A commentary on Uthayakumaran, K., Sunil, M. & Ratcliffe, E. M. Evaluating the Role of the Endocannabinoid System in Axon Guidance: A Literature Review. Cannabis Cannabinoid Res.(2024) doi:10.1089/can.2023.0138
By Jahan Marcu, PhD
The endocannabinoid system (ECS) plays important roles in our development by helping neurons or brain cells to elongate and grow into maturity. It is essential for our basic functions that our brain cells elongate to connect to each other, and to other parts of the body. A recent article published in the journal of Cannabis and Cannabinoid Research compiled an impressive amount of data regarding how our body’s biological ECS machinery is necessary for normal brain development.
The ECS machinery in our body consists of cannabinoid receptors, endocannabinoids, and enzymatic proteins that synthesize and degrade the endocannabinoids. The ECS is the same system that mediates the action of cannabis. The endocannabinoids that are made by our body share the same targets as drugs like THC. The endocannabinoids and THC both work through cannabinoid receptors. Scientists have levergaged this activity-relationship by using compounds related to cannabis to disrupt the normal activities of the ECS. For example, numerous studies have investigated the effects of overstimulating the ECS in experimental settings such as petri dishes and in animals, which demonstrates a significant role in the lifecycle of our brain cells and neurons, influencing their development and connectivity.
For the intricate network of neurons that connect our brain and body to function optimally, the nascent or ‘baby’ brain cells, neurites or axons require precise signals to reach their intended destinations. These “guidance cues” are essential for shaping the growth and direction of brain cells.
The authors of this review article introduce the “Handshake Hypothesis” to help explain how our brains grow and talk to each other like two siblings. The “Handshake Hypothesis” is a concept that illustrates the cooperative nature of brain cell interaction. I like to visualize two caterpillars navigating a plant stem or leaf. The two caterpillars pass over each other, without disrupting the other – maybe even assisting in helping the other reach their destination, somewhat resembling what researchers are seeing when two neurons pass each other. The hypothesis in this article suggests that cannabinoid receptors facilitate the mutual guidance of axons, enhancing their ability to connect effectively. In a sense, endocannabinoids are the currency of the handshake between neurons, they share signals to each other in the form of ECS stimulation that guides them to their destination. As neurons grow and slide past each other, they hand off a little dose of endocannabinoids, this cannabinoid sharing interaction may resemble two people sharing cannabis. The overall effect is the same whether it is two neurons going about a “handshake” or two humans using a cannabis product – both activities result in the exchange of cannabinoids.
You might be wondering how to best support your ECS for optimal brain health. A diet rich in omega-3 and omega-6 fatty acids is associated with brain and heart health. As these fatty molecules are the building blocks for endocannabinoids, without omega-3 and omega-6 our body would struggle to make vital molecules, which are important for maintaining our health.
What do clinicians think about the ECS and Brain Health?
The ECS is intrinsically involved in pregnancy because of its role in brain development. Additionally, this research points to concerns about the benefits and risks of cannabinoids or cannabis use. For example, during the COVID19 epidemic, many report using cannabis to relieve stress and anxiety during pregnancy, and the rate of this use has risen in recent years. Further research provides a beacon of optimism, indicating that reducing or ceasing cannabis use early in pregnancy may lessen potential risks. This parallels the beneficial effects observed when pregnant women stop drinking alcohol or take other preventative measures. However, the continued or intensive use of cannabis after confirming pregnancy underscores an urgent requirement for enhanced educational initiatives and support systems. These should be akin to the effective campaigns that have significantly decreased the prevalence of smoking during pregnancy. We must not treat cannabis any differently than any other pregnancy factor. We must pivot towards a more informed future, where caution and care in the context of prenatal cannabis use become as second nature as folic acid supplementation.
Disclaimer: This article is intended for informational purposes only and does not constitute medical advice. Always consult a healthcare professional for medical diagnosis or treatment recommendations.
