Cannabis Use Increases Psychosis Risk and Persistence of Subclinical Psychosis

Caroline Helwick

September 07, 2010

September 7, 2010 (Amsterdam, The Netherlands) — Cannabis use significantly increases the risk for incident psychotic symptoms in individuals with no prior history of psychotic experiences. In persons with evidence of psychosis, cannabis use aids in the persistence of these symptoms, according to researchers from the University of Maastricht in The Netherlands, who have done much of the existing work in the area of cannabis and psychosis.

Cecile Henquet, PhD, of the Department of Psychiatry and Neuropsychology at the University of Maastricht, reported the findings at the 23rd European College of Neuropsychopharmacology (ECNP) Congress.

"It has been known for many years that persons with schizophrenia or other psychotic illness use more cannabis than the general population, and other work has shown that individuals using cannabis during adolescence and early adulthood have a higher risk of developing psychotic symptoms. It remains unclear, however, whether the association between cannabis and psychosis is causal or whether an underlying genetic predisposition for psychosis may prompt cannabis use as a way of self-medication. A second issue is whether cannabis impacts on persistence rates of psychosis and which biological mechanisms may underlie this process," Dr. Henquet said.

Medscape Medical News reported other news on cannabis use and its effect on improving cognitive functioning in some schizophrenic patients. Those findings were also announced at the 23rd ECNP Congress (Early Use of Cannabis May Improve Cognitive Functioning in Subgroup of Patients With Schizophrenia).

Dr. Henquet and her colleagues analyzed the 8-year follow-up data from the Munich Early Developmental Stages of Psychopathology (EDSP) study of 3021 individuals aged 14 to 24 years and the Greek Birth Cohort Study of 3500 subjects assessed at ages 7 and 19 years. Dr. Henquet's team collaborated on both these studies.

The EDSP study had previously shown that cannabis use raises the risk for psychosis by 70% and nearly triples the risk when used at least 3 times a week. The current analysis of the EDSP study excluded persons who were already using cannabis and those who had demonstrated signs of psychosis at the 4-year follow-up. Substance use and clinical status were assessed using the Composite International Diagnostic Interview.

"We were looking at the effect of cannabis on new-onset psychotic symptoms at 8 years. We found what others have found, that the use of cannabis in the general population increases the risk of psychotic symptoms in young adults," she reported.

Adjusting for age, sex, socioeconomic status, use of other drugs, childhood trauma, and urbanicity (which have been associated with psychosis), there was an 8% increased risk (P = .018) for new-onset cannabis users to develop psychotic symptoms.

"Then we wanted to understand if cannabis not only increases the risk of symptoms but also the risk of psychotic illness," she said. "We know that subclinical psychotic symptoms are present in 15% to 20% of healthy individuals at some point in life, and we know these are associated with liability for psychosis. In most persons they are transitory, but when they persist, possibly as an effect of an environmental risk factor, the risk for developing psychotic disorder is much greater."

The study found that the persistence of subclinical symptoms across all follow-up assessments was associated in a "dose-response" fashion with the development of a psychotic disorder. The presence of symptoms carried the following odds ratios (ORs) for clinical psychosis at 8 years: OR of 1.5 when symptoms were present only at baseline, OR of 5.0 for subclinical symptoms at 2 time points, and OR of 9.9 for symptoms still present at year 4.

"We then wanted to see if cannabis is one of the risk factors interacting with a genetic liability for psychosis. We found the risk of persistent symptoms to be higher after cannabis use, again with a dose-response relationship," Dr. Henquet reported. The OR was 1.95 unadjusted (P = .005) and 1.63 adjusted (P = .045).

Interaction Found With Urbanicity and Childhood Trauma

To better understand how cannabis use might affect psychosis risk, the investigators looked for interactions with urbanicity (ie, population density), which has consistently been associated with both psychotic symptoms and illness. The EDSP study compared adolescents in Munich (4061 persons per square mile) to those living in the surrounding area (553 persons per square mile).

For rural residents there was no difference in risk for psychosis between cannabis users and non–cannabis users. However, among city dwellers, cannabis users had a greatly increased risk over their non–cannabis-using peers.

"You can see that the effect of cannabis use during adolescence is particularly detrimental for those growing up in the city," she said.

The proportion of subjects with psychotic symptoms at 8 years among rural youth was 6% for cannabis users and 8% for nonusers, whereas for urban youth it was 7% and 15%, respectively (P = .019).

Similar observations were made for another risk factor, childhood trauma. Using data from the longitudinal Greek Birth Cohort, the researchers found no effect of cannabis use for persons without childhood trauma but a significant increase in psychosis among those reporting childhood trauma.

"These findings indicate there is a complex association between cannabis use and psychosis. Environmental factors seem to underlie this association, possibly by interacting with cannabis exposure," Dr. Henquet said.

The investigators propose that most persons have "genetic tolerability" and exhibit no subclinical psychotic symptoms; others have subclinical schizotypal symptoms that are transitory; and the third group have subclinical symptoms that persist, and when coupled with cannabis exposure these evolve into a psychotic disorder that can be long-lasting. "Probably, a dysregulation of the dopaminergic system underlies this increased sensitivity," she suggested.

Hans-Ulrich Wittchen, MD, of Technical University Dresden in Germany, who was the principal investigator of the EDSP study, also spoke at the meeting's session on cannabis use and psychosis. He commented to Medscape Medical News that the findings regarding cannabis use and psychosis are "not an issue."

In an interview at the meeting, he noted, "Millions of people are using cannabis, and out of these millions very few become psychotic because psychosis disorder is so rare. In the EDSP study the odds ratio rose to 2.8 (with use 3 or more times per week), but here is what that means: among the 3000 subjects, 2000 used cannabis and we saw 2 cases of psychosis initially, which rose to 6 cases with cannabis use.

"The more important problem is the occurrence of severe anxiety disorders and chronic depression with cannabis use, and no one talks about this. This is a specific problem because the cannabinoid system itself is strongly related to emotional regulation. That is the core issue, and it is much more important than the issue of psychosis," Dr. Wittchen maintained.

Dr. Henquet has disclosed no relevant financial relationships. Dr. Wittchen has disclosed financial affiliations with Eli Lilly, Novartis, Pfizer, Wyeth, and Schering-Plough. He is currently or in the past 3 years has been a consultant for Eli Lilly, GlaxoSmithKline, Hoffman-Laroche, Novartis, Pfizer, and Wyeth.

23rd European College of Neuropsychopharmacology (ECNP) Congress: Abstract S.27.04. Presented September 1, 2010.


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