Cannabinoids Are a Promising Treatment For Cannabis Use Disorder in Young Adults, Review Finds

Cannabis use disorder (CUD) is described by the National Institute on Drug Abuse as a condition where cannabis users develop a dependence on the drug. People with CUD experience cravings and withdrawal symptoms when they are unable to use cannabis, such as feelings of anxiety, insomnia, weight loss, tremors, and mood problems.

CUD is a particular concern among youth, as cannabis use is most prevalent among teenagers and young adults. The young developing brain is also potentially at a greater risk of harm from frequent or heavy cannabis use, and so there is great interest in identifying potential avenues for the effective treatment of CUD in youth.

In a new review, recently published in the journal Neuroscience and Biobehavioral Reviews, researchers investigated the use of cannabinoid-based pharmacotherapies for the treatment of CUD in adults and evaluated whether they might also be suitable for the treatment of youth.

THC-based treatment strategies for CUD

The most researched type of cannabinoid pharmacotherapy for CUD involves the use of medicines containing synthetic THC. The principle is that, similar to nicotine replacement therapy, giving CUD sufferers a THC or THC:CBD medicine should alleviate withdrawal symptoms and disperse the craving for cannabis. These pharmaceutical THC formulations are thought to be a safer alternative to cannabis, and their use in managing withdrawal may help to facilitate continued participation in other treatment programs, such as motivational interviewing (MI) or cognitive behavioral therapy (CBT).

Searching the PubMed, Embase, and PsycInfo databases, the researchers identified 12 studies examining the use of THC-based treatment strategies for CUD. Of these, several studies using dronabinol (synthetic THC) showed promising reductions in the withdrawal symptoms reported by adults with CUD in both inpatient and outpatient settings.

In one randomized controlled trial, which used dronabinol in conjunction with weekly MI sessions, it was found that dronabinol improved treatment retention and reduced withdrawal symptoms compared to placebo. However, there were no significant effects seen on cannabis use or two-week abstinence.

Nabilone, another form of synthetic THC with a higher bioavailability than dronabinol, was also used in two studies. The first found that 6 milligram (mg) and 8 mg daily doses of nabilone could decrease withdrawal symptoms and relapse behavior in adult users. The second study, which used low doses (2 mg daily) of nabilone, found no significant effects on cannabis use compared to placebo. This could indicate that the effect of THC-based interventions is dose-dependent.

Studies evaluating the use of nabiximols (combination THC:CBD formulations) were seen to give more mixed results. Withdrawal symptoms were reduced in two of the four nabiximols studies picked up by the literature review, where cannabis use was reduced in just one randomized clinical trial.

Non-THC potential avenues for treatment

While THC-based treatment avenues show overall good promise in the treatment of adults with CUD, there are some lingering concerns about using THC products in youth with CUD. Products with high levels of THC are already known to have detrimental effects on mental health and cognitive function in young people, and so further research would need to be done to rule this out as a concern for the doses used to control cannabis cravings and withdrawal effects.

As an alternative, other non-intoxicating cannabinoids are also being investigated to see if they could play a role in treating the symptoms of cannabis withdrawal or reducing overall cannabis use.

The literature review identified two studies that had investigated CBD, the major non-intoxicating component of cannabis, for this purpose. One study saw improvements in reported depression and psychotic-like symptoms, with other improvements also seen in verbal learning and memory performance compared to baseline assessments. However, this study was not placebo-controlled.

The second study was a double-blind placebo-controlled phase 2a clinical trial, which examined higher doses of CBD (200 mg, 400 mg, or 800 mg daily) with concurrent MI sessions.

“Because it was the first trial of its kind, we didn’t know which doses might be effective or safe,” Dr Tom Freeman, an addiction researcher at the University of Bath and lead author of the CBD study, told Analytical Cannabis at the time. “So we started with a range of possible doses: 200 mg, 400mg, and 800mg per day. And we used a matched placebo.”

At the 400 mg and 800 mg doses, the researcher saw an increase in the number of days where cannabis users with moderate CUD remained abstinent, which was confirmed by lower levels of THC being present in the study participants’ urine samples.

“We know that CBD has contrasting effects to THC on the endocannabinoid system,” Freeman explained. “We know that THC is a partial agonist at cannabinoid receptors. But CBD has minimal direct activity at cannabinoid receptors.”

“At the same time, it does have properties that could be helpful in treating cannabis use disorder, such as inhibiting the effects of other ligands acting on the CB1 receptor and increasing endocannabinoids. And this is a potential mechanism through which it could be acting to alleviate the cannabis use disorder and help people cut down their use.”

A final non-THC study, which was picked up by the literature review, had looked at the effects of a fatty acid amide hydrolase (FAAH) inhibitor on cannabis use and withdrawal. FAAH is an enzyme that naturally breaks down endocannabinoids in the body, and so the idea is that inhibiting FAAH will increase endocannabinoid levels and potentially satisfy some of the craving and withdrawal effects present in CUD, thus allowing for longer periods of abstinence.

In the FAAH inhibitor study, which was a double-blind placebo-controlled phase 2a trial, treatment with the FAAH inhibitor PF-04457845 was found to result in reduced symptoms of cannabis withdrawal and reductions in self-reported cannabis use, which was confirmed by lowered THC levels in urine samples taken for the study.

Cannabinoid treatment options for young people with CUD

The authors of the literature review believe that, overall, the evidence supporting cannabinoid treatments for CUD is promising. Synthetic THC therapies appear to be effective; combination therapies are more mixed; CBD is well-tolerated and appears to help with maintaining abstinence; FAAH inhibitors are a promising new avenue that warrants further research.

In terms of how relevant these findings are to youth cannabis users with CUD, the authors feel that these cannabinoid treatments “may be more acceptable than traditional treatment (and other medications) among cannabis-using youth and adults, especially non-treatment seekers”, and so are deserving of further study. Specifically, the authors imply that low dropout rates in trials conducted using CBD compared to those using THC medications could indicate that non-THC treatments might address the current problem of low treatment uptake in youth.

No studies to date have directly examined the use of cannabinoid-based therapies in youth with CUD, and the authors say this is a “critical” next step for research. Using behavioral and cognitive assessments in conjunction with neuroimaging (MRI/fMRI) techniques would help to detect any potential adverse effects of these drugs on the young developing brain, they add, and so these techniques should also be implemented in future studies.