How Your Genes Influence Your Response to Cannabis

Ever Smoke the Same Flower with a Friend Only to Have Completely Different Experiences? Your Genes Might Have a lot to do with it 

So, you’re at a friend’s house, and they hand you a joint. “Be careful,” your friend warns. “This flower is really strong.” You take a drag and next thing you know, you’re feeling … absolutely nothing.

Sound familiar? It illustrates a pretty common occurrence — the same toke exhibiting different effects in different folks — one for which we might have no one to blame but ourselves. Or, more accurately, our own genes.

Cannabis is able to produce a wide array of experiences in human beings. It can make us sleepy, enhance our relationships, change our perception of the world and relieve the symptoms of debilitating diseases. And while different kinds of cannabis products produce different effects, what is even more interesting is that the same cannabis product can produce very different effects among individuals.

passing a joint

For instance, in passing a joint amongst a group of friends, some people may be completely unaffected while others experience intense intoxication of one variety or another. Why is that?

Cannabis exerts its effects through many targets and mechanisms within the brain, most notably the CB1 and CB2 receptors. These receptors are proteins that are made inside of our cells, and like all other proteins our bodies make, the “blueprints” for how to build them reside in our DNA. Although the human genome (the collection of all human genes) is strikingly similar across people, random or inherited edits (mutations) in these blueprints are extremely common. Genetic mutations can often be the source of inherited diseases, and they can also account for some of the differences in people’s reaction to cannabis.

Mutations in the human CB1 receptor (the target for THC and main site of cannabis intoxication) were first observed more than a decade ago. So far, scientists have identified nine variations of this gene in humans. When the blueprints for the protein are different, the function of the protein is almost always affected.

This means that right now, you’re walking around with one of at least nine different versions of the CB1 receptor protein. In some cases, a CB1 mutation could make you more vulnerable to diseases like anorexia, Crohn’s, or addiction, but in others it could drastically alter your sensitivity to the molecules that bind to it (like THC). This could very well explain why an individual’s sensitivity to cannabis intoxication could be greater or less than the eight other friends sharing the joint.

Weedmaps 1 in 7

There are also at least seven mutations in the human FAAH gene (an enzyme that breaks down our bodies’ naturally produced cannabinoid molecules), and four mutations in the CB2 receptor. These mutations could have major health implications, and are the subject of intense ongoing research.

But genetic mutations affected by cannabis aren’t restricted to the genes involved in our endogenous cannabinoid system. For example, some people have mutations in the Akt gene (Protein kinase B, not an endocannabinoid-specific gene). This gene can keep cells from dying and inhibit tissue growth and is associated with many types of cancer. People with this mutation are more prone to make errors in judgement and motor responses after consuming cannabis. That’s because the individual’s Akt mutation changes how cannabinoids affect them.

Another important variation outside of the endocannabinoid system is found in the liver. When cannabis is ingested orally (swallowed tincture or edibles), it passes through the digestive system and liver before the cannabinoids can get into the bloodstream and brain. The liver contains many enzymes (again, proteins encoded by our DNA) that process many kinds of medications and substances. One of the more notable enzymes in the liver converts delta-9-THC into 11-hydroxy-THC, which is even more potent at activating the CB1 receptor and inducing intoxication. There are virtually countless individual differences in the efficiency and diversity of liver functions that could affect our experience with edible cannabis.

marijuana edible

The genetic mutations that change our experience of cannabis may be present from birth, but they can also occur as a result of our experiences. Genes get turned off and turned on almost constantly throughout our daily lives, in response to many stimuli (invading viruses, diet, stress, you name it). At some point in the near future, it might be possible to do a simple DNA test (swabbing the inside of your cheek) to determine what your genes look like, and what you might be able to expect from using cannabis.