Opinions expressed in this article are my own and do not constitute medical advice.
Medical education is inundated with a systematic bias against any medication that is not mass produced in a pharmaceutical laboratory. The mere suggestion that cannabis could harbor any serious therapeutic benefits was the subject of ridicule and scorn during my clinical training. It was long assumed that anyone taking a cannabis-derived product was likely abusing it someway and somehow. For the longest time, I used to believe that.
Fast forward nearly a decade and I’ve seen my opinion on the matter completely change. I now consider myself to be a staunch advocate for patient access to medical cannabis, especially cannabidiol (CBD). But how could my opinion change so drastically in just a few short years?
I first became interested in CBD after hearing the story of one of my patients. He was an older man, with a long-standing history of diabetes complicated by peripheral neuropathy, which is a painful condition of the legs and feet. He started taking CBD as a supplement along with his other morning medications. After a period of time, he noted a gradual improvement in his sense of overall well-being.
As time went on, I heard additional stories that seemed to suggest CBD was impacting lives in a positive way. I could no longer ignore the potential therapeutic benefits that these individuals claimed to have experienced. Ultimately, this led me to undertake a thorough investigation of the medical and scientific literature to see if my patient’s experiences could be backed up by research.
What is CBD and How Does it Work?
CBD is the second most abundant cannabinoid produced naturally in plants of the Cannabis genus, with the most common being tetrahydrocannabinol (THC). CBD is uniquely different from THC, in that it is not psychoactive, meaning that it does not cause its user to feel intoxicated or “high.” Additionally, according to the World Health Organization, CBD has no potential for abuse or dependence.
In order to understand how CBD works, it’s important to first understand how any pharmaceutical drug operates within the body. For a medication to be effective, it needs to interact with systems already present within the body. Think of the medication as kind of a key and the receptor (where the medication acts) as a kind of lock. When the “key” interacts with its “lock”, it could either activate (i.e. epinephrine boosting blood pressure) or inactivate (i.e. ibuprofen reducing inflammation) the body’s normal physiologic response.
However, the exact mechanism of how CBD exerts its effects on the body is far more complicated. In fact, unlike many compounds, CBD has been shown to influence a multitude of potential receptors in animal models.
The Endocannabinoid System
The endocannabinoid system (ECS) is a collection of cell receptors and their corresponding neurotransmitters in the human body. This system helps to regulate sleep, appetite, mood, motor control, immune function, pleasure, pain, reproduction and fertility, memory and temperature regulation. This system is regulated by specific neurotransmitters, namely anandamide and 2-arachidonoylglycerol, that act directly on cannabinoid receptors (CB1 and CB2). These receptors are primarily found in neuronal synapses (the communication hub where two nerves interact with each other to transmit or modify signals going to or within the brain).
Unlike THC, which has a direct interaction with the CB1 and CB2 receptors, CBD does not seem to have any significant direct interaction with either of these receptors. Rather, the best available evidence suggests that CBD acts as a reuptake inhibitor of the neurotransmitter anandamide. Basically, this just means that there is more anandamide available within a neuronal synapse to interact with receptors in the ECS. The more anandamide within a synapse, the greater its ultimate effect will be.
The Vanilloid Receptor (TRPV1)
Anandamide also directly acts on the TRPV1 or the vanilloid receptor. This receptor is partly responsible for the transmission of painful stimuli to the brain from a variety of stimuli. Capsaicin, which is responsible for the “heat” in chili peppers, also activates this receptor. Capsaicin-based topical medications work by overstimulating this receptor, making it less effective at transmitting the pain signals. Similarly, increased levels of anandamide within nerve synapses caused by CBD could also theoretically provide analgesia through this same mechanism, but this needs more study.
Serotonin Receptors (5-HT1a)
CBD has been shown to act directly on some serotonin receptors within the nervous system. Serotonin helps to regulate mood, anxiety, appetite, sexual function, and even social behavior. Many medications have been developed to influence these receptors. Buspirone, for example, also directly acts upon the 5-HT1a receptor and is an effective treatment for anxiety. Whether or not CBD can achieve similar results remains to be seen.
After evaluating the available research on CBD, I see great potential in how CBD could benefit the well-being of individuals. More research will be required to further quantify the effects of CBD within the human body, how it achieves them, and whether or not these effects are clinically beneficial.
About Dr. Kevin Frey
Dr. Kevin Frey, MD specializes in Internal Medicine in Canton, Ohio. Dr. Frey received his medical degree from Northeast Ohio Medical University and completed his residency at the Mayo Clinic. Dr. Frey has partnered with The CBDistillery™, where his goal is to focus on educating others on the basic science behind CBD and its potential to improve well-being.
Be on the lookout for monthly blog posts from Dr. Kevin Frey on recent updates and scientific studies pertaining to CBD!
Studies referenced during my investigation.
Iseger TA, Bossong MG (March 2015). “A systematic review of the antipsychotic properties of cannabidiol in humans”. Schizophrenia Research. 162 (1–3): 153–61
Expert Committee on Drug Dependence 39th Meeting in Geneva. Cannabidiol- Pre-Review Report. The World Health Organization. November 2017. http://www.who.int/medicines/access/controlled-substances/5.2_CBD.pdf. Accessed February 19, 2018.
Ibeas et al. “Molecular Targets of Cannabidiol in Neurological Disorders.” Neurotherapeutics. 2015 Oct;12(4):699-730.
Deutsch, DG. “A Personal Retrospective: Elevating Anandamide (AEA) by Targeting Fatty Acid Amide Hydrolase (FAAH) and the Fatty Acid Binding Proteins (FABPs).” Front Pharmacol. 2016; 7:370.
Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron. 1998;21:531–543.
Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev. 1999;51:159–212.
Ross, R. “Anandamide and Vanilloid TRPV1 Receptors.” Br J Pharmacol. 2003 Nov;140(5):790-801.
Parks CL, Robinson PS, Sibille E, Shenk T, Toth M (1998). “Increased anxiety of mice lacking the serotonin1A receptor”. Proc. Natl. Acad. Sci. U.S.A. 95 (18): 10734–9.
Kennett GA, Dourish CT, Curzon G (1987). “Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression”. Eur. J. Pharmacol. 134 (3): 265–74.
De Mello Schier, A. Antidepresssant-Like and Anxiolytic-Like Effects of Cannabidiol: A Chemical Compound of Cannabis sativa. CNS & Neurolog Disorders – Drug Targets. 2014;13(6).
Prud’homme M, Cata R, Jutras-Aswad D. Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence. Substance Abuse: Research and Treatment. 2015;9:33-38