Heavy cannabis use associated with reduced dopamine release in brain

Effect similar to other addictions

April 14, 2016

Science Daily/Columbia University Medical Center

In a recent study, researchers found evidence of a compromised dopamine system in heavy users of marijuana. Lower dopamine release was found in the striatum -- a region of the brain that is involved in working memory, impulsive behavior, and attention. Previous studies have shown that addiction to other drugs of abuse, such as cocaine and heroin, have similar effects on dopamine release, but such evidence for cannabis was missing until now.

"In light of the more widespread acceptance and use of marijuana, especially by young people, we believe it is important to look more closely at the potentially addictive effects of cannabis on key regions of the brain," said Anissa Abi-Dargham, MD, professor of psychiatry (in radiology) at Columbia University Medical Center (CUMC) and a lead author of the paper.

The study included 11 adults between the ages of 21 and 40 who were severely dependent on cannabis and 12 matched healthy controls. On average, the cannabis group started using at age 16, became dependent on cannabis by age 20, and have been dependent for the past 7 years. In the month prior to the study, nearly all users in this study smoked marijuana daily.

Using positron emission tomography (PET) to track a radiolabelled molecule that binds to dopamine receptors in the brain, the scientists measured dopamine release in the striatum and its subregions, as well as in several brain regions outside the striatum, including the thalamus, midbrain, and globus pallidus. The cannabis users in this study stayed in the hospital for a week of abstinence to ensure that the PET scans were not measuring the acute effects of the drug. Participants were scanned before and after being given oral amphetamine to elicit dopamine release. The percent change in the binding of the radiotracer was taken as an indicator of capacity for dopamine release.

Compared with the controls, the cannabis users had significantly lower dopamine release in the striatum, including subregions involved in associative and sensorimotor learning, and in the globus pallidus.

The investigators also explored the relationship between dopamine release in a key area of the striatum and cognitive performance on learning and working memory tasks. Although there was no difference between groups in task performance, in all participants lower dopamine release was associated with worse performance on both tasks.

"We don't know whether decreased dopamine was a preexisting condition or the result of heavy cannabis use," said Dr. Abi-Dargham. "But the bottom line is that long-term, heavy cannabis use may impair the dopaminergic system, which could have a variety of negative effects on learning and behavior."

Jeffrey Lieberman, MD, Chair of Psychiatry at CUMC and past president of the American Psychiatric Association, noted that "these findings add to the growing body of research demonstrating the potentially adverse effects of cannabis, particularly in youth, at the same time that government policies and laws are increasing access and use."

https://www.sciencedaily.com/releases/2016/04/160414214826.htm

Long-term cannabis use may blunt the brain's motivation system

July 1, 2013

Science Daily/Imperial College London

Long-term cannabis users tend to produce less dopamine, a chemical in the brain linked to motivation, a study has found.

Researchers found that dopamine levels in a part of the brain called the striatum were lower in people who smoke more cannabis and those who began taking the drug at a younger age.

They suggest this finding could explain why some cannabis users appear to lack motivation to work or pursue their normal interests.

The study, by scientists at Imperial College London, UCL and King's College London, was funded by the Medical Research Council and published in the journal Biological Psychiatry.

The researchers used PET brain imaging to look at dopamine production in the striatum of 19 regular cannabis users and 19 non-users of matching age and sex.

The cannabis users in the study had all experienced psychotic-like symptoms while smoking the drug, such as experiencing strange sensations or having bizarre thoughts like feeling as though they are being threatened by an unknown force.

The researchers expected that dopamine production might be higher in this group, since increased dopamine production has been linked with psychosis. Instead, they found the opposite effect.

The cannabis users in the study had their first experience with the drug between the ages of 12 and 18. There was a trend for lower dopamine levels in those who started earlier, and also in those who smoke more cannabis. The researchers say these findings suggest that cannabis use may be the cause of the difference in dopamine levels.

The lowest dopamine levels were seen in users who meet diagnostic criteria for cannabis abuse or dependence, raising the possibility that this measure could provide a marker of addiction severity.

Previous research has shown that cannabis users have a higher risk of mental illnesses that involve repeated episodes of psychosis, such as schizophrenia.

"It has been assumed that cannabis increases the risk of schizophrenia by inducing the same effects on the dopamine system that we see in schizophrenia, but this hasn't been studied in active cannabis users until now," said Dr Michael Bloomfield, from the Institute of Clinical Sciences at Imperial, who led the study.

"The results weren't what we expected, but they tie in with previous research on addiction, which has found that substance abusers -- people who are dependent on cocaine or amphetamine, for example -- have altered dopamine systems.

"Although we only looked at cannabis users who have had psychotic-like experiences while using the drug, we think the findings would apply to cannabis users in general, since we didn't see a stronger effect in the subjects who have more psychotic-like symptoms. This needs to be tested though.

"It could also explain the 'amotivational syndrome' which has been described in cannabis users, but whether such a syndrome exists is controversial."

Other studies have looked at dopamine release in former cannabis users and not seen differences with people who haven't taken cannabis, suggesting that the effects seen in this study are likely to be reversible.

https://www.sciencedaily.com/releases/2013/07/130701081053.htm