Marijuana is perhaps the most polarizing of drugs: It's illegal in some places and allowed in others, hailed as a medical blessing by advocates and demonized as dangerous and addictive by critics. Researchers have produced conflicting studies regarding the effects of marijuana, but a new study from Columbia University Medical Center may have just added more evidence to the critics’ side: they detail marijuana’s detrimental effect on dopamine in the brain.

Previous studies have shown drugs like cocaine and heroin compromise dopamine release in the brain. An important neurotransmitter, dopamine is heavily involved in the brain’s reward and pleasure centers. These drugs stimulate the brain much more than natural rewards, leading the brain to adapt by reducing the number of dopamine receptors and clearing it more quickly from the synapses. As an effect, the brain becomes less responsive to the drug, forcing users to need more of the substance to get high. Evidence of this phenomenon with cannabis use 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 Dr. Anissa Abi-Dargham, professor of psychiatry at Columbia University Medical Center and a lead author of the paper.

The team used positron emission tomography (PET) to track a labeled molecule capable of binding with dopamine receptors in the brain. This allowed them to measure the dopamine release in a brain region called the striatum. The researchers could even measure release of the neurotransmitter in the subregions of the striatum responsible for associative and sensorimotor learning, as well as several surrounding regions.

The study included 11 adults aged 21 to 40 who were severely dependent on cannabis, and 12 healthy, matched controls. In the month prior to the study, nearly all of the users smoked marijuana daily, but during the test, users were kept in the hospital for a week of abstinence. This measure was taken to make sure the PET scans weren’t measuring acute effects of the drug.

Researchers administered an oral amphetamine to the participants to elicit dopamine release. Compared to the controls, cannabis users had significantly lower dopamine release in both the striatum and another brain region called the globus pallidus.

The team then explored the relationship between dopamine release in the striatum and performance on cognitive learning and working memory tasks. There was no difference in performance between controls and users, but in all participants lower dopamine release was associated with worse performance on the tasks — a poorer memory, for example.

The study had its limitations, most notably the small sample size and baseline knowledge of participants’ dopamine levels before they began using marijuana. “We don’t know whether decreased dopamine was a preexisting condition or the result of heavy cannabis use,” noted Abi-Dargham, “But the bottom line is that long-term, heavy cannabis use may impair the dopaminergic system, which could have a variety of effects on learning and behavior.”

Source: Giessen E, Weinstein J, Cassidy C, Haney M, Dong Z, Ghazzaoui R. deficits in striatal dopamine release in cannabis dependence. Molecular Psychiatry. 2016.