Researchers has isolated a gene associated with cannabis use disorder (CUD)


A large team of researchers with members from Denmark, Iceland and the U.S. has isolated a gene associated with cannabis use disorder (CUD).

In their paper published in the journal Nature Neuroscience, the group describes their genome-wide association study surrounding CUD and what they found.

For many years, users of cannabis claimed that it was not addictive. More recent research has suggested that such claims are both right and wrong.

Most people who consume cannabis do not become addicted, but some do.

Prior research has found that approximately 10 percent of users have CUD – when they stop using cannabis, they experience withdrawal symptoms similar in some respects to withdrawal from other drugs.

Symptoms include cravings and engaging in behavior to fulfill their need.

This finding has added evidence to theories that there is a genetic component involved in addiction.

In this new effort, the researchers sought to find that possible genetic component for CUD.

To isolate the possible gene or genes involved, the researchers tapped into a European genome database to compare the genomes of 2,000 people known to have CUD against another 50,000 people who it was assumed did not have the condition.

The researchers found a gene variant called CHRNA2.

The team followed up those findings by carrying out the same kind of comparison with an Icelandic database – in that instance, they were able to compare the genomes of 5,500 people who had CUD against 30,0000 controls.

They report that they found the same result – the gene variant CHRNA2.

The researchers are quick to point out that having the gene does not turn someone into a pot smoker – instead, it makes them more likely to become addicted to it if they start using it.

They also note that they believe the gene they isolated is likely one among several that are involved in cannabis addiction.

But they suggest that their findings could contribute to other studies that seek to understand the nature of addiction and perhaps lead to a treatment for people with CUD who are struggling with their addiction.

With about 166 million annual consumers (equivalent to 3.9% of the global population aged 15 to 64), cannabis is the most widely consumed illicit drug worldwide, and by far the illicit drug most commonly consumed by young people (1).

Furthermore, a broad estimation suggests that in Europe about 1% of people consume cannabis almost daily, and several European countries have reported an increase in the number of regular or intensive users (2).

Cannabis use can lead to social harms, including accidents, violence and suicide attempts (3), and regular cannabis use can lead to physical or psychological problems, and has been found to interfere with family, school, and work (48).

Law enforcement, public health costs and loss of productivity and work potential due to health problems are also an economic drain on society (25).

According to the United Nations Office on Drugs and Crime (1), cannabis use is among the most common primary reasons for entering drug related treatment.

Furthermore, cannabis use often precedes the use of other drugs, which suggests that cannabis may cause further problems as a gateway drug (911). However, the exact nature of the association between cannabis use and subsequent other illicit drug use is unclear (1214).

To deal with the problems associated with cannabis use, it is important to understand what causes some individuals to initiate cannabis use and what causes some of those individuals to become regular users or become dependent on it.

Though there may be some completely random events that cause people to vary in their cannabis use (such as changes in availability of the drug), much of the variability is likely to be due both to the nature of the environment they live in and developed in, and to their genetic makeup.

It has long been recognised that risk of cannabis and other substance (ab)use runs in families.

Studies aiming to understand the basis of familial risk include family studies, adoption studies, and twin studies.

Family studies into cannabis use have shown moderate parent-offspring correlations (ranging between 0.30 and 0.59; (1518) as well as sibling-sibling correlations (ranging between 0.39 and 0.59 (1519)).

In a recent study, Merikangas et al. (20) found elevated risks for cannabis use disorders among siblings (odds ratio [OR] = 3.6), offspring (OR = 6.9), and spouses (OR = 4.4) of probands with cannabis use disorders. However, family studies cannot determine whether familial resemblance is due to genetic factors or environmental factors shared between family members.

Adoption studies can distinguish genetic and shared environmental factors by comparing the similarity of the adopted child with its adopted parents and with its biological parents.

To our knowledge, no adoption study has specifically examined cannabis use, but adoption studies into drug and alcohol use have found that abuse or dependence of adoptees is more related to abuse or dependence of their biological parents than their adoptive parents (2126), indicating an important role for genetic factors.

Twin studies disentangle familial resemblance into genetic and shared environmental factors by comparing the similarity of identical (monozygotic; MZ) and non-identical (dizygotic; DZ) twins.

There have been numerous twin studies into cannabis use, but due to considerable variation in the results it is difficult to draw clear conclusions regarding the relative magnitude of genetic and environmental influences.

Estimates of the proportion of variance in cannabis use accounted for by genetic influences (i.e., heritability) range from close to zero (e.g., studies 2728) to over 60% (e.g., studies 293031).

Similarly, estimates of the proportion of variance accounted for by shared environmental factors range from zero (e.g., 3032) to 68% (28).

Inconsistent results have also been found for problematic cannabis use ((symptoms of) abuse and dependence).

Various explanations could be proposed for these inconsistent results, including differences in measurement scales, sample size, and demographic differences (age, sex, nationality, socioeconomic status).

In particular, very large sample sizes are required to accurately estimate genetic and shared environmental influences when using dichotomous variables (which is the case in most cannabis use studies).

For this reason, many of the individual studies barely had the power to statistically distinguish between genetic and shared environmental influences, and confidence intervals around the estimates were often very wide.

Here we carried out a meta-analysis of existing twin studies in order to provide a more accurate estimate of the magnitude of genetic and environmental influences on cannabis use initiation and problematic cannabis use ((symptoms of) abuse/dependence).

Because cannabis use in general is more prevalent among males than females (2), and some twin studies reported sex differences in contributions of genetic and environmental factors (e.g., 3334), meta-analyses were carried out separate for males and females, in order to check for sex-differences in cannabis use etiology.

More information: Ditte Demontis et al. Genome-wide association study implicates CHRNA2 in cannabis use disorder, Nature Neuroscience(2019). DOI: 10.1038/s41593-019-0416-1

Journal information:Nature Neuroscience


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