specific practice and policy recommendations so that social media is a safe place in which adolescents can thrive.
69Associations Between Time Spent Using Social Media and Internalizing and Externalizing Problems Among US Youth.PubMed
Kira E Riehm, Kenneth A Feder, Kayla N Tormohlen, et al.
JAMA Psychiatry. 2019 Dec 1;76(12):1266-1273. doi: 10.1001/jamapsychiatry.2019.2325.
IMPORTANCE: Social media use may be a risk factor for mental health problems in adolescents. However, few longitudinal studies have investigated this association, and none have quantified the proportion of mental health problems among adolescents attributable to social media use. OBJECTIVE: To assess whether time spent using social media per day is prospectively associated with internalizing and externalizing problems among adolescents. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study of 6595 participants from waves 1 (September 12, 2013, to December 14, 2014), 2 (October 23, 2014, to October 30, 2015), and 3 (October 18, 2015, to October 23, 2016) of the Population Assessment of Tobacco and Health study, a nationally representative cohort study of US adolescents, assessed US adolescents via household interviews using audio computer-assisted self-interviewing. Data analysis was performed from January 14, 2019, to May 22, 2019. EXPOSURES: Self-reported time spent on social media during a typical day (none, ≤30 minutes, >30 minutes to ≤3 hours, >3 hours to ≤6 hours, and >6 hours) during wave 2. MAIN OUTCOMES AND MEASURE: Self-reported past-year internalizing problems alone, externalizing problems alone, and comorbid internalizing and externalizing problems during wave 3 using the Global Appraisal of Individual Needs-Short Screener. RESULTS: A total of 6595 adolescents (aged 12-15 years during wave 1; 3400 [51.3%] male) were studied. In unadjusted analyses, spending more than 30 minutes of time on social media, compared with no use, was associated with increased risk of internalizing problems alone (≤30 minutes: relative risk ratio [RRR], 1.30; 95% CI, 0.94-1.78; >30 minutes to ≤3 hours: RRR, 1.89; 95% CI, 1.36-2.64; >3 to ≤6 hours: RRR, 2.47; 95% CI, 1.74-3.49; >6 hours: RRR, 2.83; 95% CI, 1.88-4.26) and comorbid internalizing and externalizing problems (≤30 minutes: RRR, 1.39; 95% CI, 1.06-1.82; >30 minutes to ≤3 hours: RRR, 2.34; 95% CI, 1.83-3.00; >3 to ≤6 hours: RRR, 3.15; 95% CI, 2.43-4.09; >6 hours: RRR, 4.29; 95% CI, 3.22-5.73); associations with externalizing problems were inconsistent. In adjusted analyses, use of social media for more than 3 hours per day compared with no use remained significantly associated with internalizing problems alone (>3 to ≤6 hours: RRR, 1.60; 95% CI, 1.11-2.31; >6 hours: RRR, 1.78; 95% CI, 1.15-2.77) and comorbid internalizing and externalizing problems (>3 to ≤6 hours: RRR, 2.01; 95% CI, 1.51-2.66; >6 hours: RRR, 2.44; 95% CI, 1.73-3.43) but not externalizing problems alone. CONCLUSIONS AND RELEVANCE: Adolescents who spend more than 3 hours per day using social media may be at heightened risk for mental health problems, particularly internalizing problems. Future research should determine whether setting limits on daily social media use, increasing media literacy, and redesigning social media platforms are effective means of reducing the burden of mental health problems in this population.
70E-Cigarette and Cannabis Social Media Posts and Adolescent Substance Use.PubMed
Julia Vassey, Junhan Cho, Erin A Vogel, et al.
JAMA Netw Open. 2025 Jun 2;8(6):e2517611. doi: 10.1001/jamanetworkopen.2025.17611.
IMPORTANCE: Adolescents are exposed to e-cigarette and cannabis content on social media. Understanding associations of these exposures with use and dual use of these products can guide regulations. OBJECTIVE: To assess whether adolescent exposure to e-cigarette and/or cannabis content on social media, including posts by various content creators, is associated with e-cigarette, cannabis, and dual use. DESIGN, SETTING, AND PARTICIPANTS: Two surveys, one longitudinal (study 1, baseline in 2021 to 2022) and one cross-sectional (study 2, fall 2023), were conducted among California high school students who completed questionnaires on computers in classrooms. EXPOSURES: In study 1, the baseline was frequent exposure (weekly or more vs less frequent or none) to e-cigarette and/or cannabis social media posts. In study 2, the exposure (yes vs no) was to e-cigarette and/or cannabis posts from specific sources (friends, celebrities, microinfluencers, e-cigarette and/or cannabis brands, or unknown sources). MAIN OUTCOMES AND MEASURES: For study 1, the primary outcome was solo e-cigarette, solo cannabis, or dual use initiation at 1-year follow-up among baseline never-users of e-cigarettes and cannabis. For study 2, the primary outcome was past-month use of e-cigarettes, cannabis, and dual use. Generalized estimating equations models adjusted for sociodemographic characteristics, mental health, other tobacco product use, social media use, and social environment. RESULTS: In study 1, of 4232 adolescents (mean [SD] age, 17.0 [0.6] years; 2205 female [52.1%]), 968 (22.9%) reported frequent baseline exposure to e-cigarette posts and 507 (12.0%) reported exposure to cannabis posts on social media, broadly; 567 (13.4%) were frequently exposed to e-cigarette posts specifically on TikTok. Frequent exposure to cannabis social media posts was associated with solo e-cigarette use (adjusted odds ratio [AOR], 1.83; 95% CI, 1.11-3.01), solo cannabis use (AOR, 1.60; 95% CI, 1.07-2.38), and dual use (AOR, 1.71; 95% CI, 1.11-2.63) initiation at 1-year follow-up. Frequent exposure to e-cigarette posts on TikTok was associated with solo cannabis use (AOR, 1.74; 95% CI, 1.17-2.58) and dual use (e-cigarette and cannabis) initiation (AOR, 1.78; 95% CI, 1.19-2.66). In study 2, of 3380 adolescents (mean [SD] age, 17.0 [0.6] years; 1840 female [54.4%]), 195 (5.8%) were exposed to microinfluencer e-cigarette posts, and 152 (4.5%) were exposed to microinfluencer cannabis posts; 151 (4.5%) were exposed to friends' e-cigarette posts, and 161 (4.8%) were exposed to friends' cannabis posts. Exposure to e-cigarette (AOR, 2.67; 95% CI, 1.55-4.59) and cannabis (AOR, 2.14; 95% CI, 1.15-4.00) microinfluencer posts was associated with past-month cannabis use. Exposure to friends' e-cigarette posts was associated with past-month dual use (AOR, 2.53; 95% CI, 1.24-5.19), whereas exposure to friends' cannabis posts was associated with past-month cannabis use (AOR, 3.35; 95% CI, 1.94-5.78) and dual use (AOR, 2.46; 95% CI, 1.28-4.71). CONCLUSIONS AND RELEVANCE: In this survey study of California adolescents, exposure to e-cigarette or cannabis posts was associated with adolescent e-cigarette, cannabis, or dual use. Improvement of social media community guidelines and greater policy attention to co-use and marketing of e-cigarettes and cannabis may help prevent youth substance use.
71The behavioral economics of young adult substance abuse.PubMed
James G Murphy, Ashley A Dennhardt
Prev Med. 2016 Nov;92:24-30. doi: 10.1016/j.ypmed.2016.04.022. Epub 2016 May 3.
Alcohol and drug use peaks during young adulthood and can interfere with critical developmental tasks and set the stage for chronic substance misuse and associated social, educational, and health-related outcomes. There is a need for novel, theory-based approaches to guide substance abuse prevention efforts during this critical developmental period. This paper discusses the particular relevance of behavioral economic theory to young adult alcohol and drug misuse, and reviews of available literature on prevention and intervention strategies that are consistent with behavioral economic theory. Behavioral economic theory predicts that decisions to use drugs and alcohol are related to the relative availability and price of both alcohol and substance-free alternative activities, and the extent to which reinforcement from delayed substance-free outcomes is devalued relative to the immediate reinforcement associated with drugs. Behavioral economic measures of motivation for substance use are based on relative levels of behavioral and economic resource allocation towards drug versus alternatives, and have been shown to predict change in substance use over time. Policy and individual level prevention approaches that are consistent with behavioral economic theory are discussed, including brief interventions that increase future orientation and engagement in rewarding alternatives to substance use. Prevention approaches that increase engagement in constructive future-oriented activities among young adults (e.g., educational/vocational success) have the potential to reduce future health disparities associated with both substance abuse and poor educational/vocational outcomes.
72Intertemporal decision-making-related brain states predict adolescent drug abuse intervention responses.PubMed
Amanda Elton, Catherine Stanger, G Andrew James, et al.
Neuroimage Clin. 2019;24:101968. doi: 10.1016/j.nicl.2019.101968. Epub 2019 Aug 5.
Adolescent drug misuse represents a major risk factor for long-term drug use disorders. However, wide individual differences in responses to first-line behavioral therapies targeting adolescent drug misuse limit critical early intervention. Identifying the neural signatures of those adolescents most likely to respond to an intervention would potentially guide personalized strategies for reducing drug misuse. Prior to a 14-week evidence-based intervention involving combinations of contingency management, motivational enhancement, and cognitive behavioral therapy, thirty adolescent alcohol and/or cannabis users underwent fMRI while performing a reward delay discounting (DD) task tapping an addiction-related cognition. Intervention responses were longitudinally characterized by both urinalysis and self-report measures of the percentage of days used during treatment and in post-treatment follow-up. Group independent component analysis (ICA) of task fMRI data identified neural processing networks related to DD task performance. Separate measures of wholesale recruitment during immediate reward choices and within-network functional connectivity among selective networks significantly predicted intervention-related changes in drug misuse frequency. Specifically, heightened pre-intervention engagement of a temporal lobe "reward motivation" network for impulsive choices on the DD task predicted poorer intervention outcomes, while modes of functional connectivity within the reward motivation network, a prospection network, and a posterior insula network demonstrated robust associations with intervention outcomes. Finally, the pre-intervention functional organization of the prospection network also predicted post-intervention drug use behaviors for up to 6 months of follow-up. Multiple functional variations in the neural processing networks supporting preference for immediate and future rewards signal individual differences in readiness to benefit from an effective behavioral therapy for reducing adolescent drug misuse. The implications for efforts to boost therapy responses are discussed.
73HIV/HCV Coinfection in Taiwan.PubMed
Ching-Sheng Hsu, Jia-Horng Kao
AIDS Rev. 2016 Oct-Dec;18(4):193-197.
Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection are important global public health problems with shared transmission routes. Although HIV/HCV coinfection is not uncommon, the prevalence rates vary significantly across different studies and regions. In Taiwan, injection drug users have become the major contributors to the HIV/AIDS epidemic since 2005. Because the prevalence of HCV infection is high in injection drug users, this HIV epidemic is also associated with a significant increase of HIV/HCV coinfection in Taiwan. To control Taiwan's HIV epidemic, Taiwan Centers for Disease Control (CDC) launched a harm-reduction program in 2006. The HIV epidemic, the percentage attributed to injection drug users, and the prevalence of HIV/HCV coinfection gradually declined thereafter. In this article, we aimed to thoroughly examine the current literatures of HIV/HCV coinfection in Taiwan and hope to provide a better understanding of the needs for the management of this coinfection. We conducted a narrative review and searched for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database untill August 2015. Studies relevant to the epidemiology and associated risk factors of HIV/HCV coinfection in Taiwan were examined and discussed.
74Drug Abuse, HIV, and HCV in Asian Countries.PubMed
Yih-Ing Hser, Di Liang, Yu-Ching Lan, et al.
J Neuroimmune Pharmacol. 2016 Sep;11(3):383-93. doi: 10.1007/s11481-016-9665-x. Epub 2016 Mar 21.
Drug abuse and co-occurring infections are associated with significant morbidity and mortality. Asian countries are particularly vulnerable to the deleterious consequences of these risks/problems, as they have some of the highest rates of these diseases. This review describes drug abuse, HIV, and hepatitis C (HCV) in Asian countries. The most commonly used illicit drugs include opioids, amphetamine-type stimulants (ATS), cannabis, and ketamine. Among people who inject drugs, HIV rates range from 6.3 % in China to 19 % in Malaysia, and HCV ranges from 41 % in India and Taiwan to 74 % in Vietnam. In the face of the HIV epidemics, drug policies in these countries are slowly changing from the traditional punitive approach (e.g., incarcerating drug users or requiring registration as a drug user) to embrace public health approaches, including, for example, community-based treatment options as well as harm reduction approaches to reduce needle sharing and thus HIV transmission. HIV and HCV molecular epidemiology indicates limited geographic diffusion. While the HIV prevalence is declining in all five countries, use of new drugs (e.g., ATS, ketamine) continues to increase, as well as high-risk sexual behaviors associated with drug use-increasing the risk of sexual transmission of HIV, particularly among men who have sex with men. Screening, early intervention, and continued scaling up of therapeutic options (drug treatment and recovery support, ART, long-term HIV and HCV care for drug users) are critical for effective control or continued reduction of drug abuse and co-infections.
75Opioids and HIV/HCV infection.PubMed
Xu Wang, Ting Zhang, Wen-Zhe Ho
J Neuroimmune Pharmacol. 2011 Dec;6(4):477-89. doi: 10.1007/s11481-011-9296-1. Epub 2011 Jul 14.
Since human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same modes of transmission and common risk factors for infection, co-infections with HIV and HCV are frequently found in injection drug users (IDUs). IDUs represent one of the largest reservoirs of HIV as well as HCV in the United States. These two pathogens are also likely to be responsible for the highest infectious disease morbidity and mortality rates among IDUs. IDUs frequently involve the abuse of heroin, the most common abused opiate. Opiates have been suggested to have a cofactor role in the immunopathogenesis of HIV disease, as they have the potential to compromise host immune responses and enhances microbial infections. Although in vitro studies have yielded relatively agreeable data that morphine, the active metabolite of heroin, exacerbate HIV infection/replication, epidemiologic studies as well as in vivo non-human primate investigations on the impact of opiate abuse on HIV disease progression have yielded the conflicting data. Given immunomodulation and immunocompromising effect as well as demonstrated impact to enhance HIV replication in vitro, it is reasonable to believe that opiate abuse is a facilitator in HIV and/or HCV disease progression. However, much remain to be learned about the mechanisms of opiate-mediated broad influence on host immunity and viral expression. Thus, more extensive studies are needed in order to determine the effects of different conditions of opiate abuse and to define the understanding of the role of opiate in modulating HIV and/or HCV disease progression.
76Hepatitis C virus transmission dynamics in injection drug users.PubMed
H Hagan
Subst Use Misuse. 1998 Apr;33(5):1197-212. doi: 10.3109/10826089809062214.
Hepatitis C virus (HCV) presents several challenges to the development of prevention programs. HCV infection is persistent in up to 80% of cases, and viremic individuals may transmit infection to others. With 65-90% of injection drug users anti-HCV positive, a large reservoir of infection exists in most drug-injector populations. Studying the genetic variability of HCV infections could permit researchers to reconstruct chains of viral transmission in IDUs. However, the relationship of HCV to HIV epidemiology remains unclear and may depend on whether the proportions of infectious persons in the population are similar for both viruses.
77Young Drug Users: a Vulnerable Population and an Underutilized Resource in HIV/HCV Prevention.PubMed
Pedro Mateu-Gelabert, H Guarino, K Quinn, et al.
Curr HIV/AIDS Rep. 2018 Aug;15(4):324-335. doi: 10.1007/s11904-018-0406-z.
PURPOSE OF REVIEW: The social networks of people who inject drugs (PWID) have long been studied to understand disease transmission dynamics and social influences on risky practices. We illustrate how PWID can be active agents promoting HIV, HCV, and overdose prevention. RECENT FINDINGS: We assessed drug users' connections and interactions with others at risk for HIV/HCV in three cities: New York City (NYC), USA (n = 539); Pereira, Colombia (n = 50); and St. Petersburg, Russia (n = 49). In all three cities, the majority of participants' network members were of a similar age as themselves, yet connections across age groups were also present. In NYC, knowing any opioid user(s) older than 29 was associated with testing HCV-positive. In NYC and St. Petersburg, a large proportion of PWID engaged in intravention activities to support safer injection and overdose prevention; in Pereira, PWID injected, had sex, and interacted with other key groups at risk. People who use drugs can be active players in HIV/HCV and overdose risk- reduction; their networks provide them with ample opportunities to disseminate harm reduction knowledge, strategies, and norms to others at risk. Local communities could augment prevention programming by empowering drug users to be allies in the fight against HIV and facilitating their pre-existing health-protective actions.
78HIV and Viral Hepatitis Among Imprisoned Key Populations.PubMed
Andrea L Wirtz, Ping T Yeh, Natalie L Flath, et al.
Epidemiol Rev. 2018 Jun 1;40(1):12-26. doi: 10.1093/epirev/mxy003.
Prisons and other closed facilities create opportunities for transmission of human immunodeficiency virus (HIV) and viral hepatitis during detention and after release. We conducted a systematic review and meta-analysis of peer-reviewed publications (2005-2015) to describe the prevalence of HIV, hepatitis C virus, and hepatitis B virus among key populations in prisons worldwide and to compare estimates of infection with those of other prison populations. Most data were reported for people who inject drugs (PWID; n = 72) and for men who have sex with men (MSM; n = 21); few data were reported on sex workers (SW; n = 6), or transgender women (n = 2). Publications were identified from 29 countries, predominantly middle- and high-income countries. Globally, PWID had 6 times the prevalence of HIV (pooled prevalence ratio (PPR) = 6.0, 95% CI: 3.8, 9.4), 8 times the prevalence of hepatitis C virus (PPR = 8.1, 95% CI: 6.4, 10.4), and 2 times the prevalence of hepatitis B virus (PPR = 2.0, 95% CI: 1.5, 2.7) compared with noninjecting prisoner populations. Among these articles, only those from Iran, Scotland, Spain, and Italy included the availability of methadone therapy; 2 articles included information on access to needle exchange programs by PWID detainees. HIV prevalence was more than 2 times higher among SW (PPR = 2.6, 95% CI: 2.2, 3.1) and 5 times higher among MSM (PPR = 5.3, 95% CI: 3.5, 7.9) compared with other prisoners. None of these articles reported HIV prevention coverage among SW or transgender women; 1 described HIV and sexually transmitted infection screening for MSM in prison. Prevention programs specific to key populations are important, particularly for populations that are criminalized and/or may cycle in and out of prison.
79Understanding the Intersection of Behavioral Risk and Social Determinants of Health and the Impact on an Outbreak of Human Immunodeficiency Virus Among Persons Who Inject Drugs in Philadelphia.PubMed
Melissa M Kim, S Caitlin Conyngham, Champagnae Smith, et al.
J Infect Dis. 2020 Sep 2;222(Suppl 5):S250-S258. doi: 10.1093/infdis/jiaa128.
BACKGROUND: In 2018, Philadelphia identified an outbreak of new human immunodeficiency virus (HIV) infections among persons who inject drugs (PWID). Although conventional HIV surveillance systems capture individual-level behavioral risk, they are not able to capture the social and environmental factors contributing to rapid transmission. METHODS: HIV surveillance data were used to assess demographic, clinical, and behavioral factors for PWID with HIV diagnosed during 2017 and 2018. Social factors such as homelessness, disruption of encampments, and trends in sexual behaviors, drug use and syringe availability among PWID were captured through National HIV Behavioral Surveillance, routine hepatitis and sexually transmitted infection surveillance, and shelter and homeless outreach data. RESULTS: In 2018, there were 71 new infections among PWID, an increase of 115% since 2016. During this time, opioid overdose deaths peaked at 59 deaths per 100 000 persons, 85% of which involved the use of fentanyl. While overall reported homelessness increased, rates of those living unsheltered rose by 13%. The Philadelphia Department of Public Health identified increased injection frequency, encampment closures, and lack of syringe access as promoters of continued HIV transmission. CONCLUSION: The use of conventional surveillance methods only is inadequate for determining HIV risk during outbreaks. Incorporation of individual and aggregate level data on social and environmental determinants is necessary to develop effective outbreak response interventions.
80Social Factors in Ethanol Sensitization.PubMed
Rosana Camarini, Priscila Marianno, Mariana Rae
Int Rev Neurobiol. 2018;140:53-80. doi: 10.1016/bs.irn.2018.07.003. Epub 2018 Jul 30.
Behavioral sensitization is a neuroadaptive process characterized by an increase in a particular behavior after repeated exposure to drugs or other stimuli, such as stress. Sensitization can also be extended to neurochemical and neuroendocrine sensitization. Several factors can influence sensitization to the effects of ethanol. For instance, stress is an important component in addiction that can strengthen ethanol-induced behaviors. In animal models, stressful situations can be induced by alterations in social aspects of the animal's environment, such as maternal separation, social conflicts, and housing conditions. Social conflict models involve acute, chronic or intermittent interaction of an animal to a conspecific and can occur at any stage of life, including preweaning, adolescence or adulthood. These events can influence ethanol-induced behavioral sensitization in different ways, such as increases in locomotion, drug reward, and drug-taking behaviors. On the other hand, environmental enrichment can produce a protective phenotype against drug-related behaviors. In this chapter, we discuss findings regarding consequences of social stress and environmental enrichment on sensitization to ethanol.
81Effects of housing condition on the development and persistence of addictive-like behavior induced by toluene.PubMed
David García-Jácome, Lucía Martínez-Mota, Nayeli Páez-Martínez
Neurotoxicology. 2024 Jul;103:9-15. doi: 10.1016/j.neuro.2024.05.004. Epub 2024 May 25.
Environmental factors can modify addictive responses induced by drugs of abuse; however, little is known about the impact of environmental conditions on behavioral responses induced by inhalants. In this study, we analyzed the effects of housing conditions, considering environmental enrichment (EE; n = 10), social isolation (SI; n = 10), and standard housing (STD; n = 10), as positive, negative, and control environments, respectively, on the development and persistence of behavioral sensitization induced by toluene. Mice exposed to air were used as a comparative control groups for each housing condition (EE: n = 11, SI: n = 10 and STD: n = 11). Results showed that a history of toluene exposure induced the development of locomotor sensitization in mice, independent of their housing conditions. However, SI increased the expression of behavioral sensitization to toluene after a drug-free period.
82Effects of Housing on Methamphetamine-Induced Neurotoxicity and Spatial Learning and Memory.PubMed
Arnold Gutierrez, Sarah A Jablonski, Robyn M Amos-Kroohs, et al.
ACS Chem Neurosci. 2017 Jul 19;8(7):1479-1489. doi: 10.1021/acschemneuro.6b00419. Epub 2017 Mar 27.
Severe stress potentiates methamphetamine (MA) neurotoxicity. However, whether moderate stress increases or decreases the neurotoxic effects of MA is unknown. We assessed the effects of MA (4 × 10 mg/kg at 2 h intervals) in combination with prior barren-cage housing in adult male Sprague-Dawley rats on monoamines and glial fibrillary acid protein (GFAP) in one cohort and spatial learning and memory in the Morris water maze in another cohort. MA reduced dopamine (DA) and serotonin (5-HT) in the neostriatum and nucleus accumbens, 5-HT in the hippocampus, and increased GFAP in neostriatum and nucleus accumbens compared with saline controls. In neostriatum, barren-cage housing protected against MA-induced increases in GFAP, but it did not prevent DA and 5-HT reductions, although it did increase hippocampal norepinephrine. MA impaired spatial learning during acquisition, reversal, and shift phases and impaired reference memory on reversal and shift probe trials. Barren-cage housing enhanced performance during acquisition but not during reversal or shift or on probe trials. The data indicate that prior barren-cage housing moderates MA-induced neostriatal astrogliosis and initial spatial learning, but has no protective effect when the platform is smaller and relocated and therefore requires cognitive flexibility in relearning.
83Differential housing and novelty response: Protection and risk from locomotor sensitization.PubMed
Erik J Garcia, Tara N Haddon, Donald A Saucier, et al.
Pharmacol Biochem Behav. 2017 Mar;154:20-30. doi: 10.1016/j.pbb.2017.01.004. Epub 2017 Jan 17.
UNLABELLED: High novelty seeking increases the risk for drug experimentation and locomotor sensitization. Locomotor sensitization to psychostimulants is thought to reflect neurological adaptations that promote the transition to compulsive drug taking. Rats reared in enrichment (EC) show less locomotor sensitization when compared to rats reared in isolation (IC) or standard conditions (SC). The current research study was designed to test if novelty response contributed locomotor sensitization and more importantly, if the different housing environments could change the novelty response to protect against the development of locomotor sensitization in both adolescence and adulthood. Experiment 1: rats were tested for their response to novelty using the inescapable novelty test (IEN) and pseudorandomly assigned to enriched (EC), isolated (IC), or standard (SC) housing conditions for 30days. After housing, they were tested with IEN. Rats were then administered amphetamine (0.5mg/kg) or saline and locomotor activity was measured followed by a sensitization test 14days later. Experiment 2: rats were tested in the IEN test early adulthood and given five administrations of amphetamine (0.3mg/kg) or saline and then either stayed in or switched housing environments for 30days. Rats were then re-tested in the IEN test in late adulthood and administered five more injections of their respective treatments and tested for locomotor sensitization. Results indicate that IC and SC increased the response to novelty. EC housing decreased locomotor response to amphetamine and saline, and SC housing increased the locomotor response to amphetamine. Mediation results indicated that the late adult novelty response fully mediates the locomotor response to amphetamine and saline, while the early adulthood novelty response did not. CONCLUSIONS: Differential housing changes novelty and amphetamine locomotor response. Novelty response is altered into adulthood and provides evidence that enrichment can be used to reduce drug vulnerability.
84Poverty and Health in Tennessee.PubMed
Kate Beatty, Olivia Egen, John Dreyzehner, et al.
South Med J. 2020 Jan;113(1):1-7. doi: 10.14423/SMJ.0000000000001055.
OBJECTIVES: Understanding the impact of poverty on health can inform efforts to target social programs and regional economic development. This study examined the effects of poverty on health among the 95 counties of Tennessee. METHODS: All of the counties of Tennessee were ranked by 5-year median household income, from the wealthiest to the poorest. The counties were divided into quintiles, from wealthiest to poorest, to reflect the general impact of wealth on health. Next, the five wealthiest counties and the five poorest counties were identified, allowing for examination of the extremes of poverty and wealth within Tennessee. Comparisons of quintiles and five wealthiest and poorest counties on key measures were performed using the independent test. RESULTS: People living in the wealthiest quintile lived on average 2.5 to 4 years longer and had lower rates of all health behaviors and health outcomes investigated compared with those in the poorest quintile. This disparity was even more pronounced when comparing the wealthiest five counties to the poorest five. The five poorest counties, for example, had twice the years of potential life lost and were overwhelmingly rural in character, with similar accompanying disparities such as median income, high unemployment, and a more aged population. CONCLUSIONS: This study highlights the fact that lower income is associated with significantly worse health outcomes in Tennessee and reinforces the importance of economic development, specifically, and addresses the social determinants, more generally, in helping to improve Tennessee's overall health statistics.
85Health Disparities in Systemic Lupus Erythematosus.PubMed
Christine A Peschken
Rheum Dis Clin North Am. 2020 Nov;46(4):673-683. doi: 10.1016/j.rdc.2020.07.010. Epub 2020 Sep 9.
Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by autoantibody production and diverse clinical manifestations. The many complex, overlapping, and closely associated factors that influence SLE susceptibility and outcomes include ethnic disparities, low adherence to medications, and poverty, and geography. Epigenetic mechanisms may provide the link between these environmental exposures and behaviors and the disproportionate burden of SLE seen in ethnic minorities. Attention to these modifiable social determinants of health would not only improve outcomes for vulnerable patients with SLE but likely reduce susceptibility to SLE as well through epigenetic changes.
86Social Stability and Unmet Health Care Needs in a Community-Based Sample of Women Who Use Drugs.PubMed
Ellesse-Roselee L Akré, Daniel J Marthey, Chisom Ojukwu, et al.
Health Serv Res Manag Epidemiol. 2021 Nov 20;8:23333928211048640. doi: 10.1177/23333928211048640. eCollection 2021 Jan-Dec.
OBJECTIVE: To examine the relationship between social stability and access to healthcare services among a community-based sample of adult female drug users. METHODS: We developed a measure of social stability and examined its relationship to health care access. Data came from a cross-sectional sample of female drug users (N = 538) in Oakland, CA who were interviewed between September 2014 and August 2015. We categorized women as having low (1-5), medium (6-10), or high (11-16) social stability based on the tertile of the index sample distribution. We then used ordered logistic regression to examine the relationship between social stability and self-reported access to mental health services and medical care. RESULTS: Compared with women in the low stability group, those with high stability experienced a 58% decline in the odds of needed but unmet mental health services [AOR: 0.42; 95% C.I.: 0.26, 0.69] and a 68% decline in the odds of unmet medical care [AOR: 0.32; 95% C.I.: 0.19, 0.54] after adjusting for confounders. The coefficients we observed reduced in size at higher levels of the stability index suggesting a positive association between social experiences and access to healthcare services. CONCLUSION: Women who use drugs are at increased risk of adverse health outcomes and often experience high levels of unmet healthcare needs. Our study highlights the importance of addressing social determinants of health and suggests that improving social factors such as housing stability and personal safety may support access to healthcare among female drug users.
87Introduction to the special issue.PubMed
Andrea Finlay, Ingrid Binswanger, Christine Timko
Addict Sci Clin Pract. 2020 Feb 5;15(1):5. doi: 10.1186/s13722-020-0182-0.
This special issue of Addiction Science & Clinical Practice, "Addiction treatment access and utilization among criminal justice involved populations", presents a series of articles on substance use disorder treatment access and utilization by people who have contact with the criminal justice system (e.g., jails, prisons, and courts). Despite the high prevalence of substance use disorders among people who experience these settings, evidence-based treatment for substance use disorders may be unavailable and/or care may be fragmented during transitions between settings. Articles in this special issue address several gaps in the literature and present a conceptual model of opioid overdose risk, the results of a randomized controlled trial to increase treatment uptake and retention during and after incarceration, descriptions of barriers to treatment after release from incarceration, and data from nationally representative surveys of substance use disorders and treatment use among people who have been involved in the criminal justice system. Importantly, the voices of people with lived experience in the criminal justice system were incorporated in two manuscripts. Together these articles advance our understanding of how to improve care coordination and expansion of services across systems and organizations to prevent overdose, improve treatment utilization, and ultimately, improve health outcomes among criminal justice involved populations in the United States who have substance use disorders or use substances.
88Drug misuse, tobacco smoking, alcohol and other social determinants of tuberculosis in UK-born adults in England: a community-based case-control study.PubMed
Patrick Nguipdop-Djomo, Laura C Rodrigues, Peter G Smith, et al.
Sci Rep. 2020 Mar 27;10(1):5639. doi: 10.1038/s41598-020-62667-8.
Addressing social determinants of tuberculosis (TB) is essential to achieve elimination, including in low-incidence settings. We measured the association between socio-economic status and intermediate social determinants of health (SDHs, including drug misuse, tobacco smoking and alcohol), and TB, taking into account their clustering in individuals. We conducted a case-control study in 23-38 years old UK-born White adults with first tuberculosis episode, and randomly selected age and sex frequency-matched community controls. Data was collected on education, household overcrowding, tobacco smoking, alcohol and drugs use, and history of homelessness and prison. Analyses were done using logistic regression models, informed by a formal theoretical causal framework (Directed Acyclic Graph). 681 TB cases and 1183 controls were recruited. Tuberculosis odds were four times higher in subjects with education below GCSE O-levels, compared to higher education (OR = 3.94; 95%CI: 2.74, 5.67), after adjusting for other TB risk factors (age, sex, BCG-vaccination and stays ≥3 months in Africa/Asia). When simultaneously accounting for respective SDHs, higher tuberculosis risk was independently associated with tobacco smoking, drugs use (especially injectable drugs OR = 5.67; 95%CI: 2.68, 11.98), homelessness and area-level deprivation. Population Attributable Fraction estimates suggested that tobacco and class-A drug use were, respectively, responsible for 18% and 15% of TB cases in this group. Our findings suggest that socio-economic deprivation remains a driver of tuberculosis in England, including through drugs misuse, tobacco smoking, and homelessness. These findings further support the integration of health and social services in high-risk young adults to improve TB control efforts.
89Racism in Drug Testing.PubMed
Jacqueline A Hubbard, Kamisha L Johnson-Davis
Clin Lab Med. 2024 Dec;44(4):607-617. doi: 10.1016/j.cll.2024.07.006. Epub 2024 Sep 20.
Racial disparities in drug testing for substance-use disorders underscore systemic inequalities. Studies reveal that minority groups, particularly Black and Hispanic Americans, are disproportionately targeted for drug testing despite similar rates of drug use across racial lines. Such bias impacts employment opportunities, legal outcomes, and access to treatment. The overrepresentation of minorities in drug testing reflects broader societal prejudices, leading to a cycle of discrimination and marginalization. Addressing these disparities requires a multifaceted approach, including policy reform, increased awareness of implicit biases, and equitable health care practices to ensure fair treatment of all individuals struggling with substance-use disorders.
90What Would Equitable Harm Reduction Look Like?PubMed
Oluwole Jegede, Julio C Nunes, Terence Tumenta, et al.
AMA J Ethics. 2024 Jul 1;26(7):E572-579. doi: 10.1001/amajethics.2024.572.
Structural determinants of health frameworks must express antiracism to be effective, but racial and ethnic inequities are widely documented, even in harm reduction programs that focus on person-centered interventions. Harm reduction strategies should express social justice and health equity, resist stigma and discrimination, and mitigate marginalization experiences among people who use drugs (PWUD). To do so, government and organizational policies that promote harm reduction must acknowledge historical and ongoing patterns of racializing drug use. This article gives examples of such racialization and offers recommendations about how harm reduction programming can most easily and effectively motivate equitable, antiracist care for PWUD.
91Cost-effectiveness of Treatments for Opioid Use Disorder.PubMed
Michael Fairley, Keith Humphreys, Vilija R Joyce, et al.
JAMA Psychiatry. 2021 Jul 1;78(7):767-777. doi: 10.1001/jamapsychiatry.2021.0247.
IMPORTANCE: Opioid use disorder (OUD) is a significant cause of morbidity and mortality in the US, yet many individuals with OUD do not receive treatment. OBJECTIVE: To assess the cost-effectiveness of OUD treatments and association of these treatments with outcomes in the US. DESIGN AND SETTING: This model-based cost-effectiveness analysis included a US population with OUD. INTERVENTIONS: Medication-assisted treatment (MAT) with buprenorphine, methadone, or injectable extended-release naltrexone; psychotherapy (beyond standard counseling); overdose education and naloxone distribution (OEND); and contingency management (CM). MAIN OUTCOMES AND MEASURES: Fatal and nonfatal overdoses and deaths throughout 5 years, discounted lifetime quality-adjusted life-years (QALYs), and costs. RESULTS: In the base case, in the absence of treatment, 42 717 overdoses (4132 fatal, 38 585 nonfatal) and 12 660 deaths were estimated to occur in a cohort of 100 000 patients over 5 years, and 11.58 discounted lifetime QALYs were estimated to be experienced per person. An estimated reduction in overdoses was associated with MAT with methadone (10.7%), MAT with buprenorphine or naltrexone (22.0%), and when combined with CM and psychotherapy (range, 21.0%-31.4%). Estimated deceased deaths were associated with MAT with methadone (6%), MAT with buprenorphine or naltrexone (13.9%), and when combined with CM, OEND, and psychotherapy (16.9%). MAT yielded discounted gains of 1.02 to 1.07 QALYs per person. Including only health care sector costs, methadone cost $16 000/QALY gained compared with no treatment, followed by methadone with OEND ($22 000/QALY gained), then by buprenorphine with OEND and CM ($42 000/QALY gained), and then by buprenorphine with OEND, CM, and psychotherapy ($250 000/QALY gained). MAT with naltrexone was dominated by other treatment alternatives. When criminal justice costs were included, all forms of MAT (with buprenorphine, methadone, and naltrexone) were associated with cost savings compared with no treatment, yielding savings of $25 000 to $105 000 in lifetime costs per person. The largest cost savings were associated with methadone plus CM. Results were qualitatively unchanged over a wide range of sensitivity analyses. An analysis using demographic and cost data for Veterans Health Administration patients yielded similar findings. CONCLUSIONS AND RELEVANCE: In this cost-effectiveness analysis, expanded access to MAT, combined with OEND and CM, was associated with cost-saving reductions in morbidity and mortality from OUD. Lack of widespread MAT availability limits access to a cost-saving medical intervention that reduces morbidity and mortality from OUD. Opioid overdoses in the US likely reached a record high in 2020 because of COVID-19 increasing substance use, exacerbating stress and social isolation, and interfering with opioid treatment. It is essential to understand the cost-effectiveness of alternative forms of MAT to treat OUD.
92Treating Opioid Dependence: Pain Medicine Physiology of Tolerance and Addiction.PubMed
Dominika Lipowska James, Maryam Jowza
Clin Obstet Gynecol. 2019 Mar;62(1):87-97. doi: 10.1097/GRF.0000000000000422.
Inappropriate and excessive opioid prescribing practices for treatment of chronic nonmalignant pain contributed to rising rates of opioid related mortality. Effective and widely available opioid addiction treatment resources are needed to ensure successful resolution of the "opioid epidemic". This chapter outlines the basic pathophysiology of addiction as well as principles of opioid addiction management focusing on the pharmacological and nonpharmacological aspects of care. Pharmacological treatment focuses on opioid substitution therapy, with aim at prevention of opioid cravings and opioid withdrawal symptoms. Nonpharmacological treatment involves psychological and supportive approaches to addiction such as group meetings, psychological counseling, and mindfulness training.
93Opioid dependence.PubMed
Joseph J Benich
Prim Care. 2011 Mar;38(1):59-70. doi: 10.1016/j.pop.2010.11.005. Epub 2010 Dec 24.
Opioid dependence is becoming a more common problem in the United States that gives rise to many negative health and social consequences for both individuals and society as a whole. Opioid dependence presents a challenging issue for physicians to identify and treat. Understanding and managing withdrawal symptoms is often a necessary first step on the road to recovery for these patients. Long-term therapy options include detoxification, nonpharmacologic treatment plans, and maintenance replacement treatment with either methadone or buprenorphine. Physicians meeting necessary requirements have the option of implementing office-based opioid-assisted maintenance therapy.
94Recommendations for buprenorphine and methadone therapy in opioid use disorder: a European consensus.PubMed
Maurice Dematteis, Marc Auriacombe, Oscar D'Agnone, et al.
Expert Opin Pharmacother. 2017 Dec;18(18):1987-1999. doi: 10.1080/14656566.2017.1409722. Epub 2017 Dec 3.
Management of patients with opioid use disorder (OUD) commonly includes opioid agonist therapy (OAT) as a part of an integrated treatment plan. These interventions are associated with proven benefits to the individual and society. Areas covered: The use of methadone and buprenorphine within an integrated treatment plan in the management of patients with OUD: this work provides consensus recommendation on pharmacotherapy in OUD to assist clinicians with practical decision making in this field. Expert opinion: Pharmacotherapy is recommended as part of an integrated OUD treatment approach with psychosocial interventions, with the goal of reducing risks of illicit opioid use, overdose mortality, infection with HIV or HCV, improving health, psychological and social outcomes. Access to OAT should be prioritised in the treatment of OUD. Treatment choices in OUD pharmacotherapy should be based on the needs of the individual and characteristics of medications. Recommendations for choices of OAT are based on clinical efficacy, safety, patient preference, side effects, pharmacological interactions, quality of life, dose titration potential and outcomes (control craving, ongoing opioids consumption or other drugs, and potentially psychiatric comorbidities). Special groups, pregnant women, prisoners, patients with mental health problems have specific needs which must be addressed with expert input.
95Treatment of opioid use disorder in primary care.PubMed
Megan Buresh, Robert Stern, Darius Rastegar
BMJ. 2021 May 19;373:n784. doi: 10.1136/bmj.n784.
Opioid use disorder (OUD) is a common, treatable chronic disease that can be effectively managed in primary care settings. Untreated OUD is associated with considerable morbidity and mortality-notably, overdose, infectious complications of injecting drug use, and profoundly diminished quality of life. Withdrawal management and medication tapers are ineffective and are associated with increased rates of relapse and death. Pharmacotherapy is the evidence based mainstay of OUD treatment, and many studies support its integration into primary care settings. Evidence is strongest for the opioid agonists buprenorphine and methadone, which randomized controlled trials have shown to decrease illicit opioid use and mortality. Discontinuation of opioid agonist therapy is associated with increased rates of relapse and mortality. Less evidence is available for the opioid antagonist extended release naltrexone, with a meta-analysis of randomized controlled trials showing decreased illicit opioid use but no effect on mortality. Treating OUD in primary care settings is cost effective, improves outcomes for both OUD and other medical comorbidities, and is highly acceptable to patients. Evidence on whether behavioral interventions improve outcomes for patients receiving pharmacotherapy is mixed, with guidelines promoting voluntary engagement in psychosocial supports, including counseling. Further work is needed to promote the integration of OUD treatment into primary care and to overcome regulatory barriers to integrating methadone into primary care treatment in the US.
96Buprenorphine-Naloxone for Opioid Use Disorder: Reduction in Mortality and Increased Remission.PubMed
Krishna K Paul, Christian G Frey, Stanley Troung, et al.
West J Emerg Med. 2024 Nov;25(6):869-874. doi: 10.5811/westjem.18569.
INTRODUCTION: As fentanyl has become more readily available, opioid-related morbidity and mortality in the United States has increased dramatically. Preliminary studies suggest that high-affinity, partial mu-opioid receptor agonists such as the combination product buprenorphine-naloxone may reduce mortality from overdose and promote remission. With the escalating prevalence of opioid use disorder (OUD), it is essential to evaluate the effectiveness of opioid agonists like buprenorphine-naloxone. This study examines mortality and remission rates for OUD patients prescribed buprenorphine-naloxone to determine the efficacy of this treatment toward these outcomes. METHODS: We carried out a retrospective analysis using the US Collaborative Network database in TriNetX, examining de-identified medical records from nearly 92 million patients across 56 healthcare organizations. The study spanned the years from January 1, 2017-May 13, 2022. Cohort 1 included OUD patients who began buprenorphine-naloxone treatment within one-year post-diagnosis, while Cohort 2, the control group, consisted of OUD patients who were not administered buprenorphine. The study measured mortality and remission rates within a year of the index event, incorporating propensity score matching for age, gender, and race/ethnicity. RESULTS: Prior to propensity matching, we identified a total of 221,967 patients with OUD. Following exclusions, 61,656 patients treated with buprenorphine-naloxone showed 34% fewer deaths within one year of diagnosis compared to 159,061 patients who did not receive buprenorphine (2.6% vs 4.0%; relative risk [RR] 0.661; 95% confidence interval [CI] 0.627-0.698; < 0.001). The remission rate was approximately 1.9 times higher in the buprenorphine-naloxone group compared to the control group (18.8% vs 10.1%; RR 1.862; 95% CI 1.812-1.914; < 0.001). After propensity matching, the effect on mortality decreased but remained statistically significant (2.6% vs 3.0%; RR 0.868; 95% CI 0.813-0.927; < 0.001) and the remission rate remained consistent (18.8% vs 10.4%; RR 1.812; 95% CI 1.750-1.876; < 0.001). Number needed to treat for benefit was 249 for death and 12 for remission. CONCLUSION: Buprenorphine-naloxone was associated with significantly reduced mortality and increased remission rates for patients with opioid use disorder and should be used as a primary treatment. The recognition and implementation of treatment options like buprenorphine-naloxone is vital in alleviating the impact of OUD.
97Treatment of Perinatal Opioid Use Disorder.PubMed
Lisa Boyars, Constance Guille
Obstet Gynecol Clin North Am. 2018 Sep;45(3):511-524. doi: 10.1016/j.ogc.2018.05.001.
Opioid agonist therapy is the standard of care for pregnant women with Opioid Use Disorder, but medication-assisted withdrawal from opioid agonist therapy is increasingly prevalent. We review available literature evaluating the risks and benefits of medication-assisted withdrawal. We highlight the importance of supporting women in making an informed treatment choice that is best for them. Although it is tempting to choose medication-assisted withdrawal to decrease the risk of newborn opioid withdrawal, we caution against this practice. Facilitating treatment that assists pregnant women in recovery ultimately produces the best outcome for women and their children.
98Advances and challenges in pharmacotherapeutics for amphetamine-type stimulants addiction.PubMed
Dan-Ni Cao, Jing-Jing Shi, Wei Hao, et al.
Eur J Pharmacol. 2016 Jun 5;780:129-35. doi: 10.1016/j.ejphar.2016.03.040. Epub 2016 Mar 24.
Addiction to amphetamine-type stimulants (ATS) is a serious worldwide public health problem with major medical, psychiatric and socioeconomic consequences. However, no approved pharmacological therapies are available to treat ATS addiction. Based on the neurobiological mechanisms underlying ATS addiction, the recent research works about pharmacological strategies have been focused on monoamine, glutamate, endogenous opioid peptide and γ-amino butyric acid (GABA) systems. This review summarizes the recent advances in the medications being developed to treat ATS addiction and discusses the remaining challenges. Although no substantial evidence for efficacious medications has emerged, some of these agents, including bupropion, naltrexone and mirtazapine, have demonstrated promise in clinical studies. Moreover, some challenges, such as the development of new preclinical animal models of drug addiction, the design of large-scale clinical trials with strict quality control, and the distinction of patients' genetic polymorphisms, need further attention. Despite the lack of success to date, much effort is being made to develop efficacious medications for treating ATS addiction.
99Pharmacotherapeutic agents in the treatment of methamphetamine dependence.PubMed
Kirsten C Morley, Jennifer L Cornish, Alon Faingold, et al.
Expert Opin Investig Drugs. 2017 May;26(5):563-578. doi: 10.1080/13543784.2017.1313229. Epub 2017 Apr 7.
Methamphetamine use is a serious public health concern in many countries and is second to cannabis as the most widely abused illicit drug in the world. Effective management for methamphetamine dependence remains elusive and the large majority of methamphetamine users relapse following treatment. Areas covered: Progression in the understanding of the pharmacological basis of methamphetamine use has provided us with innovative opportunities to develop agents to treat dependence. The current review summarizes relevant literature on the neurobiological and clinical correlates associated with methamphetamine use. We then outline agents that have been explored for potential treatments in preclinical studies, human laboratory phase I and phase II trials over the last ten years. Expert opinion: No agent has demonstrated a broad and strong effect in achieving MA abstinence in Phase II trials. Agents with novel therapeutic targets appear promising. Advancement in MA treatment, including translation into practice, faces several clinical challenges.
100Combined Pharmacotherapy and Cognitive Behavioral Therapy for Adults With Alcohol or Substance Use Disorders: A Systematic Review and Meta-analysis.PubMed
Lara A Ray, Lindsay R Meredith, Brian D Kiluk, et al.
JAMA Netw Open. 2020 Jun 1;3(6):e208279. doi: 10.1001/jamanetworkopen.2020.8279.
IMPORTANCE: Substance use disorders (SUDs) represent a pressing public health concern. Combined behavioral and pharmacological interventions are considered best practices for addiction. Cognitive behavioral therapy (CBT) is a first-line intervention, yet the superiority of CBT compared with other behavioral treatments when combined with pharmacotherapy remains unclear. An understanding of the effects of combined CBT and pharmacotherapy will inform best-practice guidelines for treatment of SUD. OBJECTIVE: To conduct a meta-analysis of the published literature on combined CBT and pharmacotherapy for adult alcohol use disorder (AUD) or other SUDs. DATA SOURCES: PubMed, Cochrane Register, MEDLINE, PsychINFO, and Embase databases from January 1, 1990, through July 31, 2019, were searched. Keywords were specified in 3 categories: treatment type, outcome type, and study design. Collected data were analyzed through September 30, 2019. STUDY SELECTION: Two independent raters reviewed abstracts and full-text articles. English language articles describing randomized clinical trials examining CBT in combination with pharmacotherapy for AUD and SUD were included. DATA EXTRACTION AND SYNTHESIS: Inverse-variance weighted, random-effects estimates of effect size were pooled into 3 clinically informative subgroups: (1) CBT plus pharmacotherapy compared with usual care plus pharmacotherapy, (2) CBT plus pharmacotherapy compared with another specific therapy plus pharmacotherapy, and (3) CBT added to usual care and pharmacotherapy compared with usual care and pharmacotherapy alone. Sensitivity analyses included assessment of study quality, pooled effect size heterogeneity, publication bias, and primary substance moderator effects. MAIN OUTCOMES AND MEASURES: Substance use frequency and quantity outcomes after treatment and during follow-up were examined. RESULTS: The sample included 62 effect sizes from 30 unique randomized clinical trials that examined CBT in combination with some form of pharmacotherapy for AUD and SUD. The primary substances targeted in the clinical trial sample were alcohol (15 [50%]), followed by cocaine (7 [23%]) and opioids (6 [20%]). The mean (SD) age of the patient sample was 39 (6) years, with a mean (SD) of 28% (12%) female participants per study. The following pharmacotherapies were used: naltrexone hydrochloride and/or acamprosate calcium (26 of 62 effect sizes [42%]), methadone hydrochloride or combined buprenorphine hydrochloride and naltrexone (11 of 62 [18%]), disulfiram (5 of 62 [8%]), and another pharmacotherapy or mixture of pharmacotherapies (20 of 62 [32%]). Random-effects pooled estimates showed a benefit associated with combined CBT and pharmacotherapy over usual care (g range, 0.18-0.28; k = 9). However, CBT did not perform better than another specific therapy, and evidence for the addition of CBT as an add-on to combined usual care and pharmacotherapy was mixed. Moderator analysis showed variability in effect direction and magnitude by primary drug target. CONCLUSIONS AND RELEVANCE: The present study supports the efficacy of combined CBT and pharmacotherapy compared with usual care and pharmacotherapy. Cognitive behavioral therapy did not perform better than another evidence-based modality (eg, motivational enhancement therapy, contingency management) in this context or as an add-on to combined usual care and pharmacotherapy. These findings suggest that best practices in addiction treatment should include pharmacotherapy plus CBT or another evidence-based therapy, rather than usual clinical management or nonspecific counseling services.
101Cognitive Behavioral Therapy and Motivational Enhancement Therapy.PubMed
Sarah S Wu, Erin Schoenfelder, Ray Chih-Jui Hsiao
Child Adolesc Psychiatr Clin N Am. 2016 Oct;25(4):629-43. doi: 10.1016/j.chc.2016.06.002.
Although cognitive behavioral therapy (CBT) is widely recognized as the preferred treatment of psychiatric disorders, less is known about the application of CBT to substance use disorders, particularly in adolescence. This article discusses how CBT conceptualizes substance use and how it is implemented as a treatment of adolescent substance abuse. The article draws on several manuals for CBT that implement it as a standalone treatment or in combination with motivational enhancement therapies. Also reviewed are several studies that examined the efficacy of CBT. Finally, the implications are discussed. Numerous starting resources are provided to help a clinician implement CBT.
102Adolescent Substance Use Disorder Treatment: an Update on Evidence-Based Strategies.PubMed
Matthew C Fadus, Lindsay M Squeglia, Emilio A Valadez, et al.
Curr Psychiatry Rep. 2019 Sep 14;21(10):96. doi: 10.1007/s11920-019-1086-0.
PURPOSE OF REVIEW: To examine the most recent published evidence (2016-2019) regarding the treatment of adolescent substance use disorders and to provide an update on evidence-based strategies, adjunctive interventions, and methods to improve currently established treatment approaches. RECENT FINDINGS: Recent evidence suggests that psychosocial treatments such as family-based therapy, cognitive behavioral therapy, and multicomponent approaches remain the most effective methods of treatment; however, innovative ways of improving these treatment strategies may include digital and culturally based interventions. New advances in adjunctive treatments such as pharmacotherapy, exercise, mindfulness, and recovery-oriented educational centers may have some clinical utility. Well-established psychosocial interventions remain the primary modality of treatment. Promising new adjunctive treatments and improvements in our currently established treatments may yield significant improvements.
103Cognitive Behavioural Therapy and Dual Diagnosis: A Systematic Review Exploring Its Effectiveness and Implications for Nursing Practice.PubMed
Dominic Nessbach, Alan Simpson
Int J Ment Health Nurs. 2025 Oct;34(5):e70129. doi: 10.1111/inm.70129.
Dual diagnosis (DD) is defined as the presence of a co-occurring mental health and substance use disorder. It is associated with poor treatment outcomes, which can be further fuelled by frequent exclusion from specialist treatment due to the separation between mental health and drug and alcohol services. Cognitive Behavioural Therapy (CBT) has an extensive evidence base in treating mental health and substance use disorders in isolation, but there is a paucity of evidence regarding its efficacy in treating DD. The current systematic review aimed to explore the use and effectiveness of CBT as a treatment for individuals with DD. Sources were derived in September 2024 from electronic databases including Medline, PsychINFO, Embase and CINAHL; topically relevant meta-analyses were also citation tracked. Twenty-three studies were included in this review from a total of 2364 which were initially retrieved. Study outcomes highlighted that CBT-based interventions provided some level of improvement to mental health or substance use symptoms, although several interventions did not display superiority when compared to typical addiction approaches. Mental health nurses are well suited to deliver CBT-based interventions and could address the current treatment gap experienced by individuals with DD. This could include supporting patients in maintaining and generalising CBT skills that have already been acquired, which would help guarantee accessibility to CBT-based interventions over a longer time period. However, additional support structures would need to be implemented to allow nurses to deliver CBT effectively, such as access to training, supervision, protected time and reflective practice.
104Motivational interviewing for substance use reduction.PubMed
Rosemarie Schwenker, Carla Emilia Dietrich, Selamawit Hirpa, et al.
Cochrane Database Syst Rev. 2023 Dec 12;12(12):CD008063. doi: 10.1002/14651858.CD008063.pub3.
BACKGROUND: Substance use is a global issue, with around 30 to 35 million individuals estimated to have a substance-use disorder. Motivational interviewing (MI) is a client-centred method that aims to strengthen a person's motivation and commitment to a specific goal by exploring their reasons for change and resolving ambivalence, in an atmosphere of acceptance and compassion. This review updates the 2011 version by Smedslund and colleagues. OBJECTIVES: To assess the effectiveness of motivational interviewing for substance use on the extent of substance use, readiness to change, and retention in treatment. SEARCH METHODS: We searched 18 electronic databases, six websites, four mailing lists, and the reference lists of included studies and reviews. The last search dates were in February 2021 and November 2022. SELECTION CRITERIA: We included randomised controlled trials with individuals using drugs, alcohol, or both. Interventions were MI or motivational enhancement therapy (MET), delivered individually and face to face. Eligible control interventions were no intervention, treatment as usual, assessment and feedback, or other active intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane, and assessed the certainty of evidence with GRADE. We conducted meta-analyses for the three outcomes (extent of substance use, readiness to change, retention in treatment) at four time points (post-intervention, short-, medium-, and long-term follow-up). MAIN RESULTS: We included 93 studies with 22,776 participants. MI was delivered in one to nine sessions. Session durations varied, from as little as 10 minutes to as long as 148 minutes per session, across included studies. Study settings included inpatient and outpatient clinics, universities, army recruitment centres, veterans' health centres, and prisons. We judged 69 studies to be at high risk of bias in at least one domain and 24 studies to be at low or unclear risk. Comparing MI to no intervention revealed a small to moderate effect of MI in substance use post-intervention (standardised mean difference (SMD) 0.48, 95% confidence interval (CI) 0.07 to 0.89; I = 75%; 6 studies, 471 participants; low-certainty evidence). The effect was weaker at short-term follow-up (SMD 0.20, 95% CI 0.12 to 0.28; 19 studies, 3351 participants; very low-certainty evidence). This comparison revealed a difference in favour of MI at medium-term follow-up (SMD 0.12, 95% CI 0.05 to 0.20; 16 studies, 3137 participants; low-certainty evidence) and no difference at long-term follow-up (SMD 0.12, 95% CI -0.00 to 0.25; 9 studies, 1525 participants; very low-certainty evidence). There was no difference in readiness to change (SMD 0.05, 95% CI -0.11 to 0.22; 5 studies, 1495 participants; very low-certainty evidence). Retention in treatment was slightly higher with MI (SMD 0.26, 95% CI -0.00 to 0.52; 2 studies, 427 participants; very low-certainty evidence). Comparing MI to treatment as usual revealed a very small negative effect in substance use post-intervention (SMD -0.14, 95% CI -0.27 to -0.02; 5 studies, 976 participants; very low-certainty evidence). There was no difference at short-term follow-up (SMD 0.07, 95% CI -0.03 to 0.17; 14 studies, 3066 participants), a very small benefit of MI at medium-term follow-up (SMD 0.12, 95% CI 0.02 to 0.22; 9 studies, 1624 participants), and no difference at long-term follow-up (SMD 0.06, 95% CI -0.05 to 0.17; 8 studies, 1449 participants), all with low-certainty evidence. There was no difference in readiness to change (SMD 0.06, 95% CI -0.27 to 0.39; 2 studies, 150 participants) and retention in treatment (SMD -0.09, 95% CI -0.34 to 0.16; 5 studies, 1295 participants), both with very low-certainty evidence. Comparing MI to assessment and feedback revealed no difference in substance use at short-term follow-up (SMD 0.09, 95% CI -0.05 to 0.23; 7 studies, 854 participants; low-certainty evidence). A small benefit for MI was shown at medium-term (SMD 0.24, 95% CI 0.08 to 0.40; 6 studies, 688 participants) and long-term follow-up (SMD 0.24, 95% CI 0.07 to 0.41; 3 studies, 448 participants), both with moderate-certainty evidence. None of the studies in this comparison measured substance use at the post-intervention time point, readiness to change, and retention in treatment. Comparing MI to another active intervention revealed no difference in substance use at any follow-up time point, all with low-certainty evidence: post-intervention (SMD 0.07, 95% CI -0.15 to 0.29; 3 studies, 338 participants); short-term (SMD 0.05, 95% CI -0.03 to 0.13; 18 studies, 2795 participants); medium-term (SMD 0.08, 95% CI -0.01 to 0.17; 15 studies, 2352 participants); and long-term follow-up (SMD 0.03, 95% CI -0.07 to 0.13; 10 studies, 1908 participants). There was no difference in readiness to change (SMD 0.15, 95% CI -0.00 to 0.30; 5 studies, 988 participants; low-certainty evidence) and retention in treatment (SMD -0.04, 95% CI -0.23 to 0.14; 12 studies, 1945 participants; moderate-certainty evidence). We downgraded the certainty of evidence due to inconsistency, study limitations, publication bias, and imprecision. AUTHORS' CONCLUSIONS: Motivational interviewing may reduce substance use compared with no intervention up to a short follow-up period. MI probably reduces substance use slightly compared with assessment and feedback over medium- and long-term periods. MI may make little to no difference to substance use compared to treatment as usual and another active intervention. It is unclear if MI has an effect on readiness to change and retention in treatment. The studies included in this review were heterogeneous in many respects, including the characteristics of participants, substance(s) used, and interventions. Given the widespread use of MI and the many studies examining MI, it is very important that counsellors adhere to and report quality conditions so that only studies in which the intervention implemented was actually MI are included in evidence syntheses and systematic reviews. Overall, we have moderate to no confidence in the evidence, which forces us to be careful about our conclusions. Consequently, future studies are likely to change the findings and conclusions of this review.
105Motivational interviewing, enhancement, and brief interventions over the last decade: A review of reviews of efficacy and effectiveness.PubMed
Carlo C DiClemente, Catherine M Corno, Meagan M Graydon, et al.
Psychol Addict Behav. 2017 Dec;31(8):862-887. doi: 10.1037/adb0000318.
Motivation is a well-established predictor of recovery for addictive behaviors. Treatments aimed at changing substance use and gambling frequently employ motivational enhancing strategies, based in the principles of Motivational Interviewing (MI). Evidence for these approaches across addictive behaviors does not always paint a clear picture. The purpose of this review was to examine existing reviews of motivational-based interventions for various substances of abuse and gambling in the last decade to gain a deeper understanding of the current evidence and implications for future research and clinical practice. Literature searches were conducted to identify review articles from January 1, 2007 to January 30, 2017 for motivational enhancing interventions for alcohol, tobacco, drugs, marijuana, cocaine, opioids, methamphetamines, and gambling. Of the 144 articles assessed we included a total of 34 review articles in our review, including 6 Cochrane reviews. This review supports use of motivationally enhancing interventions across addictive behaviors with strongest evidence supporting use in alcohol and tobacco, with brief interventions showing strong efficacy. There is strong support for MI with marijuana and some support for gambling. Insufficient evidence is available for methamphetamine or opiate use. There are important caveats. In most cases, MI is more effective than no treatment and as effective (but not necessarily more effective) than other active treatments. Findings for effectiveness of more intensive motivational interventions or combinations are mixed. Treatment fidelity assessments, limited subpopulation analyses, and differences in dose, outcomes, and protocol specification continue to pose significant problems for reviews. (PsycINFO Database Record
106Motivational interviewing training of substance use treatment professionals: A systematic review.PubMed
Michael B Madson, Margo C Villarosa-Hurlocker, Julie A Schumacher, et al.
Subst Abus. 2019;40(1):43-51. doi: 10.1080/08897077.2018.1475319. Epub 2018 Oct 9.
Through evaluations of training programs, systematic reviews, and meta-analyses, advances in identifying best practices for disseminating motivational interviewing (MI) have emerged. To advance this work further, inclusion of thorough descriptions of the following is needed in research publications: study (design, trainee characteristics, setting characteristics), training and coaching methods (if applicable), trainer qualifications, and evaluation of MI skills. The purpose of this study was to systematically evaluate the research on MI training of substance use treatment professionals for the inclusion of such descriptions. Twenty-five studies were reviewed using a scoring rubric developed by the authors. Just over two thirds of the studies (68%) were randomized controlled trials of MI training. The majority of studies provided information about (a) trainee characteristics (professional background = 76%, education = 60%, experience = 56%); (b) setting characteristics (80%); (c) training methods (format = 96%, length = 92%); (d) coaching (76%); and (e) evaluation of MI skills (92%). Findings suggest advancements in MI training studies since previous reviews, especially in regards to the inclusion of feedback and coaching. However, this review also found that inconsistencies in methods and reporting of training characteristics, as well as limited follow-up assessment of trainees' skill, continue to limit knowledge of effective training methods.
107Psychedelics action and schizophrenia.PubMed
Marzena Maćkowiak
Pharmacol Rep. 2023 Dec;75(6):1350-1361. doi: 10.1007/s43440-023-00546-5. Epub 2023 Oct 30.
Psychedelics are compounds acting by serotonin 5-hydroxytryptamine (5-HT) receptor activation and induce several behavioral responses. They are of special interest because of their positive effects on neuropsychiatric disorders (depression and posttraumatic stress disorder). However, several findings revealed that some psychedelic actions are similar to symptoms observed in schizophrenia (psychosis, sensorimotor gating impairments, attention, and working memory deficits) which might limit their clinical applications. Psychedelics activate some neurotransmitters, i.e., serotonergic, and glutamatergic, that are also impaired in schizophrenia. Therefore, the neurobiological background of psychedelics and schizophrenia is partially similar. Another important aspect to discuss is the perspective of using psychedelics in schizophrenia therapy. Postmortem studies showed a loss of synapses in schizophrenia, and the positive effects of psychedelics on neuroplasticity (synaptogenesis, neurogenesis, and neuritogenesis) might be essential in the context of schizophrenia therapy. However, because of psychedelics' psychotic action, the recommended doses of psychedelics in schizophrenia treatment are not established, and subpsychedelic dosing or microdosing are considered. Exploratory studies are needed to determine the tolerability of treatment and appropriate dosing regimen. Another therapeutic option is using non-hallucinogenic psychedelic analogs that also induce neuroplastic outcomes but do not have psychotogenic effects. Further preclinical and clinical studies are needed to recognize the potential effectiveness of 5-HT agonists in schizophrenia therapy.
108New investigational agents for the treatment of major depressive disorder.PubMed
Bartłomiej Pochwat, Anna Julia Krupa, Marcin Siwek, et al.
Expert Opin Investig Drugs. 2022 Oct;31(10):1053-1066. doi: 10.1080/13543784.2022.2113376. Epub 2022 Aug 24.
INTRODUCTION: Pharmacotherapy of depression is characterized by the delayed onset of action, chronic treatment requirements, and insufficient effectiveness. Ketamine, with its rapid action and long-lasting effects, represents a breakthrough in the modern pharmacotherapy of depression. AREAS COVERED: The current review summarizes the latest findings on the mechanism of the antidepressant action of ketamine and its enantiomers and metabolites. Furthermore, the antidepressant potential of psychedelics, non-hallucinogenic serotonergic modulators, and metabotropic glutamate receptor ligands was discussed. EXPERT OPINION: Recent data indicated that to achieve fast and long-acting antidepressant-like effects, compounds must induce durable effects on the architecture and density of dendritic spines in brain regions engaged in mood regulation. Such mechanisms underlie the actions of ketamine and psychedelics. These compounds trigger hallucinations; however, it is thought that these effects might be essential for their antidepressant action. Behavioral studies with serotonergic modulators affecting 5-HT1A (biased agonists), 5-HT4 (agonists), and 5-HT-7 (antagonists) receptors exert rapid antidepressant-like activity, but they seem to be devoid of these effects. Another way to avoid psychomimetic effects and achieve the desired rapid antidepressant-like effects is combined therapy. In this respect, ligands of metabotropic receptors show some potential.
109Non-hallucinogenic psychedelics for mood and anxiety disorders: A systematic review.PubMed
Margery J Q Chen, David Chen-Li, Noah Chisamore, et al.
Psychiatry Res. 2025 Jul;349:116532. doi: 10.1016/j.psychres.2025.116532. Epub 2025 May 8.
Psychedelics have re-emerged as promising treatments for mood disorders. The current model provides a moderate-to-high dose of a psychedelic agent (e.g., psilocybin) to reliably induce an altered state of consciousness. Unfortunately, the hallucinatory effects limit the treatment's potential scalability given patients' vulnerability and extensive monitoring costs, leading to growing interest in non-hallucinatory psychedelics (NHPs). This review's objective was to identify, summarize and synthesize all published pre-clinical and clinical studies evaluating NHPs for mood and anxiety disorders. We included five animal studies demonstrating antidepressant-like effects through assessments like forced swim test (FST) and open field test (OFT) without observing head-twitch response (HTR), and one case report that identified a patient who inadvertently combined trazodone and psilocybin and experienced potent antidepressant effects without psychedelic effects. These preliminary findings provide a strong impetus for further investigation in human samples with rigorously designed clinical trials that may delineate the potential antidepressant effects of psychedelics without hallucinatory effects.
110A non-hallucinogenic psychedelic analogue with therapeutic potential.PubMed
Lindsay P Cameron, Robert J Tombari, Ju Lu, et al.
Nature. 2021 Jan;589(7842):474-479. doi: 10.1038/s41586-020-3008-z. Epub 2020 Dec 9.
The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals. Unlike most medications for the treatment of substance use disorders, anecdotal reports suggest that ibogaine has the potential to treat addiction to various substances, including opiates, alcohol and psychostimulants. The effects of ibogaine-like those of other psychedelic compounds-are long-lasting, which has been attributed to its ability to modify addiction-related neural circuitry through the activation of neurotrophic factor signalling. However, several safety concerns have hindered the clinical development of ibogaine, including its toxicity, hallucinogenic potential and tendency to induce cardiac arrhythmias. Here we apply the principles of function-oriented synthesis to identify the key structural elements of the potential therapeutic pharmacophore of ibogaine, and we use this information to engineer tabernanthalog-a water-soluble, non-hallucinogenic, non-toxic analogue of ibogaine that can be prepared in a single step. In rodents, tabernanthalog was found to promote structural neural plasticity, reduce alcohol- and heroin-seeking behaviour, and produce antidepressant-like effects. This work demonstrates that, through careful chemical design, it is possible to modify a psychedelic compound to produce a safer, non-hallucinogenic variant that has therapeutic potential.
111Tabernanthalog, a Non-Hallucinogenic Psychedelic, Alleviates Cancer-Induced Cognitive Deficits via Serotonergic Pathways.PubMed
Masahide Arinaga, Jun Yamada, Shoichiro Maeda, et al.
Int J Mol Sci. 2025 Aug 4;26(15):7519. doi: 10.3390/ijms26157519.
Cancer-related cognitive impairment (CRCI)-encompassing anxiety, depression, and memory deficits-significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a Lewis lung carcinoma (3LL) mouse model. Behavioral assessments revealed heightened anxiety-like behavior and memory impairment following 3LL cell transplantation. Biochemical analysis revealed reduced tryptophan levels in both blood and hippocampal tissue, accompanied by the downregulation of serotonergic receptor genes and upregulation of pro-inflammatory cytokine genes in the hippocampus of tumor-bearing mice. Additionally, microglial density and morphological activation were markedly elevated. TBG treatment reversed these behavioral deficits, improving both anxiety-related behavior and memory performance. These effects were associated with the normalization of microglial density and morphology, as well as the restoration of serotonergic receptor and cytokine gene expression. In vitro, TBG partially suppressed neuroinflammatory gene expression in BV-2 microglial cells exposed to conditioned medium from 3LL cells. Collectively, these findings suggest that TBG alleviates CRCI-like symptoms by modulating neuroinflammation and microglial activation. This study highlights TBG as a promising therapeutic candidate for improving cognitive and emotional functioning in patients with cancer.
112Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation.PubMed
Gilly Wolf, Sandeep Singh, Karin Blakolmer, et al.
Mol Psychiatry. 2023 Jan;28(1):44-58. doi: 10.1038/s41380-022-01832-z. Epub 2022 Oct 24.
Schizophrenia is a widespread psychiatric disorder that affects 0.5-1.0% of the world's population and induces significant, long-term disability that exacts high personal and societal cost. Negative symptoms, which respond poorly to available antipsychotic drugs, are the primary cause of this disability. Association of negative symptoms with cortical atrophy and cell loss is widely reported. Psychedelic drugs are undergoing a significant renaissance in psychiatric disorders with efficacy reported in several conditions including depression, in individuals facing terminal cancer, posttraumatic stress disorder, and addiction. There is considerable evidence from preclinical studies and some support from human studies that psychedelics enhance neuroplasticity. In this Perspective, we consider the possibility that psychedelic drugs could have a role in treating cortical atrophy and cell loss in schizophrenia, and ameliorating the negative symptoms associated with these pathological manifestations. The foremost concern in treating schizophrenia patients with psychedelic drugs is induction or exacerbation of psychosis. We consider several strategies that could be implemented to mitigate the danger of psychotogenic effects and allow treatment of schizophrenia patients with psychedelics to be implemented. These include use of non-hallucinogenic derivatives, which are currently the focus of intense study, implementation of sub-psychedelic or microdosing, harnessing of entourage effects in extracts of psychedelic mushrooms, and blocking 5-HT2A receptor-mediated hallucinogenic effects. Preclinical studies that employ appropriate animal models are a prerequisite and clinical studies will need to be carefully designed on the basis of preclinical and translational data. Careful research in this area could significantly impact the treatment of one of the most severe and socially debilitating psychiatric disorders and open an exciting new frontier in psychopharmacology.
113Buprenorphine prescribing and treatment accessibility in response to regulation changes due to the COVID-19 public health emergency.PubMed
Taylor J Paiva, Rachel S Wightman, Kristen St John, et al.
J Subst Use Addict Treat. 2024 Jul;162:209382. doi: 10.1016/j.josat.2024.209382. Epub 2024 Apr 25.
BACKGROUND: In 2021, over 80,000 fatal overdoses occurred in the United States. Since 2020, the federal government has enacted multiple regulatory changes around buprenorphine prescribing for opioid use disorder (OUD) to increase access to buprenorphine. This study aims to explore trends in buprenorphine treatment initiation pre- and post-public health emergency to evaluate changes in the context of X-waiver relaxations and telehealth allowances. METHODS: In a cross-sectional study, all RI residents who filled a buprenorphine prescription at a pharmacy in Rhode Island (RI), Massachusetts, and Connecticut between January 2017 and December 2023 were obtained from the RI Prescription Drug Monitoring Program (PDMP). The study excluded buprenorphine products not approved for OUD treatment from the analysis. Identified individuals had initiated buprenorphine for OUD during the study period if they did not have a prior prescription or if they had >30 days without buprenorphine exposure between their prescriptions. Spearman's rank correlation tests were used to identify significant associations between outcomes and regulation changes. RESULTS: The average number of patients dispensed buprenorphine did not significantly change over the study period, however the average number of initiates significantly decreased (ρ = -0.38255, p = .0003). The average number of providers prescribing CII-CV substances in RI has increased 3.4 % over the study period. The average percentage of prescribers in the PDMP prescribing buprenorphine for OUD doubled (ρ = 0.96075, p < .0001). CONCLUSION: Though efforts have been made to increase buprenorphine initiation, buprenorphine initiates remain well below pre-PHE levels. Efforts must continue to eliminate existing barriers to treatment and improve access to individuals seeking treatment.
114Kratom use disorder: case reports on successful treatment with home induction of buprenorphine-naloxone.PubMed
Miki Kiyokawa, Anthony K Kwon, Micaiah C Cape, et al.
Fam Pract. 2023 Nov 23;40(4):596-598. doi: 10.1093/fampra/cmad081.
BACKGROUND: Kratom has been used for different reasons such as pain, opioid withdrawal, and relaxation. Kratom can cause dependence and overdose, and it's classified under 'drugs of concern' by the US Drug Enforcement Administration. Despite these concerns, kratom is legal in most of the United States and many countries around the world with easy accessibility. Literature searches reveal recommendations to use buprenorphine (or buprenorphine-naloxone), which are medications to treat opioid use disorder, in order to treat patients with kratom use disorder; however, there are no formal guidelines available. Buprenorphine (or buprenorphine-naloxone) induction is recommended to be conducted under observation (i.e. in the clinic) in the United States, but COVID-19 has resulted in shifts toward telehealth. OBJECTIVES: Describe case series of successful management of kratom use disorder using telehealth followed by unobserved buprenorphine-naloxone home induction and highlight implications for future management, including maintenance dosage and induction method. METHODS: We present 2 very similar kratom use disorder patients who reported taking 35 g of kratom per day who underwent unobserved buprenorphine-naloxone home induction. RESULTS: Both were seen via telehealth initially. They reported no adverse effects before, during, or after the unobserved home induction on buprenorphine-naloxone but stabilized on significantly different dosages. CONCLUSION: Telehealth followed by unobserved buprenorphine-naloxone induction at home may be an alternative to traditional buprenorphine-naloxone induction where treatment accessibility is limited. In addition to daily doses of kratom use, other factors, such as duration of kratom use and individual psychological factors may determine the most comfortable dose of buprenorphine-naloxone.
115Retention rates and cost-effectiveness of telehealth vs. in-person buprenorphine treatment for opioid use disorder (OUD).PubMed
Rana Saad, Melissa H Roberts, Julie G Salvador, et al.
J Subst Use Addict Treat. 2025 Oct;177:209764. doi: 10.1016/j.josat.2025.209764. Epub 2025 Jul 30.
BACKGROUND: Management of opioid use disorder (OUD) has evolved with integration of telehealth, particularly during COVID-19. This study evaluated effectiveness (retention to therapy) and cost-effectiveness of office-based versus telehealth buprenorphine treatment for OUD. METHODS: Retrospective chart review included 135 buprenorphine-treated patients at a New Mexico addiction and substance abuse program. Patients were categorized by treatment modality (office-based vs. telehealth). Retention, the effectiveness measure, was defined as continuous OUD treatment for ≥180 days. Logistic regression estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for retention, controlling for demographics. Incremental cost-effectiveness ratios (ICERs) were calculated for direct medical, direct non-medical (transportation), and indirect costs (productivity losses) from a societal perspective. RESULTS: Analyses showed no statistically significant difference in retention between office-based (51 %) and telehealth (42 %) modalities (p > 0.05). Males were less likely to remain in treatment (OR = 0.48 [95 % CI: 0.24-0.96], p = 0.04). Female retention rates were high (58 % in both modalities). Male rates were lower for office-based (45 %) and telehealth (34 %). The ICER analysis indicated that office-based modalities incurred additional costs of $3750 per 1 % increase in retention compared to telehealth, suggesting higher overall costs for retained patients in the office-based modality. CONCLUSION: OUD patient retention rates were not significantly different between treatment modalities. However, office-based treatment incurred higher costs, emphasizing telehealth's potential as a cost-effective alternative. Future research should explore long-term outcomes, sex differences in treatment adherence, and the integration of telehealth into standard practice to enhance resource allocation and treatment accessibility.
116Substance abuse vaccines.PubMed
Frank M Orson, Berma M Kinsey, Rana A K Singh, et al.
Ann N Y Acad Sci. 2008 Oct;1141:257-69. doi: 10.1196/annals.1441.027.
Conventional substance-abuse treatments have only had limited success for drugs such as cocaine, nicotine, methamphetamine, and phencyclidine. New approaches, including vaccination to block the effects of these drugs on the brain, are in advanced stages of development. Although several potential mechanisms for the effects of antidrug vaccines have been suggested, the most straightforward and intuitive mechanism involves binding of the drug by antibodies in the bloodstream, thereby blocking entry and/or reducing the rate of entry of the drug into the central nervous system. The benefits of such antibodies on drug pharmacodynamics will be influenced by both the quantitative and the qualitative properties of the antibodies. The sum of these effects will determine the success of the clinical applications of antidrug vaccines in addiction medicine. This review will discuss these issues and present the current status of vaccine development for nicotine, cocaine, methamphetamine, phencyclidine, and morphine.
117Future perspectives of emerging novel drug targets and immunotherapies to control drug addiction.PubMed
Jonaid Ahmad Malik, Javed N Agrewala
Int Immunopharmacol. 2023 Jun;119:110210. doi: 10.1016/j.intimp.2023.110210. Epub 2023 Apr 24.
Substance Use Disorder (SUD) is one of the major mental illnesses that is terrifically intensifying worldwide. It is becoming overwhelming due to limited options for treatment. The complexity of addiction disorders is the main impediment to understanding the pathophysiology of the illness. Hence, unveiling the complexity of the brain through basic research, identification of novel signaling pathways, the discovery of new drug targets, and advancement in cutting-edge technologies will help control this disorder. Additionally, there is a great hope of controlling the SUDs through immunotherapeutic measures like therapeutic antibodies and vaccines. Vaccines have played a cardinal role in eliminating many diseases like polio, measles, and smallpox. Further, vaccines have controlled many diseases like cholera, dengue, diphtheria, Haemophilus influenza type b (Hib), human papillomavirus, influenza, Japanese encephalitis, etc. Recently, COVID-19 was controlled in many countries by vaccination. Currently, continuous effort is done to develop vaccines against nicotine, cocaine, morphine, methamphetamine, and heroin. Antibody therapy against SUDs is another important area where serious attention is required. Antibodies have contributed substantially against many serious diseases like diphtheria, rabies, Crohn's disease, asthma, rheumatoid arthritis, and bladder cancer. Antibody therapy is gaining immense momentum due to its success rate in cancer treatment. Furthermore, enormous advancement has been made in antibody therapy due to the generation of high-efficiency humanized antibodies with a long half-life. The advantage of antibody therapy is its instant outcome. This article's main highlight is discussing the drug targets of SUDs and their associated mechanisms. Importantly, we have also discussed the scope of prophylactic measures to eliminate drug dependence.
118Immunotherapy for treating methamphetamine, heroin and cocaine use disorders.PubMed
Tang Xiaoshan, Yang Junjie, Wang Wenqing, et al.
Drug Discov Today. 2020 Mar;25(3):610-619. doi: 10.1016/j.drudis.2019.07.009. Epub 2019 Aug 13.
Drug addiction is a serious health problem prevalent worldwide. Currently available therapies including pharmacotherapy and psychotherapy are insufficient to meet the clinical needs for treating drug abuse. Recently, immunotherapy has emerged as a promising approach to treat such drug-use disorders. Pharmacokinetic antagonists are used in immunotherapy, functioning by sequestering the drugs in the periphery but without allowing the drug to cross the blood-brain barrier. This can reduce the toxic and rewarding effects of the drugs, while preventing addiction and facilitating reduced relapse rates. Herein, we update recent developments in the immunotherapeutic strategies to treat abuse of drugs like methamphetamine, heroin and cocaine. In addition, we summarize the drug design used so far and its optimization strategies. Further, we document the efficacy of anti-drug vaccines and monoclonal antibodies, with an aim to promote development of new anti-drug immunotherapies.
119Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?PubMed
Rachel J Stephenson, Istvan Toth
J Med Chem. 2023 Jun 8;66(11):7086-7100. doi: 10.1021/acs.jmedchem.3c00366. Epub 2023 May 25.
Cocaine is one of the oldest and most widely used illicit drugs in the world and is responsible for major worldwide medical and social problems. Drug addiction is a disease state where the body relies on a substance for normal functioning and develops a physical dependence leading to compulsive and repetitive use despite negative consequences to the user's health, mental state, or social life. The primary driver for the development of anti-cocaine vaccines has been the failure to develop effective pharmacological treatments to combat cocaine dependence. Despite several decades of research, no approved pharmacological treatments for cocaine dependence are available to assist addicts to overcome cocaine withdrawal or to prevent drug relapse. This Perspective highlights the challenges associated with anti-cocaine vaccines, including the current state of anti-cocaine vaccines and catalytic antibody research to aid in the fight against cocaine addiction.
120Development of a rational scale to assess the harm of drugs of potential misuse.PubMed
David Nutt, Leslie A King, William Saulsbury, et al.
Lancet. 2007 Mar 24;369(9566):1047-53. doi: 10.1016/S0140-6736(07)60464-4.
Drug misuse and abuse are major health problems. Harmful drugs are regulated according to classification systems that purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages. We developed and explored the feasibility of the use of a nine-category matrix of harm, with an expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion. We also included five legal drugs of misuse (alcohol, khat, solvents, alkyl nitrites, and tobacco) and one that has since been classified (ketamine) for reference. The process proved practicable, and yielded roughly similar scores and rankings of drug harm when used by two separate groups of experts. The ranking of drugs produced by our assessment of harm differed from those used by current regulatory systems. Our methodology offers a systematic framework and process that could be used by national and international regulatory bodies to assess the harm of current and future drugs of abuse.
121Prevention and Treatment of Opioid Misuse and Addiction: A Review.PubMed
Nora D Volkow, Emily B Jones, Emily B Einstein, et al.
JAMA Psychiatry. 2019 Feb 1;76(2):208-216. doi: 10.1001/jamapsychiatry.2018.3126.
IMPORTANCE: More than 42 000 Americans died of opioid overdoses in 2016, and the fatalities continue to increase. This review analyzes the factors that triggered the opioid crisis and its further evolution, along with the interventions to manage and prevent opioid use disorder (OUD), which are fundamental for curtailing the opioid crisis. OBSERVATIONS: Opioid drugs are among the most powerful analgesics but also among the most addictive. The current opioid crisis, initially triggered by overprescription of opioid analgesics, which facilitated their diversion and misuse, has now expanded to heroin and illicit synthetic opioids (fentanyl and its analogues), the potency of which further increases their addictiveness and lethality. Although there are effective medications to treat OUD (methadone hydrochloride, buprenorphine, and naltrexone hydrochloride), these medications are underused, and the risk of relapse is still high. Strategies to expand medication use and treatment retention include greater involvement of health care professionals (including psychiatrists) and approaches to address comorbidities. In particular, the high prevalence of depression and suicidality among patients with OUD, if untreated, contributes to relapse and increases the risk of overdose fatalities. Prevention interventions include screening and early detection of psychiatric disorders, which increase the risk of substance use disorders, including OUD. CONCLUSIONS AND RELEVANCE: Although overprescription of opioid medications triggered the opioid crisis, improving opioid prescription practices for pain management, although important for addressing the opioid crisis, is no longer sufficient. In parallel, strategies to expand access to medication for OUD and improve treatment retention, including a more active involvement of psychiatrists who are optimally trained to address psychiatric comorbidities, are fundamental to preventing fatalities and achieving recovery. Research into new treatments for OUD, models of care for OUD management that include health care, and interventions to prevent OUD may further help resolve the opioid crisis and prevent it from happening again.
122An intervention program for ADHD in patients with substance use disorders: preliminary results of a field trial.PubMed
M Anne Goossensen, Geurt van de Glind, Pieter-Jan Carpentier, et al.
J Subst Abuse Treat. 2006 Apr;30(3):253-9. doi: 10.1016/j.jsat.2005.12.004.
The comorbidity of attention deficit hyperactivity disorder (ADHD) is frequently not well recognized in substance abuse treatment institutions in The Netherlands. As a consequence, patients with substance use disorder (SUD) and ADHD often receive suboptimal treatment. To prevent every treatment center from having to invent its own diagnostic procedure and intervention for ADHD, a national working group was established. This group developed an intervention program for the screening, diagnosis, and treatment of ADHD in patients with SUD. This article describes the development and content of this intervention program. An important part of this development was testing the intervention program in two addiction treatment centers in The Netherlands. Systematic screening of ADHD was part of the test. A self-report questionnaire was used. Subjects with positive screening results were referred for the diagnostic procedure. Nine hundred twenty-eight screenings were performed: 207 screened positive, 115 came for further diagnostics, and 65 were ultimately diagnosed with ADHD.
123Harm Reduction in Health Care Settings.PubMed
Carolyn A Chan, Bethany Canver, Ryan McNeil, et al.
Med Clin North Am. 2022 Jan;106(1):201-217. doi: 10.1016/j.mcna.2021.09.002.
Harm reduction is an approach to reduce the risk of harms to an individual using substances without requiring abstinence. This review discusses substance-specific interventions for opioids, alcohol, and stimulants that can minimize harms for individuals who use these substances. Topics discussed include overdose prevention, infection prevention, and low-barrier substance use disorder treatment.
124Aftercare in drug abuse treatment.PubMed
J D Hawkins, R F Catalano
Int J Addict. 1985 Jun-Jul;20(6-7):917-45. doi: 10.3109/10826088509047759.
Preventing relapse among treated drug abusers is the primary goal of aftercare. This paper identifies posttreatment factors associated with relapse and links these findings to known aftercare approaches. The literature on the effectiveness of these approaches is summarized and limitations in this literature are noted. Promising directions for policy, program development, and research (R&D) in aftercare are described.