The evidence for the association between cannabis use and persistent psychosis comes from both cross-sectional studies (
192–
196) and longitudinal epidemiological studies, including the Swedish military conscript cohort (
197–
199), the Netherlands Mental Health Survey and Incidence Study (NEMESIS) (
20), the German prospective Early Developmental Stages of Psychopathology Study (EDSP) (
24), the Dunedin cohort (
19,
200), and the Christchurch Health and Development Study (CHDS) birth cohort (
23). ...
The EDSP study, which used in-person interviews in the assessment of 923 individuals from the general population (aged 14–24 years), showed that cannabis use was associated with an increased risk of psychotic symptoms and persistent use increased this risk further (
28). Importantly, this study yields evidence for a unidirectional relationship between cannabis use and psychosis...
The Dunedin cohort study (
19) examined data from 759 subjects of the population birth cohort comprising 1037 individuals born in Dunedin, New Zealand, in 1972–1973. The study collected information on psychotic symptoms at age 11, drug use at ages 15 and 18 years, and assessed psychiatric symptoms at age 26. Cannabis use by age 15 and 18 years was found to be associated with more schizophrenia symptoms at age 26 years; and the association remained significant despite controlling for the presence of psychotic symptoms at age 11 years. The association was also found to be stronger with earlier use. Those who used cannabis by age 15 years were also four times more likely to have a diagnosis of schizophreniform disorder...
Fergusson et al. attempted to validate a possible causal link between cannabis use and psychosis in a dataset of a 25-year longitudinal study in New Zealand (the CHDS birth cohort comprising 1265 children) (
23). The study showed that daily use of cannabis was associated with 2.3- to 3.3-fold higher risk of psychosis than among non-users. One of the limitations of the study is that the data was derived from 10 items of the Symptom Checklist-90, the items on which overlap with personality traits such as schizotypy and paranoia and that the study did not attempt to delineate psychotic symptoms due to the acute effects of cannabis use from persistent effects (
204).
This finding of increased psychosis risk has been reported in several other prospective studies (
19–
21,
24). The cumulative evidence for the association between cannabis and psychosis have been examined in five systematic reviews (
25,
205–
208), four of which (
25,
205,
207,
208) found a consistent association between cannabis use and psychosis...
Age of Exposure
Epidemiological evidence suggest that the earlier the age of exposure to cannabis, the greater the risk of a psychosis outcome (
19). Dragt et al. showed that younger age of onset of cannabis use is associated with earlier symptoms of anxiety, social withdrawal, derealization, memory impairment, and difficulties in concentration, with effects being more pronounced in patients with heavier cannabis use (
250). Another recent study found that early onset cannabis use was only associated with earlier onset of psychosis when cannabis use began by age 14 (
251). A large meta-analysis of 83 studies found that the age of onset of psychosis in cannabis users was 2.7 years younger than in non-users (
252). Animal studies have shown that exposure to cannabinoids in adolescence has more deleterious effects than exposure in adulthood (
253–
257). ...
Further studies that have followed patients over time have shown that among patients who are admitted with an initial diagnosis of cannabis-induced psychosis, almost 50% convert to schizophrenia or some other psychotic disorder (
181,
188). Boydell et al., found, in a retrospective study of 757 first-episode schizophrenia patients (24% who used cannabis in the year prior to presentation), that among patients with schizophrenia, cannabis users did not differ significantly from those not using cannabis in terms of a positive family history of schizophrenia (15 vs. 12%) (
274)...
Temporal Relationship
As discussed above, evidence from experimental studies shows a clear temporal relationship between exposure to cannabinoids and symptoms of psychosis. Despite a number of limitations (discussed previously), several epidemiological studies have concluded that cannabis use generally precedes the development of psychotic disorder. In one of the earliest such studies, Allebeck and colleagues found that cannabis use preceded the onset of schizophrenia by at least 1 year in 69% of cases; in only 11% of cases did cannabis succeed psychosis (
309). In a prospective cohort study, Linszen et al. found that in all but 1 patient from a sample of 24 cannabis-abusing patients, cannabis abuse preceded FEP by at least 1 year (
310).
Studies from recent years suggest that in the majority of cases, cannabis use precedes the onset of psychosis, rather than vice versa. In a study of 28 FEP patients, cannabis use preceded psychosis in all patients (
267). Another study of 45 psychotic disorder patients with a history of cannabis use showed that the onset of cannabis use preceded hallucinations in 74% of cases and preceded persecutory ideas in 90% of cases by at least on year (
250). Schimmelmann and associates (
251) reported that in 88% of cases (
n = 201 FEP patients with cannabis use), drug exposure preceded psychotic symptoms by a mean of 5 years. ...
In a longitudinal study of over 18,000 patients hospitalized for substance-induced psychosis, the 8-year cumulative risk of conversion to schizophrenia was 46% when the offending substance was cannabis. In contrast, the conversion rate to schizophrenia over the same period of time for alcohol-induced psychosis was 5%. Notably, the risk for the development of schizophrenia when the diagnosis was amphetamine-induced psychosis was 30% (
188). ...
In summary, the relationship between cannabinoids and psychosis fulfills many but not all of the traditional criteria for causality. Given the evidence presented above, it is likely that cannabis is an important component cause in the development of psychotic disorders (
16,
205)...