CANNABINOID SCIENCE

Endocannabinoid System

The Endocannabinoid System (ECS) is a vast biological system, expressed throughout the vertebrate central nervous system, peripheral nervous system, and peripheral organs. The ECS influences the activity of multiple receptor types and neurotransmitters involved in a wide variety of physiological and psychological functions. [1, 3]

Decades of scientific research reveal the ECS plays a major homeostatic role in:

  • Neurological function
  • Sleep
  • Inflammation
  • Sensation
  • Pain
  • Appetite
  • Digestion
  • Immune function
  • Psychological function
  • Cellular growth & proliferation
  • Metabolism
  • Learning
  • Memory
  • and others…
    [1, 3]

Some organs and systems with CB Receptors [1]

The ECS is a complex interplay between:

  1. Endogenous neurotransmitter “endocannabinoids”, mainly N-arachidonoyl ethanolamide (AEA, “anandamide”) and 2-arachidonoyl glycerol (2-AG). [1, 3]

  2. Two G-protein-coupled receptors (GPCRs), named Cannabinoid Receptor 1 (CB1) and 2 (CB2), found across the body, as well as various receptor types like 5-HT, GABA, Glutamate, and others, TRP ion channels, plus CB receptor heterodimers with Opioid, Dopamine, and other major receptor types – all modulated by the endocannabinoids. [1-3]

  3. Endogenous enzymes that synthesize and degrade the endocannabinoids (FAAH, MAGL,…). [1, 3]

Additional science and history of the ECS can be discovered here in the Cannacea-verse.


Phytocannabinoid Supplementation

The phytocannabinoids produced by cannabis have been proven to supplement the endocannabinoids through their interaction with the ECS [12]. The phytocannabinoids demonstrate:

  • Unique affinities and activities at CB1 and CB2 receptors, at TRP ion channels, and at various receptor types: 5-HT, GABA, Glutamate, Opioid, Dopamine, and others. [1-3, 12]

  • Unique abilities to inhibit the reuptake of the endocannabinoids and the enzymes that degrade the endocannabinoids. [13]

Click these prevalent phytocannabinoids in Cannacea hemp oils to uncover added information and structure/function effects for each:

“Physicians assist Nature.”
– Galen

Original image by Bernard Gagnon (Creative Commons)

Growing peer-reviewed scientific research from human, animal, and in vitro studies evidences significant health benefits from supplementing the ECS with phytocannabinoids. [4-8, 14, 15, 21, 22]

While added randomized, controlled clinical studies are needed to give a more detailed picture of the health benefits provided by phytocannabinoid supplementation, there is already ample scientific evidence to support this reality. For example, these 3 prospective studies:

  • One prospective study of 901 subjects over age 65 undergoing phytocannabinoid therapy resulted in 93.7% of respondents reporting improvement in their wellness, with 41.9% reporting significant improvement. For example, prior to treatment 66.8% of respondents reported high pain intensity (“8 – 10” on scale of 10), while after 6 months of treatment only 7.6% reported high pain intensity. [7]

  • One 8-week prospective study gave oral CBD-rich full spectrum hemp extract to 97 subjects aged 39 – 70 suffering from chronic pain and taking opioids for at least 1 year. Nearly all subjects (94%) took 30 mgCBD/day. 94% of subjects reported improved quality of life and 53% significantly reduced or eliminated opioid use. Significant reductions in pain intensity and interference were reported, along with significant improvements in sleep quality. [14]

  • One prospective study analyzed 2,431 subjects experiencing at least one of the six most common Palliative Care issues, who were vaporizing cannabis varieties across a wide range of CBD:THC ratios. On an 11-point scale of issue severity (0 – 10), there was at least a 3-point improvement from pre-use to post-use severity for the following percentage of subjects experiencing such issues:
    • PTSD-related flashbacks: 78%
    • Anorexia: 77%
    • Insomnia: 71%
    • Anxiety: 66%
    • Depression: 61%
    • Neuropathic pain: 42%
      [15]

Full Spectrum Synergy

Superior therapeutic efficacy of whole plant extracts over single compounds is frequently reported in the scientific literature. [16-18]

Studies also demonstrate a broader range of efficacies and reduced adverse effects if using cannabis preparations containing multiple phytocannabinoids and other natural compounds produced in cannabis versus only using isolated or purified cannabinoids. [13, 19-24]

Such synergistic effects of a natural complete cannabis phytochemical profile are evidenced by the research examples below, and have been famously named the “Entourage Effect”. [19]

The mature Cannabis flower – a phytochemical powerhouse.

Multiple peer-reviewed scientific studies confirm the therapeutic superiority of full spectrum hemp oil phytochemical profiles over purified CBD or CBD isolates:

  • A meta-analysis with 670 subjects showed intakes of full spectrum CBD-rich preparations resulted in significantly increased benefits compared with intakes of isolated or purified CBD, also reducing CBD intake by 75%, reducing mild adverse effect rates by 50%, and reducing severe adverse effects rates by over 65%. [21]

  • One study with 10 pediatric subjects also showed the use of full spectrum CBD-rich preparations resulted in significantly increased benefits and reduction in adverse side effects compared with using isolated or purified CBD. [22]

  • One study in mice showed CBD isolate oral intake was limited by a “bell-shaped” intake response for anti-nociception and anti-inflammation. In contrast, oral intake of full spectrum CBD-rich preparation did not have such dose limitation, and demonstrated continuously increasing effects upon increasing intakes that required ~2.5x less CBD for equivalent therapeutic effect (see Figure A, below). [23]
Figure A: Comparing therapeutic effect of oral intakes by mice of CBD isolate vs. CBD in a full spectrum. (a) & (b) – Prevention of zymosan-induced swelling of hind paw. (c) & (d) – Anti-nociception in a von Frey nociceptive filament assay.
Adapted from Gallily et al. (2015). [23]
  • One human study found a panel of 30 subjects was consistently experiencing specific subjective effects in relation to specific phytocannabinoid and phytoterpene chemotypes they were using. [24]

  • Several human studies demonstrate that CBD suppresses various side effects of THC when the two are taken together, particularly when more CBD than THC is taken. [25-27]

  • One in vitro study compared phytocannabinoid isolates to full spectrum preparations having those same phytocannabinoids at 40% – 70% with the remainder a complex mixture of other phytocannabinoids and non-cannabinoid natural compounds.  Various assays showed the full spectrum preparations almost always displayed significantly higher potency and efficacy in inhibiting the enzymes responsible for degrading the main endocannabinoids (AEA and 2-AG), and in inhibiting the cellular reuptake of AEA. [13]

A holistic scientific approach to plant therapy.

Complete harnessing of hemp’s unique powers.

Genuine Full Spectrum Hemp Oils.

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References
  1. Aizpurua-Olaizola, O et al. (2017). Targeting the endocannabinoid system: future therapeutic strategies. Drug Discovery Today 22(1): 105-110.
  2. Morales, P, Reggio, PH (2017). An Update on Non-CB1, Non-CB2 Cannabinoid Related G-Protein-Coupled Receptors. Cannabis and Cannabinoid Research 2(1): 265-273.
  3. Stasiulewicz, A et al. (2020). A Guide to Targeting the Endocannabinoid System in Drug Design. International Journal of Molecular Sciences 21(8): 2778.
  4. VanDolah, HJ et al. (2019). Clinician’s Guide to Cannabidiol and Hemp Oils. Mayo Clinic Proceedings 94(9): 1840-1851.
  5. Sholler, DJ et al. (2020). Therapeutic Efficacy of Cannabidiol (CBD): A Review of the Evidence from Clinical Trials and Human Laboratory Studies. Current Addiction Reports 7(3): 405-412.
  6. Khan, R et al. (2020). The therapeutic role of Cannabidiol in mental health: a systematic review. Journal of Cannabis Research 2:2.
  7. Abuhasira, R et al. (2018). Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly. European Journal of Internal Medicine 49: 44-50.
  8. National Academies of Sciences, Engineering, and Medicine (2017). The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press.
  9. Russo, EB, Marcu, J (2017). Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Advances in Pharmacology 80: 67-134.
  10. Orsavova, J et al. (2015). Fatty Acids Composition of Vegetable Oils and Its Contribution to Dietary Energy Intake and Dependence of Cardiovascular Mortality on Dietary Intake of Fatty Acids. International Journal of Molecular Sciences 16(6): 12871-12890.
  11. Krut, LH, Bronte-Stewart, B (1964). The fatty acids of human depot fat. Journal of Lipid Research 5(3): 343-351.
  12. Turner, SE et al. (2017). Molecular Pharmacology of Phytocannabinoids. In Kinghorn, AD; Falk, H; Gibbons, S; Kobayashi, J (eds.). Phytocannabinoids: Unraveling the Complex Chemistry and Pharmacology of Cannabis sativa. Progress in the Chemistry of Organic Natural Products 103. Springer International Publishing: 61–101.
  13. De Petrocellis, L et al. (2011). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. British Journal of Pharmacology 163(7): 1479-1494.
  14. Capano, A et al. (2020). Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. Postgraduate Medicine 132(1): 56-61.
  15. Casarett, DJ et al. (2019). Benefit of Tetrahydrocannabinol versus Cannabidiol for Common Palliative Care Symptoms. Journal of Palliative Medicine 22(10): 1180-1184.
  16. Wagner, H, Ulrich-Merzenich, G (2009). Synergy research: Approaching a new generation of phytopharmaceuticals. Phytomedicine 16(2-3): 97-110.
  17. Rasoanaivo, P et al. (2011). Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions. Malaria Journal 10(Suppl.1): 1-12.
  18. Yuan, H et al. (2017). How Can Synergism of Traditional Medicines Benefit from Network Pharmacology? Molecules 22(7): 1135-1153.
  19. McPartland, JM, Russo, EB (2001). Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts? Journal of Cannabis Therapeutics 1(3-4): 103-132.
  20. Russo, E (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology 163(7): 1344-1364.
  21. Pamplona, FA et al. (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.
  22. Zafar, R et al. (2021). Medical cannabis for severe treatment resistant epilepsy in children: a case-series of 10 patients. BMJ Paediatrics Open 5: e001234.
  23. Gallily, R et al. (2015). Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol. Pharmacology and Pharmacy 6: 75-78.
  24. Lewis, MA et al. (2018). Pharmacological Foundations of Cannabis Chemovars. Planta Medica 84(04): 225-233.
  25. Karniol, IG et al. (1974). Cannabidiol interferes with the effects of delta 9- tetrahydrocannabinol in man. European Journal of Pharmacology 28(1): 172– 177.
  26. Zuardi, AW et al. (1982). Action of cannabidiol on the anxiety and other effects produced by δ9-THC in normal subjects. Psychopharmacology (Berl) 76(3): 245–250.
  27. Bhattacharyya, S et al. (2010). Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 35(3): 764-774.
  28. Izzo, L et al. (2020). Analysis of Phenolic Compounds in Commercial Cannabis sativa L. Inflorescences Using UHPLC-Q-Orbitrap HRMS. Molecules 25(3): 631.

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