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 exposures, this interaction may result in positive (i.e.: nutrition) or negative (ie: toxins) impacts on our health.
Pretty exciting, since this means 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 (1).
Correctly applied Nutrigenomics (genetically-individualized nutrition) is a positive environmental factor with the potential to improve your genetic predisposition to illness, and slow or halt many contributing factors of disease (1). 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 and other alternatives to pharma, I’ve seen some amazing results like successful weaning off harmful pharmaceuticals, and reversals of difficult to treat conditions (ie: cancer, autoimmune). My knowledge of genetics 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 allowing for genetic individualization of cannabis therapy.
As you may have already guessed, genetically-guided cannabis is very cutting edge, and a bit complex. It’s the overlap of several emerging sciences: 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). Our ECS produces endocannabinoids that interact with our body’s ECS receptors, which then work to promote overall balance throughout the body. (4)
The role of the ECS is homeostasis or balance, and the underlying cause of most chronic illness is some sort of imbalance (2). So it makes perfect sense that endocannabinoid deficiency, or lack of what we need to maintain balance, is linked to chronic illness (5). Since plant derived phytocannabinoids exactly mimic our internally-made endocannabinoids, cannabis supplementation can help fill the EC deficiency gap, and promote the needed balance necessary to recover health. (3)
This explains how medical cannabis therapy may benefit those suffering chronic illness, and many report cannabis is more effective than pharmaceuticals, sans the dangerous pharma side effects. Cannabis is overall very safe, and since it promotes underlying balance, it’s also potentially curative for many diseases. (3) Very few pharmaceuticals exert a curative effect, making cannabis a far superior intervention for chronic illness.
Endocannabinoid deficiency is especially prevalent in today’s society, thanks to nearly a century of cannabis prohibition. This epidemic was caused by human ECS pathway mutations/inability to produce ample endocannabinoids, combined with lacking availability and intake of phytocannabinoids. (5)
Every individual has a unique genetic profile, and mutations may reflect predisposition to ECS deficiency, along with many other contributors to imbalance. The cannabis plant contains many medicinal components, including 140+ phytocannabinoids and 200+ terpenes, thereby providing a broad spectrum of the components needed to fill an individual’s ECS deficiency profile (4).
Assessing an individual’s genetics specific to the Endocannabinoid System (including other system pathways that overlap) can help to guide cannabis therapy, and is proving useful to decrease the “trial and error” phase upon starting cannabis, and also provide more consistently positive health 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...
The process of genetic screening is especially important in pediatric applications of cannabis therapy, because methylation pathway mutations predispose neurodevelopmental risks with child/adolescent use of cannabis (7). Methylation mutations are linked to chronic illness, by contributing to harmful systemic inflammation, and dysfunction in both the immune system and detoxification (8). The main reason most seek cannabis therapy for a minor child is chronic illness, making this is a common consideration for children who may benefit from cannabis therapy.
TO BE VERY CLEAR: This doesn’t mean that children and adolescents (even with methylation mutations) 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.
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 other unique cannabis considerations such as medication interactions, etiology of 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.
Luckily there are knowledgeable practitioners available to screen for genetic cannabis risk factors, and optimize health further through nutrigenomics. In addition to screening genetics to improve cannabis therapy, full genome assessment and applied nutrigenomics may help optimize other pathway mutations implicated in chronic illness.
My favorite analogy to describe the potential of combining nutrigenomics and cannabis therapy is a sink that’s overflowing with imbalances, leading to chronic 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 slow or 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 approach represents the future of medical cannabis, and offers a viable option for comprehensive healing of 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