Cannabis is able to produce a wide array of experiences in human beings. It can make us sleepy, alter our interactions with people, 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.
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 depending on marijuana sensitivity and different reactions to weed.
Can some people be immune to weed?
Cannabis exerts its effects through many targets and mechanisms within the brain and body, most notably the CB1 and CB2 receptor sites. 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 reactions 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 15 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 15 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 explain why an individual's sensitivity to cannabis intoxication could be greater or lesser than the 14 other friends sharing the joint.
There are also at least 11 mutations in the human FAAH gene (an enzyme that breaks down our bodies' naturally produced cannabinoid molecules), and at least seven mutations in the CB2 receptor. These mutations could have major health implications, and are the subject of intense ongoing research.
But genetic mutations that affect the cannabis experience 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, capsules, 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.
The genetic mutations that change our experiences of cannabis may be present from birth, but they can also occur as a result of day-to-day life. Genes get turned off and 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, how to solve certain genetic diseases, and what you might be able to expect from using cannabis.
Major contributions from Dr. Adie Rae.