Please consult Section for additional information on the adverse psychiatric effects associated with the use of cannabis and psychoactive cannabinoids (such as THC), and the role of genetic predisposition on the risk of developing a psychotic disorder. In the case of opioids, in vitro and in vivo studies have shown significant physiological and pharmacological overlap, cross-tolerance, mutual potentiation, and cross-talk between the endocannabinoid and the endogenous opioid systems (see Section 1065Reference 1066.

In addition, both of these endogenous physiological mechanisms have been implicated in the mechanism of action of several other drugs with abuse and dependence potential such as ethanol, nicotine, and psychostimulantsReference 1065. A recent systematic review found "insufficient evidence" around the benefits and harms of cannabis in treating PTSD among adults. The authors emphasized that evidence was too limited to draw any conclusions and clinical trials and more cohort-based studies are needed to determine the safety and efficacy of plant-based cannabis for PTSDReference 1064. These findings are consistent with evidence suggesting that, at least at low doses, THC may have an anxiolytic effect in central mechanisms of fear behaviours.

PTSD is a psychiatric disorder of significant prevalence and morbidityReference 1039. In the overall population, more than two thirds of individuals may experience a serious traumatic event at some point in their lifetimeReference 1039. PTSD refers to the development of a cluster of characteristic symptoms that follow exposure to an extreme traumatic stressor and which appears to involve aberrant memory processing and impaired adaptation to changed environmental conditionsReference 1040.

Characteristic symptoms include persistent, intrusive recollections, or a re-experiencing of the original traumatic event (through dreams, nightmares, and dissociative flashbacks), numbing and avoidance, and increased arousalReference 578. Patients with PTSD are also at risk for other psychological disorders, including but not limited to generalized anxiety disorder, major depressive disorder, and substance use disorder as well as physical problems including chronic pain, hypertension, and asthmaReference 1041. There appears to be a link between exposure to a traumatic event and cannabis use, especially in military veterans, and research suggests that individuals with PTSD may be particularly likely to use cannabis specifically to alleviate symptoms of PTSD and associated distressReference 1039Reference 1041Reference 1042. There is also evidence to suggest that particular symptoms and correlates of PTSD including anxiety, stress, insomnia and depression are among the most frequently cited reasons for cannabis useReference 1042. Despite much anecdotal evidence suggesting the benefits of cannabis use to treat PTSD, there is a lack of standardized large-scale controlled trials to make any firm conclusions regarding the efficacy or safety of cannabis for the treatment of PTSDReference 1043.

In contrast to the harmful effects seen with THC and THC-predominant cannabis in psychosis and schizophrenia, there is some evidence from observational, and preliminary pre-clinical and clinical studies that suggests that CBD may protect against THC-induced psychosis and could even serve as a potential treatment for schizophrenia. A number of studies have investigated the influence of potential genetic factors in the development of psychosis and schizophrenia, and more specifically as a function of interaction with cannabis use. Some studies have focused on the role of genetic polymorphisms at the COMT geneReference 1116-Reference 1123, and others have focused on polymorphisms at the AKT1 geneReference 1124-Reference 1127. Taken together, the data from these studies strongly suggest that single-nucleotide polymorphisms at either the COMT or AKT1 genes interact with cannabis use to predict the age at onset, as well as the likelihood of developing psychosis or schizophrenia in vulnerable individuals. More recently, evidence has also emerged implicating polymorphisms at the CNR1, neuregulin 1 (NRG1) as well as the DAT1 gene and the BDNF gene and THC/cannabis use with onset of psychotomimetic effects as hemp seed oil well as earlier age of onset of schizophreniaReference 1085Reference 1128-Reference 1130.