Project details:
In March 2024, Bristol ESG were asked to undertake a systematic review of the evidence for the effectiveness and safety of pharmacological interventions for the treatment of cannabis use disorder. The review is funded by the NIHR Evidence Synthesis Programme (project number: NIHR165373) and is one of four projects allocated to Bristol ESG examining the effects and safety of psychosocial or pharmacological interventions for the treatment of drug use disorders.
Project status: completed
Contact: bristol-esg@bristol.ac.uk
What is the problem?
Cannabis is commonly used worldwide as a recreational drug. Cannabis use disorder is a condition characterised by frequent use, craving and inability to stop using cannabis even when it is causing physical or psychological problems for the user. This condition has become much more common during the past three decades and this has led to an increase in the number of people seeking treatment for it.
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 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 predominantly 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 constituent 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.
For stopping cannabis use by the end of treatment, THC preparations, CBD, N-acetylcysteine, oxytocin and PF-04457845 were 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 have been effective, and we were uncertain about the effect of THC preparations. THC preparations, cannabidiol, N-acetylcysteine and PF-04457845 were probably no more likely to cause side effects (e.g., headache, nausea or sleep disturbance) than placebo. Participants treated with anticonvulsants and mood stabilisers were 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. that required medical attention).
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 small number of 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.
Contact: bristol-esg@bristol.ac.uk
