It is not unusual to meet people who claim cannabis that doesn’t do anything for them. No matter how hard you try to convince them of the calming and relaxing effects of marijuana, they insist that they just don’t get it. Some of these people even say that instead of feeling good, they experience the exact opposite reaction, even to the point of decreasing their feelings of happiness. To people who take cannabis to lower their anxieties, it is difficult to understand people getting anxiety from smoking pot.
Apparently, it’s not cannabis that causes this reaction per se. According to published studies, yes, cannabidiol (CBD) and tetrahydrocannabinol (THC), the main cannabinoids in marijuana, do have counteractive effects on each other – THC induces anxiety while CBD relieves it – but there is another piece to the puzzle. In a study published in Nature Communications last year, researchers from Weill Cornell Medical College hypothesized that there is a genetic variation in the brain which makes people inherent to be anxious or less anxious and this mutation relates to individual cannabis effects.
Before we discuss the gene variation, let’s backtrack a bit on the endocannabinoid system. The endocannabinoid system is named so because the active drug in cannabis (THC) is structurally related to anandamide. Anandamide is the major naturally occuring cannabinoid in the brain. It produces a calming effect when it binds to the cannabinoid receptor – which is the same target of marijuana to produce its calming effect.
Anandamide is broken down or deactivated by the enzyme, fatty acid amide hydrolase (FAAH). Everyone has anandamide but there’s a variation of the FAAH enzyme among people – there are people with a genetic mutation of having less FAAH. Less of this enzyme leads to less breakdown of anandamide. Individuals with this variant FAAH gene tend to have more anandamide in their brains and are, in turn, less anxious and less predisposed to like cannabis. The explanation in the current study is that you have little use for cannabis if you naturally have more of the real thing in your brain.
Those with the normal variant gene, on the other hand, find marijuana pleasurable and suffer withdrawals when they quit using it. To illustrate this more clearly, portion of the data from one of the communities studies had 2,100 volunteers where people with the variant gene only demonstrated 11% of cannabis dependence versus 26% with no mutant gene.
Other scientists have expressed opinions about how this hypothesis is an extreme reductionism of genetic accounts of complex characteristics and behaviors. However, the general science community is excited about the implications of this study. These current findings may just be a small part of a bigger story in addiction biology: having the FAAH gene mutation basically predisposes one to be able to say no to cannabis and generally protects from marijuana dependence. This idea translates to genetic variation in other receptors like the mu opioid receptor and that it may also be protective against opiate addiction.
The occurrence of this advantageous FAAH mutation differs across all ethnic groups. Carriers of this gene variant is roughly 21% Americans of European descent, 14% Han Chinese, and 45% of Yoruba Nigerians. So the next time you invite one of these guys to smoke but he refuses because it makes him anxious, it would probably be best to take his word for it.