Table 3. Summary of Pharmacotherapy Trials for Cannabis Withdrawal.

Study	No. of Participants	Setting and Design	Treatment Conditions	Primary Outcomes	Results
Haney et al., (2001)41	10	Inpatient; double-blind, placebo-controlled crossover	Bupropion 300 mg/day or placebo	Withdrawal symptoms, subjective effects, psychomotor performance	Bupropion worsened withdrawal symptoms (increased irritability, sleep disturbances, and depressed mood)
Haney et al., (2003)43	7	Inpatient; double-blind, placebo-controlled crossover	Nefazodone 450 mg/day or placebo	Withdrawal symptoms, subjective effects, psychomotor performance	Nefazodone decreased anxiety and muscle pain; it had no effect on irritability, difficulty sleeping, or ratings of feeling miserable
Haney et al., (2004)45	14	Inpatient; double-blind, placebo-controlled crossover	Oral THC 10 mg 5 times/day or placebo (n=7); divalproex 1500 mg or placebo (n=7)	Withdrawal symptoms, subjective effects, psychomotor performance	Oral THC decreased marijuana craving and withdrawal symptoms; divalproex increased ratings of anxiety, irritability, sleepiness, and “bad effect,” and worsened performance on psychomotor tasks
Budney et al., (2007)46	8	Outpatient; double-blind, placebo-controlled, crossover	Oral THC 10 mg 3 times/day, oral THC 30 mg 3 times/day, or placebo	Withdrawal symptoms	Oral THC reduced withdrawal symptoms, with a greater reduction seen with the higher dose than the lower dose
Haney et al., (2008)47	8	Inpatient; double-blind, placebo-controlled crossover	Oral THC 20 mg 3 times/day, lofexidine 2.4 mg/day, oral THC 20 mg 3 times/day and lofexidine 2.4 mg/day, or placebo	Withdrawal symptoms, cannabis relapse behavior, psychomotor performance	Oral THC decreased some withdrawal symptoms but had no effect on self-administration; lofexidine did not improve withdrawal symptoms but decreased self-administration; the combination or oral THC and lofexidine decreased withdrawal symptoms, craving, and self-administration
Winstock et al., (2009)49	20	Inpatient; open-label	Lithium 500 mg twice/day	Withdrawal symptoms, cannabis use at follow-up	Lithium reduced depressive symptoms and cannabis-related problems; a 87.5% self-reported abstinence rate was observed at follow-up
Haney et al., (2010)44	21	Inpatient; double-blind, placebo-controlled crossover	Baclofen 60 mg/day or 90 mg/day (n=10); mirtazapine 30 mg/day or placebo (n=11)	Withdrawal symptoms, cannabis relapse behavior, psychomotor performance	Baclofen decreased cannabis craving but did not reduce self-administration and worsened cognitive performance; mirtazapine improved sleep but had no effect on withdrawal symptoms and did not reduce self-administration
Vandrey et al., (2011)51	20	Inpatient; double-blind, placebo-controlled crossover	Extended-release zolpidem 12.5 mg/day or placebo	Sleep architecture, withdrawal symptoms	Sleep architecture improved with zolpidem; it had no effect on sleep latency or cannabis withdrawal symptoms
Penetar et al., (2012)42	22	Outpatient; randomized, double-blind, placebo-controlled	Bupropion 150 mg twice/day or placebo	Withdrawal symptoms, cognitive testing	A greater proportion of withdrawal symptoms was reported in placebo-treated subjects; no significant difference in cognitive performance was reported between buproprion- and placebo-treated subjects
Cooper et al., (2013)52	14	Inpatient; double-blind, placebo-controlled crossover	Quetiapine 200 mg/day or placebo	Withdrawal symptoms, cannabis relapse behavior, psychomotor performance	Quetiapine improved sleep quality and appetite during cannabis withdrawal but increased cannabis craving and self-administration
Haney et al., (2013)48	11	Inpatient; double-blind, placebo-controlled crossover	Nabilone 6 mg/day, nabilone 8 mg/day, or placebo	Withdrawal symptoms, cannabis relapse behavior, psychomotor performance	Both nabilone doses reduced withdrawal symptoms and cannabis self-administration; nabilone 8 mg/day worsened psychomotor task performance
Johnston et al., (2014)50	38	Inpatient; randomized, placebo-controlled	Lithium 500 mg twice/day or placebo	Withdrawal symptoms, cannabis use at follow-up	No significant differences in withdrawal symptoms or cannabis use at follow-up were noted between the groups

THC = delta-9-tetrahydrocannabinol.