Cannabis and psychosis

The relationship between cannabis use and psychosis has, in recent decades, become a focus of controversy.^[1] The National Institute of Mental Health has stated that "research has found increasing evidence of a link between marijuana and schizophrenia symptoms."^[2] In a report issued in 2000, the National Academy of Sciences noted that some researchers had proposed a link between cannabis use and schizophrenia, as well as between cannabis use and a unique type of psychosis. They observed that "marijuana use alone—without the influence of additional risk factors—is unlikely to provoke a psychosis that persists longer than intoxication."^[3] Likewise, a number of reviews have concluded that cannabis use only results in a significant increase in risk of psychosis when coupled with additional risk factors, in particular, an underlying genetic vulnerability.^[4][5]

There is evidence that the brains of people with psychosis who previously used cannabis differ from those of healthy individuals with respect to areas such as the cingulate and prefrontal cortex.^[6] Research has consistently found that people with psychosis have higher rates of cannabis use, and that there exists an association between cannabis use and schizophrenia and other forms of psychosis.^[7][8] Some studies have also concluded that cannabis use is associated with an earlier age at onset of schizophrenia.^[7] However, it is less clear whether this association is a result of the specific effects of cannabis use.^[9] Proposed mechanisms by which this possible link could occur include the effects of dronabinol, a pure isomer of THC, and its ability to induce "acute psychotic states," which, in turn, have been called "the early signs of schizophrenia and related disorders."^[10] Further complicating the establishment of causation, another cannabinoid found in cannabis, cannabidiol (CBD), is thought to have antipsychotic properties. CBD has been shown to have anxiolytic properties and inhibit the psychotomimetic effects of THC, yet CBD content varies widely and has rarely been accounted for in epidemiological studies.^[11] It is believed that cannabis' effects on the risk of schizophrenia is especially pronounced among those who begin using the drug early.^[12]

Systematic reviews

• In 2000, a review by researchers from the National Drug and Alcohol Research Centre in Australia examined two hypotheses:

1. That heavy use of cannabis causes "cannabis psychosis," which would never have happened had the patient never used cannabis, and
2. That cannabis use may precipitate, or exacerbate the symptoms of, schizophrenia.

The authors concluded that there was limited evidence to support the first hypothesis, but more support for the second, citing a large prospective study which found a linear relationship between cannabis use before the age of 18 and risk of being diagnosed with schizophrenia over the next 15 years.^[13]

• In 2004, a review was published in the British Journal of Psychiatry which concluded that discouraging cannabis smoking would result in the rate of schizophrenia decreasing by 8%.^[14] Also that year, a review was published in the journal Addiction which reported that "antecedent cannabis use appears to act as a risk factor in the onset of schizophrenia, especially in vulnerable people, but also in people without prior history."^[15]
• In 2005, a review by researchers from Sheba Medical Center in Haifa concluded that while it is true that studies have shown an association between cannabis use and risk of schizophrenia, that this might be explicable not by a causal link between the two, but rather by a deficit in the function of the endocannabinoid system in some people, which puts them at an increased risk of both cannabis use and schizophrenia.^[16]
• In 2007, a review published in the Lancet concluded that "there is now sufficient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life."^[17]
• In 2009, a review was published in the European Archives of Psychiatry and Clinical Neuroscience which found that "Converging lines of evidence suggest that cannabinoids can produce a full range of transient schizophrenia-like positive, negative, and cognitive symptoms in some healthy individuals."^[18]
• In 2010, the Global burden of disease study found that cannabis use as a risk factor for schizophrenia accounted for an estimated 7,000 disability adjusted life years globally and that "cannabis use as a risk factor for schizophrenia is not a major contributor to population-level disease burden".^[19] Also that year, Italian researchers published an overview of reviews on the subject of cannabis and psychosis in which they noted a consistent association between cannabis use and psychotic symptoms. However, they were unable to draw firm conclusions regarding whether this association was causal.^[20]
• In 2011, a review by researchers from the Schizophrenia Research Institute in Darlinghurst, Australia listed three risk factors for schizophrenia which it considered to be supported by the "highest quality evidence"; cannabis use was one of these factors.^[21]
• In 2013, a review by researchers at the Icahn School of Medicine at Mount Sinai stated that there exists "a strong association between schizophrenia and cannabis use...". They found that cannabis use alone does not predict the transition to subsequent psychiatric illness. Many factors are involved, including genetics, environment, time period of initiation and duration of cannabis use, underlying psychiatric pathology that preceded drug use, and combined use of other psychoactive drugs.^[8]
• In 2014, a review was published in Frontiers in Psychiatry which concluded that "The relationship between cannabis and schizophrenia fulfills many but not all of the standard criteria for causality, including temporality, biological gradient, biological plausibility, experimental evidence, consistency, and coherence," and that this potential relationship "warrants serious consideration from the point of view of public health policy."^[11]
• A 2014 review said that "Because longitudinal work indicates that cannabis use precedes psychotic symptoms, it seems reasonable to assume a causal relationship" between cannabis and psychosis, but that "more work is needed to address the possibility of gene-environment correlation."^[22]
• A 2016 meta-analysis found that cannabis use increases the risk of psychosis, and that a dose-response relationship exists between the level of cannabis use and risk of psychosis. The analysis was not able to establish a causal link.^[23]
• Another 2016 meta-analysis found that cannabis use only predicted transition to psychosis among those who met the criteria for abuse of or dependence on the drug.^[24]
• A 2016 review found that the epidemiologic evidence regarding cannabis use and psychosis was strong enough "to warrant a public health message that cannabis use can increase the risk of psychotic disorders," but also cautioned that additional studies are needed to determine the size of the effect.^[25]
• A 2016 review said that the existing evidence did not show that cannabis caused psychosis, but rather that early or heavy cannabis use were among many factors more likely to be found in those at risk of developing psychosis.^[26]

References