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November 11, 2011 — Marijuana use can lead to a loss of brain volume in individuals who are at risk of developing schizophrenia, new research shows.

"It is now accepted by most psychiatrists that smoking cannabis increases an individual's risk of psychosis, and more specifically schizophrenia," lead author Killian A. Welch, MD, from the University of Edinburgh, Royal Edinburgh Hospital, United Kingdom, told Medscape Medical News.

However, the risk associated with using the drug does not seem to be equally distributed across the population, Dr. Welch added.

"People with a family history of schizophrenia are particularly vulnerable to the psychotomimetic effects of the drug, and are likely at particular elevated risk of developing schizophrenia if they use cannabis," he said. "Still, it has remained unclear how cannabis affects the brain to result in this increased risk."

The study was published in the November issue of the British Journal of Psychiatry.

Highly Significant Volume Reduction

In the current study, Dr. Welch and colleagues compared structural changes in the thalamus and amygdala-hippocampal complex over time in 57 people aged between 16 and 25 years who were well but who had a strong family history of schizophrenia.

Each person had a full assessment, including a magnetic resonance imaging scan.

Two years later, each person returned for another scan and were also asked about their use of illicit drugs, including marijuana, as well as their use of alcohol and tobacco in the period between the scans.

Of the 57 participants, 25 had used marijuana between the 2 assessments.
The researchers found that those participants who had used marijuana showed a reduction in their thalamic volume that was significant on the left side of the thalamus (F = 4.47; P = .04), and highly significant on the right (F = 7.66; P = .008). However, no loss of thalamic volume was noted in those who did not use marijuana during the 2-year period.

Some of the participants who used marijuana also used other drugs such as ecstasy and amphetamines. After controlling for the use of these other drugs, the results remained significant.

Potentially Devastating Consequences

"This is the first longitudinal study to show that cannabis use by individuals at increased risk of schizophrenia is resulting in their brain developing in a different way from the way it develops if they do not use the drug," Dr. Welch noted.

"These are people who are currently well, not psychotic, and their use of the drug is associated with volume loss in a critical brain structure. By far the most likely explanation for this is that it is the cannabis exposure which is causing these abnormalities of brain development," he said.

The thalamus is a very important brain structure that acts as an information processing and relay station for the brain, he added. "Given this role in interconnecting diverse brain regions, anything that affects its structure, and consequently, one assumes, its function, would be expected to have widespread and potentially devastating consequences."

Dr. Welch warned that these findings should not be misconstrued to suggest that marijuana use is safe if one has no such family history. However, "it seems safe to say that if you do have such a background you should be particularly wary of the drug," he said.

Novel Finding

Jean Bidlack, PhD, Paul Stark Professor of Pharmacology at the University of Rochester School of Medicine and Dentistry in New York, told Medscape Medical News that the study by Dr. Welch and colleagues adds something useful to what is already known on the subject.

"This is the first study to show an association between a decrease in the volume of the thalamus and the use of marijuana in currently unaffected people who are at a high risk of developing schizophrenia due to family history," Dr. Bidlack said.

"A decrease in the volume of the thalamus has been associated with psychosis and schizophrenia. The thalamus has a high level of cannabinoid receptors, which bind the active ingredient in marijuana and may contribute to the decrease in the volume of the thalamus," she explained.

This research begins to explain the link between marijuana use and the development of schizophrenia in this high-risk group, she said.

Dr. Welch and Dr. Bidlack have disclosed no relevant financial relationships.
Br J Psych. 2011;199:386-390. Abstract