New research published in drug and alcohol addiction Evidence shows that experiencing depressive symptoms at the same time as cannabis use reduces the efficiency of communication throughout the brain compared to cannabis use alone. This study suggests that while cannabis use tends to increase overall connectivity in the brain, the presence of depression attenuates this effect, resulting in reduced brain network integration.
Scientists conducted this study to better understand the biology underlying why cannabis use and depression often co-occur. Although heavy or chronic use of cannabis can increase the risk of developing depression, people with depression often turn to cannabis to self-medicate. Cannabis use and depression both independently alter the way different areas of the brain communicate with each other.
This baseline brain communication is known as resting-state functional connectivity, which refers to brain activity that occurs when a person is awake but not focused on a specific task. Previous studies have shown changes in resting connectivity in cannabis users and patients with depression, but the combined effects of both factors on the brain remained largely unknown. The researchers wanted to find out whether depression strengthens or weakens the changes in brain connectivity normally associated with cannabis use.
The human brain contains the endocannabinoid system, a biological network that plays a role in regulating mood and responding to stress. Deficiencies in this biological signaling are often associated with depression. Because cannabis contains compounds that interact directly with these same biological receptors, researchers wondered if cannabis might affect the brain differently depending on a person’s level of depression.
“Based on behavioral and epidemiological studies, there is a high rate of comorbidity between cannabis use and depressive symptoms. However, the underlying brain mechanisms that link them have remained largely unknown. “We wanted to investigate how this might interact to influence the way we interact with each other,” said study author Choi Liu, a postdoctoral fellow at the University of Texas at Dallas and a member of the Francesca M. Philby Award for Neuroimaging. Dynamics (NiRD) Laboratory
For the study, the researchers analyzed brain imaging and behavioral data from 395 adults between the ages of 18 and 55 across four different research facilities. The sample included 223 people who used cannabis weekly and tested positive for cannabis in their urine. The mean age of this group was 26.8 years and 61.9% were male. The control group consisted of 172 people with a mean age of 25.0 years, and 48.3% were male.
Participants completed a detailed questionnaire about their drug use, including a timeline of their cannabis, alcohol, and nicotine habits. They also administered the Beck Depression Inventory-II, a standard survey used to measure the severity of recent depressive symptoms. After completing the questionnaire, participants underwent magnetic resonance imaging (MRI) to scan their resting brain activity.
Scientists used a mathematical approach called graph theory to analyze the MRI data. This method maps the brain as a complex network of hubs and connections between hubs, allowing researchers to measure how efficiently information is transferred. They focused on global measurements that capture how well the whole brain communicates over long distances, and local measurements that look at activity within local functional neighborhoods.
These specific functional neighborhoods included the default mode network, which handles introspection and emotional processing. The researchers also focused on the fronto-parietal network, which governs decision-making and attention. Finally, they looked at the saliency network, which helps the brain prioritize important stimuli, and the subcortical network involved in reward processing.
The data revealed that individuals in the cannabis group had higher overall efficiency and shorter communication pathways across the brain compared to the control group. This pattern indicates a state of increased connectivity, meaning information is being sent faster and more widely between different regions. The cannabis group also showed increased local connectivity in salience, fronto-parietal networks, and subcortical networks.
However, the presence of depressive symptoms appears to alter these results. As depression scores increased among participants who used cannabis, the increased global efficiency and integrativeness typically associated with cannabis use attenuated. The researchers noted that combining cannabis use and depression tends to make brain networks less efficient and less integrated than cannabis use alone.
“Our findings suggest that the presence of depressive symptoms may attenuate the effects of cannabis on brain communication, resulting in less efficient and less integrated brain network function compared to cannabis use alone,” Liu told SciPost.
The scientists also investigated whether an individual’s frequency of cannabis use changed these results. A closer look at the drug’s direct effects revealed that smoking more frequently further increases brain connectivity and integration. However, researchers were surprised to find that frequency of use did not change how depression affected the brain. The brain connectivity-reducing effects of depression occurred simply because the person was a regular cannabis user.
“We were surprised to find that while depressive symptoms moderated the brain effects of cannabis use status, frequency of cannabis use did not seem to matter,” Liu said. “This suggests a potential ‘threshold effect’ where even minimal use may be sufficient to interact with depression and change the way the brain communicates, rather than increasing the effect with increasing doses.”
As with all research, there are limitations that should be considered. Because the study observed participants at a single time point, the scientists cannot conclusively prove that cannabis use and depression caused the observed changes in brain connectivity. The results show only statistical associations between these factors. Additionally, the study sample included few participants with moderate or severe depression.
“Most of the participants in this study had relatively mild symptoms of depression, which may limit our ability to fully detect the effects of depression on the brain,” Liu said. “Furthermore, because we only looked at the data at a single point in time, we cannot determine whether cannabis use or depression occurred first.”
“We aim to conduct longitudinal studies that follow cannabis users over time to better understand the causal relationships between cannabis use, depression, and brain function. We also hope to test brain function during specific tasks and expand our reach by including participants with a broader range of depression severity, including clinical major depressive disorder.”
“Our findings highlight the ‘intersectionality’ of depression and cannabis use, showing that they don’t just exist next to each other, but actively interact to shape our brains,” Liu added.
The study, “Intersectionality of Cannabis Use and Depressive Symptoms in Adult Functional Brain Topology,” was authored by Che Liu, Janna Cousijn, Emese Kroon, and Francesca M. Filbey.
