Your Genes & Marijuana: Friend or Foe?
Ever wonder why some people feel calm and relaxed after using marijuana, while others feel anxious and paranoid? The answer may lie in your genes.
Research has long tried to determine how our genes affect our reaction to marijuana. In celebration of Virginia’s recent legalization of recreational marijuana, we have compiled the research to tell you which genes may be affecting your response to cannabis.
The new marijuana law in Virginia moved up the date of the legalization of recreational marijuana for those 21+ from 2024 to July 1, 2021. Under this law, you can possess up to one ounce of marijuana, and be fined $25 if found with over one ounce but less than one pound. The sale of marijuana is still illegal and will be so until 2024, but the drug can be gifted to others. You can also now grow up to 4 of your own marijuana plants, but they must be tagged with the grower’s name, driver’s license or state ID number, and a notation for personal use.
Medicinal marijuana is legal for purchase in Virginia. Patients with a prescription can purchase cannabis oil with no more than 10 mg THC and 5 mg of CBD or THCA per dose from pharmaceutical processors who have gained approval from the state. A list of those sellers can be found here. Before applying for registration with the Board of Pharmacy, one must first receive written certification from a registered practitioner. Qualified professionals can be found here. For patients, registration is $50 per year and $25 for parents or legal guardians. You must renew your certification and registration annually.
But first, why use marijuana in the first place?
Marijuana is the most used drug by far in the country; and for many people, it generates a positive response. However, due to its Schedule 1 classification by the Drug Enforcement Administration (DEA), the research on the medicinal benefits of marijuana are few and far between.
As of 2021, the FDA has approved medical marijuana for the treatment of only two very severe and rare forms of epilepsy. Nonetheless, over half of US states have approved marijuana for medical use. Every day, researchers are studying to determine if medical marijuana can help treat conditions such as:
The active chemical in medical marijuana are cannabinoids, similar to chemicals made by the body that are related to memory, movement, pain, and appetite. When the chemicals enter your brain, you might feel euphoric, relaxed, creative, and amused. Or, you might feel anxious, confused, delirious, and paranoid.
How does marijuana stimulate a “high”?
The body has two types of cannabinoid receptors, CB1 and CB2. Both serve different roles and are present in different regions of the body.
CB1 → This receptor is mainly expressed in the central nervous system. It is found in the brain, specifically in the amygdala, prefrontal cortex, and hippocampus. CB1 is also present on the spinal cord and in cells in the thyroid, intestines, and fat. When you use marijuana, most of the cannabinoids bind to CB1 receptors, due to their prevalence throughout the body.
CB2 → This receptor is found in some neurons but mostly in the immune system. CB2 receptors are expressed on immune cells at 10-100 times higher than CB1. Stress and neuroinflammation appear to increase the presence of CB2, relating the receptor to depression and osteoporosis.
When cannabinoids synthesized by our body bind to the CB1 and CB2 receptors, they create acids to be used in various processes throughout the body. These acids are essential in the formation of other cannabinoids, such as anandamide. Anandamide binds to both CB1 and CB2 and assists in the generation of feelings of bliss and pleasure. When cannabinoids from marijuana bind to CB1 and CB2, for some it will produce the euphoric feelings associated with being “high.”
CB1 and CB2 are activated by THC, the psychoactive component of cannabis. But your genes can determine how effectively the molecules bind and how they are applied in the body.
CB1 and CB2 are subject to variations due to one’s genetics.
CB1 has been determined to have 15 variations. However, these variations don’t all necessarily have to do with your reaction to cannabis. For example, certain CB1 variations can make you more vulnerable to diseases like Crohn’s disease, depression, and anorexia. But other mutations will modify your reaction to THC. Certain genetic variations in the CB1 receptor will increase your likelihood of developing an addiction to cannabis and other narcotics.
Those with the C allele (the risk allele) who use cannabis during adolescence were 5.4 times more likely to persist with persistent use throughout adulthood. The C allele is also associated with an increased risk of cannabis use and addiction.
Those with the TT genotype of the CB1 gene are more likely to develop cocaine, opioid, and alcohol addiction. Females with the TT genotype are more at risk of developing a nicotine addiction.
Researchers have identified at least 7 variations in the CB2 receptor. One variant will cause a decreased expression of the receptor, which leads to increased inflammation throughout the brain and body. This variation can increase the risk for health issues like depression and osteoporosis.
Genes that affect your euphoria:
In 2009, the first clinical study on genetics and THC metabolization was performed on the CYP2C9 gene. Researchers discovered that certain variations of the gene impact how effective your body is at breaking down THC. Variations of CYP2C9 rely on either having a C or A allele. Those that had a C allele were much less efficient at breaking down THC. Two copies of the C allele caused the carrier to have three times more active THC in their system than those with AA. Having the C allele will also affect drowsiness levels and impact the time it takes for the effects of THC to completely wear off.
There is some benefit to having the CC genotype, however. After using marijuana, those with the CC variation do not have as much THC-COOH, the metabolite used to identify cannabis use in drug tests. This is because the body is not converting TCH into THC-COOH and storing it in fat. While it may take 30 days for an AA carrier to completely rid their body of THC, it will only take a CC carrier several days.
Other genes that affect the way you react to marijuana include:
The FAAH gene: This gene will impact your neurological reward response to THC, largely affecting cravings after stopping marijuana use. For those with the A allele, FAAH expression is decreased, which can lead to a greater sensitivity to CBD and an increased appetite and pain sensitivity. A genetic variation of the FAAH gene, causes hyperconnectivity between two areas of the brain’s reward system. This will cause a decrease in the regulation of cannabinoids binding to receptors. Without proper regulation, more dopamine will be released and the likelihood of developing an addiction will increase.
It is estimated that 10-30% of people struggle with marijuana addiction, and researchers hypothesize this gene is the blame
The COMT gene: This gene influences how cannabis will affect your short-term memory. Variations in the COMT gene will affect the body’s ability to carry out executive functions while under the influence of THC. The GG genotype has also been linked to decreased attention when introduced to THC. Those with the GG genotype have an increased difficulty in observation, monitoring, and completion of tasks when compared to people with the AA genotype. One variation of the COMT gene has also been linked to psychotic and schizophrenic symptoms after marijuana use.
The SLC66A gene: This gene determines a person’s decision-making skills after using marijuana. The effects of this gene are very similar to the COMT gene. Variations in genotype will affect efficiency in attention, motor skills, and executive functions under the influence of THC.
The PENK gene: This is another gene that determines a person’s likelihood of developing an addiction to cannabis. This gene is strongly expressed in regions of the brain highly relevant to addiction disorders. Researchers studying the PENK gene and addiction have found that early cannabis use will alter the expression of this gene, causing lifelong disturbances and the tendency to seek drugs later in life.
The ATK1, CNR1, and ABC1 gene: Variations in these genes are associated with the likelihood of having negative or psychosis-like symptoms under the influence of TCH. The most studied gene is ATK1, one study found that a genotype of ATK1 was associated with increased psychotomimetic symptoms when under the influence of THC. Psychotomimetic symptoms include delusions and delirium- symptoms of psychosis.
So, what now?
Obviously, as more states legalize marijuana for recreational use, overall rates of TCH use will increase. While we are not saying not to use cannabis, you should proceed with caution, as there are serious mental and physical effects if your genes do not align with the use of cannabis.