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Cannabis addiction is linked to genetic variants

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

A study in human volunteers found that the acute effects of cannabinoids on endophenotypes linked to drug addiction are moderated by the genes coding for the CB1 receptor and the FAAH enzyme.

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

decryption

The main psychoactive component of cannabis is tetrahydrocannabinol (THC), which activates the cannabinoid receptor type 1 (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 are not fully understood. It is important to note that CBD may actually protect against the development of cannabis-related disorders and the psychotic effects of THC, so the ratio of THC to CBD in cannabis is particularly important, said researchers.

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

About 9% of people who start using cannabis will develop cannabis use disorders, the authors wrote. Problematic drug use is influenced by both environmental and genetic factors which, in the case of cannabis, may include genetic differences in the body's endocannabinoid system, on which the drug acts. With attitudes towards cannabis use generally becoming more relaxed, it is becoming increasingly evident that it is imperative to study the differences in vulnerability and resilience to the harmful effects of the drug. "This is all the more important as cannabis is on the verge of joining alcohol and tobacco as a legal drug worldwide, which means that rates of cannabis use 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 requests for cannabis use disorder. 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. "FAAH inhibition is a mechanism that is currently being studied as a treatment for cannabis use disorders in humans," added the team.

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

Experience

The team developed an experiment to determine whether one of the three genetic variations of the genes coding for CB1R and FAAH had an impact on the response of individuals to acute administration of cannabinoids. Forty-eight volunteers carrying genetic variations were recruited and each took a controlled dose of cannabis compounds using a spray bottle. During four sessions, participants received either a controlled dose of THC, CBD, a combination of CBD + THC, or a placebo. The researchers then evaluated the measures of three different endophenotypes of cannabis use disorders while the participants were under the influence. This included determining the extent to which participants' attention was biased towards 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.

Result

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

"We are reporting for the first time that the genes that code for the CB1 receptor and the FAAH enzyme are involved in the acute response to disorders associated with acute cannabinoid use," said the authors. “It was found for the importance of appetite signals and state satiety, but not for the urge to smoke. These results have important pharmacogenetic implications for recreational cannabis users who may be more vulnerable to the effects of THC and who may therefore be at greater risk of causing a disorder. ”

The team recognizes that their experiences will need to be replicated on a much larger number of people to confirm their conclusions. " 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 reproduce these results with a larger sample to allow the analysis of a dose-response relationship between the genotype and the 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 respond to cannabis, "said Hindocha. "Our discoveries have the potential to shed light on precision medicine targeting the growing clinical need for the treatment of cannabis use disorders," added co-author Tom Freeman, PhD, senior lecturer, department of psychology at 'University of Bath.

In addition 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 THC psychoactive. "We have now discovered that CBD appears to protect the user from some of the acute effects of THC on the brain," commented Matt Wall, PhD, from the clinical psychopharmacology unit at UCL, who is the lead author. work.

In addition to producing a cannabis-related high, THC can also affect memory and produce effects that increase anxiety and cause 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, if not minimal, levels of CBD that could counterbalance them.

Conclusion

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

source: GEN

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