Cannabis addiction is linked to genetic variants


Some people may be genetically more predisposed than others to cannabis addiction.

A study in human volunteers found that the acute effects of cannabinoids on endophenotypes Drug-related disorders are moderated by the genes encoding the CB1 receptor and the FAAH enzyme.

La research, led by a team from University College London (UCL), linked specific variants of the cannabinoid receptor 1 (CNR1) and the fatty acid amide hydrolase gene (FAAH) to behavioral dependence predisposition measures, or endophenotypes, that are characteristic of cannabis use disorders.


The main psychoactive component of cannabis is tetrahydrocannabinol (THC), which activates the cannabinoid receptor 1 type (CB1R), encoded by the CNR1 gene. The second most abundant cannabinoid found in cannabis plants is cannabidiol (CBD), but this component has no psychoactive effects, and in fact has psychopharmacologically opposite effects to THC, although the mechanisms of action do not not fully understood. It is important to note that CBD can actually protect against the development of cannabis-related disorders and the psychotic effects of THC, so that the ratio of THC to CBD in cannabis is particularly important, said the researchers.

"We wanted to know if these genetic markers could predict addiction-related reactions after inhaling doses of cannabis, for example, how much attention is drawn to cannabis-related images," said Chandni Hindocha, principal researcher and researcher. postdoctoral research associate at the Clinical Psychopharmacology Unit at UCL. The researchers report on their studies in addiction biology in an article entitled "The acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and the FAAH enzyme."

About 9% of people who start using cannabis will develop disorders related to cannabis use, wrote the authors. Problem drug use is influenced by both environmental and genetic factors that, in the case of cannabis, may include genetic differences in the endocannabinoid system of the body, on which the drug acts. With attitudes towards cannabis use generally becoming more relaxed, there is growing evidence that it is imperative to study the differences in vulnerability and resilience to the harmful effects of drugs. "This is all the more important as cannabis is poised to join alcohol and tobacco as a legal drug around the world, which means that rates of cannabis-related disorders could also increase. .

It is interesting to note that the relative amount of THC in Cannabis has increased over the past two decades, along with higher rates of treatment demands for cannabis use disorders. In addition to acting on CB1R, CBD also increases the inhibition of FAAH, an enzyme involved in endocannabinoid signaling, which indirectly regulates the activity of CB1R. "The inhibition of FAAH is a mechanism that is currently being studied as a treatment for cannabis-related disorders in humans," the team added.

Previous studies have linked variations in the CNR1 gene with cannabis, alcohol, nicotine, and cocaine dependence, and may also be related to endophenotypes, such as reward-related brain activity. . "Thus, genetic influences can, therefore, alter other mechanisms related to disorders, such as cravings, satiety and the importance of drugs.", commented the researchers.


The team developed an experiment to determine if any of the three genetic variations of the genes encoding CB1R and FAAH had an impact on the response of individuals to acute cannabinoid administration. Forty-eight volunteers carrying genetic variations were recruited and each took a controlled dose of cannabis compounds using a vaporizer. In four sessions, participants received either a controlled dose of THC, CBD, a combination of CBD + THC, or a placebo. The researchers then assessed measures of three different endophenotypes of cannabis-related disorders while the participants were under influence. This included determining how biased participants' attention was in favor of images containing cannabis-related stimuli, compared to very close images that contained diet-related stimuli. Participants also completed a short questionnaire to assess their need for cannabis and were tested for satiety using the Bodily Symptoms Scale (Symptom scales are psychometric instruments designed to assess the frequency or severity of any type of symptom associated with a state of mental or physical health.


Although the results showed differences in the relevance of drug indices and state saturation for the three genetic variants, participants who carried one of the single nucleotide polymorphism (NHP) variants in the CB1R gene had a tendency to want more cannabis after using it, and to continue to be drawn to cannabis-related images under the influence of their inhaled dose. The results suggest that people with this genetic marker may be more prone to cannabis addiction.

"We report for the first time that the genes that code for the CB1 receptor and the FAAH enzyme are involved in the acute response of acute cannabinoid-related disorders," said the authors. "This was found for the importance of the appetite signals and the satiety of the state, but not for the urge to smoke. These findings have important pharmacogenetic implications for recreational users of cannabis who may be more vulnerable to the effects of THC and who may, therefore, be at greater risk of causing disorders. "

The team recognizes that their experiments will have to be replicated on a much larger number of people to confirm their findings. " it is important to consider these results as preliminary "Wrote the team. "Given the small size of the cells, this study was only conducted to detect small and medium effect sizes. It would be important to replicate these results with a larger sample to allow analysis of a dose-response relationship between genotype and risk. "

"We hope that our results could lead to the development of a test that could inform clinicians who are considering prescribing a cannabis-derived drug, as we learn more about the genes that affect how people are treated." react to cannabis, "said Hindocha. "Our discoveries have the potential to inform precision medicine targeting the growing clinical need to treat cannabis-related disorders," added co-author Tom Freeman, PhD, Senior Lecturer, Department of Psychology at the University of Toronto. University of Bath.

Parallel to the publication of Hindocha in Addiction Biology, a separate team from UCL published the results of studies indicating that CBD in cannabis can help compensate for the degree of action psychoactive THC. "We have now discovered that CBD appears to protect the user against some of the acute effects of THC on the brain," commented Matt Wall, PhD, of UCL's clinical psychopharmacology unit, who is lead author work.

In addition to producing a cannabis-related "high", THC can also affect memory and produce effects that increase anxiety and psychotic behavior, while studies have suggested that CBD has opposite effects to THC and is antipsychotic, and potentially anxiolytic. There is growing concern, however, that today's cannabis strains contain high levels of THC, and minimal or even minimal levels of CBD that could offset them.


The results also provide insights into why CBD can be used for medicinal purposes. "If the CBD can restore the disruption of the saliency network, it could be a neuroprotective mechanism to explain its potential to treat saliency disorders such as psychosis and addiction," added Val Curran, professor of psychopharmacology. at UCL.

source: GEN

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