Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle
Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle
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DOI：
10.1038/s41386-018-0050-8
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发表时间：
2018-09-01
影响因子：
7.6
通讯作者：
Weiss, Friedbert
中科院分区：
文献类型：
--
作者：
Gonzalez-Cuevas, Gustavo;Martin-Fardon, Remi;Weiss, Friedbert
大麻二酚 (CBD) 是大麻的主要非精神活性成分，因其在治疗神经和精神疾病方面的治疗潜力而受到关注。最近，人们还探索了 CBD 在治疗毒瘾方面的潜力。物质使用障碍是一种慢性复发性疾病，复发风险持续存在的原因有多种，包括药物环境引起的渴望、对压力的敏感性、焦虑加剧和冲动控制受损。在这里，我们评估了透皮 CBD 制剂在寻求药物、焦虑和冲动的动物模型中的“抗复发”潜力。有酒精或可卡因自我给药史的大鼠在 7 天中每隔 24 小时接受一次透皮 CBD 治疗，并测试环境和压力诱导的恢复情况，以及高架十字迷宫上的实验性焦虑。在从 7 天的依赖性诱导酒精中毒方案中恢复后，使用延迟贴现任务确定了对冲动行为的影响。 CBD 减弱了环境诱发和压力诱发的药物寻求，而没有耐受性、镇静作用或干扰正常的动机行为。治疗终止后，尽管血浆和大脑 CBD 水平仅在 3 天内可检测到，但恢复效果在长达大约 5 个月的时间内仍然减弱。 CBD 还可以减少有酒精依赖史的老鼠的实验焦虑并防止其高度冲动的发展。结果提供了原理证明，支持 CBD 在预防复发方面的潜力，涉及两个方面：跨多个脆弱状态的有益作用以及仅进行短暂治疗的长期效果。这些发现还为正在进行的医用大麻辩论提供了信息，这些辩论涉及非精神活性大麻素的医疗益处及其开发和用作治疗药物的前景。
Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders. Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control. Here, we evaluated the "anti-relapse" potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity. Rats with alcohol or cocaine self-administration histories received transdermal CBD at 24 h intervals for 7 days and were tested for context and stress-induced reinstatement, as well as experimental anxiety on the elevated plus maze. Effects on impulsive behavior were established using a delay-discounting task following recovery from a 7-day dependence-inducing alcohol intoxication regimen. CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. Following treatment termination, reinstatement remained attenuated up to approximate to 5 months although plasma and brain CBD levels remained detectable only for 3 days. CBD also reduced experimental anxiety and prevented the development of high impulsivity in rats with an alcohol dependence history. The results provide proof of principle supporting potential of CBD in relapse prevention along two dimensions: beneficial actions across several vulnerability states and long-lasting effects with only brief treatment. The findings also inform the ongoing medical marijuana debate concerning medical benefits of non-psychoactive cannabinoids and their promise for development and use as therapeutics.