Key messages
Based on current research, we are uncertain about the effects of different medicines for cannabis use disorder.
What is cannabis use disorder?
Cannabis use disorder is when someone finds it hard to stop using cannabis even though it is causing problems in their life, like with health, work, or relationships. Cannabis use is relatively common and widespread worldwide. Demand for treatment for cannabis use disorder has been increasing in most regions of the world. Moves in some countries to decriminalise or legalise cannabis use are likely to result in this trend continuing.
How is cannabis dependence treated?
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Currently, psychological treatments are the only recommended treatment for cannabis use disorder.
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There are currently no medicines specifically for the treatment of cannabis use disorder.
What did we want to find out?
We wanted to assess what medicines are effective and safe for the treatment of cannabis dependence.
What did we do?
We searched many scientific databases to find clinical studies that looked at medicines to treat cannabis use disorder. We included studies where participants were described as having a cannabis use disorder. We included studies where people were allocated at random to one of two or more treatment groups. We assessed how good the study methods were to get a sense of how confident we were in their results. We grouped studies together for analysis depending on what type of medication was used.
What did we find?
We identified 37 randomised controlled trials involving 3201 participants.
The average age of participants in studies of adults ranged from 22 to 41 years, while four additional studies included only young people. In most studies (32) participants were mostly male. While most studies recruited participants with cannabis dependence from the general population, five studies focused on participants who had a mental health condition alongside cannabis dependence, including depression (2 studies), attention deficit hyperactivity disorder (2 studies) and bipolar disorder (1 study). Most of the studies (29) were undertaken in the USA, with four occurring in Australia, two in Israel, one in Canada, and one in the United Kingdom.
The studies tested a wide range of medicines to reduce the symptoms of cannabis withdrawal and to promote cessation or reduction of cannabis use, including: cannabinoid preparations containing Δ9-tetrahydrocannabinol (THC, the major constituent in cannabis with psychoactive properties); cannabidiol (CBD, a compound in cannabis that doesn't produce a high); medicines belonging to the 'anticonvulsants and mood stabilisers' (medicines to prevent seizures and treat epilepsy); N-acetylcysteine (a medicine used to treat respiratory disorders and paracetamol poisoning); the hormone oxytocin and a medication called PF-04457845 (which affects how cannabinoids are broken down in the body). In most of the studies, the effect of these medicines was compared with the effect of placebo (a pretend treatment that looks the same as the active medicine but does not contain any active ingredient).
Eleven studies received medications from manufacturing companies, and none were funded by pharmaceutical companies. Three studies did not report funding, or the funding was unclear.
Main results
For stopping cannabis use by the end of treatment, THC preparations, CBD, N-acetylcysteine, oxytocin and PF-04457845 are probably ineffective, and we are uncertain about the effect of anticonvulsants and mood stabilisers.
For completing treatment, CBD, anticonvulsants and mood stabilisers, N-acetylcysteine and PF-04457845 may not be effective, and we are uncertain about the effect of THC preparations.
THC preparations, cannabidiol, N-acetylcysteine and PF-04457845 are probably no more likely to cause side effects (e.g. headache, nausea or sleep disturbance) than placebo. Participants treated with anticonvulsants and mood stabilisers are more likely to terminate the study earlier than those treated with placebo. None of the medicines tested increased the likelihood of severe side effects (i.e. those that required medical attention).
What are the limitations of the evidence?
The quality of the evidence for less than a third of the outcomes in this review was moderate (30%), and for some it was low (37%) or very low (31%). This was due to there being only a few studies for each medicine (ranging from one to seven). Each study involved small numbers of participants, there were some inconsistencies in the findings between the studies (i.e. some found a beneficial effect of intervention and some found no effects or harmful effects), and there was a risk of bias due to study participants dropping out of treatment.
How up to date is this evidence?
This review updates a previous review. The evidence is up-to-date to May 2024.
Читать полную аннотацию (абстракт)
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.
Задачи
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.
Методы поиска
We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO in May 2024.
Критерии отбора
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.
Сбор и анализ данных
We used standard methodological procedures expected by Cochrane.
Основные результаты
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.
Выводы авторов
There is incomplete evidence for all the clinically-important pharmacotherapies investigated and, for half of their outcomes, the quality of the evidence was low (44%) or very low (11%). Given the limited evidence of efficacy, those pharmacotherapies should still be considered experimental for treating cannabis use disorder. The greater withdrawal from treatment due to adverse effects seen with anticonvulsants and mood stabilisers may limit their therapeutic value.
Финансирование
FS, TP, JS: Received funding from the National Institute for Health and Care Research to directly support the conduct of this review.
SN: National Health and Medical Research Council to directly support her time in the conduct of this review.
Регистрация
Protocol [and previous versions] available via DOI: 10.1002/14651858.CD008940 [DOI: 10.1002/14651858.CD008940.pub2 and DOI: 10.1002/14651858.CD008940.pub3].
