New neuroimaging research suggests that prolonged use of cannabidiol (CBD) may influence the connections between key brain regions, namely the hippocampus and the amygdala, which are involved in memory and emotional processing. However, the implications of these changes for mental health are still unclear. The findings have been published in Cannabis and Cannabinoid Research.
Previous research has linked cannabis use to various psychosocial issues, including cannabis use disorders, elevated stress levels, and symptoms of depression, anxiety, and psychosis. These problems are partly attributed to the main psychoactive compound in cannabis, delta-9-tetrahydrocannabinol (THC), which interacts with brain cannabinoid receptors.
Neuroimaging studies have shown that cannabis use can lead to structural and functional changes in brain regions rich in cannabinoid receptors, such as the hippocampus and the amygdala. These changes have been associated with mental health problems, particularly psychotic symptoms. The study aimed to investigate whether CBD, another compound found in cannabis, could counteract these neurobiological differences observed in cannabis users.
CBD is known to antagonize the effects of THC and bind to cannabinoid type 2 (CB2) receptors in the brain and body. It has been suggested that CBD may reduce THC-related mental health symptoms, including psychosis, paranoia, intoxication, and anxiety. Additionally, preliminary evidence has shown that CBD can impact brain function and connectivity in various cognitive tasks, particularly in areas like the hippocampus and amygdala.
“As a neuroscientist, I am interested in understanding how brain-related changes in chronic cannabis users can be ameliorated and how this is associated with mental health implications. This new knowledge can be helpful for people who use cannabis, clinical practitioners and public health experts on the implications of medicinal cannabis products,” said study author Valentina Lorenzetti, an associate professor at the Australian Catholic University and deputy director of the Healthy Brain and Mind Research Centre.
“Some people who use cannabis can experience psychosocial problems. Some scientists theorise that these problems could be attributable to the effect of cannabis’ main psychoactive compound: THC, particularly in brain areas that THC binds to to exert its effects. These areas include the hippocampus – a brain region shaped like a seahorse that supports learning and memory functions – and the amygdala – a brain region shaped like an almond, which is broadly responsible for the experience of emotions, attention, stress and craving.”
For their study, the researchers recruited 20 individuals who used cannabis recreationally, with 18 participants completing the entire study. Participants were given 200mg of CBD daily for 10 weeks, and their brain connectivity was assessed using functional magnetic resonance imaging (fMRI) scans.
The inclusion criteria for participants were an age range of 18 to 55 years, current cannabis use, and a minimum of six months of cannabis use at least once per month. Exclusion criteria included the use of other illicit substances, past dependence on substances other than cannabis, seeking treatment for substance use, and various medical and psychiatric conditions.
The primary goal was to examine whether prolonged exposure to CBD could lead to changes in resting-state functional connectivity in the hippocampus and amygdala. Resting-state functional connectivity measures the correlation between the activity of different brain areas when the brain is at rest and not engaged in specific tasks.
Participants had mild symptoms of cannabis dependence, depression, state anxiety, and psychotic-like symptoms at the beginning of the 10-week trial. After the trial, depressive and negative psychotic-like symptoms decreased, while state anxiety symptoms increased.
The study found significant changes in resting-state functional connectivity in two pairs of brain regions. Connectivity decreased between the left anterior hippocampus and the right precentral gyrus and increased between the left amygdala and the right lingual gyrus.
“We found it interesting that CBD changed how the brain connects different regions and in different ways,” Lorenzetti told PsyPost. “The functional connectivity of the hippocampus increased with a part of the brain involved in detecting salient stimuli in the environment (lingual gyrus). We also found a small increase in the volume of the hippocampus after the 10 weeks of CBD administration.”
“The functional connectivity of the amygdala instead decreased with a different part of the brain that supports motor control and reward processing (precentral gyrus). This suggests that CBD could affect the brain in complex ways that we are just beginning to uncover.”
Surprisingly, however, these changes in brain connectivity were not correlated with participants’ mental health symptoms, including depression and anxiety.
“The brain changes pre-to-post CBD were not associated with people’s mental health and wellbeing,” Lorenzetti said. “We don’t yet know what these brain changes mean for people’s mental health and wellbeing.”
Several limitations should be considered when interpreting the study’s results. These include the absence of a placebo group, a small sample size, and a predominantly male participant group. Future research should involve larger, more diverse samples and placebo-controlled conditions to confirm and expand upon these findings.
“We need to be cautious when interpreting the findings,” Lorenzetti explained. “First, we don’t yet know if CBD-related brain changes have implications for people’s mental health and wellbeing: the brain changes we found were not associated with mental health, but we only tested 18 people and this small sample could have been insufficient to find subtle effects.”
“Second, there was no placebo group, meaning that the brain changes in the CBD group over time could be caused by CBD, or be just normal changes that occur in the brain over time when people participate in a research study.”
“Even if this was a relatively small study, Professor Nadia Solowij has run the project with a very large team from many different disciplines (psychopharmacology, neuroscience, clinicians, engineers, MR technologists, MR data analysts, statisticians) and Dr Lisa Greenwood was one such key scientist to the project,” Lorenzetti added. “A large team was required to run this study over a number of years. This work would not have been feasible with the support of an extraordinary team.”
The study, “Daily Cannabidiol Administration for 10 Weeks Modulates Hippocampal and Amygdalar Resting-State Functional Connectivity in Cannabis Users: A Functional Magnetic Resonance Imaging Open-Label Clinical Trial“, was authored by Valentina Lorenzetti, Eugene McTavish, Samantha Broyd, Hendrika van Hell, Eleni Ganella, Akhil Raja Kottaram, Camilla Beale, Jennifer Martin, Peter Galettis, Nadia Solowij, and Lisa-Marie Greenwood.