Finally, it has beneficial effects in the treatment of anxiety, depression and psychosis by alleviating some symptoms of these diseases. In terms of toxicity, CBD has few adverse effects, the most frequent side effects reported being sedation and dizziness.In 2012, a pioneering randomized, double-blind, controlled clinical trial of cannabidiol versus amisul pride, a potent antipsychotic medication, demonstrated that CBD has comparable antipsychotic properties in alleviating both positive and negative schizophrenia symptoms and yields to similar significant clinical improvement than amisulpride in the treatment of acute schizophrenia .Moreover, CBD displayed a substantially superior side-effect profile than that of amisulpride. Indeed, compared to amisulpride, treatment with CBD was associated with significantly fewer extrapyramidal symptoms , less weight gain and lower prolactin increase, a predictor of galactorrhea and sexual dysfunction .
Furthermore, CBD was well tolerated and did not significantly affect cardiac or hepatic functions. Interestingly, the results of Leweke et al. were correlated with increased levels of anandamide, suggesting that inhibition of anandamide deactivation may contribute to the antipsychotic effects of CBD which potentially represents a completely new mechanism of action in the treatment of schizophrenia.In summary, studies conducted with cannabidiol show that cannabis types with a high concentration of cannabidiol are significantly less strongly associated with psychotic symptoms. By regulating dopaminergic activities, CBD has the features of a potential efficient antipsychotic medication, while being deprived of the deleterious side effects of the conventional antipsychotic pharmacotherapies.In fact, CBD exerts clinically relevant antipsychotic effects and has a better safety and tolerability profile compared with current antipsychotic medications . A dose-response relationship exists between the amounts of cannabis used and the likelihood of developing psychosis or psychotic features: the risk increases with the quantity, frequency and duration of cannabis consumption.Similarly, early age of cannabis use is correlated with an increased probability of manifesting such symptoms.
This observation could be explained by the fact that the brain of young people aged between 14 and 25 years has not reached its complete maturation and therefore is more vulnerable to the psychotomimetic effects of THC and the adverse central manifestations of cannabis . These observations illustrate the critical role played by the endo cannabinoid system in the brain maturation, particularly during adolescence.Regarding genetic susceptibility, it has been demonstrated that psychosis inducing effects of cannabis use are related to genetic variability in the catechol-0-methyltransferase gene. This vulnerability increases when individuals are exposed to childhood abuse. Cannabis consumption increases the likelihood of developing psychotic experiences in Val carriers only when they are exposed to childhood abuse. Similarly, AKT1 and DRD2 genotypes are involved in the likelihood of developing psychosis.The characterization of potential genes presenting a risk of psychotic outcomes will facilitate the comprehension of the cannabis-psychosis link and will help identify the persons who present a genetic vulnerability to the psychotogenic effects of cannabis.
Child trauma plays also a deleterious role in the expression of psychosis or psychotic features by a progressive sensitization mechanism: exposure to traumatic experiences during childhood may induce neurobiological changes characterized by an over-reactivity of the hypothalamus and the hypothalamic-pituitary adrenal axis, abnormalities in the neurotransmitter system and structural brain changes .Cigarette smoking has also been considered a risk factor for the development of psychosis or psychotic symptoms.A biological mechanism involving dopamine release and nicotinic cholinergic neurotransmission could be involved .Finally, urbanicity increases the strength of the cannabis-psychosis relationship.This phenomenon could be explained by the fact that living in urban areas may enhance cannabis use and render people more vulnerable to the psychotomimetic effects of THC by neurobiological mechanisms .None of each of the six risk factors described is neither necessary, nor sufficient to do so alone.On the other hand, cannabidiol plays a protective role in the cannabis-psychosis relationship.
Cannabis species with a high concentration of cannabidiol are significantly less strongly associated with psychotic symptoms, rendering CBD a promising efficient antipsychotic medication. Large randomized-controlled clinical trials will eventually confirm or infirm the qualitative and quantitative antipsychotic potential of cannabidiol .However, the causal and temporal association between the use of cannabis and the development of psychosis or psychotic features is not clear and remains controversial. Population statistics argue against the causal relationship.While cannabis use among adolescents has increased substantially in the past 40 years , the population trends in schizophrenia incidence have not .Macleod and colleagues have suggested that a non-causal explanation is possible for most of the associations between cannabis use and psychosis: “Cannabis use could be a marker, rather than a cause of a life trajectory more likely to involve adverse outcomes” .Moreover, a large number of studies cannot determine if psychotic features predispose individuals to use cannabis or if cannabis use increases psychotictraits.