How Does Cannabis Affect the Body? The Endocannabinoid System Explained

One of the most intriguing aspects of cannabis is its ability to interact with the body’s endocannabinoid system (ECS), a complex cell-signaling network involved in regulating essential physiological functions such as sleep, mood, appetite, immune response, and pain sensation. Understanding how cannabinoids from cannabis engage with the ECS provides valuable insights into their therapeutic potential and psychoactive effects.

The Endocannabinoid System: An Overview

The ECS consists of three main components:

Endocannabinoids: Naturally occurring compounds produced by the body, including anandamide (AEA) and 2-arachidonoylglycerol (2-AG).
Cannabinoid Receptors: Proteins found on cell surfaces that interact with cannabinoids.
Enzymes: Responsible for synthesizing and breaking down endocannabinoids, including fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) (Battista et al., 2012).

Key Cannabinoid Receptors and Their Function

The ECS operates primarily through two types of receptors:

CB1 Receptors: Found mainly in the brain and central nervous system, CB1 receptors play a role in regulating mood, cognition, pain perception, and appetite.
CB2 Receptors: Located primarily in the immune system and peripheral tissues, CB2 receptors are associated with inflammation regulation and immune response (Mackie, 2008).

How THC and CBD Interact with the ECS

Cannabis contains more than 100 cannabinoids, but tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most well-studied for their effects on the ECS.

THC: Direct Agonist of CB1 Receptors

THC mimics anandamide and directly binds to CB1 receptors, leading to its psychoactive effects.
This binding alters neurotransmitter release, resulting in euphoria, altered sensory perception, and changes in memory and coordination.
Additionally, THC has a moderate affinity for CB2 receptors, which may contribute to its anti-inflammatory properties (Pertwee, 2008).

CBD: Indirect Modulator of the ECS

Unlike THC, CBD does not bind strongly to CB1 or CB2 receptors.
Instead, CBD influences the ECS by inhibiting FAAH, which breaks down anandamide, leading to increased levels of this "bliss molecule" in the body.
CBD also interacts with other non-cannabinoid receptors, such as serotonin (5-HT1A) and TRPV1 receptors, which contribute to its anti-anxiety and pain-relieving effects (Ibeas Bih et al., 2015).

The Role of the ECS in Homeostasis

The ECS is crucial for maintaining homeostasis, or the body’s internal balance. It helps regulate:

Pain and Inflammation: Activation of CB1 and CB2 receptors can reduce pain and inflammation, making cannabis a promising treatment for conditions like arthritis and neuropathic pain.
Mood and Stress Response: Endocannabinoids influence serotonin and dopamine levels, affecting mood stability and stress resilience.
Immune System Modulation: CB2 receptor activation can reduce excessive immune responses, potentially benefiting conditions like autoimmune disorders (Lu & Mackie, 2016).

Potential Therapeutic Applications of Targeting the ECS

Research on the ECS has paved the way for cannabis-based therapies:

Chronic Pain Management: Cannabinoids have been used to alleviate pain by interacting with CB1 receptors in the nervous system.
Neuroprotection: The ECS plays a role in protecting neurons, with studies exploring its potential in treating neurodegenerative diseases like Alzheimer’s and Parkinson’s.
Mental Health Disorders: CBD’s interaction with serotonin receptors suggests potential benefits for anxiety, depression, and PTSD.
Epilepsy Treatment: FDA-approved Epidiolex, a CBD-based medication, has demonstrated effectiveness in reducing seizures in conditions like Dravet syndrome (Devinsky et al., 2017).

Conclusion

The endocannabinoid system is a fundamental regulatory network in the body, and cannabis compounds interact with it in ways that can impact health and wellness. While THC directly activates CB1 receptors to produce psychoactive effects, CBD works as an indirect modulator, offering therapeutic benefits without intoxication. As research into the ECS continues, new cannabis-based treatments may emerge, providing hope for various medical conditions.

References

Battista, N., Di Tommaso, M., Bari, M., & Maccarrone, M. (2012). The endocannabinoid system: An overview. Frontiers in Behavioral Neuroscience, 6(9), 1–16. https://doi.org/10.3389/fnbeh.2012.00009

Devinsky, O., Patel, A. D., Thiele, E. A., Wong, M. H., Appleton, R., Harden, C. L., ... & O’Brien, T. J. (2017). Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 58(1), 15-27. https://doi.org/10.1111/epi.13693

Ibeas Bih, C., Chen, T., Nunn, A. V., Bazelot, M., Dallas, M., & Whalley, B. J. (2015). Molecular targets of cannabidiol in neurological disorders. Neurotherapeutics, 12(4), 699-730. https://doi.org/10.1007/s13311-015-0377-3

Lu, H. C., & Mackie, K. (2016). An introduction to the endogenous cannabinoid system. Biological Psychiatry, 79(7), 516-525. https://doi.org/10.1016/j.biopsych.2015.07.028

Mackie, K. (2008). Cannabinoid receptors: Where they are and what they do. Journal of Neuroendocrinology, 20(s1), 10-14. https://doi.org/10.1111/j.1365-2826.2008.01671.x

Pertwee, R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin. British Journal of Pharmacology, 153(2), 199-215. https://doi.org/10.1038/sj.bjp.0707442