Cannabis Pharmacogenomics: A Path to Personalized Medicine

Abstract

Cannabis and related compounds have created significant research interest as a promising therapy in many disorders. However, the individual therapeutic effects of cannabinoids and the incidence of side effects are still difficult to determine. Pharmacogenomics may provide the answers to many questions and concerns regarding the cannabis/cannabinoid treatment and help us to understand the variability in individual responses and associated risks. Pharmacogenomics research has made meaningful progress in identifying genetic variations that play a critical role in interpatient variability in response to cannabis. This review classifies the current knowledge of pharmacogenomics associated with medical marijuana and related compounds and can assist in improving the outcomes of cannabinoid therapy and to minimize the adverse effects of cannabis use. Specific examples of pharmacogenomics informing pharmacotherapy as a path to personalized medicine are discussed.

Supporting Machine Learning Model in the Treatment of Chronic Pain

“…Additionally, it is possible to evaluate the impact of specific genetic variants in patients and explain part of the great inter-individual variability observed in pain reduction. Part of this is significantly correlated with four polymorphic candidate genes which have been studied to be involved in the therapeutic activity of cannabis [26]: ABCB1 rs1045642, TRPV1 rs8065080, UGTB7 rs7438135, and COMT rs4680.…”

“…Additionally, there is still a lack of knowledge on the medicinal benefits of cannabinoids. A possible solution could be given by pharmacogenetics, supposing that the patient's response to cannabinoid treatment may have a genetic background and is dependent on gene polymorphisms involved in the action, metabolism, and transport of these substances in the organism [26]. This information leads us to select potential genes whose variants may affect both the therapeutic effect and the occurrence of possible side effects and adverse reactions [27].…”

Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges

“…When THC is consumed by inhalation or mucosal sprays, it is absorbed through the lungs into the bloodstream and concentrations in the plasma will typically peak in less than 10 min [ 31 ] and when it is orally congested, concentrations may peak at ~2 h. THC is distributed into well vascularises organs as well as the brain. THC and CBD are highly protein-bound and has a half-life of 25–36 and 18–32 h, respectively [ 31 , 34 ], with some of the metabolites (THCCOOH) having a very long half-life up to 52 h [ 35 ]. Chronic users have much longer half-lives.…”

“…Therefore, it is particularly important to investigate any potential drug–drug interactions to avoid toxicity or therapeutic failure for any of the medications. THC primarily is metabolised via oxidation by CYP2C9, CYP2C19 and CYP3A4 into several metabolites with 11‐hydroxy‐THC (11‐OH‐THC) and 11‐carboxy‐THC (11‐COOH‐THC) being the most abundant [ 34 , 37 ]. 11-OH-THC is metabolised by the UGT1A9 and UGT1A10 enzymes and 11-COOH-THC is metabolised mostly by the UGT1A3 and UGT2B7enzyme [ 34 , 35 ].…”

“…THC primarily is metabolised via oxidation by CYP2C9, CYP2C19 and CYP3A4 into several metabolites with 11‐hydroxy‐THC (11‐OH‐THC) and 11‐carboxy‐THC (11‐COOH‐THC) being the most abundant [ 34 , 37 ]. 11-OH-THC is metabolised by the UGT1A9 and UGT1A10 enzymes and 11-COOH-THC is metabolised mostly by the UGT1A3 and UGT2B7enzyme [ 34 , 35 ]. CBD is also metabolised in the liver via mostly CYP3A4, CYP2C19 and CYP2C9 and other CYPs to a lesser degree via hydroxylation to form metabolites, 7-OH-CBD and 7-COOH-CBD, which is then undergoes glucuronidation by UGT1A9 and UGT2B7 [ 31 , 34 ].…”