New neuroimaging research provides new insight into how tetrahydrocannabinol, or THC, the main psychoactive compound in cannabis, affects the human brain. The study found that THC increases glutamate concentrations in the striatum, a major brain structure involved in the coordination of body movement, decision-making and the initiation of action.

The new findings appear in the journal European Neuropsychopharmacology.

“Cannabis remains the most widely used illicit drug in the world. However, despite its widespread use, the underlying mechanisms of THCs behavioural effects have not yet been fully elucidated,” said study author Natasha L. Mason of the Department of Neuropsychology and Psychopharmacology at Maastricht University.

“By applying a cutting edge research design, i.e. a multimodal brain imaging strategy, the present study aimed to provide a neurochemical context for THC induced behavioural alterations. We believe that this information has a timely and broad application, which extends beyond those in the field of psychopharmacology and neuroscience.”

“Namely, in light of changing legalization status and a growing interest in therapeutic utility, it is important to understand the biochemical alterations that occur during use, and that may give rise to experienced therapeutic effects. Additionally, as 10% of cannabis users develop daily use patterns, understanding the underlying neuroadaptations that are involved in this process are important for treating addiction and realizing potential consequences of long-term use,” Mason explained.

The double-blind, placebo-controlled study of 20 healthy, occasional cannabis users found THC intoxication was associated with functional connectivity alterations in the brain, which in turn were associated with decreased performance on an attention task.

“There are two main findings from this study that are important in a broader sense. First of all, when people think of THC and cannabis, they think of dopamine as the main underlying mechanism of the (rewarding) effects. Although not incorrect, our results suggest that glutamate plays a significant role in this as well. This is important when establishing not only how cannabis works in the brain, but also when thinking about treatments for things like cannabis use disorder,” Mason told PsyPost.

“Secondly, our results extend previous research demonstrating that a certain level of THC (specifically 2 ng/ml) has to be present in blood in order to affect brain and cognitive function. As cannabis use becomes more popular, and access to medical cannabis grows, these findings are important in forensic settings when inferring impairment levels from THC levels in blood.”

But there is still much to learn about how THC affects the brain.

“In this study we were testing occasional cannabis users, who use on average around once a week. Thus, the next step in this line of research will be to utilize the same design in chronic (daily) cannabis users,” Mason said.

“This allows us to compare brain changes between the two (those who use cannabis every once in a while vs those who smoke every day), and ultimately assess long-term neuroadaptions which may play a role in e.g. substance addiction, or may result from prescription (therapeutic) use.”

The study, “Cannabis induced increase in striatal glutamate associated with loss of functional corticostriatal connectivity“, was authored by Natasha L. Mason, Eef L. Theunissen, Nadia R.P.W. Hutten, Desmond H.Y. Tse, Stefan W. Toennes, Peter Stiers, and Johannes G. Ramaekers.