In fact, studies have shown a correlation between genetic polymorphism of the CB1 receptor and schizophrenia, suggesting that gene variants may confer susceptibility to this disorder.Chronic cannabis consumption results in an increase in dopamine concentrations in the mesolimbic regions of the brain and a decrease in dopamine concentrations in the prefrontal cortex which mimics the neurochemical state observed in schizophrenia .In the past ten years, several works have suggested that differential sensitivity to environmental stress produced by the Val158 Met polymorphism of the catechol-O-methyltransferase gene, probably by interacting with other factors, might be responsible for increasing the risk to develop psychosis .
A genetic analysis conducted among New Zealand participants in the Dunedincohort study demonstrated that the relationship between cannabis use and the risk of developing psychosis was moderated by a COMT gene polymorphism:cannabis users who first consumed cannabis prior to the age of 18 years and who carried the COMT Val/Val genotype were 10.9 times more likely to develop schizophreniform disorders at age 26, whereas individuals Met/Methomozygotes did not present such a risk while exposed to cannabis use .However, different studies have failed to replicate the findings of Caspi’s team. Other studies reported the Caspi’s interaction only in subgroups of individuals .Despite this discrepancy, several researchers have demonstrated that the Val158Met polymorphism of the catechol-0-methyltransferase gene moderates both the association between cannabis use and psychosis and the association between childhood trauma and schizotypal traits .Spanish investigators have demonstrated that variability in the COMT geneconfers different neurobiological vulnerability to cannabis consumption in the risk of developing psychotic experiences , the milder forms of psychoticsymptoms. In accordance with previous works, the researchers concluded that Val carriers are more vulnerable to the psychosis-inducing effects of cannabis than Met/Met individuals, but only when exposed to childhood abuse .
The authors further suggested that sensitization mechanisms involving dopaminergic signalling may be underlying this gene-environment interaction .Moreover, a Dutch study confirmed the COMT genetic association: weekly cannabis users had more severe positive psychotic symptoms if they were carriers of the COMT Val allele and even more so if they were Val/Valhomozygotes.In addition, a team of Dutch and British investigators has illustrated that agenetic variation in AKT 1 may mediate both short term and long term effects on psychosis expression associated with cannabis use,possibly through a mechanism of cannabinoid-regulated AKT 1/GSK-3 signalling downstream of the dopamine D2 receptor.A vast body of scientific literature suggests that the experience of childhood trauma, physical or psychological, including bullying and sexual abuse, is a risk factor for the development of schizophreniaor psychotic symptoms.In addition, exposure to a greater number of traumas is correlated with a higher risk of psychosis. Moreover, it has been demonstrated that childhood trauma increases the risk of substance abuse, including cannabis consumption, in adolescence and adult hood.Taken together, these strands of evidence point to the possibility that childhood trauma may play a role in the association between cannabis use and psychosis.
All these observations raise the question of the causal link and the direction of the association: it is important to determine if child abuse, in different forms and circumstances, caused first the consumption of cannabis or induced primarily the appearance of psychosis or psychotic symptoms. It is also a matter of concern to know if cannabis is consumed to alleviate first the traumatic events of childhood or the symptoms of psychosis, or both situations simultaneously when they are concomitantly present.Data on cannabis use and sexual trauma experiences from 5877 American citizensaged between 15 and 54 years revealed that the impact of sexual trauma on clinically assessed diagnoses of psychosis was statistically significant in individuals who used cannabis under 16 years but not for those who had not used cannabis under16 years . In fact, those who used cannabis under the age of 16 years and had also been sexually abused were almost 12 times more likely to receive a diagnosis of psychosis .The authors stated that the mediating role of cannabis suggests that early cannabis use may increase the strength of the proposed trauma-psychosis relationship.They proposed that this correlation could be explained by both cannabis use and trauma acting indirectly on the dopaminergic system, as sexual traumas produce elevated cortisol levels which in turn are associated with dopamine activity .
The researchers also postulated that childhood abuse enhances an individual’s vulnerability to psychotic symptoms and that cannabis use acts as an exacerbating agent heightening psychotic experience in those persons who have suffered abuse. Alternatively, cannabis consumption could be considered the vulnerability factor and childhood sexual abuse the environmental factor that increases the likelihood of psychosis . Finally, the investigators suggested that exposure to a trauma followed by cannabis use and cannabis use followed by trauma produce significantly different likelihoods of psychosis.