Daily, long-term marijuana use may be linked to abnormalities in parts of the brain that regulate emotion and memory, as well as fear and aggression, according to a new study.

The part of the brain believed to regulate emotion and memory, known as the hippocampus, was on average 12 per cent smaller in marijuana users compared to non-marijuana users. The amygdala, which regulates fear and aggression, was on average just more than 7 per cent smaller.

Australian researchers conducted high-resolution structural magnetic resonance imaging (MRI) on the brains of 15 men who smoked five joints a day for more than 10 years. They compared these MRIs to those of 16 control subjects who did not use marijuana.

The researchers also found that the marijuana users had early symptoms of psychotic disorders, such as schizophrenia and mania. However, those symptoms were considered sub-threshold, meaning they were below the level required for a diagnosis.

The findings add to the ongoing debate about the potential ramifications that regular marijuana use can have on a user's health. Some argue that it does not have negative health effects and its use should be made legal. However, many doctors and scientists believe marijuana use is linked to a variety of health problems.

"With nearly 15 million Americans using cannabis in a given month, 3.4 million using cannabis daily for 12 months or more and 2.1 million commencing use every year, there is a clear need to conduct robust investigations that elucidate the long-term consequences of long-term cannabis use," the study's authors wrote.

"Although modest use may not lead to significant neurotoxic effects, these results suggest that heavy daily use might indeed be toxic to human brain tissue."

The research was conducted by Murat Yucel, PhD, of Orygen Research Centre and the Melbourne Neuropsychiatry Centre at the University of Melbourne, along with colleagues from the University of Wollongong. The findings are published in the June issue of the Archives of General Psychiatry.

The researchers said that further study needs to be conducted on the long-term consequences of marijuana use and how quitting may reverse the potential adverse health effects.


Regional Brain Abnormalities Associated With Long-term Heavy Cannabis Use

Murat Yucel, PhD, MAPS; Nadia Solowij, PhD; Colleen Respondek, BSc; Sarah Whittle, PhD; Alex Fornito, PhD; Christos Pantelis, MD, MRCPsych, FRANZCP; Dan I. Lubman, MB ChB, PhD, FRANZCP

Context: Cannabis is the most widely used illicit drug in the developed world. Despite this, there is a paucity of research examining its long-term effect on the human brain.

Objective: To determine whether long-term heavy cannabis use is associated with gross anatomical abnormalities in 2 cannabinoid receptor-rich regions of the brain, the hippocampus and the amygdala.

Design: Cross-sectional design using high-resolution (3-T) structural magnetic resonance imaging.

Setting: Participants were recruited from the general community and underwent imaging at a hospital research facility.

Participants: Fifteen carefully selected long-term (_10 years) and heavy (_5 joints daily) cannabis-using men (mean age, 39.8 years; mean duration of regular use, 19.7 years) with no history of polydrug abuse or neurologic/ mental disorder and 16 matched nonusing control subjects (mean age, 36.4 years).

Main Outcome Measures: Volumetric measures of the hippocampus and the amygdala combined with measures of cannabis use. Subthreshold psychotic symptoms and verbal learning ability were also measured.

Results: Cannabis users had bilaterally reduced hippocampal and amygdala volumes (P=.001), with a relatively (and significantly [P=.02]) greater magnitude of reduction in the former (12.0% vs 7.1%). Left hemisphere hippocampal volume was inversely associated with cumulative exposure to cannabis during the previous 10 years (P=.01) and subthreshold positive psychotic symptoms (P_.001). Positive symptom scores were also associated with cumulative exposure to cannabis (P=.048). Although cannabis users performed significantly worse than controls on verbal learning (P_.001), this did not correlate with regional brain volumes in either group.

Conclusions: These results provide new evidence of exposure-related structural abnormalities in the hippocampus and amygdala in long-term heavy cannabis users and corroborate similar findings in the animal literature. These findings indicate that heavy daily cannabis use across protracted periods exerts harmful effects on brain tissue and mental health.