Why is a neuromodulatory system found in vertebrates referred to as the endocannabinoid system?
The endocannabinoid system is an ENDOgenous system whose components interact with or resemble delta-9-tetrahydrocannabinol (THC), a CANNABINOID derived from the cannabis plant.
Atakan, Z. “Cannabis, a complex plant: different compounds and different effects on individuals.” Therapeutic advances in psychopharmacology 2012; 2(6): 241-54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736954/
Which receptor is more prevalent in the human central nervous system – the cannabinoid receptor 1 (CB1) or the μ-opioid receptor?
It was only in 1990 that researchers mapped the locations of the CB1 receptors and determined that the CB1 receptor is very highly expressed throughout the brain. In humans, the CB1 receptor is 10 times more prevalent in the central nervous system, as compared to the μ-opioid receptor.
Burns HD, Van Laere K, Sanabria-Bohorquez S, et al. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci USA. 2007;104:9800–9805. https://pubmed.ncbi.nlm.nih.gov/17535893/
True or false? The cannabinoid receptor 2 (CB2) is primarily immunomodulatory and anti-inflammatory.
True. CB2 receptors are expressed on the cell membranes of B cells, T cells and macrophages. When signaled, CB2 receptors are generally inhibitory to immune cell activation, and proinflammatory cytokine production is inhibited. Expression of CB2 receptors is inducible, and the number of receptors is increased by inflammation.
Maresz K, Carrier EJ, Ponomarev ED, Hillard CJ, and Dittel BN. Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem, 2005; 95(2): 437-45. https://pubmed.ncbi.nlm.nih.gov/16086683/
Actually, no. Cannabis is a flowering plant, while marijuana is defined as a substance composed of parts of the Cannabis sativa plant, including the leaves, flowers, seeds, and the resin extracted from any part of the plant.
The endocannabinoid system (ECS) is an internal homeostatic system present in all vertebrates that plays a critical role in the nervous system and regulates multiple physiological processes, including appetite, digestion, mood, coordination, and other processes. The ECS also influences immunomodulation, cardiovascular functions, sensory integration, tumor surveillance, fertility, bone physiology, the hypothalamic-pituitary-adrenal axis, neural development, and intraocular pressure.
Di Marzo V. The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation. Pharmacological Research. 2009; 60(2):77–84. https://pubmed.ncbi.nlm.nih.gov/19559360/
True or false? Patients who are allergic to cherries, tangerines, peaches, tomatoes, hazelnuts, latex and/or tobacco may also be allergic to cannabis products.
True. These listed fruits and vegetables have non-specific lipid proteins that are similar to the ones found in cannabis. As a result, cross-sensitivity may occur, and a patient may develop an allergic reaction.
Bih CI, Chen T, Nunn AV, Bazelot M, Dallas M, Whalley BJ. Molecular Targets of Cannabidiol in Neurological Disorders. Neurotherapeutic. Oct 2015; 12(4):699-730. doi: 10.1007/s13311-015-0377-3. PMID: 26264914; PMCID: PMC4604182. https://pubmed.ncbi.nlm.nih.gov/26264914/
Research suggests that THC’s effects include reduction of nausea and vomiting, stimulation of appetite, reduction of pain and inflammation, and increase in muscle relaxation. Are these effects modulated through CB1 receptor activation?
The anti-emetic effects and increased appetite are modulated through antagonist activity on 5-HT3A receptors, and possibly other effects on the serotonergic system. THC’s effects on inflammation and pain may be modulated through the cyclooxygenase enzymes – “THC has been implicated as an inhibitor of cyclooxygenase enzymes and a potential inducer of COX-2 with prolonged exposure”
Joshua Brown, Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug–Drug Interactions , J of Clinical medicine, 27 march 2020. https://pubmed.ncbi.nlm.nih.gov/32230864/
In PRECLINICAL studies, it has been shown that cannabinoids induce apoptosis of cancer cells. Do cannabinoids induce apoptosis of normal non-malignant cells?
According to the results of PRECLINICAL studies, including in vitro studies and studies in mice, cannabinoids induce apoptosis of cancer cells without causing negative effect on the viability of normal non-malignant cells. In some mouse models, it has been noted that cannabinoids act synergistically with standard anti-cancer drugs or radiation therapy to reduce tumor growth. These studies have not detected overt signs of toxicity in the treated animals. NOTE: The observations noted in culture or animal models do NOT always readily translate into clinical benefit.
What is the most common qualifying condition reported by medical marijuana patients?
Currently and historically, the most common qualifying condition reported by medical marijuana patients is chronic pain. In fact, according to Boehnke et al’s analysis of 2016 data, chronic pain was the qualifying condition reported by medical marijuana patients nearly 65 percent of the time.
Epidiolex is an FDA-approved seizure medication derived from plant material (it is not a synthetic CBD product). Is it possible that a patient taking Epidiolex will test positive for THC?
Epidiolex is cannabidiol (CBD) derived from marijuana, not hemp, and therefore there may be traces of cannabinoids other than CBD. Patients using Epidiolex may test positive for marijuana/THC on drug screening.
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Cannabinoids and Adaptive Immuno-Modulation
The COVID epidemic has accelerated research of the immune system’s integrated response to viral diseases. This 30-minute video sponsored by the American Osteopathic Association discusses cannabinoids’ impact on optimal immune function. It is presented by physician author, Jeffrey S. Block, MD – founder and principal partner of an independent professional consultancy providing client organizations with advanced scientific guidance. Dr. Block’s industry-wide expertise provides insight by translating the evolving science’s objective evidence-based data into clinical applications.
About the Author
Jeffrey Sherwood Block, M.D.. is a Board-certified physician anesthesiologist and adjunct Professor at the University of Miami Miller School of Medicine. Additionally, he is a highly awarded horticulturist and certified Master Gardener educator with the University of Florida’s UF/IFAS Extension Program. Dr. Block’s textbook chapter “Endocannabinoid Receptors and Medical Cannabis” (Advanced Therapeutics in Pain Medicine – CRC Press 2020) is a sentinel work on integrated pain management. Block served as the Florida Medical Association’s “Designated Expert on Botanical Medicines” authoring mandated physician education; and in 2014 was appointed by Florida’s Surgeon General to determine the rules for Florida’s first cannabis law. His consultancy’s demonstrated insight and responsible leadership are valued by both allied professionals and new industries seeking knowledge of future uses for Cannabinoid medicines.
Cannabinoids and Adaptive Immuno-Modulation References
E.V. Berdyshev, 2000. Cannabinoid receptors and the regulation of immune response. Chemistry and Physics of Lipids 108 (2000) 169–190; www.elsevier.com/locate/chemphyslip
Biles, Mary 2019. Cannabis and the Immune System – A Complex Balancing Act. Project CBD (May 8, 2019).
Block, Jeffrey S., 2019. Endogenous Cannabinoid Receptors and Medical Cannabis. (pre-publication chapter) Advanced Therapeutics in Pain Medicine, January 2021. CRC Press.
Cabral, Guy A., Rogers, Thomas J., and Lichtman, Aron H., 2015. Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function. J Neuroimmune Pharmacol. 2015; 10(2): 193–203. Published online 2015 Jun 9. doi: 10.1007/s11481-015-9615-z
Centers for Disease Control and Prevention. CDC Urges Clinicians to Report Possible Cases of Unexplained Vaping-associated Pulmonary Illness to their State/Local Health Department. Clinician Outreach and Communication Activity. 2019. Published August 14, 2019.
Hernández-Cervantes R., Méndez-Díaz M., Prospéro-García Ó., and Morales-Montor J. 2017. Immunoregulatory Role of Cannabinoids during Infectious Disease. Neuroimmunomodulation 2017;24:183–199.
Klein TW (2005) Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol 5, 400–411.
Li et al. 2019, Cell 176, 459-467.
James M. Nichols and Barbara L.F. Kaplan, 2020. Immune Responses Regulated by Cannabidiol. Cannabis and Cannabinoid Research, Vol. 5, No. 1
National Academies of Science, Engineering and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press; 2017.
Pacher P, Kunos G. Modulating the endocannabinoid system in human health and disease–successes and failures. FEBS J. 2013;280(9):1918-1943.
Shmerlig, Robert H., MD, 2015. Senior Faculty Editor. First, Do No Harm. Harvard Health Publishing.
Siddappa N. Byrareddy, Mahesh Mohan, 2020. SARS-CoV2 induced respiratory distress: Can cannabinoids be added to anti-viral therapies to reduce lung inflammation? Brain, Behavior, and Immunity 87 (2020) 120–121.
Jeffrey Sherwood Block, M.D. . is a Board-certified physician anesthesiologist and adjunct Professor at the University of Miami Miller School of Medicine. Additionally, he is a highly awarded horticulturist and certified Master Gardener educator with the University of Florida’s UF/IFAS Extension Program. Dr. Block’s textbook chapter “Endocannabinoid Receptors and Medical Cannabis” (Advanced Therapeutics in Pain Medicine – CRC Press 2020) is a sentinel work on integrated pain management. Block served as the Florida Medical Association’s “Designated Expert on Botanical Medicines” authoring mandated physician education; and in 2014 was appointed by Florida’s Surgeon General to determine the rules for Florida’s first cannabis law. His consultancy’s demonstrated insight and responsible leadership are valued by both allied professionals and new industries seeking knowledge of future uses for Cannabinoid medicines.