Haney Margaret, Hart Carl L, Vosburg Suzanne K, Comer Sandra D, Reed Stephanie Collins, Foltin Richard W
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY, 10032, USA.
Psychopharmacology (Berl). 2008 Mar;197(1):157-68. doi: 10.1007/s00213-007-1020-8. Epub 2007 Dec 27.
Individuals seeking treatment for their marijuana use rarely achieve sustained abstinence.
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.
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.
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.
These data suggest the combination of lofexidine and THC warrant further testing as a potential treatment for marijuana dependence.
寻求大麻使用治疗的个体很少能实现持续戒断。
本研究的目的是确定大麻素激动剂四氢大麻酚（THC）和α2-肾上腺素能受体激动剂洛非西定单独使用及联合使用时，是否能减轻大麻戒断症状和复发情况，复发定义为在一段时间的戒断后重新开始使用大麻。
平均每天吸食12支大麻烟的非寻求治疗的男性志愿者（n = 8），在四种药物治疗条件下各维持7天：安慰剂、四氢大麻酚（THC）（60毫克/天）、洛非西定（2.4毫克/天）以及THC（60毫克/天）与洛非西定（2.4毫克/天）联合使用；每个住院阶段之间有一个门诊洗脱期。在住院的前三天，可自行使用安慰剂大麻（戒断期）。接下来的4天，可自行使用活性大麻（复发期）。参与者用研究所得报酬支付自行使用的大麻费用。测量自行给药情况、情绪、任务表现、食物摄入量和睡眠情况。
THC逆转了与大麻戒断相关的厌食和体重减轻，并减轻了一部分戒断症状，但增加了入睡潜伏期，且未减少大麻复发。洛非西定有镇静作用，加重了与戒断相关的厌食，且未有力地减轻戒断症状，但改善了睡眠并减少了大麻复发。与单独使用任何一种药物相比，洛非西定和THC联合使用对日常吸食大麻者的睡眠改善最为显著，并减少了大麻戒断、渴望和复发。
这些数据表明，洛非西定和THC联合使用作为大麻依赖的潜在治疗方法值得进一步测试。
