Nielsen Suzanne, Gowing Linda, Sabioni Pamela, Le Foll Bernard
Monash Addiction Research Centre, Monash University, Peninsula Campus, McMahons Road, Frankston, VIC, Australia, 3199.
Cochrane Database Syst Rev. 2019 Jan 28;1(1):CD008940. doi: 10.1002/14651858.CD008940.pub3.
Globally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.This is an update of a Cochrane Review first published in the Cochrane Library in Issue 12, 2014.
To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use.
We updated our searches of the following databases to March 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and Web of Science.
Randomised controlled trials (RCTs) and quasi-RCTs involving the use of medications to treat cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in people diagnosed as cannabis dependent or who were likely to be dependent.
We used standard methodological procedures expected by Cochrane.
We included 21 RCTs involving 1755 participants: 18 studies recruited adults (mean age 22 to 41 years); three studies targeted young people (mean age 20 years). Most (75%) participants were male. The studies were at low risk of performance, detection and selective outcome reporting bias. One study was at risk of selection bias, and three studies were at risk of attrition bias.All studies involved comparison of active medication and placebo. The medications were diverse, as were the outcomes reported, which limited the extent of analysis.Abstinence at end of treatment was no more likely with Δ-tetrahydrocannabinol (THC) preparations than with placebo (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.64 to 1.52; 305 participants; 3 studies; moderate-quality evidence). For selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine, there was no difference in the likelihood of abstinence at end of treatment compared to placebo (low- to very low-quality evidence).There was qualitative evidence of reduced intensity of withdrawal symptoms with THC preparations compared to placebo. For other pharmacotherapies, this outcome was either not examined, or no significant differences was reported.Adverse effects were no more likely with THC preparations (RR 1.02, 95% CI 0.89 to 1.17; 318 participants; 3 studies) or N-acetylcysteine (RR 0.94, 95% CI 0.71 to 1.23; 418 participants; 2 studies) compared to placebo (moderate-quality evidence). For SSRI antidepressants, mixed action antidepressants, buspirone and N-acetylcysteine, there was no difference in adverse effects compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of withdrawal from treatment due to adverse effects with THC preparations, SSRIs antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of treatment completion with THC preparations, SSRI antidepressants, mixed action antidepressants and buspirone compared to placebo (low- to very low-quality evidence) or with N-acetylcysteine compared to placebo (RR 1.06, 95% CI 0.93 to 1.21; 418 participants; 2 studies; moderate-quality evidence). Anticonvulsants and mood stabilisers appeared to reduce the likelihood of treatment completion (RR 0.66, 95% CI 0.47 to 0.92; 141 participants; 3 studies; low-quality evidence).Available evidence on gabapentin (anticonvulsant), oxytocin (neuropeptide) and atomoxetine was insufficient for estimates of effectiveness.
AUTHORS' CONCLUSIONS: There is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N-acetylcysteine is weak, but these medications are also worth further investigation.
在全球范围内，大麻使用普遍且广泛。目前尚无获批用于治疗大麻使用障碍的药物疗法。这是一篇Cochrane系统评价的更新版，该评价首次发表于《Cochrane图书馆》2014年第12期。
评估药物疗法相较于彼此、安慰剂或无药物治疗（支持性护理）在减轻大麻戒断症状以及促进大麻使用停止或减少方面的有效性和安全性。
我们更新了对以下数据库截至2018年3月的检索：Cochrane对照试验中心注册库（CENTRAL）、MEDLINE、Embase、PsycINFO和科学引文索引。
随机对照试验（RCT）和半随机对照试验，涉及使用药物治疗大麻戒断或促进大麻使用停止或减少，或两者皆有，与其他药物、安慰剂或无药物（支持性护理）相比较，受试对象为被诊断为大麻依赖或可能依赖的人群。
我们采用了Cochrane预期的标准方法程序。
我们纳入了21项RCT，涉及1755名参与者：18项研究招募的是成年人（平均年龄22至41岁）；3项研究针对的是年轻人（平均年龄20岁）。大多数（75%）参与者为男性。这些研究在实施、检测和选择性结果报告偏倚方面风险较低。一项研究存在选择偏倚风险，三项研究存在失访偏倚风险。所有研究均涉及活性药物与安慰剂的比较。药物种类多样，所报告的结果也各不相同，这限制了分析的范围。与安慰剂相比，Δ-四氢大麻酚（THC）制剂在治疗结束时实现戒断的可能性并无差异（风险比（RR）0.98，95%置信区间（CI）0.64至1.52；305名参与者；3项研究；中等质量证据）。对于选择性5-羟色胺再摄取抑制剂（SSRI）类抗抑郁药、混合作用抗抑郁药、抗惊厥药和心境稳定剂、丁螺环酮和N-乙酰半胱氨酸，与安慰剂相比，治疗结束时实现戒断的可能性没有差异（低至极低质量证据）。与安慰剂相比，有定性证据表明THC制剂可减轻戒断症状的强度。对于其他药物疗法，该结果要么未被研究，要么未报告有显著差异。与安慰剂相比，THC制剂（RR 1.02，95% CI 0.89至1.17；318名参与者；3项研究）或N-乙酰半胱氨酸（RR 0.94，95% CI 0.71至1.23；418名参与者；2项研究）出现不良反应的可能性并无差异（中等质量证据）。对于SSRI类抗抑郁药、混合作用抗抑郁药、丁螺环酮和N-乙酰半胱氨酸，与安慰剂相比，不良反应没有差异（低至极低质量证据）。与安慰剂相比，THC制剂、SSRI类抗抑郁药、混合作用抗抑郁药、抗惊厥药和心境稳定剂、丁螺环酮和N-乙酰半胱氨酸因不良反应而退出治疗的可能性没有差异（低至极低质量证据）。与安慰剂相比，THC制剂、SSRI类抗抑郁药、混合作用抗抑郁药和丁螺环酮完成治疗的可能性没有差异（低至极低质量证据），与安慰剂相比，N-乙酰半胱氨酸完成治疗的可能性也没有差异（RR 1.06，95% CI 0.93至1.21；418名参与者；2项研究；中等质量证据）。抗惊厥药和心境稳定剂似乎会降低完成治疗的可能性（RR 0.66，95% CI 0.47至0.92；141名参与者；3项研究；低质量证据）。关于加巴喷丁（抗惊厥药）、催产素（神经肽）和托莫西汀的现有证据不足以估计其有效性。
对于所有所研究的药物疗法，证据均不完整，且对于许多结果而言，证据质量较低或极低。研究结果表明，SSRI类抗抑郁药、混合作用抗抑郁药、安非他酮、丁螺环酮和托莫西汀在治疗大麻依赖方面可能价值不大。鉴于疗效证据有限，THC制剂应仍被视为试验性药物，其对戒断症状和渴望有一些积极作用。抗惊厥药加巴喷丁、催产素和N-乙酰半胱氨酸的证据基础薄弱，但这些药物也值得进一步研究。
