Feature Article: January 2019 – Full Spectrum Cannabis – Benefits Beyond THC & CBD

Full Spectrum Cannabis - Benefits Beyond THC & CBD

Betty Wedman-St. Louis, Ph.D.

The cannabis plant contains more than 500 unique compounds- cannabinoids, terpenoids and flavonoids- but research into the health benefits and synergy between compounds has been limited due to federal regulations. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major cannabinoids with the most testing but awareness and testing is beginning to focus on the therapeutic properties of whole plant efficacy. E.B. Russo, M.D. in 2011 (1) identified the “entourage effect” whereby the efficacy of a single cannabinoid was less than the combination of cannabinoids, terpenoids and flavonoids.

Now that the U.S. Farm Bill 2018 has been signed into law, hemp products are legal despite the taxonomy of the genus Cannabis indicating hemp and marijuana to be one single species – Cannabis sativa L.- with 3 subspecies- indica, sativa, ruderalis (2). Cannabinoids in raw cannabis are synthesized and accumulate as cannabinoid acids (CBDa, THCa) but when dried, stored or heated, the acids decarboxylize gradually or completely into neutral forms (CBD, THC). The amount of cannabinoids in the raw cannabis are present in different parts of the plant at different stages in the growth cycle which is a challenge for growers and researchers, but let’s save that for another paper.

Endocannabinoid System

The human body contains an endocannabinoid system (ECS) that influences and controls all functions within the nervous, endocrine and gastrointestinal systems. Endocannabinoid receptors throughout the body govern inflammation signaling, bone building, insulin sensitivity and pain responses. When the innate ECS is not regenerated, a deficiency results which can cause migraines, irritable bowel disorders. multiple sclerosis, dementia, Parkinson’s disease, and other inflammatory issues (3). Cannabis can provide phytocannabinoids to replenish the innate ECS like other plants- echinacea, pepper, thyme, rosemary, hops, chocolate, carrots and cloves.

Cannabis is inherently polypharmaceutical according to McPartland who emphasizes that synergy arises from the interactions between its multiple components (4). With more than 140 cannabinoids and 150 to 200 terpenoids, cannabis products need to be “full spectrum” to produce the most therapeutic benefit. The phytocannabinoids and terpenoids offering therapeutic benefit are predominately synthesized inside glandular trichomes of the unfertilized female flower (5).

Cannabis As Medicine

The use of plants in medicine is the basis of pharmacology- meaning “the study of poisons” in Greek. The difference between a drug and a poison can be the dose. A drug used in a high dose can cause toxicity while a low dose can be a useful therapeutic agent. Phytocannabinoids in cannabis were dilute until the 1970’s and 1980’s when high THC became the rage. Nature does not give us drugs as isolated chemicals or pure single molecules. As Mechoulam in 2005 indicated, the biochemical and pharmacological benefits of cannabis depend on “strains” or chemovars related to terpenoid content and the ratio of cannabinoids produced in the plant (6).

Terpenoids

Terpenoids form the largest group of plant chemicals numbering between 15,000 to 20,000 (7) with over 200 reported in cannabis but only a few have been studied (8). Terpenoids are essential for the viability of plants and have a variety of functions within the plant by acting as growth regulators, insect defense secretors and pollinator attractants (9). In human nutrition, they have provided flavors and scents and have GRAS (Generally Recognized As Safe) status by the U.S. Food and Drug Administration (10). As essential oil components they provide the aroma of cannabis despite their yield being less than 1 percent of the total product weight (11) in addition to having significant pharmacological interest.

Monoterpenes- limonene, myrcene, pinene- dominate. Sesquiterpenoids like beta-caryophyllene are found in higher proportion. Myrcene displays opioid-like analgesic effect (12) while beta-caryophyllene demonstrates anti-inflammatory activity (13) and both pinene and linalool have been found to inhibit PGE-1 as an anesthetic (14). D-limonene found in lemons and other citrus fruits is the second most widely distributed terpenoid in nature (15) and other studies (16,17) suggest it is a powerful anxiolytic agent. Komari et al. in 1995 described a hospital study of depressed patients who were exposed to citrus fragrance in ambient air who discontinued anti-depressant medication in 9 out of 12 patients with normalization of Hamilton Depression scores (18).

Terpenoid production increases in the plant based on light exposure and decreases with poor soil quality (19). Terpenoids are lipophilic and interact with cell membranes, neurons and muscle ion channels, neurotransmitter receptors and G-protein receptors (20). Therefore, therapeutic properties of terpenoids- neuroprotection, bone stimulation, anti-epileptic, anti-bacterial, anti-malarial, anti-spasmodic, vasorelaxant, anti-nausea, anti-diabetic, anxiolytic and pain relief – need to be considered when advising patients about selecting cannabis use. An estimated daily intake of 10-200 mg full spectrum cannabis oil may be a dietary factor in modulating inflammation in the endocannabinoid system (21).

Cannabinoids

With over 140 cannabinoids identified in cultivars of the cannabis plant, clinical application of THCV, CBC and CBG needs to be recognized for their beneficial therapeutic effects. Delta-9 tetrahydrocannabivan (THCV) has been shown to work with CBD to modulate the effects of THC via a blockade of CB1 receptors. THCV also has a high affinity for CB2 receptors which differs from CBD activity (22). More recent findings show that THCV at low concentrations has potential for management of chronic liver diseases and inflammation-associated obesity (23).

Cannabichromene (CBC) and cannabidiol (CBD) are known to modulate in vitro activity of proteins involved in nociceptive pain mechanisms (24). Nociceptive pain is the most common form of pain caused by harmful stimuli by nociceptors around the body while neuropathic pain is associated with damage to the neurons following an infection or injury to the area resulting in pain messages sent to the central nervous system and brain.

Cannabichromene is a non-psychotropic plant cannabinoid with anti-inflammatory and analgesic properties described in the 1980s. Both CBC and cannabigerol (CBG) have been shown to have anti-fungal properties and anti-depressant activity (25).CBG has demonstrated modest anti-fungal properties and recently shown to be an effective cytotoxin on human epithelial carcinoma (26) and an effective phytocannabinoid against breast cancer along with CBD (27). Russo further describes anti-depressant, anti-hypertensive and MRSA antagonist activities of CBG (28).

Cannabinol (CBN) has a low affinity for CB1 and CB2 but produced a sedative effect as well as anti-convulsant and anti-inflammation properties (29,30).

Cannabinoid & Terpenoid Synergy

The interactions of cannabinoids and terpenoids produce a combined greater benefit than something either could produce independently. Here is a brief summation from a literature review.

Cannabinoid
Terpenoid
Pharmacology
THC
limonene analgesic
pinene antioxidant
linalool bronchodilatory
muscle relaxant
CBD
limonene antioxidant
linalool anti-anxiety
pinene anti-convulsant
MRSA
cytotoxic (breast cancer)
CBC
caryophyllene anti-fungal
limonene anti-depressant
anti-inflammatory
analgesic
CBG
caryophyllene anti-fungal
limonene anti-depressant
anti-inflammatory
analgesic
THCV
linalool anti-convulsant
bone formation
modulates THC
CBV
linalool anti-convulsant
CBN
 myrcene sedative
pinene MRSA
linalool psoriasis

A more complete look at the endocannabinoid system and cannabis use can be found in Cannabis- A Clinician’s Guide published by CRC Press in May 2018.

References

  1. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol 2011 Aug;163(7):1344-1364.
  2. Gray DJ, Baker H, Clancy K, et al. Current and future needs and applications for cannabis. Critical Reviews in Plant Sciences 35(5-6):425-426.
  3. Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraines, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuroendocrinol Lett 2004;25:31-39.
  4. McPartland J, Duncan M, DiMarzo V et al. Are cannabidiol and D 9-tetrahydrocannabivan negative modulators of the endocannabinoid system? A systemic review. Br J Phramacol 2015;172(3):737-753.
  5. Potter D. Growth and morphology of medical cannabis. In: Guy GW,Whittle BA, Robson P (eds). Medicinal Uses of Cannabis and Cannabinoids. Pharmaceutical Press, London; 2004, p17-54.
  6. Mechoulam R. Plant cannabinoids: a neglected pharmacological treasure trove. Br J Pharmacol 146:913-915.
  7. Langenheim JH. Higher plant terpenoids: a phytocentric overview of their ecological roles. J Chem Ecol. 1994;20:1223-1279.
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  9. Hoffman D. Medical Herbalism- the science and practice of herbal medicine. Healing Arts Press, Rochester, VT. 2003.
  10. Adams TB, Taylor SV. Safety evaluation of essential oils: a constituent-based approach. In: Baser KHC, Buchbauer G (eds). Handbook of Essential Oils: Science, Technology, and Applications 2010. CRC Press, p 185-208.
  11. Rothschild M, Bergstrom G, Wangberg S-A. Cannabis sativa: volatile compounds from pollen and entire male and female plants of two variants, Northern Lights and Hawaiian Indica. Bot J Linn Soc 147:387-397.
  12. Rao VS, Menezes AM, Viana GS. Effect of myrcene on nociception in mice. J Pharm Pharmacol 1990;42(12):877-8.
  13. Tamba Y, Tsujiuchi H, Honda G, et al. Gastric cytoprotection of non-steroidal anti-inflammatory sesquiterpene, beta-caryphyllene. Planta Med 1996;62(5):469-470.
  14. Gil ML, Jimenez J, Oceete MA, et al. Comparative study of different essential oils of Bupleurum gibraltarium Lamarck. Pharmazie 1989;44(4):284-287.
  15. Noma Y, Asakaw Y. Biotransformation of monoterpenoids by microorganisms, insects, and mammals. In: Baser KHC, Buchbauer G (eds). Handbook of Essential Oils: science, technology, and applications. CRC Press 2010. p 589-736.
  16. Carvalho-Freitas M I, Costa M. Anxiolytic and sedative effects of extracts and essential oils from Citrus auranthium L. Biol Pharm Bull 2002; 25:1629-1633.
  17. Pultrini Ade M, Galindo LA, Costa M. Effects of the essential oil in Citrus aurantium L in experimental anxiety models in mice. Life Sci 2006;78:1720-1725.
  18. Komori T, Fujiwara R, Tanida M, et al. Effects of citrus fragrance on immune function and depressive states. Neuroimmunomodulation 1995;2:174-180.
  19. Potter D. Growth and morphology of medicinal cannabis. In: Guy GW, Whittle BA, Robson P (eds). Medicinal Uses of Cannabis and Cannabinoids. Pharmaceutical Press, London 2004; p 17-54.
  20. Bowles EJ. The Chemistry of Aromatherapic Oils, 3rd ed. Allen & Unwin:Crow’s Nest 2003 NSW.
  21. Gertsch J, Leonti M, Raduner S et al. Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci USA 2008; Jul 1;105(26):9099-9104.
  22. McPartland J, Duncan M, DiMarzo V et al. Are cannabidiol and D 9-tetrahydrocannabivan negative modulators of the eendocannabinoid system? A systemic review. Br J Phramacol 2015;172(3):737-753.
  23. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: DD-9-tetrahydrocannabinol, cannabidiol and D-9-tetrahydrocannabivarin. Br J Pharmacol 2008;153(2):199-215.
  24. Malone S, Piscitelli F, Gatta L, et al. Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. Br J Pharmacol 2011;162(3):584-596.
  25. Elsohly HN, Turner CE, Clark AM, et al. Synthesis and anti-microbial activities of certain cannabichromene and cannabigerol related compounds. J Pharm Sci 1982;71:1319-1323.
  26. Baek SH, Kim Yo, Kwag JS, et al. Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells. Arch Pharm Res 1998;21:353-356.
  27. Ligresti A, Moriello AS, Starowicz K, et al. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther 2006;318:1375-1387.
  28. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol 2011 Aug;163(7):1344-1364.
  29. Musty RE, Karniol IG, Shirikawa I, et al. Interactions of delta-9-tetrahydrocannabinol and cannabinol in man. In: Braude MC, Szara S (eds). The Pharmacology of Marijuana, vol 2 Raven Press, NY p 559-563.
  30. Turner CE, ElSohly MA, Boeren EG. Constituents of Cannabis sativa L. XVII. A reveiew of the natural constituents. J Nat Prod 1980;43:169-234.

 

Betty Wedman-St. Louis, Ph.D., RD, is an Assistant Professor at New York Chiropractic College, an Adjunct Professor at Everglades University, Sarasota, Florida, and an Adjunct Professor at South University-Tampa, Florida. She will be presenting Full Spectrum Cannabis – Benefits Beyond THC & CBD on Sunday, April 14th at the 26th Clinical Applications in Age Management Medicine Conference in Miami. See www.agemed.org for details.

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