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可卡因和甲基苯丙胺产生不同模式的主观和心血管效应。

Cocaine and methamphetamine produce different patterns of subjective and cardiovascular effects.

作者信息

Newton Thomas F, De La Garza Richard, Kalechstein Ari D, Nestor Liam

机构信息

Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Semel Institute for Neuroscience and Human Behavior, Room A7-372, 740 Westwood Plaza, Los Angeles, CA 90024, USA.

出版信息

Pharmacol Biochem Behav. 2005 Sep;82(1):90-7. doi: 10.1016/j.pbb.2005.07.012. Epub 2005 Aug 19.

Abstract

The stimulant effects of cocaine and methamphetamine are mediated by changes in synaptic concentrations of brain monoamines; however, the drugs alter monoamine levels via different mechanisms. This study examined the subjective and cardiovascular responses produced by investigational administration of cocaine or methamphetamine, in order to examine the onset and patterns of subjective and cardiovascular responses. Subjects included 14 non-treatment seeking cocaine-dependent and 11 non-treatment seeking methamphetamine-dependent volunteers. As part of ongoing research studies, cocaine and methamphetamine subjects received cocaine (40 mg, IV) or methamphetamine (30 mg, IV), respectively. Subjective and cardiovascular responses were assessed for 30 min and 60 min, respectively. The data reveal significant within groups differences for all subjective effects and cardiovascular effects (p<0.05). Significant between group differences in subjective effects were observed for "Any Drug Effect" (p<.008 for group, and p<.029 for group x time), for "High" (p<.002 for group, and p<.0001 for group x time) and for "Stimulated" (p<.001 for group, and p<.006 for group x time). Significant between group differences in cardiovascular effects were observed for Systolic blood pressure (p<.0001 for group, and p<.002 for group x time), Diastolic blood pressure (p<.0001 for group, though p=NS for group x time), and for Heart Rate (p<.0001 for group, and p<.0001 for group x time). The only difference between the groups for placebo was for heart rate, where there was a significant group x time effect (p<.005). Taken together, the data reveal that the subjective effects of cocaine tended to peak and then decline more rapidly than those produced by methamphetamine. The subjective effects of methamphetamine tended to rise more slowly, and remain elevated longer. Cardiovascular effects of cocaine and methamphetamine had similar onset, but effects of cocaine tended to decline more rapidly. Overall, the results reveal differences in the onset, pattern, and duration of subjective and cardiovascular responses following cocaine or methamphetamine administration in stimulant addicted patients. We predict that these differences may impact drug use and relapse patterns, and may have implications in medications development for these addictive disorders.

摘要

可卡因和甲基苯丙胺的兴奋作用是由脑单胺类神经递质突触浓度的变化介导的;然而,这两种药物通过不同机制改变单胺水平。本研究检测了可卡因或甲基苯丙胺试验性给药所产生的主观及心血管反应,以探究主观及心血管反应的起始和模式。研究对象包括14名未寻求治疗的可卡因依赖志愿者和11名未寻求治疗的甲基苯丙胺依赖志愿者。作为正在进行的研究的一部分,可卡因组和甲基苯丙胺组的受试者分别接受了静脉注射可卡因(40毫克)或静脉注射甲基苯丙胺(30毫克)。分别在30分钟和60分钟内评估主观及心血管反应。数据显示,所有主观效应和心血管效应在组内均存在显著差异(p<0.05)。在主观效应方面,观察到组间在“任何药物效应”(组间p<.008,组×时间p<.029)、“兴奋感”(组间p<.002,组×时间p<.0001)和“刺激感”(组间p<.001,组×时间p<.006)上存在显著差异。在心血管效应方面,观察到组间在收缩压(组间p<.0001,组×时间p<.002)、舒张压(组间p<.0001,组×时间p=无显著性差异)和心率(组间p<.0001,组×时间p<.0001)上存在显著差异。两组在安慰剂方面的唯一差异在于心率,存在显著的组×时间效应(p<.005)。综合来看,数据显示可卡因的主观效应往往达到峰值后比甲基苯丙胺产生的主观效应下降得更快。甲基苯丙胺的主观效应上升较为缓慢,且持续升高的时间更长。可卡因和甲基苯丙胺的心血管效应起始相似,但可卡因的效应下降得更快。总体而言,结果揭示了兴奋剂成瘾患者在使用可卡因或甲基苯丙胺后主观及心血管反应的起始、模式和持续时间存在差异。我们预测这些差异可能会影响药物使用和复发模式,并且可能对这些成瘾性疾病的药物研发具有启示意义。

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