mise à jour du
8 javier 2003
2004; 29; 158-170
Marijuana withdrawal in humans: effects of oral THC or divalproex  
Margaret Haney, Carl L Hart, Suzanne K Vosburg, Jennifer Nasser, Andrew Bennett, Carlos Zubaran and Richard W Foltin
Division on Substance Abuse, New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York


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.
Subjective-Effects Ratings
Figure 5 and Table 4 portray the average daily ratings on selected VAS scales during each day of each marijuana condition. Data will be discussed by first describing any significant effects of marijuana abstinence by comparing placebo baseline conditions to placebo abstinence conditions, and then the effect of divalproex under each marijuana condition will be described.
Table 4 shows that under placebo divalproex maintenance, ratings of 'Content', 'Mellow', 'Social', 'Energetic', 'Friendly', and 'Talkative' were all decreased during marijuana abstinence compared to baseline. In terms of the effects of maintenance condition during each marijuana condition, divalproex under baseline conditions decreased ratings of 'Content', 'Mellow', 'Social', 'Friendly', and 'Talkative'. During active marijuana smoking, divalproex continued to decrease ratings of 'Talkative', while significantly increasing ratings of 'High' compared to placebo. Figure 5 demonstrates that divalproex substantially worsened ratings of 'Anxious', 'Irritable', 'On Edge', and 'Sleepy' during marijuana abstinence. Divalproex also increased ratings of 'Withdrawn' and 'Yawning' during marijuana abstinence (Table 4).