I. Introduction
Medical cannabis has become increasingly popular as a treatment option for a range of medical conditions, including chronic pain, anxiety, sleep issues and inflammatory disorders. Despite its growing acceptance among the general public, most doctors however remain reluctant to recommend medical cannabis to their patients. This reluctance can be attributed, by large, to a lack of education about the role and importance of the endocannabinoid system (ECS) in human physiology, which plays a crucial role in mediating the effects of cannabis in the body. Without an understanding of the ECS, medical cannabis simply does not make much sense.
The ECS is a complex regulatory system that plays a fundamental role in regulating a wide range of physiological processes, including appetite, pain sensation, mood, and immune function (1). It is composed of endocannabinoids, receptors, and enzymes that work together to maintain homeostasis in the body (2). The endocannabinoids are chemical messengers that are produced by the body to interact with the ECS receptors. The two primary endocannabinoids are 2-arachidonoylglycerol (2-AG) and anandamide (AEA). These molecules bind to the ECS receptors, which are found throughout the body, including in the brain, immune system, and peripheral tissues.
The ECS also interacts with external cannabinoids, such as those found in cannabis. THC, the primary psychotropic component of cannabis, binds to the CB1 receptor in the brain (2). This binding produces a wide array of biological effects, one of which is the intoxicating feeling of a “high” commonly associated with cannabis use. CBD, another cannabinoid found in cannabis, does not produce the same psychotropic effects as THC but has been shown to have a range of therapeutic benefits, including reducing the frequency of epileptic seizures, inflammation, and anxiety (3).
Despite the growing body of research on the ECS and medical cannabis, many doctors remain hesitant to recommend medical cannabis to their patients. This may be due, in part, to concerns about the legality of cannabis use, lack of knowledge about dosing and administration, and negative societal perceptions of cannabis. However, it is essential to recognize the crucial role of the ECS in mediating the effects of medical cannabis and the potential benefits of cannabis use for patients with certain medical conditions. To ensure that all patients have access to safe and effective treatment options, it is critical that healthcare professionals receive education and training on the ECS and its role in mediating the effects of medical cannabis. By increasing awareness and understanding of the ECS, doctors can provide patients with evidence-based treatment options that may improve their quality of life.
II. The Endocannabinoid System (ECS)
The endocannabinoid system (ECS) is a complex regulatory system that plays a crucial role in mediating the effects of cannabis in the body. It is composed of endocannabinoids, receptors, and enzymes that work together to maintain homeostasis in the body (2). The endocannabinoids are chemical messengers that are produced by the body to interact with the ECS receptors. The two main endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Endocannabinoids bind to and activate the two primary ECS receptors, CB1 and CB2 (4,5). The CB1 receptor is primarily located in the brain and central nervous system, while the CB2 receptor is mainly found in the peripheral tissues and immune system (6,7).
The ECS is involved in regulating a wide range of physiological processes, including appetite, pain sensation, mood, and immune function (2). For example, AEA has been shown to play a role in regulating food intake and body weight, while 2-AG has been implicated in pain sensation and inflammation (8). The ECS also plays a crucial role in mediating the effects of stress on the body. Studies have shown that chronic stress can lead to changes in the ECS, which in turn can affect mood and behavior (9,10).
In addition to its role in regulating physiological processes, the ECS also plays a key role in mediating the effects of cannabis on the body. THC, the primary psychotropic component of cannabis, binds to the CB1 receptor in the brain as a partial agonist, with similar potency and efficacy to AEA, and produces the euphoric effects commonly associated with cannabis use (2). In addition to being an intoxicant, THC produces a wide array of potential therapeutic effects, including analgesia, relief of nausea, appetite stimulation and change in mood (11). CBD, another cannabinoid found in cannabis, does not produce feelings of intoxication but has similarly been shown to have a wide range of potential therapeutic benefits, including reductions in epileptic seizure frequency, inflammation, and anxiety (12,13,14).
Understanding the role of the ECS in mediating the effects of cannabis and the therapeutic potential of cannabinoids like THC and CBD is essential for healthcare professionals. Without a basic understanding of the ECS, the scientific rationale for using medical cannabis is lost. Worse yet is that without a basic comprehension of the ECS and its importance in homeostasis, medical students exit medical school with an incomplete understanding of human physiology.
III. Medical Cannabis
Medical cannabis has been increasingly recognized as a potential treatment option for a range of conditions. One of the most prevalent uses for medical cannabis is in the management of chronic pain, which can be a debilitating and life-altering condition. Studies have shown that cannabis can be effective in reducing pain levels in patients with conditions such as neuropathic pain, arthritis, and cancer (15,16,17). Additionally, medical cannabis has been found to have anxiolytic effects, making it a potential treatment option for individuals with anxiety disorders (18). Inflammatory disorders such as Crohn’s disease and multiple sclerosis have also been identified as conditions that may benefit from medical cannabis (19). The anti-inflammatory properties of cannabis may help to reduce inflammation and alleviate symptoms in individuals with these conditions. However, it is important to stress that medical cannabis is not a cure for any of these conditions and should be used in conjunction with other treatment options. Additionally, the use of medical cannabis should be supervised by a healthcare professional to ensure its long-term safety and efficacy.
Cannabis contains over 100 cannabinoids, but the two by far most well-known and studied cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the primary psychoactive compound in cannabis, and it binds to the CB1 receptor in the ECS, producing the characteristic euphoric effects associated with cannabis use (2). On the other hand, CBD does not produce psychoactive effects, but has been shown to modulate the effects of THC and other cannabinoids by acting as a negative allosteric modulator (NAM) at the CB1 receptor. CBD also binds to and blocks the FABP protein from transporting AEA to the FAAH enzyme, increasing levels of AEA and endocannabinoid tone (3). Both THC and CBD have been shown to have several potential therapeutic benefits, with THC shown to provide analgesia, relief of nausea, appetite stimulation, but also potential dose-dependent transient negative neuro-cognitive performance, while CBD has been shown to have anti-inflammatory, anti-anxiety, and anti-seizure effects (20).
Other cannabinoids found in cannabis include cannabigerol (CBG), cannabichromene (CBC), and tetrahydrocannabivarin (THCV), among others. CBG has been shown to have potential analgesic, anti-inflammatory and anti-tumoral effects, while CBC has been shown to have potential anti-depressant and anti-inflammatory effects (21,22). THCV has been shown to have potential appetite-suppressing effects and may also have anti-inflammatory and anti-convulsant properties (22). While more research is needed to fully understand the effects of these lesser-known cannabinoids, their potential therapeutic benefits are promising. Overall, the various cannabinoids found in cannabis interact with the ECS in complex ways, and their individual effects on the body will likely be extensively researched in the coming decade.
Several studies have shown that using full-spectrum cannabis extracts rather than pure cannabinoid isolates often provide better efficacy and less side-effects (23,24,25). This phenomenon is known as the entourage effect. It provides a sound scientific reasoning for treating different medical conditions with specific cannabis chemovars to achieve more tailored therapeutic effects. More research is needed to understand its details and the extent of its impact on the body, as well as its potential for medical use.
IV. Doctors’ Reluctance to Using Medical Cannabis
Despite the growing body of research on the potential benefits of medical cannabis, many doctors remain hesitant to recommend it to their patients. There are several reasons for this reluctance, including concerns about legality, lack of knowledge about dosage and administration, lack of clinical guidelines, lack of standardization in cannabis products, and negative societal perceptions of cannabis. While these are all valid concerns, the main reason for doctors’ reluctance may very well be a lack of education and understanding about the endocannabinoid system (ECS) and its role in mediating the effects of medical cannabis. It is worrying that medical textbooks in physiology used in medical schools and universities around the world barely touches on the existence of the ECS, despite its undisputed importance in human physiology. In a national survey conducted in 2017, medical school curriculum deans from 101 accredited American medical schools in the US reported that close to 90% of their residents and fellows do not feel at all prepared to prescribe medical cannabis and 85% reported that they had received no education whats-so-ever about the ECS or medical cannabis (26).
It is a fact that most doctors are not trained in the ECS and have inadequate knowledge about the potential therapeutic uses of medical cannabis, which consequently contributes to the general low willingness to prescribe medical cannabis among doctors. Additionally, the legality of medical cannabis varies between countries, further complicating the issue.
As more research is conducted on the ECS and the potential benefits of medical cannabis, it is becoming increasingly clear that it can be a valuable tool in treating a variety of conditions. To overcome the reluctance of doctors to recommend medical cannabis, there is a need for increased education and training on the ECS and its role in mediating the effects of medical cannabis. By improving doctors’ understanding of this complex system, they can make informed decisions about recommending medical cannabis to their patients, leading to better health outcomes and improved quality of life for those who may benefit from its use.
V. Implications and Solutions
The lack of education about the endocannabinoid system (ECS) and medical cannabis among healthcare professionals can have significant implications for patients. Without sufficient knowledge, doctors may miss opportunities to recommend medical cannabis to patients who could benefit from it. This may lead to patients being prescribed more traditional medications that are less effective, more expensive, or have more adverse side effects. Additionally, the lack of education can perpetuate negative societal perceptions of cannabis, leading to stigma and hindering patients’ access to potentially life-changing treatments.
To address this issue, medical schools and universities should incorporate information about the ECS and medical cannabis into their curricula. Medical professionals should also be required to receive ongoing education and training to stay up-to-date with the latest research and prescribing guidelines.
Examples of successful implementation of such solutions can be seen in other jurisdictions, such as in Israel and Canada, where medical cannabis education and training have been integrated into medical school curricula and continuing education programs.
In Israel, the Ministry of Health has established a medical cannabis unit to provide education and training to healthcare professionals. They offer online courses, workshops, and conferences to keep doctors informed about the latest research and best practices (27). Similarly, in Canada, medical schools have begun incorporating information about medical cannabis into their curricula. The University of British Columbia, for example, has launched a continuing education program for healthcare professionals that includes modules on medical cannabis (28).
By incorporating education about the ECS and medical cannabis into medical school curricula and providing ongoing education and training for healthcare professionals, we can ensure that doctors have the knowledge and tools necessary to provide the best possible care to their patients. This can improve patient outcomes and quality of life, reduce healthcare costs, and help break down the stigma surrounding medical cannabis.
VI. Conclusion
In conclusion, the endocannabinoid system (ECS) plays a critical role in regulating numerous physiological processes, and medical cannabis has emerged as a potential therapeutic option for a variety of medical conditions. However, the reluctance of healthcare professionals to recommend medical cannabis to their patients remains a significant barrier to its widespread use. This hesitancy is likely due, at least to a significant degree, to a lack of education and understanding about the ECS and its role in mediating the effects of medical cannabis.
It is essential to address this knowledge gap by incorporating information about the ECS and medical cannabis into medical school curricula’ and providing ongoing education and training for practicing healthcare professionals. As demonstrated in other jurisdictions such as Israel and Canada, implementing such solutions can increase healthcare professionals’ knowledge and awareness of medical cannabis and helps to ensure that patients have access to safe and effective treatment options.
It is crucial to recognize the potential implications of doctors’ lack of education about the ECS and medical cannabis, including missed treatment opportunities for patients. Continued education and awareness among healthcare professionals are necessary to ensure that medical cannabis is used appropriately and effectively as a therapeutic option.
As the scientific understanding of the ECS and medical cannabis continues to evolve, it is critical for healthcare professionals to stay informed and up-to-date on the latest research and best practices. Only by doing so can they provide patients with the highest quality of care and improve their quality of life.
Stefan Broselid, Ph.D.
Molecular Pharmacology
Editor-In-Chief, Aurea Care Medical Science Journal
References:
- Piomelli, D., & Alger, B. E. (2003). Endocannabinoid signaling and the regulation of synaptic transmission. Neuropharmacology, 45(1), 72-81. doi: 10.1016/s0028-3908(03)00269-5
- Pacher, P., Bátkai, S., & Kunos, G. (2006). The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacological reviews, 58(3), 389–462. doi:10.1124/pr.58.3.2
- Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55(6):791-802. doi:10.1111/epi.12631
- Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258(5090):1946-1949. doi:10.1126/science.1470919
- Sugiura, T., Kondo, S., Sukagawa, A., Nakane, S., Shinoda, A., Itoh, K., … & Waku, K. (1995). 2-arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochemical and biophysical research communications, 215(1), 89-97.
- Devane, W. A., Dysarz, F. A., III, Johnson, M. R., Melvin, L. S., & Howlett, A. C. (1988). Determination and characterization of a cannabinoid receptor in rat brain. Molecular pharmacology, 34(5), 605-613. doi: 10.1016/0024-3205(88)90616-3.
- Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365(6441):61-65. doi:10.1038/365061a0
- Di Marzo, V., & Piscitelli, F. (2015). The Endocannabinoid System and its Modulation by Phytocannabinoids. Neurotherapeutics, 12(4), 692-698. doi: 10.1007/s13311-015-0374-6.
- Hill MN, McLaughlin RJ, Bingham B, et al. Endogenous cannabinoid signaling is essential for stress adaptation. Proc Natl Acad Sci U S A. 2010;107(20):9406-9411. doi:10.1073/pnas.0914661107
- Bluett RJ, Gamble-George JC, Hermanson DJ, Hartley ND, Marnett LJ, Patel S. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation. Transl Psychiatry. 2014;4(7):e408. Published 2014 Jul 8. doi:10.1038/tp.2014.53
- Grotenhermen F, Müller-Vahl K. The therapeutic potential of cannabis and cannabinoids. Dtsch Arztebl Int. 2012;109(29-30):495-501. doi:10.3238/arztebl.2012.0495
- Devinsky, O., Cross, J. H., Laux, L., Marsh, E., Miller, I., Nabbout, R., … & Wright, S. (2017). Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. New England Journal of Medicine, 376(21), 2011-2020.
- Hobbs JM, Vazquez AR, Remijan ND, et al. Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults. Phytother Res. 2020;34(7):1696-1703. doi:10.1002/ptr.6651
- Dahlgren MK, Lambros AM, Smith RT, Sagar KA, El-Abboud C, Gruber SA. Clinical and cognitive improvement following full-spectrum, high-cannabidiol treatment for anxiety: open-label data from a two-stage, phase 2 clinical trial. Commun Med (Lond). 2022;2(1):139. Published 2022 Nov 2. doi:10.1038/s43856-022-00202-8
- Reference: Lynch, M. E., Cesar-Rittenberg, P., & Hohmann, A. G. (2014). A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. The Journal of Pain, 15(4), 422-434.
- Nowell WB, Gavigan K, L Silverman S. Cannabis for Rheumatic Disease Pain: a Review of Current Literature. Curr Rheumatol Rep. 2022;24(5):119-131. doi:10.1007/s11926-022-01065-7
- Johnson JR, Burnell-Nugent M, Lossignol D, et al. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010;39(2):167-179.
- Cuttler, C., Spradlin, A., & McLaughlin, R. J. (2019). A naturalistic examination of the perceived effects of cannabis on negative affect. Journal of clinical psychopharmacology, 39(5), 483-489.
- Russo EB. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 2016;1(1):154-165. Published 2016 Jul 1. doi:10.1089/can.2016.0009
- Bridgeman MB, Abazia DT. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P T. 2017;42(3):180-188.
- Nachnani R, Raup-Konsavage WM, Vrana KE. The Pharmacological Case for Cannabigerol. J Pharmacol Exp Ther. 2021;376(2):204-212. doi:10.1124/jpet.120.000340
- Walsh KB, McKinney AE, Holmes AE. Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses. Front Pharmacol. 2021;12:777804. Published 2021 Nov 29. doi:10.3389/fphar.2021.777804
- Gallily, R., Yekhtin, Z., & Hanuš, L. O. (2018). Overcoming the bell-shaped dose-response of cannabidiol by using cannabis extract enriched in cannabidiol. Pharmacology & Pharmacy, 9(02), 75-85.
- Pamplona, F. A., da Silva, L. R., & Coan, A. C. (2018). Potential clinical benefits of CBD-rich Cannabis extracts over purified CBD in treatment-resistant epilepsy: observational data meta-analysis. Frontiers in neurology, 9, 759.
- Russo, E. B., & Marcu, J. (2017). Cannabis pharmacology: the usual suspects and a few promising leads. Advances in pharmacology, 80, 67-134.
- Evanoff AB, Quan T, Dufault C, Awad M, Bierut LJ. Physicians-in-training are not prepared to prescribe medical marijuana. Drug Alcohol Depend. 2017;180:151-155. doi:10.1016/j.drugalcdep.2017.08.010
- Sznitman, S. R., Vulfsons, S., Meiri, D., Weinstein, G., & Linder, I. (2019). Medical Cannabis in Israel: An Overview. Journal of Pain and Symptom Management, 57(1), e1-e8.
- https://ubccpd.ca/learn/resources-recordings/toolkits/cannabis-education-toolkit