Cannabis Use and Psychosis

There is growing interest in the relationship between cannabis use and psychosis.  Epidemiologic studies support higher rates of cannabis use in those that develop psychosis, but this could just be an association finding rather than a causal effect.  For example, a genetic factor that increases risk for psychosis could also increase risk for cannabis use.   Alternatively, subtle pre-psychosis onset symptoms may increase risk for the use of cannabis—cannabis may be used to treat some premorbid symptoms of psychosis.  Additionally, epidemiologic studies can be confounded by unmeasured variables. 

I have to admit that I started out in the skeptical camp for a significant link between cannabis use and psychosis.  But recent evidence is making me re-think this issue and the complexity of the relationship.  Two research studies have recently added important understanding to the issue.

McGrath and colleagues in Australia used a sibling pair analysis to examine the effect of cannabis use on later psychotic symptoms.  Sibling pairs provide a strategy to attempt to minimize the potential for unmeasured confounding variables.

Three thousand eight hundred and one young adults born between 1981 and 1984 were followed and assessed.  Cannabis use was assessed and psychosis was measured in three domains:

• Presence of a non-affective psychosis (i.e. schizophrenia)
• Presence of hallucinations
• Score on a inventory of delusions (Delusions Inventory score)

 Subjects with six years or more since cannabis use were examined for the key psychosis domains with the following results:

• Odds ratios elevated for all three domains in the sample as a whole (non-affective psychosis odds ratio 2.2, presence of hallucinations odds ratio 2.8 and scoring highest quartile of delusion odds ratio 4.2)
• When only the sib pairs were examined the relationship between duration since first use and delusions inventory remained significant—this supports a true relationship not confounded by unmeasured variables

Another study from the Netherlands adds insight into the relationship between cannabis and psychosis.  The study used two designs a sibling-non-sibling control and a cross sibling comparison.  Cannabis use in this study was assessed by urinalysis and a lifetime frequency of use instrument.  Psychosis in this study included a structured interview for schizotypy and the Community Assessment of Psychic Experiences.   The key findings from this study included:

• Siblings currently using cannabis  were much more likely than controls to  show sensitivity to positive symptoms of psychosis (i.e. hallucinations/delusions)
• Siblings using cannabis with a relative with psychosis showed increased positive psychotic symptomatology compared to siblings not using cannabis

 The authors note the double design study supports a interpretation that “genetic risk for psychotic disorder may be expressed in part as sensitivity to the psychotomimetic effect of cannabis”.  In other words, familial psychosis risk is moderated through a sensitivity to psychotic symptoms with cannabis.  Their findings are less supportive of a role for familial psychotic risk to increase the use of cannabis (mediation).

I interpret these studies to indicate that for the population as a whole, cannabis use may have a very limited effect on risk of psychosis.  However, if you carry a familial (genetic) risk for psychosis, cannabis use may potentiate that risk.  This potentiation may depend in part on the quantity and duration of use as well as which brain developmental period use begins.  Heavy adolescent onset use may be the most concerning period of vulnerability in those with a genetic risk for psychosis.  Experiencing psychotic symptoms with cannabis use may be a marker for increased risk for a later persistent psychotic disorders.   The take home messages for clinicians—1.) patients with a family history of psychosis should not use cannabis, 2.) patients experiencing psychotic symptoms with cannabis use should be educated that this is not a good sign and they may be most vulnerable to psychosis with continued heavy use.

Photo of Signage on San Antonio Riverwalk Courtesy of Yates Photography

McGrath J, Welham J, Scott J, Varghese D, Degenhardt L, Hayatbakhsh MR, Alati R, Williams GM, Bor W, & Najman JM (2010). Association between cannabis use and psychosis-related outcomes using sibling pair analysis in a cohort of young adults. Archives of general psychiatry, 67 (5), 440-7 PMID: 20194820

Genetic Risk and Outcome in Psychosis (GROUP) Investigators (2010). Evidence That Familial Liability for Psychosis Is Expressed as Differential Sensitivity to Cannabis: An Analysis of Patient-Sibling and Sibling-Control Pairs. Archives of general psychiatry PMID: 20921112