Cannabis compound THC disrupts communication between brain networks

A new study published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging provides evidence that the psychoactive component in cannabis, delta-9-tetrahydrocannabinol (THC), weakens communication between brain networks in young adult users. Researchers found that even a moderate dose of THC reduced internal connectivity in brain circuits responsible for emotional regulation, bodily awareness, sensory processing, and higher thinking. The findings help explain the mental and behavioral changes that many people experience when intoxicated with cannabis.

As cannabis use continues to rise among young adults, scientists are increasingly focused on how the drug affects the brain. In particular, THC, the main compound responsible for the “high,” is drawing attention because of its potential to interfere with how different parts of the brain work together.

Past research has shown that THC interacts with the brain’s natural cannabinoid system, a network that helps regulate mood, reward, attention, and sensory experiences. THC increases dopamine activity in this system, which can affect behavior and cognition. However, many earlier studies have only looked at specific brain circuits or have used small samples.

The researchers behind this new study wanted to take a broader approach, examining THC’s effects across the entire brain. They used a type of brain imaging that measures how brain regions naturally coordinate with each other when a person is at rest, rather than performing a specific task.

“Many people use cannabis and we know little about how different cannabinoids like delta-9-THC impact the brain,” said study author Natania A. Crane, an assistant professor and director of the REWARD Laboratory at the University of Illinois at Chicago. “Delta-9-THC is only one of the over 100 different cannabinoids that make up cannabis. Delta-9-THC is important because it is the main psychoactive compound of cannabis, linked to the addictive and rewarding properties of cannabis. We wanted to understand how delta-9-THC impacts communication between different areas of the brain compared to placebo.”

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The study included 33 young adults between 18 and 25 years old who occasionally used cannabis but were otherwise healthy. To isolate the effects of THC, each participant took part in two sessions. In one session, they received a 7.5 milligram dose of oral THC. In the other, they received a placebo.

Both sessions were separated by several days, and participants did not know which substance they were receiving. About two hours after taking the pill — when THC’s effects are typically strongest — participants underwent a type of brain scan called resting-state functional magnetic resonance imaging (fMRI).

During the scan, participants stared at a fixed point while letting their thoughts wander. The researchers analyzed the brain data using a method that identifies patterns of activity across the whole brain. They examined both how well different parts of each network were working together (called “within-network connectivity”) and how well different networks were interacting with each other (“between-network connectivity”).

After taking THC, participants reported stronger feelings of intoxication, as expected. But the brain data revealed more than just a general effect. THC reduced internal communication in several key networks.

Some of the most affected networks involved areas of the brain tied to memory, emotion, and motivation. These included regions like the hippocampus and basal ganglia. Other impacted networks were connected to sensory processing and spatial reasoning. For example, a network linking the parahippocampus and visual cortex showed weakened coordination.

The researchers also found that THC disrupted communication between two networks that include the insula and anterior cingulate cortex — regions often associated with bodily awareness and emotional monitoring. Specifically, THC reduced the connection between the upper and lower parts of these networks, suggesting that these brain systems were not working together as smoothly when the participants were intoxicated.

Importantly, the study did not find a link between the strength of these brain changes and how high the participants felt or how often they used cannabis in the past month. This suggests that the observed changes in brain communication happen regardless of how intense the intoxication feels or how frequently someone uses the drug, at least among people who use it occasionally.

The researchers also looked at how brain activity varied across different frequency bands — essentially, the rhythm of brain signals. They found that THC changed the amount of activity in both low and high frequency bands in certain networks, including those involved in self-awareness and emotional regulation. These changes may reflect shifts in how information is processed throughout the brain.

Overall, the findings suggest that THC has widespread effects on how brain systems function together, especially in areas related to thinking, feeling, and sensing. These disruptions could help explain why cannabis use is linked with changes in attention, working memory, and emotional experience.

“Among healthy young adults who occasionally use cannabis, delta-9-THC reduces connections throughout the brain compared to placebo. Specifically, we found that delta-9-THC acutely reduces connections between brain areas involved in emotion, interoception (internal sense of what is happening in your body), processing sensory information, and executive functioning,” Crane told PsyPost.

“This may help to explain why individuals who use cannabis often report that cannabis acutely decreases strong emotions, changes how they feel, and increases the intensity of perceptual experiences. It also helps to explain how cannabis acutely decreases attention, working memory, and other executive functioning measures- these networks aren’t communicating the way they usually do when someone is intoxicated with delta-9-THC.”

The study provides a broader look at how THC affects the brain, but some limitations should be considered. The sample size was relatively small and included only occasional cannabis users without major psychiatric conditions. As a result, the findings might not apply to people who use cannabis more heavily or who have mental health disorders.

The researchers used a moderate dose of THC, which may be lower than the amount found in some recreational products. Because the drug was given in a controlled lab setting, the results might differ from what happens when cannabis is smoked or consumed in other ways.

Another limitation is that the study relied on short brain scans taken during a single session. Longer or repeated scans could provide a more complete picture of how THC changes brain function over time. The researchers also note that their method, while sensitive, may not capture all aspects of how the brain responds to THC.

Future studies may want to examine different doses of THC, include people with anxiety or depression, or compare THC with other compounds in cannabis, such as cannabidiol (CBD). The researchers are also interested in tracking how repeated cannabis use over time affects brain networks, especially in people who use the drug to manage mood symptoms.

“I am really interested in understanding how different cannabinoids impact the brain among individuals with psychiatric disorders like depression and anxiety, who have high rates of cannabis use. So many patients I see report that they use cannabis to help with depression and/or anxiety. The research tells us that cannabis can reduce symptoms of depression and anxiety acutely, yet over time regular cannabis use, especially cannabis with high delta-9-THC content, actually increases symptoms of depression and anxiety.”

“This leads to a vicious cycle — using cannabis to relieve anxiety or depression, but these symptoms just get worse as use continues. I want to better understand the mechanisms of this—how cannabinoids like delta-9-THC act in the brain acutely and over time among individuals with psychiatric disorders like depression and anxiety.”

The study, “Δ9-Tetrahydrocannabinol Alters Limbic and Frontal Functional Brain Connectomes Among Young Adult Cannabis Users,” was authored by Zachary Anderson, Matthew Gunn, Emily Jones, Olusola Ajilore, K.Luan Phan, Harriet de Wit, Heide Klumpp, Vince Calhoun, and Natania A. Crane.