Table 1. Placebo-Controlled Human Laboratory Studies of Medications in Non-treatment-seeking Participants with CUD.
| Medication and publication | Number of participants | Participant characteristics | Key study design elements | Outcomes |
|---|---|---|---|---|
| Bupropion 300 mg/day (divided over two doses) Haney et al, 2001 | N=10 completers | Baseline cannabis use: 6±1 days/week; 6±7 joints/day Gender: 2 women Age: 27±4 years Tobacco use: N=6 cigarette smokers | Outpatient medication maintenance with inpatient phases Cross-over with PBO, double blind Model of steady-state medication effects on withdrawal | Self-reports of mood VAS, sleep VAS, food intake, psychomotor task performance |
| Nefazodone 450 mg/day (divided over two doses) Haney et al, 2003 | N=7 completers (4 additional volunteers were not included) | Baseline cannabis use: 6.4±0.4 days/week; 6±1.3 joints/day Gender: 1 woman Age: 30±3 years Tobacco use: N=5 cigarette smokers | Outpatient medication phases Cross-over with PBO, double blind Model of steady-state medication effects on withdrawal | Self-reports of mood VAS, sleep VAS, food intake, psychomotor task performance |
| Mirtazapine 30 mg nightly Haney et al, 2010 | N=11 completers (1 additional volunteer dropped out) | Baseline cannabis use: 6.9±0.2 days/week; 11.9±5.3 joints/day Gender: 0 women Age: 27±5 years Tobacco use: N=7 cigarette smokers | Outpatient medication maintenance with inpatient phases Cross-over with PBO, double blind Model of medication effects on behavior, withdrawal, and relapse to marijuana smoking | Self-reports of mood VAS, sleep VAS, subjective effects VAS, craving VAS, food intake, psychomotor task performance, Actiwatch data, mean money spent to purchase marijuana following abstinence |
| Divalproex 1500 mg/day (divided over two doses) Haney et al, 2004 | N=7 completers (1 additional volunteer dropped out) | Baseline cannabis use: 6.6±0.3 days/week; 6.3±2 joints/day Gender: 1 women Age: 26±1 years Tobacco use: N=4 cigarette smokers | Outpatient medication maintenance with inpatient phases Cross-over design with PBO, double blind Model of medication effects on behavior and withdrawal | Self-reports of mood VAS, sleep VAS, subjective effects VAS, MWC (including craving), food intake and weight, psychomotor task performance, social task Nightcap system data on sleep |
| Quetiapine 200 mg/day (divided over two doses) Cooper et al, 2013 | N=14 completers (6 additional volunteers dropped out) | Baseline cannabis use: 6.6±0.9 days/week; 10.0±6.5 joints/day Gender: 2 women Age: 26±4 years Tobacco use: N=10 cigarette smokers using 5.7±3.7 cigarettes/day | Inpatient phases Cross-over, double blind Model of medication’s effects on withdrawal and relapse prevention | Self-reports of VAS on affective and physical symptoms, sleep VAS, Actiwatch, psychomotor task battery, food intake, mean money spent to purchase marijuana following abstinence |
| Baclofen 60 and 90 mg/day (divided over three doses) Haney et al, 2010 | N=10 completers (3 additional volunteers dropped out) | Baseline cannabis use: 6.7±0.9 days/week; 9.4±3.9 joints/day Gender: 0 women Age: 29±6 years Tobacco use: N=8 cigarette smokers | Inpatient phases Cross-over, double blind Model of medication effects on behavior, withdrawal, and relapse to marijuana smoking | Self-reports of mood VAS, sleep VAS, subjective effects VAS, craving VAS, food intake, psychomotor task performance, Actiwatch data, mean money spent to purchase marijuana following abstinence |
| Zolpidem 12.5 mg nightly Vandrey et al, 2011 | N=20 completers (5 additional volunteers dropped out) | Baseline cannabis use: daily cannabis smokers who smoked up to 4 × /day±3 times Gender: 3 women Age: 29±8 years Tobacco use: N=16 cigarette smokers smoked 9±6 times/day | Outpatient and inpatient phases Cross-over design with PBO Model of natural cannabis withdrawal effects on sleep and zolpidem’s effects on sleep in the context of withdrawal | PSG PSQI MWC MCQ Side effects Cognitive performance battery |
| Dronabinol 50 mg/day (divided in five doses) Haney et al, 2004 | N=7 completers (4 additionally volunteers dropped out) | Baseline cannabis use: 6.2±1.3 days/week; 9.6±6.2 joints/day Gender: 0 women Age: 24±1 years Tobacco use: N=6 cigarettes smokers | Outpatient medication maintenance with inpatient sessions Cross-over design with PBO, double blind Model of medication effects on behavior and withdrawal | Self-reports of mood VAS, sleep VAS, subjective effects VAS, drug effects, MWC (including craving), food intake and weight, psychomotor task performance, social task Nightcap system data on sleep |
| Dronabinol 30 or 90 mg/day (divided in three doses) Budney et al, 2007 | N=8 completers (14 additional non-completers) | Baseline cannabis use: 28.5±1.9 days of cannabis use/30 days; using 2.6±0.5 times/day Gender: 2 women Age: 32.5 years (21–54 years) Tobacco use: N=4 cigarette smokers | Outpatient study; multiple sessions Cross-over with PBO, double blind Model of medication’s effects on withdrawal symptoms in more naturalistic setting (as compared to inpatient) | MWC MCQ BSI POMS Sleep self-report ARCI Drug effects VAS Side effects |
| Dronabinol 60 mg/day+lofexidine 2.4 mg/day (divided by four doses) Haney et al, 2008 | N=8 completers | Baseline cannabis use: daily cannabis users; 12.2±8.1 joints/day Gender: 0 women Age: 29±7 years Tobacco use: N=6 cigarette smokers; 9.3±5.9 cigarettes/day | Inpatient phases Cross-over with four arms, double blind Model of medication’s effects on withdrawal and relapse prevention | Subjective effects VAS, mood VAS, craving VAS, observer ratings, food intake and weight, psychomotor task performance, social task, sleep VAS, blood pressure, nightcap system data on sleep, mean money spent to purchase marijuana following abstinence |
| Nabilone 6 and 8 mg/day (divided in two doses) Haney, 2013b | N=11 completers (1 additional participant dropped out) | Baseline cannabis use: 6.9±0.3 days/week; 8.3±3.1 joints/day Gender: 3 women Age: 30±10 years Tobacco use: N=11 cigarettes smokers; 5.7±5.5 cigarettes/day | Inpatient phases Cross-over with PBO, double blind Model of medication’s effects on withdrawal and relapse prevention | Self-reports of mood VAS, sleep VAS, subjective effects VAS, craving VAS, food intake, psychomotor task performance, Actiwatch data, mean money spent to purchase marijuana following abstinence |
| Nabilone 6 mg/day+zolpidem 12.5 mg nightly (divided by three doses) Herrmann et al, 2016 | N=11 completers (4 additional volunteers dropped out) | Baseline cannabis use: 6.8±0.4 days/week; 9.6±4.6 joints/day Gender: 0 women Age: 27.5±6.1 years Tobacco use: N=9 cigarette smokers; 3.9±2.3 cigarettes/day | Inpatient phases Cross-over with three arms, double blind Model of medication’s effects on withdrawal and relapse prevention | Self-reports of mood VAS, sleep VAS, subjective effects VAS capsule, craving VAS, food intake and body weight, cognitive task performance, Actiwatch data, mean money spent to purchase marijuana following abstinence |
| Cannabidiol 20, 400, and 800 mg 1 × dose Haney et al, 2016 | N=31 completers (19 additional volunteers dropped out) | Baseline cannabis use: 6.5±1.0 days/week; 5.1±5.3 joints/day Gender: 14 women Age: 29.1±9.1 years Tobacco use: N=18 cigarette smokers | Outpatient study, multiple sessions Within subject, double blind Model of medication’s subjective and physiological effects and self-administration of marijuana | Self-reports of mood VAS, sleep VAS, subjective effects VAS, drug effects VAS, and marijuana effects VAS, capsule VAS, performance task battery, HR, BP, plasma CBD |
| Rimonabant 1, 3, 10, 30, or 90 mg 1 × dose Huestis et al, 2001 | N=63 randomized participants (N/group range from 6 to 10 participants/group) | Baseline cannabis use: 4.6–25.0 days/30 days Gender: 0 women Age: 21–45 years | Inpatient phase Participants randomized to one of eight groups (combinations of PBO medication, escalating doses of rimonabant, active cannabis, PBO cannabis) Model of medication’s dose effects on physiological and subjective effects of smoked cannabis | HR Subjective effects of smoked cannabis VAS ARCI Plasma cannabinoid concentrations Plasma rimonabant concentrations |
| Rimonabant 40 mg/day or 90 mg 1 × dose Huestis et al, 2007 | N=36 completers; N=12 in each arm (6 additional volunteers dropped out) | Baseline cannabis use: 20.3±9.6 days/last 30 days Gender: 0 women Age: 28.9±6.3 years | Inpatient phase Randomized, double-blind, parallel group design of three groups (maintenance rimonabant, PBO+1 high-dose rimonabant, or PBO) Model of medication’s effects on physiological and subjective effects of smoked cannabis | HR Subjective effects of smoked cannabis VAS ARCI Plasma cannabinoid concentrations Plasma rimonabant concentrations |
| Naltrexone 12, 25, 50, and 100 mg 1 × dose Cooper and Haney, 2010 | N=29 completers (20 additional participants dropped out) | Baseline cannabis use: 6.7±0.1 days/week; 8.3±1.2 joints/day; $83.2±13.1/week spent on cannabis Gender: 14 women Age: 28±1 years Tobacco use: N=24 cigarette smokers; 6.8±0.9 cigarettes/day | Outpatient study, multiple sessions Within subject, double blind Model of medications’ dose effects on subjective, physiological, and cognitive effects of smoked cannabis | Subjective effects VAS, drug effects VAS, and marijuana effects VAS, capsule VAS, cognitive task battery, HR, BP |
| Naltrexone 50 mg/day Haney et al, 2015 | N=51 randomized completers (N=23 on naltrexone; 17 additional volunteers dropped out; 9 on naltrexone) | Baseline cannabis use: PBO, smoked 6.3±1 days/week; 6.0±4.0 joints/day; naltrexone, 6.4±l days/week; 5.5±3.6 joints/day Gender: 7 women (N=5 on naltrexone) Age: PBO, 31.6±8 years; naltrexone: 28.6±7 years | Outpatient study, multiple sessions Randomized to PBO or naltrexone given as maintenance dosing over 16 days Model of medication’s effects on self-administration of cannabis | Self-reports of mood VAS, sleep VAS, subjective effects VAS, drug effects VAS, and marijuana effects VAS, capsule VAS, cognitive task battery, HR, BP, plasma naltrexone |
Abbreviations: ARCI, Addiction Resource Center Inventory; BP, blood pressure; BSI, Brief Symptom Inventory; HR, heart rate; MCQ, Marijuana Craving Questionnaire; MWC, Marijuana Withdrawal Checklist; PBO, placebo; POMS, profile of mood states; PSG, polysomnography; PSQI, Pittsburgh Sleep Quality Inventory; VAS, Visual Analog Scale.
Numbers provided in mean±SD.
Note that if the numbers for dropouts, baseline cannabis use, or tobacco use are not provided, they were not presented in the primary article.