Haney Margaret, Hart Carl L, Vosburg Suzanne K, Nasser Jennifer, Bennett Andrew, Zubaran Carlos, Foltin Richard W
New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Neuropsychopharmacology. 2004 Jan;29(1):158-70. doi: 10.1038/sj.npp.1300310.
Abstinence following daily marijuana use can produce a withdrawal syndrome characterized by negative mood (eg irritability, anxiety, misery), muscle pain, chills, and decreased food intake. Two placebo-controlled, within-subject studies investigated the effects of a cannabinoid agonist, delta-9-tetrahydrocannabinol (THC: Study 1), and a mood stabilizer, divalproex (Study 2), on symptoms of marijuana withdrawal. Participants (n=7/study), who were not seeking treatment for their marijuana use, reported smoking 6-10 marijuana cigarettes/day, 6-7 days/week. Study 1 was a 15-day in-patient, 5-day outpatient, 15-day in-patient design. During the in-patient phases, participants took oral THC capsules (0, 10 mg) five times/day, 1 h prior to smoking marijuana (0.00, 3.04% THC). Active and placebo marijuana were smoked on in-patient days 1-8, while only placebo marijuana was smoked on days 9-14, that is, marijuana abstinence. Placebo THC was administered each day, except during one of the abstinence phases (days 9-14), when active THC was given. Mood, psychomotor task performance, food intake, and sleep were measured. Oral THC administered during marijuana abstinence decreased ratings of 'anxious', 'miserable', 'trouble sleeping', 'chills', and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication. Study 2 was a 58-day, outpatient/in-patient design. Participants were maintained on each divalproex dose (0, 1500 mg/day) for 29 days each. Each maintenance condition began with a 14-day outpatient phase for medication induction or clearance and continued with a 15-day in-patient phase. Divalproex decreased marijuana craving during abstinence, yet increased ratings of 'anxious', 'irritable', 'bad effect', and 'tired.' Divalproex worsened performance on psychomotor tasks, and increased food intake regardless of marijuana condition. Thus, oral THC decreased marijuana craving and withdrawal symptoms at a dose that was subjectively indistinguishable from placebo. Divalproex worsened mood and cognitive performance during marijuana abstinence. These data suggest that oral THC, but not divalproex, may be useful in the treatment of marijuana dependence.
每日吸食大麻后戒断会产生一种戒断综合征，其特征为情绪消极（如易怒、焦虑、痛苦）、肌肉疼痛、发冷以及食物摄入量减少。两项安慰剂对照的自身对照研究调查了一种大麻素激动剂Δ-9-四氢大麻酚（THC：研究1）和一种情绪稳定剂丙戊酸（研究2）对大麻戒断症状的影响。参与者（每项研究n = 7）并非因吸食大麻寻求治疗，报告称每天吸食6 - 10支大麻烟，每周吸食6 - 7天。研究1采用15天住院、5天门诊、15天住院的设计。在住院阶段，参与者每天五次在吸食大麻（THC含量0.00%、3.04%）前1小时口服THC胶囊（0、10毫克）。在住院第1 - 8天吸食活性大麻和安慰剂大麻，而在第9 - 14天仅吸食安慰剂大麻，即处于大麻戒断状态。除了在其中一个戒断阶段（第9 - 14天）给予活性THC外，每天给予安慰剂THC。测量情绪、心理运动任务表现、食物摄入量和睡眠情况。在大麻戒断期间口服THC可降低“焦虑”“痛苦”“睡眠困难”“发冷”以及对大麻的渴望程度评分，与安慰剂相比可逆转食物摄入量的大幅下降，且不会产生中毒反应。研究2采用58天门诊/住院设计。参与者分别在每种丙戊酸剂量（0、1500毫克/天）下维持29天。每个维持阶段开始是为期14天的门诊用药诱导或清除阶段，接着是为期15天的住院阶段。丙戊酸可降低戒断期间对大麻的渴望，但会提高“焦虑”“易怒”“不良反应”和“疲倦”的评分。丙戊酸会使心理运动任务表现变差，且无论大麻状态如何都会增加食物摄入量。因此，口服THC以一种主观上与安慰剂无差异的剂量降低了对大麻的渴望和戒断症状。丙戊酸在大麻戒断期间使情绪和认知表现变差。这些数据表明口服THC而非丙戊酸可能对治疗大麻依赖有用。
