Rationale for Genetically Guided Cannabis Therapy
By Janna Champagne, BSN, RN
I was first introduced to the topic of Epigenetics in 2008 at a business conference in Florida, and as a medical professional I was immediately intrigued. Epigenetics is defined as the environmental impact on gene expression, which explains how genes can be influenced to alter our genetic health expression (like an on/off switch).
Depending on the environmental factors, this interaction may result in positive (i.e.: nutrition) or negative (ie: toxic exposure) impacts on our health. Very exciting as this exemplifies that our overall health is not determined solely based on what our parents contributed. Instead we as individuals have the ability to positively affect our inherited risk factors for familial diseases, by applying components that exert a beneficial influence on our genetic predisposition (1).
Correctly applied Nutrigenomics (genetically-individualized nutrition) is one example with the potential to improve your genetic predisposition to illness, and halt many contributing factors of disease states (1). Basically, this means that positive environmental influences can switch off gene expression that may contribute to illness. This supports what we’ve known for a long time: that given what it needs, the body can balance and heal itself.
Over the years of helping clients optimize their health through nutrigenomics, I’ve seen some amazing results including successful weaning off harmful pharmaceuticals, and reversals of difficult to treat conditions (ie: cancer, autoimmune). My knowledge of Epigenetics has has since crossed over another area of passion: medical cannabis therapy.
Contrary to it’s abhorrent social reputation the last century or so, cannabis is proving to be a source of vital nutrients needed to maintain balance in the body, and is therefore a perfect compliment to almost any nutrigenomic regimen. Of course, unique varieties of cannabis exert varying effects on individuals, an issue that may be solved through a new process that allows for genetic individualization of cannabis therapy.
As you may have already guessed, the subject of genetically guided cannabis therapy is very cutting edge and a bit complex. It’s the overlap of several emerging sciences combined: the endocannabinoid system, human genetics, cannabis genetics and botany are all in the mix. If this intrigues you, then you’re definitely a kindred cannabis nerd.
Here’s a little background info: All humans have an Endocannabinoid System (ECS), which is so important that it’s widely argued that life would not be possible without this master control system (1). The ECS produces endocannabinoids that interact with our ECS receptors, which then work to promote overall balance throughout our bodies. Endocannabinoids are even found in breastmilk, and research supports that they promote newborn survival, making them a vital nutrient for humans (4).
The role of the ECS is homeostasis or balance, and the underlying cause of most chronic illness is imbalance(s) (2). Endocannabinoid deficiency is exemplified in research as a leading underlying cause of chronic illness, reflecting that rampant underlying imbalances in the body contribute to every chronic illness state (5). Cannabis supplementation can help fill the nutrient gaps created by endocannabinoid deficiency, while promoting homeostasis in the area(s) of imbalance, thereby potentially improving this contributing factor.
This explains how cannabis therapy may be beneficial in those suffering a chronic illness, and from experience it’s often more helpful than pharmaceuticals (which have harmful side effects and rarely promote true healing). That’s because the cannabis plant contains the most prolific source of phytocannabinoids, which are able to improve endocannabinoid deficiency symptoms by activating the human ECS. Phytocannabinoids from the cannabis plant exactly mimic the endocannabinoids we produce internally, making cannabis a common sense approach to improving chronic illness outcomes (3).
Endocannabinoid deficiency is especially prevalent in today’s society thanks to nearly a century of cannabis prohibition. The ECS deficiency state often results from a perfect storm of individual gene mutations negatively influencing ECS receptors, along with lacking intake of vital cannabinoid nutrients (ie: cannabis).
Each individual has a unique genetic profile that specifically reflects which cannabinoids may be deficient, representing limitless combinations of optimal cannabis formulations. The cannabis plant contains 144 cannabinoids and 200+ terpenes, thereby providing a broad spectrum of the cannabinoids needed to fill an individual’s ECS deficiency profile (6).
Assessing an individual’s genetics specific to the Endocannabinoid System (including other system pathways that overlap) helps to guide cannabis therapy. Using genetic information to formulate a unique cannabis blend can decrease the “trial and error” phase upon starting cannabis, and provide more consistency in improving patient outcomes.
There are several pathways assessed to determine which cannabis components might best fit an individual’s needs, and genes considered include those from the following pathways (6):
-Serotonin/Dopamine and GABA/Glutamate -Neurotransmitter pathways (cannabinoid profiling, terpene guidance) 9
-Vitamin d3/gcmaf (ECS receptors affected) 10
-Choline pathways (mutation predispose ECS deficiency) 11
-Immune system pathways (for targeted cannabinoid therapy) 12
-AKT1/Schizophrenia predisposition-only known contraindication to THC (13)
-Methylation pathways (addressing mutations mitigates risk factors) 7
and many more…
Genetics are important, but it’s equally imperative to work with a medical professional that understands the basis of the individual’s condition(s), plus any other unique considerations such as medications, symptoms, and lifespan risk factors. Mitigating as many contributing factors as possible, balancing risk vs benefit, and assessing client goals as a holistic process reinforces optimal medical outcomes.
This process of genetic screening is especially important in pediatric applications of cannabis therapy, because methylation pathway mutations predispose neurodevelopmental risks with childhood/adolescent use of cannabis (7). Methylation mutations are linked with chronic illness (the main reason most seek cannabis therapy for a minor child), and these mutations also increase the risk for neurological deficits with cannabis use, making this is a common consideration for minors who may benefit from cannabis therapy.
TO BE VERY CLEAR: This doesn’t mean that children and adolescents with methylation issues shouldn’t use medical cannabis when it’s indicated. Instead this supports that methylation should be optimized with targeted supplementation (nutrigenomics) to mitigate this risk factor. This legitimizes the importance of genetic screening for methylation mutations, especially in children and adolescents that may benefit from cannabis therapy.
What is methylation exactly? The technical term methylation is used to describe a chemical reaction where a methyl donor is required for optimal completion of the chemical cycle. When a person has a methylation mutation (ie: mthfr), the result is a deficiency in methyl donors, which are required for a wide variety of mechanisms in the body. Common results of methyl donor deficiency include inflammation, and dysfunction in both the immune system and detoxification ability (8).
Luckily there are knowledgeable medical nutrigenomic practitioners (like myself) who are able to advise how to decrease this methylation/cannabis pediatric risk factor, through genetic screening that is accessible to most everyone. The cost of testing is affordable, and in the form of a saliva kit submitted by mail, which doesn’t require a physician order.
One more aspect I want to touch on, from my holistic nurse perspective of addressing as many contributing factors as possible. In addition to applying epigenetic screening to guide cannabis therapy, full genome testing can be used to optimize many additional pathway mutations implicated in chronic illness states.
My favorite analogy to describe the potential of combining nutrigenomics and cannabis therapy is a sink that’s overflowing with imbalances, leading to illness symptoms. Starting cannabis therapy helps the body start balancing, and can be likened to taking the plug out of the drain in this overflowing sink scenario. Applied nutrigenomics can turn off the running faucet. Powerful duo for chronic illness indeed.
My hope is to spread knowledge about this very pertinent issue, so that patients and medical professionals alike are aware of the power of using human genetics to guide cannabis therapy. I truly believe this represents the future of cannabis as medicine, which offers our best possibility for healing the widespread chronic illness found in our society today.
1. Watters, E.(2008) DNA is not destiny. Accessed online at: http://www.geneimprint.com/media/pdfs/1162334912_fulltext.pdf
2. Piomeli, Daniele (2002). The molecular logic of endocannabinoid signaling. Nature Reviews Neuroscience 4, 873-884 (November 2003). https://www.nature.com/nrn/journal/v4/n11/full/nrn1247.html
3. Department of Chemistry, Kennesaw State University, 1000 Chastain Road, Kennesaw, GA 30144, USA (2002). Endocannabinoid structure-activity relationships for interaction at the cannabinoid receptors. Prostaglandins Leukot Essent Fatty Acids. 2002 Feb-Mar;66(2-3):143-60. https://www.ncbi.nlm.nih.gov/pubmed/12052032
4. Grant, I., & Cahn, B. R. (2005). Cannabis and endocannabinoid modulators: Therapeutic promises and challenges. Clinical Neuroscience Research, 5(2-4), 185–199. http://doi.org/10.1016/j.cnr.2005.08.015
5. Smith, SC, Wagner, MS(2014). Clinical endocannabinoid deficiency (CECD) revisited: can this concept explain the therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2014;35(3):198-201. https://www.ncbi.nlm.nih.gov/pubmed/24977967
6. DiMarzo, V., Lutz. B.(2014). Genetic dissection of the endocannabinoid system and how it changed our knowledge of cannabinoid pharmacology and mammalian physiology. http://onlinelibrary.wiley.com/doi/10.1002/9781118451281.ch4/summary
7.Neuroscience & Biobehavioral Reviews. High times for cannabis: Epigenetic imprint and its legacy on brain and behavior. Neuroscience & Biobehavioral Reviews, May 12, 2017. http://www.sciencedirect.com/science/article/pii/S0149763417300659
8. Lertratanangkoon K, Wu CJ, Savaraj N, Thomas ML. Alterations of DNA methylation by glutathione depletion. Cancer Lett. 1997 Dec 9;120(2):149-56. https://www.ncbi.nlm.nih.gov/pubmed/9461031
9. Sammit, S., Owen, MJ, Evand, J., et al (1995). Cannabis, COMT and psychotic experiences. Br J Psychiatry. 2011 Nov;199(5):380-5. https://www.ncbi.nlm.nih.gov/pubmed/21947654
10. Siniscalco, D., Bradstreet, J., et al (2014). The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages. Journal of Neuroinflammation 2014, 11:78. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996516/
11. Basavarajappa, B. S. (2007). Neuropharmacology of the Endocannabinoid Signaling System-Molecular Mechanisms, Biological Actions and Synaptic Plasticity. Current Neuropharmacology, 5(2), 81–97.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2139910/
12. Cabral GA1, Staab A.(2005). Cannabis effects on the immune system. Handb Exp Pharmacol. 2005;(168):385-423. https://www.ncbi.nlm.nih.gov/pubmed/16596782
13. DiForti, M., et al (2012). Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users. Biol Psychiatry. 2012 Nov 15;72(10):811-6. https://www.ncbi.nlm.nih.gov/pubmed/22831980