In the past few years, scientists have been paying close attention to the so-called gut-brain axis, leading to new understandings of how our gut bacteria influence our moods, cognition and mental health. According to the latest research, cannabinoids play a key role in mediating these effects, indicating that some of the damage caused by harmful microbes in our intestines can in fact be reversed by some of the compounds found in cannabis.
Cannabinoids And The Gut-Brain Axis
Only recently have researchers come to appreciate the control that the gut microbiome exerts over the central nervous system, and vice versa. Indeed, while the brain is able to send chemical messengers to the gut in order to regulate appetite and digestion, an increasing body of research suggests that the bacteria therein also release metabolites that travel in the opposite direction in order to alter brain function.
As such, it is now widely accepted that the make-up of a person’s microbiome significantly contributes to their risk of mental health conditions such as depression. The latest evidence for this link can be found in a new study in the journal Nature Communications[i], which suggests that certain harmful gut bacteria suppress the production of cannabinoids in the brain, leading to negative mental health outcomes.
The study authors began by studying mice that suffered from an animal model of depression. When gut bacteria from these rodents was transplanted into the intestines of healthy mice, these recipients quickly began to display symptoms similar to those seen in the donors, including depressive behaviours.
Upon further analysis, the researchers noted that levels of an endocannabinoid called 2-arachidonoylglycerol (2-AG) plummeted in the hippocampus of any healthy mouse that received these depression-associated gut bacteria. This, in turn, caused a sudden decrease in neurogenesis within the hippocampus, meaning that these mice lost the ability to form new neurons in a key part of the brain that controls memory and learning.
However, when the study authors injected 2-AG into the brains of these mice, hippocampal neurogenesis was restored and depressive behaviours were alleviated. Similarly, transplanting healthy gut bacteria into rodents suffering from depression sparked an increase in 2-AG levels, leading to enhanced neurogenesis and a reduction in symptoms.
Interestingly, 2-AG binds to some of the same receptors as plant-based cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD). This is significant, especially as the contribution of gut bacteria to certain cognitive disorders becomes clearer. In light of this understanding, some scientists are beginning to suspect that cannabis could help to treat a number of conditions by undoing the harmful effects of these bacterial species.
Plant Cannabinoids And Gut Bacteria
It’s not just endocannabinoids that have the potential to protect the brain from pathogenic gut microbes. Both THC and CBD have been found to help reverse certain cognitive and emotional disorders by directly interfering with the microbiome.
For instance, a recent study in the journal Brain, Behavior and Immunity[ii] revealed that mice suffering from a murine form of multiple sclerosis (MS) tend to contain high levels of a bacteria called Akkermansia muciniphila (A. muc) in their gut. These particular microbes release a type of toxin that causes inflammation in the brain, and are a major cause of MS-related symptoms.
However, by administering both THC and CBD, the study authors were able to alter the microbiome of these mice. Specifically, these cannabinoids caused a notable reduction in A. muc populations within the intestines of these rodents. This, in turn, led to a decrease in the concentration of toxins in the brain, and a significant improvement in MS symptoms.
Taken together, all of this evidence suggests that cannabinoids – including those found in cannabis – may have a major role to play in the gut-brain axis, and appear to protect the brain against many of the harmful metabolites released by unhealthy gut bacteria.
[i] Chealier et al., ‘Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system’, Nature communication, 2020 – https://www.nature.com/articles/s41467-020-19931-2
[ii] Al-Ghezi ZZ, Busbee PB, Alghetaa H, Nagarkatti PS, Nagarkatti M. Combination of cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), mitigates experimental autoimmune encephalomyelitis (EAE) by altering the gut microbiome. Brain, behavior, and immunity. 2019 Nov 1;82:25-35. – https://www.sciencedirect.com/science/article/abs/pii/S0889159119306476