Cannabis use disorder affects millions globally, yet approved medication options remain unavailable. A comprehensive review of 37 studies involving 3,201 participants reveals the current state of pharmacological interventions and highlights why psychological approaches remain the primary treatment method.

Understanding the Scale of the Problem

Globally, cannabis use is prevalent and widespread, with an estimated 228 million people using cannabis in 2022, the highest estimate to date, representing more than a 100% increase over a 10-year period. Cannabis use disorders are now the leading reason for seeking drug treatment for the first time worldwide, representing half of all new drug treatment entrants.

Research indicates that approximately one in five people (22%) who use cannabis will develop cannabis use disorder, with the highest risk seen in people who use cannabis daily or weekly, and in young people.

What Is Cannabis Use Disorder?

Cannabis use disorder is defined as a problematic pattern of cannabis use that leads to clinically significant impairment or distress. The condition has become increasingly concerning due to trends towards higher potency cannabis products. In the United States, THC content increased from approximately 3% in the 1980s to 17% in 2017, with some products exceeding 90% THC.

This increased potency is associated with greater harm, including increased development of psychosis and cannabis use disorder. People with cannabis use disorders typically have a long history of cannabis use and multiple previous attempts to quit.

Current Treatment Approaches

Psychological Interventions Remain Primary

Currently, psychological treatments such as cognitive behavioural therapy and motivational enhancement therapy are the only recommended treatments for cannabis use disorder. No medications are specifically approved for treating this condition.

Cannabis Use Disorder Treatment Research: Limited Evidence for Medications

The systematic review examined various pharmacological approaches, including:

• THC preparations (such as nabiximols and dronabinol)
• Cannabidiol (CBD)
• Antidepressants (SSRIs and mixed-action antidepressants)
• Anticonvulsants and mood stabilisers (including gabapentin and topiramate)
• N-acetylcysteine (a glutamatergic modulator)
• Other medications including oxytocin and various psychiatric medications

Key Findings on Cannabis Use Disorder Treatment Effectiveness

THC Preparations

Studies examining THC-based medications found moderate-certainty evidence that these preparations probably do not increase the likelihood of abstinence at the end of treatment. However, evidence suggests these medications may reduce cannabis withdrawal symptoms and cravings. Five to seven studies showed that THC preparations did not increase adverse events or treatment dropout rates.

Cannabidiol

Evidence from one or two studies suggests that cannabidiol may reduce cannabis withdrawal symptoms but does not significantly affect abstinence rates or treatment completion. The medication was well-tolerated, with no increase in adverse events. However, the evidence quality was moderate to low, and more research is needed.

Anticonvulsants and Mood Stabilisers

These medications showed a concerning pattern. Evidence from five studies indicates that withdrawal from treatment due to adverse effects was more likely with these medications. This negative effect on treatment retention may limit their clinical utility for cannabis use disorder.

N-Acetylcysteine

Two studies examining this dietary supplement found moderate to low-certainty evidence that it may not have effectiveness in treating cannabis use disorder. Results were inconclusive, and further research is needed.

Cannabis Use Disorder: Why Treatment Evidence Remains Limited

Several factors contribute to the incomplete evidence base:

Small Study Sizes

Most studies were small pilot investigations with short timeframes. The certainty in evidence was moderate in less than a third of outcomes, with approximately two-thirds rated as low or very low certainty.

Diverse Participant Populations

Studies included participants with various characteristics and comorbidities, making it difficult to generalise findings. Some studies focused on adults, others on adolescents, and participant groups ranged from those with no other health conditions to those with specific mental health diagnoses.

Variable Outcome Measures

The multitude of definitions and measures of abstinence used across studies made direct comparisons challenging. Different studies measured abstinence at different time points and used various assessment methods.

Withdrawal Symptoms and Cannabis Use Disorder

Cannabis withdrawal syndrome is now recognised in diagnostic manuals. The DSM-5 defines cannabis withdrawal by development of three or more signs and symptoms within approximately one week of cessation of heavy and prolonged cannabis use, including:

• Irritability, anger or aggression
• Nervousness or anxiety
• Sleep difficulty
• Decreased appetite or weight loss
• Restlessness
• Depressed mood
• Physical symptoms such as stomach pain, shakiness, sweating, fever, chills or headache

Onset of symptoms is usually within 24 to 48 hours of abstinence, reaching peak intensity within the first week. Symptoms may persist for up to three to four weeks, though there appears to be significant individual variability.

The Growing Treatment Demand

Demand for treatment by people with cannabis use disorders has generally increased worldwide since the mid to late 2000s. The World Drug Report 2024 shows that people with cannabis use disorders have dominated the demand for drug treatment in Africa since the mid to late 2000s, with treatment rates consistently over 60%.

Demand for cannabis use disorder treatment has grown significantly in some regions, more than doubling in Europe and South America and more than trebling in Oceania. With moves to decriminalise or legalise cannabis use in some parts of the world, the trend of increasing demand for treatment is likely to continue.

Health Consequences of Cannabis Use

Long-term or heavy use of cannabis has been associated with:

• Development of cannabis use disorder
• Chronic bronchitis
• Increased risk of chronic psychotic disorders in people with a predisposition
• Altered brain development when use is commenced early in adolescence
• Poor educational outcomes
• Cognitive impairment
• Diminished life satisfaction and achievement

Cannabis use can also increase the risk of cardiac arrhythmias, stroke and myocardial infarction. Risks of severe adverse events such as psychosis appear to be dose-dependent and are increased with the use of higher THC concentration products.

What This Means for Cannabis Use Disorder Treatment

The review’s conclusions are clear: there is incomplete evidence for all the clinically important pharmacotherapies investigated. The quality of evidence was low (44%) or very low (11%) for half of the outcomes assessed. Given the limited evidence of efficacy, pharmacotherapies should still be considered experimental for treating cannabis use disorder.

The authors note that THC preparations, cannabidiol, N-acetylcysteine and the FAAH inhibitor PF-04457845 may be of potential value, but further research is needed. However, research should determine whether pharmacotherapies based on cannabis constituents pose the same risks in the long term as chronic cannabis use, including risk for psychosis and other mental disorders.

At this point in time, psychological approaches such as motivational enhancement therapy and cognitive-behavioural therapy remain the mainstay of treatment for cannabis use disorder.

The Importance of Early Intervention

Given that approximately one in five people who use cannabis will develop cannabis use disorder, with higher risk in daily or weekly users and young people, early intervention is crucial. The earlier initiation of cannabis use, use of more potent forms of cannabis and greater use have led to increased rates of cannabis use disorders.

Understanding the risks associated with cannabis use, particularly high-potency products, is essential for preventing the development of cannabis use disorder. The increase in THC content and the trend towards higher-potency products may be factors in the increasing demand for treatment.

Conclusion

Whilst research continues into pharmacological treatments for cannabis use disorder, the current evidence base remains insufficient to guide clinical practice. Psychological interventions remain the recommended approach for treating cannabis use disorder. The growing global demand for treatment, combined with trends towards legalisation and higher-potency products, underscores the importance of evidence-based prevention strategies and continued research into effective treatments.

Source: dbrecoveryresources