How Your DNA Can Affect How Your Body Responds to Cannabis Consumption

Introduction

Hi there. This is Sean, the publisher of CannaHealth. Recently we covered 5 new, exciting products we were excited about, and I started chatting with Nicco Regente, one of the co-founders of Strain Genie. Nicco’s a sharp guy with a lot of great medical experience. I asked him if he’d be interested in contributing a monthly column here at CannaHealth.

He agreed. 🙂

I told him he could write about anything he wants at the intersection of health and cannabis, and it’s no surprised he chose this topic–a topic he is clearly passionate and very knowledgable about. 

Keep an eye out for his column every month, and enjoy!

Individual differences in reactions to cannabis

Does the following scene sound familiar? After passing a joint around a smoke circle, one person can’t stop laughing at the fact that penguins exist, another is proclaiming the profundities of J. Cole’s lyricism, and yet another is “resting their eyes”. This common setting includes an important observation amidst its amusement: the same cannabis product can affect multiple people in entirely different ways.

Naturally, aspects of an individual’s lifestyle like how much exercise they’ve been getting, their sleep patterns, and diet all play a role in how someone will respond to a cannabis product on any given day. However, the most critical factor in determining how someone will react to a particular cannabis strain or product is the makeup of their endocannabinoid system– the chemicals and neurons in your brain and body that respond to the cannabinoids and terpenes found in cannabis. DNA holds the specific instructions for how an individual’s endocannabinoid system gets “wired up” compared to other people, permitting for individual differences in reactions to cannabis.

A quick introduction to DNA 

DNA (deoxyribonucleic acid) is a long molecule that contains the instructions for building every single part of an organism. Many readers may be familiar with the term “gene”, which is simply a section of DNA that carries the codes for making and organizing specific molecules that eventually serve as the building blocks for different parts and functions of an organism. Most of the population shares the same DNA, but “variants” make us unique. Variants at specific genes have been identified as the determinants for thousands of different traits, from whether you’ll have blue or brown eyes to whether or not you’ll have Angelman syndrome. Through intense research, genetic profiles have started to be able to pinpoint more nuanced physiologies. Given the proliferation of research into medical cannabis, genetic links that can affect your response to cannabinoids and terpenes are beginning to surface.

How your DNA affects your cannabis consumption

With genes holding the instructions for the creation of enzymes and proteins that go on to make up all the constituents of your brain and body, it is a small leap of understanding to see how variants at specific genes can affect your endocannabinoid system and, subsequently, your experience with cannabis. An extreme example of this is Clinical Endocannabinoid Deficiency (CECD)—a genetic condition on the CNR1 and DAGLA genes—where the carrier’s body produces significantly less endogenous cannabinoids and receptors as compared to a healthy person. CECD presents an obvious linkage between DNA and cannabis use: if you carry a gene for CECD, you will require substantially more cannabis in order to achieve the same medical effectiveness as someone without that gene. Other genetic links that predict your response to cannabis can be a bit more insidious.

For example, there exist genes that code for the building of an enzyme that eventually goes on to break down THC (CYP2C9) and CBD (CP2C19). If an individual has a variant on these particular genes, then the construction of the enzymes that the gene codes for is impacted in a way that makes those resultant enzymes operate with 30% less effectiveness. This is a big deal; it means that consumers with those variants would be less effective in breaking down THC and/or CBD. If the THC or CBD is not broken down, then it remains in the system longer and produces “more” of the intended outcome. In fact, some pharmaceuticals are designed specifically to encourage this delay in breakdown. For example, SSRIs (Selective Serotonin Reuptake Inhibitors; the leading anti-depressant) delay the breakdown of serotonin (a positive mood regulating neurotransmitter) in the synapse (the small space that allows transmission of neurotransmitters across neurons) so that an individual’s serotonin (which is usually not as present in depressed populations) can continue to operate, yielding a “happier” person. Similarly, the sluggish breakdown of THC will result in a user feeling “higher” for longer. Unfortunately, this also creates drowsiness in users with the variant for up to three days after initial consumption.

Naturally, insights into which variants on the CYPC9 and CYP2C19 an individual has can help guide dosage and titration models as well identify which product categories to choose. For instance, a consumer that is pre-disposed to sub-optimal breakdown would be wise to choose vape products over edible since inhalation bypasses what is known as first-pass metabolism, which occurs in the liver after during digestion of edible. Such information into drug metabolism has fueled the burgeoning field of pharmacogenetics, where medical doctors take a personalized approach to pharmaceutical medication based on the patient’s DNA. This trend is now starting to make its way into the medical and recreational cannabis space.

DNA insights for personalized cannabis use

The effectiveness of cannabis as a treatment option for a wide variety or disorders and diseases, coupled with the reliability of DNA in determining an individual’s likelihood of developing a particular condition, provides an information-bridge for precision medicine with cannabis. Taking into account the tens of thousands of cannabis products and strains available on the legal market, there exist a seemingly endless number of options with varying cannabinoid and terpene ratios—the most critical variables that determine the different effects and medical benefits of cannabis.

Such a range of products, coupled with an understanding of one’s DNA, allows for a personalized product selection by connecting the dots across different research findings. These biomarkers can create even more precise recommendations that go much further than just warning an individual that they should shy away from edibles. For example, a host of genes can predispose someone to developing Alzheimer’s and dementia. On the other side of the equation, studies have shown that pinene (a terpene found in cannabis and other plants like pine trees) has a neuroprotective effect that specifically enhances memory. Cannabis users with such predispositions wanting to take preventative health measures could do so by routinely choosing cannabis products high in alpha-pinene. Similar associations exist for users with a tendency to develop schizophrenia or have psychotic episodes, where low-THC, high-CBD products can provide anti-psychotic effects. Similar reasoning applies to individuals at a high-risk for cancer being able to take advantage of  anti-cancer products that emphasize alpha-humulene, iso-caryophyllene, and beta-caryophyllene. Cannabis DNA tests (like Strain Genie) look at over 150 such biomarkers to generate personalized cannabis consumption suggestions.

There are still some glaring issues facing product and strain reliability in the cannabis industry. As such, specific product recommendations require consistent lab testing and updates, which new California legislation mandates as part of compliance. Nonetheless, insights from one’s DNA could provide a user with meaningful information when making a purchasing choice where lab testing data is available. For instance, a user likely to develop dementia could scan a lab report for products highest in alpha-pinene. This process could often yield a product different than what they found on their last trip to the dispensary due to the multitude of factors that can influence cannabinoid and terpene expression in the cannabis plant (e.g. curing method, averse weather, etc.). That’s a good perspective for consumers to have anyway; the combination of chemicals they are ingesting is far more important than loyalty to some esoteric strain. All things considered, this process is leaps and bounds more informative than simply providing a response to the standard “Sativa or Indica” question that most budtenders use to start the product selection conversation.

As regulation allows for scientists to gain access to cannabis for research studies, more insights that can help predetermine the effectiveness of cannabis use at the level of an individual is certainly on the horizon. Other avenues could also provide insights as to other aspects of cannabis use as well. For example,  new research from 2018 has even unveiled 35 genes that make you 11% more likely to be a cannabis consumer and revealed an interesting overlap in cannabis use with a gene (CADM2) that has been traditionally associated with risk taking. Information such as this, combined with genes that predispose individuals for abuse could be used to guide scheduled tolerance breaks. Regardless of the application, additional research into DNA, cannabinoids, and terpenes promises to refine the personalized approach to cannabis that all consumers should consider taking.

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