Full Spectrum Cannabis – Benefits Beyond THC & CBD

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).