Progression to Daily Cannabis, Tobacco Use Linked to Earlier Onset of Psychosis

Pauline Anderson

November 18, 2009

November 18, 2009 — Daily use of cannabis or tobacco has been linked to an earlier age of onset of prodromal and psychotic symptoms, new research shows.

Results of the study suggest that escalation of cannabis use may promote the onset of prodromal and subsequent psychotic symptoms, lead author Michael T. Compton, MD, MPH, assistant professor, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, told Medscape Psychiatry.

If this is so, young people at risk for psychotic disorders should refrain from using marijuana, said Dr. Compton. "Adolescents who are at elevated risk for schizophrenia and other psychotic disorders, because of a family history of such disorders or evidence of early prodromal symptoms, should probably be advised not to use cannabis as there is now some early evidence that such use could hasten the onset of psychotic symptoms."

The study, one of the first to analyze escalation of frequency of substance use over time, is published in the November issue of the American Journal of Psychiatry.

Changes Over Time

According to the study, cannabis is the most abused illicit substance among people with schizophrenia. In patients with first-episode psychosis, rates of cannabis misuse have been reported to be as high as 65%. Many studies of first-episode patients show that initiation of substance use typically precedes onset of psychosis, often by several years.

The study included 109 patients (24% women) aged 18 to 40 years who were admitted to a psychiatric unit of a university-affiliated, public sector hospital or a county psychiatric crisis center. All patients were experiencing a first episode of psychotic symptoms. The sample was from an urban, low-income, primarily African-American community.

Using the Structured Clinical Interview for DSM-IV Axis I disorders, researchers determined that the primary diagnoses among the sample were schizophrenia (56.9%), schizophreniform disorder (20.2%), schizoaffective disorder (7.3%), psychotic disorder not otherwise specified (11.0%), brief psychotic disorder (3.7%), and delusional disorder (0.9%).

Investigators classified patients according to their frequency of cannabis, alcohol, and tobacco use (none, ever, weekly, daily) before the onset of prodromal and psychotic symptoms.

The study showed that daily cannabis use (40.6%) and daily tobacco use (44.1%) were common, although daily alcohol use was relatively rare (7.9%). Of those who abused cannabis, almost 88% were classified as weekly (43.8%) or daily (43.8%) users before the onset of psychosis. Of those with cannabis dependence, 90% were classified as weekly (7.5%) or daily (82.5%) users before onset.

The researchers found no significant effects of cannabis or tobacco use on the risk for onset of psychotic symptoms when they simply categorized participants by their highest ever level of use. However, when examining changes in substance use over time, they found significant effects of progression to both daily cannabis use and daily tobacco use on the risk for onset of psychosis.

Earlier Onset in Women

There appeared to be a greater effect in female patients. Women who progressed to daily cannabis use had an even earlier onset of psychotic symptoms compared with their male counterparts. Researchers were unable to definitively explain this finding. "However," said Dr. Compton, "it appears that escalation of cannabis use may diminish the known effect of gender on age at onset — women typically have a later age at onset."

Although it is not clear why escalating cannabis use may hasten onset of psychosis, Dr. Compton noted that studies have shown increased cannabinoid receptor density in areas of the brain and elevated levels of endogenous cannabinoids in the blood of some patients with psychosis.

Earlier onset of psychotic symptoms generally results in more severe disease, so delaying onset could result in substantial improvements in outcomes.

The link between progression to daily cannabis use and psychosis should prompt efforts to get at-risk adolescents to refrain from substance use, said Dr. Compton. He added that further research is needed to determine how best to curtail their substance use.

Modifiable Risk Factor

Asked by Medscape Psychiatry to comment on the study findings, Cheryl Corcoran, MD, said the good news is that cannabis use is a modifiable risk factor.

"You can't change who your family is, we don't think you can change exposures in utero, and you can't change your genes. On the other hand, we can intervene with people who are at risk in terms of trying to reduce their cannabis use," said Dr. Corcoran, who is assistant professor of clinical psychiatry and director of the Center of Prevention and Evaluation, Columbia University, New York City.

One of the limitations of the study is that the escalating frequency of substance abuse may be an effect rather than a cause of psychosis; young people who are headed for psychosis may use cannabis at an escalating rate simply to try to ward off or cope with very early symptoms.

"We can't prove the directionality of findings or causality," said Dr. Compton. "However, the substance use escalation that we measured occurred before the onset of any symptoms that we could detect retrospectively. Clearly, longitudinal studies are crucial, though difficult, to conduct."

Dr. Corcoran pointed out that there could be some other factor — perhaps anxiety — that might explain the association between cocaine use and psychosis. "When people are anxious, they're going to be using more drugs and then the drug is not causal; it's still a marker. So you could have the drug use and the psychosis both resulting from some third factor."

She praised the study authors for being the first to look at prodromal symptoms and psychotic symptoms and to include a large sample size. She found that the investigation of patterns of drug use over time was "novel" and the difference between men and women noted by the researchers was "intriguing."

However, one of her "caveats" is that the study did not include a statistical model that analyzed tobacco and cannabis together.

"The findings for either one of those drugs could be confounded or explained by the use of the other one," she said. "It may be that tobacco is not relevant [but] the cannabis use is, but the people who smoke cannabis also happen to be using tobacco. It may also be true the other way around — that tobacco is important but those people also happen to be using marijuana as well."

Dr. Corcoran noted that the study is retrospective and based on self-reports and that its findings may not be applicable outside the population studied.

She said her own research has found a link between cannabis use and psychosis in a high-risk population. She and her colleagues assessed prodromal patients at baseline and every 3 months and found that during periods when the patients were using more cannabis, their attenuated psychotic symptoms worsened.

She is convinced that methamphetamine abuse is also probably related to the onset of psychosis and that future studies will confirm this.

Dr. Compton and Dr. Corcoran have disclosed no relevant financial relationships.

Am J Psychiatry. 2009;166:1251–1257. Abstract

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