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Meta-Analysis
, 1 (1), CD008940

Pharmacotherapies for Cannabis Dependence

Affiliations
Meta-Analysis

Pharmacotherapies for Cannabis Dependence

Suzanne Nielsen et al. Cochrane Database Syst Rev.

Abstract

Background: Globally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.This is an update of a Cochrane Review first published in the Cochrane Library in Issue 12, 2014.

Objectives: To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use.

Search methods: We updated our searches of the following databases to March 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and Web of Science.

Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs involving the use of medications to treat cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in people diagnosed as cannabis dependent or who were likely to be dependent.

Data collection and analysis: We used standard methodological procedures expected by Cochrane.

Main results: We included 21 RCTs involving 1755 participants: 18 studies recruited adults (mean age 22 to 41 years); three studies targeted young people (mean age 20 years). Most (75%) participants were male. The studies were at low risk of performance, detection and selective outcome reporting bias. One study was at risk of selection bias, and three studies were at risk of attrition bias.All studies involved comparison of active medication and placebo. The medications were diverse, as were the outcomes reported, which limited the extent of analysis.Abstinence at end of treatment was no more likely with Δ9-tetrahydrocannabinol (THC) preparations than with placebo (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.64 to 1.52; 305 participants; 3 studies; moderate-quality evidence). For selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine, there was no difference in the likelihood of abstinence at end of treatment compared to placebo (low- to very low-quality evidence).There was qualitative evidence of reduced intensity of withdrawal symptoms with THC preparations compared to placebo. For other pharmacotherapies, this outcome was either not examined, or no significant differences was reported.Adverse effects were no more likely with THC preparations (RR 1.02, 95% CI 0.89 to 1.17; 318 participants; 3 studies) or N-acetylcysteine (RR 0.94, 95% CI 0.71 to 1.23; 418 participants; 2 studies) compared to placebo (moderate-quality evidence). For SSRI antidepressants, mixed action antidepressants, buspirone and N-acetylcysteine, there was no difference in adverse effects compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of withdrawal from treatment due to adverse effects with THC preparations, SSRIs antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of treatment completion with THC preparations, SSRI antidepressants, mixed action antidepressants and buspirone compared to placebo (low- to very low-quality evidence) or with N-acetylcysteine compared to placebo (RR 1.06, 95% CI 0.93 to 1.21; 418 participants; 2 studies; moderate-quality evidence). Anticonvulsants and mood stabilisers appeared to reduce the likelihood of treatment completion (RR 0.66, 95% CI 0.47 to 0.92; 141 participants; 3 studies; low-quality evidence).Available evidence on gabapentin (anticonvulsant), oxytocin (neuropeptide) and atomoxetine was insufficient for estimates of effectiveness.

Authors' conclusions: There is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N-acetylcysteine is weak, but these medications are also worth further investigation.

Conflict of interest statement

SN: was supported by an National Health and Medical Research Council Fellowship while completing this review. SN is an investigator on untied educational grants Indivior on studies unrelated to this work.

LG: none known.

PS: none known.

BLF: is performing clinical research evaluating the utility of nabiximols for cannabis dependence treatment using drug supplies donated by GW Pharma. The research is supported by the Centre for Addiction and Mental Health, the Canadian Institute of Health Research (CSU 115548) and the National Institute On Drug Abuse of the National Institutes of Health (R21DA031906). Research on cannabis with product provided by Aurora and Canopy unrelated to the topic of this review. Future research planned with Alkermes on CUD.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Figure 3
Figure 3
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Analysis 1.1
Analysis 1.1
Comparison 1 Δ9‐Tetrahydrocannabinol (THC) preparation versus placebo, Outcome 1 Participants abstinent at end of treatment.
Analysis 1.2
Analysis 1.2
Comparison 1 Δ9‐Tetrahydrocannabinol (THC) preparation versus placebo, Outcome 2 Participants experiencing adverse effects.
Analysis 1.3
Analysis 1.3
Comparison 1 Δ9‐Tetrahydrocannabinol (THC) preparation versus placebo, Outcome 3 Participants withdrawn due to adverse effects.
Analysis 1.4
Analysis 1.4
Comparison 1 Δ9‐Tetrahydrocannabinol (THC) preparation versus placebo, Outcome 4 Completion of scheduled treatment.
Analysis 2.1
Analysis 2.1
Comparison 2 Selective serotonin‐reuptake inhibitor (SSRI) antidepressant versus placebo, Outcome 1 Participants abstinent at end of treatment.
Analysis 2.2
Analysis 2.2
Comparison 2 Selective serotonin‐reuptake inhibitor (SSRI) antidepressant versus placebo, Outcome 2 Participants experiencing adverse effects.
Analysis 2.3
Analysis 2.3
Comparison 2 Selective serotonin‐reuptake inhibitor (SSRI) antidepressant versus placebo, Outcome 3 Participants withdrawn due to adverse effects.
Analysis 2.4
Analysis 2.4
Comparison 2 Selective serotonin‐reuptake inhibitor (SSRI) antidepressant versus placebo, Outcome 4 Completion of scheduled treatment.
Analysis 3.1
Analysis 3.1
Comparison 3 Mixed action antidepressant versus placebo, Outcome 1 Participants abstinent at end of treatment.
Analysis 3.2
Analysis 3.2
Comparison 3 Mixed action antidepressant versus placebo, Outcome 2 Participants experiencing adverse effects.
Analysis 3.3
Analysis 3.3
Comparison 3 Mixed action antidepressant versus placebo, Outcome 3 Participants withdrawn due to adverse effects.
Analysis 3.4
Analysis 3.4
Comparison 3 Mixed action antidepressant versus placebo, Outcome 4 Completion of scheduled treatment.
Analysis 4.1
Analysis 4.1
Comparison 4 Anticonvulsants and mood stabilisers versus placebo, Outcome 1 Participants abstinent at end of treatment.
Analysis 4.2
Analysis 4.2
Comparison 4 Anticonvulsants and mood stabilisers versus placebo, Outcome 2 Participants withdrawn due to adverse effects.
Analysis 4.3
Analysis 4.3
Comparison 4 Anticonvulsants and mood stabilisers versus placebo, Outcome 3 Completion of scheduled treatment.
Analysis 5.1
Analysis 5.1
Comparison 5 Bupropion versus placebo, Outcome 1 Completion of scheduled treatment.
Analysis 6.1
Analysis 6.1
Comparison 6 Buspirone versus placebo, Outcome 1 Participants abstinent at end of treatment.
Analysis 6.2
Analysis 6.2
Comparison 6 Buspirone versus placebo, Outcome 2 Participants experiencing adverse effects.
Analysis 6.3
Analysis 6.3
Comparison 6 Buspirone versus placebo, Outcome 3 Participants withdrawn due to adverse effects.
Analysis 6.4
Analysis 6.4
Comparison 6 Buspirone versus placebo, Outcome 4 Completion of scheduled treatment.
Analysis 7.1
Analysis 7.1
Comparison 7 Atomoxetine versus placebo, Outcome 1 Participants experiencing adverse effects.
Analysis 7.2
Analysis 7.2
Comparison 7 Atomoxetine versus placebo, Outcome 2 Participants withdrawn due to adverse effects.
Analysis 7.3
Analysis 7.3
Comparison 7 Atomoxetine versus placebo, Outcome 3 Completion of scheduled treatment.
Analysis 8.1
Analysis 8.1
Comparison 8 N‐acetylcysteine versus placebo, Outcome 1 Participants abstinent at end of treatment.
Analysis 8.2
Analysis 8.2
Comparison 8 N‐acetylcysteine versus placebo, Outcome 2 Participants experiencing adverse effects.
Analysis 8.3
Analysis 8.3
Comparison 8 N‐acetylcysteine versus placebo, Outcome 3 Participants withdrawn due to adverse effects.
Analysis 8.4
Analysis 8.4
Comparison 8 N‐acetylcysteine versus placebo, Outcome 4 Completion of scheduled treatment.
Analysis 9.1
Analysis 9.1
Comparison 9 Oxytocin versus placebo, Outcome 1 Participants abstinent at end of treatment.
Analysis 9.2
Analysis 9.2
Comparison 9 Oxytocin versus placebo, Outcome 2 Participants experiencing adverse effects.
Analysis 9.3
Analysis 9.3
Comparison 9 Oxytocin versus placebo, Outcome 3 Completion of scheduled treatment.

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