Bupropion SR worsens mood during marijuana withdrawal in humans

Rationale: Symptoms of withdrawal after daily marijuana smoking include inc reased ratings of irritability and depression. Similar mood symptoms are re ported by cigarette smokers during nicotine abstinence. Objective: Given th e successful use of sustained-release bupropion in treating nicotine depend ence, this study investigated how maintenance on bupropion influenced sympt oms of marijuana withdrawal compared to maintenance on placebo. Methods: Ma rijuana smokers (n=10) were maintained outpatient on active (300 mg/day) or placebo (0 mg/day) bupropion for 11 days, and were then maintained inpatie nt on the same bupropion dose for 17 days. For the first 4 inpatient days, participants smoked active marijuana [2.8% Delta9-tetrahydrocannabinol (THC )] 5 times/day. For the remaining inpatient days, participants smoked place bo marijuana (0.0% THC) 5 times/day. Participants were then maintained outp atient on the alternate dose of bupropion for 11 days, followed by a second inpatient residential stay, paralleling the first. Medication administrati on was double-blind. Mood, psychomotor task performance, food intake, and s leep were measured daily during each inpatient phase. The order of active a nd placebo bupropion maintenance was counterbalanced between groups. Result s: Bupropion had few behavioral effects when participants smoked active mar ijuana. During placebo marijuana smoking, i.e., active marijuana withdrawal , ratings of irritability, restlessness, depression, and trouble sleeping w ere increased by bupropion compared to placebo maintenance. Conclusions: Th ese data suggest that bupropion does not show promise as a potential treatm ent medication for marijuana dependence.