Your DNA contains the instruction manual for assembling each cell in your body. Organized into actionable instructions called genes, DNA provides a code that allows the chemical soup inside your body to produce proteins needed to build and keep your body running. Variation in your DNA is what makes you different, and tiny changes in your DNA’s instruction manual can strongly affect how each cell makes and responds to important internal and external chemicals.
For example, do you think cilantro tastes like soap when everyone else sprinkles it onto their guacamole? If so, you likely possess a variant in the OR6A2 gene, which changes the way your body perceives the aldehydes that give cilantro its flavor. It should come as no surprise then that your DNA also dictates how you respond to cannabis, but how?
The endocannabinoid system
Any physiological response you have to cannabis is mediated through your endocannabinoid system. This system plays a diverse role within your body by regulating appetite, digestion, sleep, mood, and pain. However, a number of factors also influence how your endocannabinoid system works.
If you take a look at this biological system, you’ll notice that it’s made up of two receptors (CB1 and CB2), and two endocannabinoids known as anandamide (AEA) and 2-Arachidonoylglycerol (2-AG), which are all produced by the body (endo means within). In addition, the endocannabinoid system is modulated by countless other enzymes like fatty acid amide hydrolase (FAAH), a protein the body produces to break down endocannabinoids. On top of all that, any cannabinoids that enter your body also affect how your endocannabinoid system works.
With so many factors influencing this biological system, it’s clear that gene variations that encode specific proteins in the endocannabinoid system can strongly influence how you respond to cannabis. Depending on your genes and which cannabis strain or product you consume, you may be predisposed for a negative experience.
How genetics determine what dosage you need
One example illustrating how your DNA affects your response to cannabis is if you have Clinical Endocannabinoid Deficiency (CECD). This genetic condition suggests that people with chronic ailments such as migraines, irritable bowel syndrome, and fibromyalgia experience symptoms because their bodies produce fewer endocannabinoids and receptors.
However, this malfunction in the endocannabinoid system can also impact how your body responds to cannabis. If you carry a gene for CECD, you would need to increase the amount of cannabis you consume to garner a similar result as someone without the gene. Otherwise, you wouldn’t notice the effects of cannabis, leading to an ineffective experience due to dosage alone.
Research also suggests that you could be genetically predisposed to experiencing a cannabis-induced psychosis, a rare but serious condition that manifests as a result of the dosage you take. If you have variants on the DRD2 and AKT1 genes, for example, you’re more likely to develop a psychotic disorder if you consume a higher dosage of cannabis—specifically, high-THC products—and use that dosage often.
How genetics dictate the best consumption methods
The way in which you consume cannabis also has a substantial impact on your cannabis experience. Consider the CYP2C9 and CYP2C19 genes — they encode an enzyme that is responsible for breaking down CBD and THC. Variants on CYP2C9 and CYP2C19 genes, however, can decrease the effectiveness of the enzyme, making it harder for carriers of the gene variation to break down CBD and THC. How does that information apply to you?
If you have specific variants at your CYP2C9 and CYP2C19 genes, you would not want to ingest an edible, a consumption method that mandates a cycle through first-pass metabolism via the liver where those ineffective enzymes resides. If your genetics indicate that you can’t break down THC efficiently, an edible will make you experience a substantially longer and more intense high, followed by long periods of lethargy compared to someone who doesn’t carry the gene variation. Informed consumers would opt to bypass first-pass metabolism with a different consumption method (e.g. vaporizers, sublinguals).
Why personalization matters
More robust scientific research into the factors involved in the transport, function, and breakdown of cannabinoids still has to be done. But with additional analysis, you can start to choose personalized products and consumption methods that will guarantee you have a good cannabis experience each and every time.
Nicco Reggente is a co-founder of Strain Genie, a Los Angeles based startup that offers a cannabis DNA test to match patients and recreational users with the right cannabis products, strains, terpenes, and dosage recommendations.Nicco received his Ph.D. in Cognitive Neuroscience from UCLA where he focused on using machine learning and neuroimaging to predict the efficacy of treatment regimens. Nicco is passionate about bringing personalized medicine to the cannabis industry by analyzing patients and recreational users’ DNA to recommend effective cannabis remedies.