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Effects of Long-Term Marijuana Use on the Brain Shown Similar to Other Addicting Drugs

A team of TSRI scientists led by George Koob, Ph.D., has determined that long-term use of marijuana produces changes in the brain that are similar to those seen after long-term use of other major drugs of abuse such as cocaine, heroine and alcohol. Moreover, these changes may increase a user's vulnerability to addiction to other abusable dugs by "priming" the brain to be more easily changed by drugs in the future. This study was published in Science magazine.

"We know that a substantial number of chronic marijuana users become addicted, and previous research with animals has shown that stopping heavy marijuana use suddenly can cause distinct withdrawal symptoms," said Dr. Alan I. Leshner, director of the National Institute on Drug Abuse, National Institutes of Health, which supported this research. "This study shows that marijuana use shares common brain changes and mechanisms with other drugs of abuse."

This study was conducted by the scientists at TSRI with collaborators from Spain to discover whether CRF (corticotropin-releasing factor), a brain chemical which increases during emotional times and periods of stress, plays a role in dependence on cannabis, the plant from which marijuana and hashish are derived. Earlier studies have suggested that CRF plays a role in the neurobiological and behavioral effects of withdrawal from addiction to cocaine, alcohol and opiates, and possibly a role in drug dependence in general.

Rats were injected with HU-210, a potent substance that mimics the effects of marijuana. An analysis of the rats' brains showed that one injection of HU-210 reduced the release of CRF in the amygdala, a key brain structure involved in emotions.

After 14 days of HU-210 treatment, the researchers induced drug withdrawal by injecting rats with the antagonist SR 141716A, a substance that blocks the many effects of marijuana. The marijuana-treated rats showed many withdrawal symptoms after marijuana antagonist injection. Moreover, these rats showed an increased release of CRF at the same time they demonstrated dramatic behavioral withdrawal symptoms. Importantly, the specific brain areas that were activated during cannabinoid withdrawal are quite active during withdrawal from other drugs of abuse and play a key role in stress responses in general.

"These results provide evidence that long-term exposure to cannabinoids leads to changes in the brain that activate stress-like responses during cannabinoid withdrawal," said TSRI scientist Friedbert Weiss, Ph.D. "These changes in CRF functioning in the brain are similar to those seen during withdrawal from alcohol, cocaine, and opiates, as well as during exposure to environmental stressors," he added.

George Koob, Ph.D., Professor of Neuropharmacology at TSRI, observed that "the finding from this and other studies that long-term exposure to cannabinoids can produce changes in the brain that resemble those associated with other major drugs of abuse suggests that addiction to one drug may make a person more vulnerable to abuse and addiction to other drugs. Cannabinoid abuse, by activating CRF mechanisms, may lead to a subtle disruption of brain processes that are then primed' for further and easier disruption by other drugs of abuse."

The study was supported in the United States by the National Institute on Drug Abuse and the National Institute of Diabetes, Digestive and Kidney Diseases, both parts of the National Institutes of Health, and in Spain, by the Comision Interministerial de Ciencia y Tecnologia, and Comunidad Autonoma de Madrid.

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