Thealing powers of Cannabis have been utilized by humans since time immemorial, with references to its therapeutic use found in Egyptian scrolls dating back to 1700 BC and Chinese tombs from 550 BC.1,2 Over the past century, Cannabis has experienced a resurgence of interest in the scientific community, with numerous studies confirming its healing properties. Cannabis phytochemicals, including phytocannabinoids and terpenoids, offer tremendous health benefits to your patients by naturally shifting the activity of critical bioregulatory pathways, bringing the body back to a state of balance.
Phytocannabinoids: Plant Defense Mechanisms that Benefit the Human Body
Phytocannabinoids are compounds widely distributed throughout the plant kingdom that are highly concentrated in Cannabis, the genus that includes both hemp and marijuana. They accumulate in Cannabis trichomes, small crystalline structures on the plant’s leaves and buds that serve as a defense mechanism against pests and pathogens.
THC, arguably the most well-known phytocannabinoid, is responsible for the psychoactive effects of marijuana. However, it does not work alone! Cannabis plants also contain a spectrum of non-psychoactive phytocannabinoids, including cannabidiol (CBD), cannabichromene (CBC), and cannabigerol (CBG). Together, these molecules interact with the body’s endocannabinoid system (ECS) and an array of non-ECS receptors and signaling pathways, offering a treasure trove of health benefits to the human body.
Tap into the Endocannabinoid System
The human endocannabinoid system (ECS) is a complex network of receptors and signaling molecules that regulate numerous aspects of our physiology, including appetite, cognition, immune function, inflammation, pain, and sleep. The ECS endogenously produces two endocannabinoids, anandamide and 2-arachidonoylglycerol, that interact with its G-protein-coupled CB1 and CB2 receptors, as well as enzymes that control endocannabinoid synthesis and degradation.
In a fascinating convergence between the plant and animal kingdoms, it turns out that plant-derived phytocannabinoids also interact with mammalian CB1 and CB2 receptors, modulating the numerous processes in our bodies governed by the ECS. These interactions help explain the healing properties of Cannabis, but don’t tell the whole story; it turns out the phytocannabinoids also exert physiological effects well beyond the ECS.3
Effects Beyond the ECS
Emerging research indicates that phytocannabinoids have a spectrum of effects beyond the ECS, further explaining their impressive range of health benefits.
THC, CBD, and the other non-psychoactive phytocannabinoids interact with an array of non-ECS receptors, including the 5-HT1a serotonin receptor, peroxisome-proliferator-activated receptor, the vanilloid receptor TRPV1, G-protein-coupled receptor GPR55, and the Wnt/beta-catenin signaling pathway.4-8 These interactions regulate functions ranging from neurotransmitter signaling to cell proliferation.
Inhibition of Endocannabinoid Breakdown
CBD has been found to inhibit the breakdown and reuptake of anandamide and 2-arachidonoylglycerol. Inhibition of endocannabinoid degradation and reuptake boosts circulating levels of endocannabinoids, potentiating their anti-inflammatory and analgesic effects.9
Allosteric Receptor Modulation
Finally, phytocannabinoids allosterically modulate cell receptors. This process can either amplify or reduce the responsiveness of receptors to their corresponding signaling molecules, resulting in an altered biological response.10
The Healing Powers of Phytocannabinoids
Phytocannabinoids have beneficial effects throughout the human body due to their broad spectrum of interactions with cell receptors and signaling pathways.
Boost Brain Function
Phytocannabinoids optimize brain function by balancing GABA/glutamate neurochemistry. CBD is a positive allosteric modulator at brain GABAA receptors, increasing GABA levels and inducing a calm, relaxed state. Conversely, CBD decreases glutamate, inhibiting excessive excitatory neurotransmission. These effects balance brain activity in disorders ranging from epilepsy to autism.11,12
CBD also boosts mood by modulating serotonin signaling and protecting the brain from environmental stressors.13,14 Promising preclinical research also indicates that phytocannabinoids inhibit the neuronal degeneration and dysfunction characteristic of Alzheimer’s, Parkinson’s, and Huntington’s diseases.15-17
Cannabis phytocannabinoids have potent effects on sleep, significantly decreasing sleep latency and enhancing sleep quality.18 High-quality sleep translates into better health for your patients.
Quench Pain and Inflammation
Phytocannabinoids have powerful anti-inflammatory effects. CBD enhances the transcription of genes involved in Nrf2 antioxidant pathway and balances the inflammatory response in the gut.19,20 Tetrahydrocannabivarin (THCV) reduces the production of inflammatory lipids in skin cells, exerting anti-acne effects.21
Phytocannabinoids also have inhibitory effects on multiple pain pathways, modulating the pain response in neuropathy and osteoarthritis.22,23
Overweight and obesity are an epidemic in the U.S., making natural compounds with beneficial effects on body weight much sought-after. Phytocannabinoids show great promise in weight management – the CBD derivative VCE 004.8 inhibits fat cell formation while THCV improves glucose tolerance, a critical factor in weight regulation.24,25
Terpenoids: Overlooked Players in the “Entourage Effect”
Terpenoids, also known as terpenes, are secondary metabolites found in the essential oils of many plants, including Cannabis. Emerging research indicates that Cannabis terpenoids boost the therapeutic effects of phytocannabinoids in a phenomenon referred to as the “entourage effect.”26 β-caryophyllene, one of the most abundant terpenoids in hemp, supports healthy brain function while β-myrcene inhibits the inflammatory COX pathway, inducing anti-inflammatory and analgesic effects.27,28
Liposomal Delivery Systems for Rapid Delivery of Phytocannabinoids
The bioavailability of phytocannabinoids is significantly enhanced by liposomal delivery systems, which allow phytocannabinoids to gain immediate access to the lymphatic system, bypassing first-pass metabolism in the liver, and results in fast-acting, noticeable effects.29,30
Phytocannabinoids support whole-body health, making them a must-have in your natural medicine repertoire. Whether your patients struggle with brain fog, chronic inflammation, or sleep difficulties, phytocannabinoids and hemp-based terpenes can help. New therapeutic applications of these compounds will undoubtedly emerge as this fascinating area of research continues to grow!
Sponsored by Quicksilver Scientific, the makers of Full Spectrum Hemp Extract, a liposomal full spectrum phytocannabinoid formulation.
- Russo EB. History of cannabis and its preparations in science, saga, and sobriquet. Chem Biodivers. 2007; 4(8): 1614-1648.
- Jiang HE, et al. A new insight into Cannabis sativa (Cannabaceae) utilization from 2500-year-old Yanghai tombs, Xinjiang, China. J Ethnopharmacol. 2006; 108(3): 414-42
- Di Marzo V. New approaches and challenges to targeting the endocannabinoid system. Nat Rev Drug Discov. 2018; 17(9): 623-639.
- De Mello Schier AR, et al. Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa. CNS Neurol Disord Drug Targets. 2014; 13(6): 953-960.
- Esposito G, et al. Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement. PLoS One. 2011; 6(12): e28668.
- Muller C, et al. Cannabinoid ligands targeting TRP channels. Front Mol Neurosci. 2018; 11: 487.
- Whyte LS, et al. The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci USA. 2009; 106(38): 16511-16516.
- Esposito G, et al. The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells. J Mol Med (Berl). 2006; 84(3): 253-25
- Bisogno T, et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001; 134(4): 845-852.
- LaPrairie RB, et al. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol. 2015; 172(20): 4790-4805.
- Pretzsch CM, et al. Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder. Neuropsychopharmacol. 2019; 0:1-8.
- Reddy DS. The utility of cannabidiol in the treatment of refractory epilepsy. Clin Pharmacol Ther. 2017; 101(2): 182-184.
- Fogaca MV, et al. Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: involvement of 5HT1A receptors and previous stressful experience. Eur Neuropsychopharmacol. 2014; 24(3): 410-419.
- Campos AC, et al. Plastic and neuroprotective mechanisms involved in the therapeutic effects of cannabidiol in psychiatric disorders. Front Pharmacol. 2017; 8: 269.
- Watt G, Karl T. In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease. Front Pharmacol. 2017; 8:20.
- Diaz-Alonso J, et al. VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease. Sci Rep. 2016; 6: 29789.
- Garcia C, et al. Benefits of VCE-003.2, a cannabigerol quinone derivative, against inflammation-driven neuronal deterioration in experimental Parkinson's disease: possible involvement of different binding sites at the PPARγ receptor. J Neuroinflammation. 2018; 15(1): 19.
- Babson KA, et al. Cannabis, cannabinoids, and sleep: a review of the literature. Curr Psychiatry Rep. 2017; 19(4): 23.
- Kozela E, et al. Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells. J Neuroinflammation. 2016; 13:136.
- Hasenoehrl C, et al. Cannabinoids for treating inflammatory bowel diseases: where are we and where do we go? Expert Rev Gastroenterol Hepatol. 2017; 11(4): 329-337.
- Olah A, et al. Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment. Exp Dermatol. 2016; 25(9): 701-707.
- Vuckovic S, et al. Cannabinoids and pain: New insights from old molecules. Front Pharmacol. 2018; 9: 1259.
- O’Brien M, McDougall JJ. Cannabis and joints: scientific evidence for the alleviation of osteoarthritis pain by cannabinoids. Curr Opin Pharmacol. 2018; 40: 104-109.
- Palomares B, et al. VCE-004.8, a multitarget cannabinoquinone, attenuates adipogenesis and prevents diet-induced obesity. Sci Rep. 2018; 8(1): 16092.
- Wargent ET, et al. The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutr Diabetes. 2013; 3(5): e68.
- Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011; 163(7): 1344-1364.
- Machado KDC, et al. A systematic review on the neuroprotective perspectives of beta-caryophyllene. Phytother Res. 2018; 32(12): 2376-2388.
- Brugnatelli V. Anti-inflammatory and anti-nociceptive properties of β-myrcene. Fundacion Canna. Accessed 30 May 2019.
- Zgair A, et al. Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines. Am J Transl Res. 2016; 8(8): 3448-3459.
- Zgair A, et al. Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation. Sci Rep. 2017; 7(1): 14542.