Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse
Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse
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DOI：
10.1007/s00213-007-1020-8
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发表时间：
2008-03-01
影响因子：
3.4
通讯作者：
Foltin, Richard W.
中科院分区：
文献类型：
--
作者：
Haney, Margaret;Hart, Carl L.;Foltin, Richard W.
目的本研究的目的是确定单独和联合应用大麻素类激动剂THC和α(2)-肾上腺素能受体激动剂洛非西定是否能减少大麻的戒断和复发症状，定义为戒断一段时间后重新使用大麻。材料和方法不寻求治疗的男性志愿者(n=8)，平均每天12支大麻烟，在四种药物条件下维持7天：安慰剂，四氢大麻酚(THC)(60 mg/天)，洛非西定(2.4 mg/天)，THC(60 mg/d)联合洛非西定(2.4 mg/d)；每个住院阶段由门诊冲刷阶段隔开。在最初的三天住院期间，安慰剂大麻可用于自我管理(戒断)。在接下来的4天里，活跃的大麻可用于自我管理(复发)。参与者用研究收入支付自己管理的大麻。结果THC可逆转戒断后的厌食和体重减轻，减轻部分戒断症状，延长入睡潜伏期，但不能降低大麻复发率。洛非西定具有镇静作用，加重了与戒断相关的厌食症，并没有有力地缓解戒断，但改善了睡眠，减少了大麻复发。与单独使用任何一种药物相比，洛非西定和THC联合使用可显著改善每日吸食大麻的人的睡眠，并减少大麻的戒断、渴求和复发。结论这些数据表明，洛非西定和THC联合使用作为一种潜在的大麻依赖治疗方法值得进一步试验。
Introduction Individuals seeking treatment for their marijuana use rarely achieve sustained abstinence.Objectives The objectives of the study are to determine if THC, a cannabinoid agonist, and lofexidine, an alpha(2)-adrenergic receptor agonist, given alone and in combination, decreased symptoms of marijuana withdrawal and relapse, defined as a return to marijuana use after a period of abstinence.Materials and methods Nontreatment-seeking, male volunteers (n=8), averaging 12 marijuana cigarettes/day, were maintained on each of four medication conditions for 7 days: placebo, tetrahydrocannabinol (THC) (60 mg/day), lofexidine (2.4 mg/day), and THC (60 mg/day) combined with lofexidine (2.4 mg/day); each inpatient phase was separated by an outpatient washout phase. During the first three inpatient days, placebo marijuana was available for self-administration (withdrawal). For the next 4 days, active marijuana was available for self-administration (relapse). Participants paid for self-administered marijuana using study earnings. Self-administration, mood, task performance, food intake, and sleep were measured.Results THC reversed the anorexia and weight loss associated with marijuana withdrawal, and decreased a subset of withdrawal symptoms, but increased sleep onset latency, and did not decrease marijuana relapse. Lofexidine was sedating, worsened abstinence-related anorexia, and did not robustly attenuate withdrawal, but improved sleep and decreased marijuana relapse. The combination of lofexidine and THC produced the most robust improvements in sleep and decreased marijuana withdrawal, craving, and relapse in daily marijuana smokers relative to either medication alone.Conclusions These data suggest the combination of lofexidine and THC warrant further testing as a potential treatment for marijuana dependence.