Cannabis and human genetics

Dr Sona A Pungavkar
Cannabis has been used since centuries for the various experiences,that it is capable in producing in humans, by it’s ability to change the mood. It can make one sleepy, happy, change one’s perception of the world, and can also be used as a medicine to help in relieving harsh symptoms of chronic and terminal diseases. And while different effects are seen and known, one important point that has to be focussed on, is that the same cannabis product can produce different effects in different people.
For instance, in a group of pot-smokers, the same joint could leave some people unaffected, make some ecstatic, make some laugh or make some cry. Research is now directed to find out what controls the variations in the effect caused by Cannabis in individuals.
So, let’s begin with a question as to why do a few people feel good with Cannabis, some don’t feel any change and some feel worse, while some feel so good that they get addicted? All substance abuse conditions, including Cannabis, have environmental and genetic causes. Studies have indicated that 51 to 70 % of the effect of Cannabis, on an individual, is linked to the genetic make up.
While 91% individuals do not face any issues when they stop using Cannabis,  approximately 9 % of the users, or one in every ten users, develop drug dependency in the form of cravings, when they discontinue the use of Cannabis.
The entire set of genes, also called as human genome, is usually similar in most human beings. Mutations or alterations, due to inheritance or even without any known cause, can occur within the genome, causing mild variations in the phenotype or manifestations of the genetic signature, eg. colour of eyes, hair, height etc.
Genetic mutations can lead to several inherited diseases, and may also explain the diversity in the responses of people to Cannabis.
A study was conducted in Denmark, headed by Dr Ditte Demontis of Aarhus University, in which genomes of 2000 Danish people who were dependent on Cannabis, were compared with 50000 people who were not dependent. This study was repeated in 5500 Icelandic dependent and 3,00,000 control subjects to verify the results. A genetic variation, also called as a mutation, linked to nicotine receptor encoding gene CHRNA2 (cholinergic receptor nicotinic á2 subunit), was found in the dependent individuals, in this study published in Nature Neuroscience in June 2017.
The individuals with mutation have reduced number of nicotine receptors in the brain, though the link between the mutation and cannabis addiction has not been established and only a correlation has been documented.
The inference is that, the presence of this gene mutation in an individual does not lead him or her to become a Cannabis user, but may explain, why some people are more likely to become dependent, if they try using Cannabis.
As this research is limited to north Europe, there is a need to study the genomic pattern in individuals in the rest of the world. 
Other researchers are trying to check their databases for this gene and discover other genes, which could be responsible to the reaction produced by Cannabis in an individual.
A psychiatry professor at Yale School of Medicine, Joel Gelernter, suggests that there could be shared genetic risk in individuals who are schizophrenic and Cannabis abuse, based on previous research in which an inverse relationship has been established between the two conditions.
The action of Cannabis in the brain and body is mediated through various ways, commonest, being via the receptors called as CB1 and CB2. The production of these receptors is linked to our DNA or our genes.  At least fifteen variations have been found in the human CB1 receptor, some of which could lead to diseases such as Crohn’s, anorexia or it could reduce sensitivity to molecules, which are known to bind with them, such as tetrahydrocannabidiol (THC). Thus, it could explain why one pot-smoker in a group of 15 individuals experience more or less high, than the other people using the same joint.
Also known are seven mutations in CB2 receptors and eleven mutations in the FAAH gene (enzyme responsible for the breakdown of the natural cannabinoids).
Other than genetic alterations affecting the cannabinoid system, genes affecting few other body systems could also be involved in the variable response to Cannabis.
For example, the Akt gene (protein kinase B) prevents cells from dying and inhibits tissue growth and is associated with various cancers. Mutational change in the Akt gene affects how people react to the cannabinoids. These people are more prone to making errors in judgement and motor responses after consuming cannabis.
Enzymes in the liver (also encoded by a genetic signature) can affect, how people respond after ingesting Cannabis. Cannabis ingested in the form of tincture, capsules and edibles, passes through the digestive system and liver before being released into the blood and reaching the brain. Delta-9-THC, the psycho-active cannabinoid, is converted into 11-hydroxy-THC, an even more potent psycho-active agent, which in turns activates the CB1 receptor and induces intoxication. Also, liver dysfunction due to various causes can bring about a different effect in an individual depending on how Cannabis is metabolized.
It may soon be possible to do a simple DNA test (obtaining a swab from the buccal mucosa) to determine the genetic code, prevent certain genetic diseases from evolving, and prediciting response that could be expected in an individual using Cannabis.
The author is a Cannabis researcher, a senior radiologist and Vice President, Cannabis Health and Sciences.