Cannabis is the most commonly used illegal drug in the world and demand for cannabis dependency treatment has increased substantially in recent years. Up to a quarter of cannabis users “meet criteria for cannabis-use disorders”. The success of agonist replacement treatments for opioids and nicotine have led scientists to think that cannabinoid agonists might be helpful for treating cannabis dependency.
This study explores the “combined effects of the synthetic cannabinoid agonist nabilone and Δ9-tetrahydrocannabinol (Δ9-THC)”. This was to “provide initial safety and tolerability data” and to establish whether drug interactions are problematic.
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The researchers used 6 subjects who first learned to tell the difference between THC and a placebo, and who were then given nabilone. They then completed a multiple choice test to “assess drug reinforcement”.
Results were promising. They were the same as a previous study, which demonstrated that “nabilone shares agonist effects with the active constituent of cannabis in cannabis users” and that nabilone would “be safe and well tolerated when combined with cannabis”.
This test replicated the findings of an earlier test, which was that nabilone had few adverse effects (heart rate increase was the most pronounced effect) in isolation or when used with THC. This is important because nabilone works as an agonist, meaning it binds to the same receptor as THC, blocking its action.
This is very useful in the world of drug dependency therapy: if someone can be administered nabilone while they are dependent on cannabis, the active ingredient, THC, will not work as well and the high becomes less appealing. Not only does the high not work but the body will not suffer as many withdrawal symptoms because nabilone mimics THC in the body.
Nabilone was found by the test subjects to have significantly different psychoactive effects to THC. Through self-reporting, the test subjects noted that nabilone and THC were different enough that they could always be told apart.
As a legal, synthetic alternative to THC, nabilone can potentially be used in therapies where THC would be inappropriate. Because it uses the same mechanism of action, nabilone can be used as an alternative. The lower psychoactivity of nabilone when compared to THC is preferable for a potential CB1 receptor targeted therapy.
Diseases such as parkinsonism, muscle spasticity, IBS, fibromyalgia, and the nausea during chemotherapy are all known to be affected positively by THC. However, THC is sometimes intolerable due to its psychoactivity. Nabilone presents a less psychoactive and potentially more tolerable alternative.
However, even though nabilone does target the same receptor, it produces slightly different effects. These need to be explored more fully.
Agonist therapy has not been well explored for use in cannabis dependency. Cannabis dependency has historically been overlooked as a serious cause of harm but there is more attention being paid to it now, especially since cannabis has been found to be addictive in a similar way that other drugs are, but to a lesser extent.
The long term efficacy, tolerability and safety of nabilone still need to be established. There is a lack of reliable data from human studies, both for cannabinoids and synthetic cannabinoids, and the scientific record needs to be substantially filled before the full uses and safety profile can be established.
Nabilone looks like a safe and tolerable drug that has definite applications in cannabis dependency agonist therapy and other applications where the administration of THC would be inappropriate or illegal. Synthetic cannabinoids represent a wealth of possible interactions with the endocannabinoid system, with the potential for many different therapies being explored.
The authors think that future studies should focus on determining if “nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use.”