As cannabis use becomes more prevalent, it is critical for the public to be educated on its potential therapeutic benefits, but more importantly, on the associated risks and variability in individual responses (Government of Canada n.d.-a; Government of Canada n.d.-b). Users of cannabis often select their product of choice through trial-and-error, which often can lead to adverse outcomes. Pharmacists are highly accessible health care professionals who are trained to provide evidence-based guidance to current and potential users of cannabis (Dattani and Mohr 2019). Historically, pharmacists’ involvement in cannabis education has been limited by their training and cannabis-related experience. This is further made difficult from the lack of standardization of cannabis products and availability of tools to predict individual response and tolerance from genetic variability (Hryhorowicz et al. 2018). In recent years, clinical pharmacogenetic research has made significant progress in defining which genetic variations are important for influencing inter-patient variability in drug response including cannabis (Hryhorowicz et al. 2018) (Hirota et al. 2013). Moreover, technology for pharmacogenetic testing has been made available to practitioners in frontline clinical settings. In Canada, commercial tests are available through several providers including GeneYouIn, Lobo Genetics and GeneXys. This availability, in combination with the pharmacist’s expertise in pharmacology and pharmacokinetics make them ideally suited to champion implementation of this novel technology to best optimize cannabis use by patients (American Society of Health-Systems Pharmacists n.d.).

The objective of this study is to evaluate the practicality and impact of implementing a pharmacogenetic screening program in the community pharmacy. This program is intended to help guide current or potential users of cannabis in both selection and pattern of use with the goal of minimizing potential adverse effects due to individual genetic variabilities. Pharmacogenomic testing involves identifying the polymorphism of key genes and pathways in cannabis metabolism (Hryhorowicz et al. 2018). This information can be used by pharmacists to more accurately predict the likelihood of short and long-term negative risks of cannabis use in individuals (Hryhorowicz et al. 2018). While both cannabinoids, THC and CBD, have reported therapeutic indications, specific genetic polymorphism have been demonstrated to be major determinants of an individual’s rate of cannabinoid metabolism, predisposition to the development of psychosis, and risk of cognitive and memory impairments (Hirota et al. 2013).

The primary metabolic pathway of THC metabolism involves CYP2C9 (Hirota et al. 2013). The cannabinoid is hydroxylated to its active form (OH-THC) that has significant psychotropic activity (Bland et al. 2020). It is then further oxidized by CYP2C9 to its carboxylic acid form (COOH-THC) which is pharmacologically inactive (Bland et al. 2020). Genetic epidemiology studies have shown 15–20% of the population have the CYP2C9*3 allele (Hirota et al. 2013). This variant of the gene results in a much slower conversation of THC to its non-psychoactive form when compared to the “normal” CYP2C9*1 allele variant (Hryhorowicz et al. 2018). Consequently, these individuals with *3 alleles can accumulate levels of THC that are 200–300% higher than those with the normal allele (Hirota et al. 2013) and, hence, may be more predisposed to THC’s negative psychoactive effects including anxiety, hallucinations, paranoia, rapid heart rate and panic attacks (Hirota et al. 2013). It is often these negative effects that lead to motor vehicle accidents, workplace injuries, and hospitalizations (Hirota et al. 2013; Hartman and Huestis 2013).

Furthermore, guidance from Health Canada and the National Institute on Health Abuse strongly suggest that polymorphisms of AKT1 and COMT genes can impact response to cannabis use and predict the potential risk of developing psychosis and cognitive impairment, respectively (Morgan et al. 2016; Radhakrishnan et al. 2014; Health Canada n.d.). AKT1 is a gene that encodes for protein kinase which is required for multiple cellular functions including dopamine signaling (Radhakrishnan et al. 2014).

Three case control studies (Van Winkel et al. 2011; Di Forti et al. 2012; Morgan et al. 2016) demonstrated that, depending on frequency of cannabis use, users with the AKT1 C/C genotype had between a two-fold (history of use) and seven-fold (daily use) increased risk in the development of psychosis compared to T/T carriers (Morgan et al. 2016; Radhakrishnan et al. 2014; Van Winkel et al. 2011; Di Forti et al. 2012). Van Winkel et al. 2011 examined cannabis induced cognitive alterations in psychotic disorder using standardized verbal memory and sustained attention testing measures in relation to ATKI variability (Van Winkel et al. 2011). Siblings or parents were used when possible as case controls. Di Forti et al. 2012 is a retrospective case-control study that recruited patients aged 18 to 65 years who presented with their first episode of psychosis. Over the same period, at same mental health sites, healthy control subjects with similar characteristics were recruited (Di Forti et al. 2012). Morgan et al. 2016 recruited healthy young cannabis users who were assessed with the Psychotomimetic States Inventory, a 48-item questionnaire, for schizotypal symptoms (Morgan et al. 2016). These studies strongly support using AKT1 as a genetic marker to assess the genetic predisposition for psychosis in cannabis users (Radhakrishnan et al. 2014).

COMTis a second gene of interest, which encodes for catechol-O-methyltransferase (COMT) (Henquet et al. 2006). This enzyme plays a critical role in dopamine degradation in the brain. Two double-blind, placebo-controlled studies (Henquet et al. 2006; Tunbridge et al. 2015) have reported that functional polymorphism in the COMT gene may increase the risk of the immediate neurocognitive impairments associated with cannabis use (Henquet et al. 2006; Tunbridge et al. 2015). There are two common variants of COMT (Val and Met) corresponding to high and low enzymatic activity, respectively (Henquet et al. 2006). Henquet et al. 2006 used a cross-over design enrolling patients with a psychotic disorder, relatives of patients with a psychotic disorder, and healthy controls who were exposed to THC or placebo. This followed a cognitive assessment and an evaluation of current psychotic experiences. This study determined that carriers of the COMT Val allele were more sensitive to THC’s memory and attention impairments compared to carriers of the Met allele. Tunbridge et al. 2015 assessed cognitive performance in participants without a psychiatric diagnosis, using a between-subjects design (THC vs. placebo) and administered the treatment intravenously. The results showed that COMT genotype moderates the cognitive, but not psychotic effects of acutely administered THC. These studies demonstrated that carriers of the Val allele were more sensitive to THC-induced cognitive, memory and attention impairments (Tunbridge et al. 2015). As such, polymorphisms in COMT can be used as a possible marker of cannabis induced neurocognitive impairments such as memory loss or poor reaction time (Tunbridge et al. 2015).