ReviewCannabis and psychosis: Have we found the missing links?
Introduction
The psychotropic properties of cannabis have been known since time immemorial, but whether cannabis has detrimental effects on health has been a matter of debate. In 1893, Indian Hemp Commission established by the British government concluded in its seven-volume report that there was no evidence of any weight regarding mental and moral injuries from moderate use of cannabis (Kaplan, 1969). Even after the passage of a century, it continued to be widely accepted in the medical fraternity that smoking cannabis did not cause long-term harm to health and cannabis came to be perceived as a drug of recreational use like alcohol and tobacco. However, over the last decade or so, there has been a spate of evidence on the mental health risks of long-term use of cannabis and a number of studies have furthered our understanding of the effects of cannabis on the brain, though it remains to be seen if all the missing links are in place.
There is ample evidence from case reports and surveys of cannabis users in the general population that cannabis can produce acute psychotic symptoms which are transient and recover completely on abstinence (Chopra and Smith, 1974, Keeler et al., 1971, Talbott and Teague, 1969, Thomas, 1996). In relation to this, some researchers proposed that “cannabis-induced psychosis” be considered a distinct diagnostic entity (Mathers and Ghodse, 1992, Rottanburg et al., 1982, Thakore and Shukla, 1976). However, others argued that cannabis-induced psychosis is not clinically different from other psychotic disorders and could be an early sign of schizophrenia rather than a distinct clinical entity (Arendt et al., 2005, McGuire et al., 1994). In further support of this, a population-based cohort study found no difference in familial predisposition to psychotic disorders between patients with cannabis-induced psychosis and those with schizophrenia (Arendt et al., 2008).
Section snippets
Is there an association between cannabis and schizophrenia?
It is well known that regular cannabis use and psychotic disorders such as schizophrenia are associated in the general population (Degenhardt and Hall, 2001, Tien and Anthony, 1990) and heavy cannabis users are over-represented among new cases of schizophrenia (Barbee et al., 1989). However, the strongest evidence that cannabis use may have a causal association with schizophrenia comes from longitudinal studies of large representative samples of the population who have been followed up to see
Can the association be explained by reverse causality?
A possible explanation of the association is that cannabis use is a consequence, rather than a cause, of schizophrenia. Cannabis is known to improve negative and depressive symptoms and may be used to self-medicate symptoms of schizophrenia (Schneier and Siris, 1987). In order to counter this, some longitudinal studies excluded patients with psychotic symptoms at baseline or made statistical adjustments for the same and yet found an increased risk of psychosis in cannabis users (Arseneault et
Impact of cannabis on course of schizophrenia
Negrete et al. (1986) conducted a restrospective study of the relationship between self-reported cannabis use and schizophrenia and found higher rates of positive symptoms, and more hospitalizations among active cannabis users. These relationships persisted after statistical adjustment for age and sex differences between the user groups. In a prospective study over one year of follow-up, Linszen et al. (1994) found that cannabis users relapsed to psychotic symptoms sooner, and had more frequent
Is the association biologically plausible?
Although the epidemiological link between cannabis and psychosis has been investigated extensively, the biological basis of this association remains poorly understood. There is ample indirect evidence for the biological basis in the form of the presence of alterations in the endocannabinoid system in schizophrenia. Studies on schizophrenic patients have shown up-regulation of cannabinoid-1 (CB1) receptors in cortical brain regions such as the dorsolateral prefrontal cortex (Dalton et al., 2011,
Why is it that only a small proportion of cannabis users develop psychosis?
Although there is strong evidence that use of cannabis is associated with a higher risk of psychosis and also that the association is biologically plausible, the fact remains that the vast majority of cannabis users never go on to develop any psychotic symptoms. Some of the factors that influence the development of psychotic symptoms have been elucidated.
Does cannabis also have antipsychotic effects?
Delta-9-tetrahydrocannabinol and cannabidiol are the two major constituents found in cannabis, of which delta-9-tetrahydrocannabinol is the main psychoactive ingredient and is thought to be the ingredient responsible for the increased risk of developing schizophrenia following regular cannabis use. Cannabidiol, on the other hand, has been shown to have opposite effects to delta-9-tetrahydrocannabinol and may even have antipsychotic properties. A functional neuroimaging study reported that
Cannabis as a component cause of psychosis
Heavy cannabis use, especially in the adolescence, is likely to increase the risk of psychotic disorder in later life, but by itself it is neither a necessary nor a sufficient cause. That is why, many cannabis users never go on to develop psychosis. It is only some people who have a high genetic liability to psychosis and may also have exposure to environmental stressors like childhood trauma and urban upbringing, who are highly vulnerable to the psychotogenic effects of cannabis, especially
Conclusion
It is now known beyond doubt that cannabis acts as a component cause of psychosis, that is, it increases the risk of psychosis in people with certain genetic or environmental vulnerabilities, though by itself, it is neither a sufficient nor a necessary cause of psychosis. Genetic vulnerability, exposure to cannabis in adolescence, frequent heavy use of cannabis and use of potent forms of cannabis containing higher levels of tetrahydrocannabinol and lower levels of cannabidiol are the important
Funding source
None.
Conflicts of interest
The authors have no conflicts of interest to disclose with this submission.
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