title: Marijuana withdrawal in humans: effects of oral THC or divalproex.
abstract: 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.
authors.affiliation: New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. mh235@columbia.edu
authors.forename: Margaret
authors.initials: M
authors.lastname: Haney
authors.forename: Carl L
authors.initials: CL
authors.lastname: Hart
authors.forename: Suzanne K
authors.initials: SK
authors.lastname: Vosburg
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nasser
authors.forename: Andrew
authors.initials: A
authors.lastname: Bennett
authors.forename: Carlos
authors.initials: C
authors.lastname: Zubaran
authors.forename: Richard W
authors.initials: RW
authors.lastname: Foltin
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002188:Cannabis / Q000009:adverse effects*; D004311:Double-Blind Method; D013759:Dronabinol / Q000627:therapeutic use*; D004435:Eating / Q000187:drug effects; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D012890:Sleep / Q000187:drug effects; D012907:Smoking / Q000188:drug therapy; D012919:Social Behavior; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D011795:Surveys and Questionnaires; D013997:Time Factors; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D011619:Psychotropic Drugs; D014635:Valproic Acid; D013759:Dronabinol