Hopeful Research into Cannabis Treatment for Cannabis Dependency
Whether you believe you’re addicted to cannabis, or severely dependent on it, if you’re trying to reduce consumption and have been unable to do so with behavioral therapy alone, there may be some hopeful news. Researchers at the University of Sydney have found promising results from their study of a cannabinoid agonist medication that targets brain receptors in reducing cannabis relapse rates.
The study, which was published in the JAMA Internal Medicine noted that cannabis is the most widely-used psychoactive substance worldwide, with some 10% of Australians saying they’ve consumed it in the last year. About 10% of those individuals reported patterns of use that were dependent.
Yet, existing cannabis dependence treatments are ineffective, with relapse rates of about 80% within 6 months to a year of cannabis withdrawal or psychotherapy in the form of cognitive behavioral therapy (CBT). Therefore, there’s a great deal of interest in a cannabinoid agonist medication that may be combined with CBT to help improve treatment outcomes and reduce relapse rates.
To gain more insight into this research, I spoke with the study’s lead author, Conjoint Professor Nicholas Lintzeris, of the University of Sydney’s Faculty of Medicine and Health, and Director of Drug & Alcohol Services at the South East Sydney Local Health District.
Describe what led your team to study using nabiximols in connection with cannabis dependency?
Nicholas Lintzeris: There is a long history of studies looking at different medication approaches for cannabis dependence. Researchers have looked at a wide variety of different types of medications (e.g. antidepressants), although none have shown much promise across studies. In contrast, researchers over the past 10 years have been looking at cannabinoid medications, such as THC-based medications, and these have shown considerable promise. Nabiximols is particularly interesting, as it is a combination of THC and CBD extracted from cannabis plants. CBD dampens some of the side effects of THC (e.g. anxiety, paranoia) and may be considered a safer combination of cannabinoids than high-THC cannabis that predominates in illicit markets in countries such as Australia. Nabiximols also has the advantage of being an oral spray, avoiding the need for patients to smoke cannabis. Finally, nabiximols is licensed in many countries (for multiple sclerosis) and it is always easier to undertake research with a licensed pharmaceutical medication than unlicensed products.
More broadly, the concept of replacement therapy, whereby we prescribe patients a safer form of the drug on which they are dependent, is common in addiction treatment. We use this approach widely in treating nicotine dependence (e.g. nicotine patches) and heroin dependence (e.g. methadone treatment). The rationale is that the medication enables patients to make the behavioral lifestyle changes necessary in stopping an addiction (e.g. routine patterns of behavior, links to certain social networks, etc.), while gradually reducing the medication over time, such that withdrawal and cravings are minimized. This approach is extremely effective in treating other drugs of addiction, and we were optimistic this would also work in treating cannabis dependence.
What did you learn from that first study that helped shape the latest research you did on how using nabiximols can help cannabis users make long-term behavioral changes?
NL: The first study (Allsop et al., 2014) looked at a short course (5 days) of nabiximols compared to placebo in an inpatient withdrawal unit to see whether nabiximols could successfully reduce withdrawal severity, the doses we needed to use, and whether it would be tolerated by cannabis-dependent patients. While all the data indicated that [use of] nabiximols was very effective in managing cannabis withdrawal, when we followed up with patients a month after discharge, most had relapsed to heavy cannabis use. That did not discourage us, as this is the normal course following detox from any drug. Most people relapse if they do not engage in ongoing treatment.
While the first study demonstrated that nabiximols was pharmacologically effective, we needed a more robust treatment model to help patients address their cannabis dependence on a longer-term basis. Hence, the recent study combined nabiximols with counseling and case management approaches over a 12-week period.
What’s in the nabiximols spray, such as concentration/type of CBD and THC?
NL: Nabiximols is a combination of plant-extracted THC and CBD in approximately equal proportions. Each spray contains about 2.5 mg of THC and 2.5 mg CBD, and it is administered as a spray into the mouth to be absorbed across the mucosa (lining) in the mouth. This reduces the extent to which the liver breaks down the drugs before reaching the brain, and is a much more efficient way of administering THC and CBD. We were using on average 20 sprays a day, which is equivalent to about 50 mg THC and 50 mg CBD. This is much higher than when treating patients without regular cannabis use and reflects the phenomenon of tolerance.
How, specifically, does the nabiximols spray work?
NL: In this context, patients were seeking to stop their use of illicit cannabis. The nabiximols alleviates withdrawal and cravings that they would normally experience when stopping cannabis use and allows them to start making the lifestyle and behavioral changes required to deal with addiction. This was supported through counseling approaches (cognitive behavioral therapy-based counseling) and case management that identified and started to address some of the other health and social concerns that patients may have.
With time, patients can reduce the medication and cope with any minor withdrawal discomfort. This is a very similar approach to how we use nicotine replacement to assist patients to stop tobacco use.
Is the nabiximols spray in any way addictive, or are there any potential or recorded negative or adverse effects to using this treatment?
NL: Perhaps surprisingly, we examined the effects of nabiximols in the patient group and identified no significant cognitive impairment or intoxication following routine dosing. The medication was enough to prevent withdrawal, has a slow onset of effect (compared to smoking a joint or a bong) and resulted in minimal intoxication. The nabiximols was well tolerated in these patients – even at such high doses. This suggests that the medication can be used for this indication and enable patients to continue to function in their routine daily activities.
Nabiximols contains THC and, with long-term use, some patients will develop dependence to it. In our context, patients were already dependent on cannabis, and we were using the nabiximols spray a relatively short period (12 weeks), so long-term dependence was not a concern.
How long before this product will be in the marketplace?
NL: Nabiximols is already approved in Australia for multiple sclerosis. Technically, an Australian doctor can prescribe nabiximols today. However, because THC is a Schedule 8 medication in Australia (same scheduling as opioids), doctors need authorization from their local health department to prescribe nabiximols. Also, since nabiximols is not subsidized in Australia, the cost may be prohibitive for many patents. Furthermore, the medication is not licensed for treatment of cannabis dependence, so it would be considered “off label” prescribing. Off label prescribing is legitimate in medicine where a doctor has enough evidence of efficacy and safety, and where the patient understands that the medication is not licensed for the indication. We believe that the findings of this and previous studies are providing the evidence to support off-label prescribing of nabiximols for cannabis dependence. There are two randomized controlled trials now supporting the use of nabiximols for cannabis dependence, and a further pilot study from Canada is also consistent with our findings. A pharmaceutical company usually applies to the regulating body (in Australia, it’s called the TGA; in the U.S., it’s the FDA) to have a medication licensed for a particular indication.
Kane, S. (2019). Hopeful Research into Cannabis Treatment for Cannabis Dependency. Psych Central. Retrieved on April 8, 2020, from https://psychcentral.com/lib/hopeful-research-into-cannabis-treatment-for-cannabis-dependency/