Cannabinoids are chemical compounds found in cannabis, hemp and hops. These compounds, also known as Phytocannabinoids, are found in highest concentrations in the flowering portion of the plants, specifically within the resin glands located on the flower. Until today it have been discovered more than 140, and increasing.
 

Cannabinoids are a diverse set of chemical compounds that bind to special receptors in the human body that make up what is known as the endocannabinoid system. The “key and lock” metaphor is often used to describe this process. The human body possesses specific binding sites (“locks”) on the surface of many cell types, and our body produces several endocannabinoids (“keys”) that bind to these cannabinoid receptors (CB) to activate or “unlock” them.

In 1992, researchers detected an endogenous substance that binds to cannabinoid receptors for the first time. This substance, known as anandamide, comes from the Sanskrit word “Ananda” for bliss and “amide” due to its chemical structure. A second endocannabinoid was discovered in 1995, 2-arachidonoylglycerol (2-AG). These two endocannabinoids are the best studied so far. Today, it is thought that about 200+ related substances exist, which resemble the endocannabinoids and complement their function in what has been termed the “entourage effect.” Several endocannabinoids do not only bind to cannabinoid receptors, but also to a possible CB3 receptor (the GPR55 receptor), to vanilloid receptors and further receptors.

In addition to endocannabinoids, scientists have now identified cannabinoids found in the cannabis plant (phytocannabinoids) that work to mimic or counteract the effects of some endocannabinoids. Phytocannabinoids and terpenes are manufactured in resin glands (trichomes) present on the flowers and main fan leaves of late-stage cannabis plants. The amount of resin produced and its cannabinoid content varies by plant gender, growing conditions and harvesting time. The chemical stability of cannabinoids in harvested plant material is affected by moisture, temperature, light and storage, but will degrade over time in any storage conditions.

When a cannabinoid causes a receptor to act in the same way as it would to a naturally occurring hormone or neurotransmitter, then it is labeled “agonist.” On the other hand, if the cannabinoid prevents the receptor from binding to the naturally occurring compound, thereby causing the resulting event (e.g., pain, appetite, alertness) to be altered or diminished, it is labeled “antagonist.” Research is mounting to better understand how specific cannabinoids can unlock (or lock in some cases) specific receptors.

Over 140 phytocannabinoids have been identified in the cannabis plant, many of which have documented medicinal value. Most are closely related or differ by only a single chemical part. The most talked-about and researched cannabinoids found in the cannabis plant are tetrahydrocannabinol (THC) for its psychoactive properties (“high feeling”) and cannabidiol (CBD) for its healing properties.

Cannabinoids can be administered by smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, sublingual absorption or rectal suppository.

Below we describe the more popular ones and their benefits:
 

Tetrahydrocannabinolic Acid (THCA)

Research studies show that cannabinoids have positive impacts in the treatment of chronic pain, spasticity, nausea and chemotherapy as related to vomiting and sleep disorders. THCA may be a more potent alternative to THC in the treatment of nausea and vomiting. 
 

Delta-9-Tetrahydrocannabinol (Δ-9-THC)

Research shows that delta-9 THC slows down the growth of cancer cells and was even more effective when combined with CBD. Other studies indicate that delta-9 THC affects the TRPV1-4 and has therapeutic applications regarding the gastrointestinal tract and inflammation. THC and/or CBD have been found to assist in lessening fear memories in post-traumatic stress disorder patients. It has also been found to assist in the treatment of chronic pain and with the modulation of the immune system.

Delta-8-Tetrahydrocannabinol (Δ-8-THC)

Delta-8 THC is said to exhibit a lower psychotropic potency and effect than delta-9 THC. However, it has appetite stimulating, analgesic and neuroprotective properties. Studies have analyzed it in the prevention of nausea and vomiting for chemotherapy patients, as well as its anticonvulsant effects. 

Tetrahdrocannabivarin (THCV)

Research shows THCV may delay progression of disease, including symptoms associated with Parkinson’s disease. Research also indicates that THCV decreases signs of inflammation and inflammatory pain in mice (12) and has anticonvulsant effects. 

Cannabidiol (CBD)

CBD alone, or in conjunction with THC, may assist in reducing fear memories for post-traumatic stress disorder patients. Research shows that CBD affects the TRPV1-4 and may have therapeutic applications for the gastrointestinal tract and inflammation. It may also inhibit prostate carcinoma and modulate the immune system.

Cannabidiolic Acid (CBDA)

CBDA may assist in treating nausea, vomiting, emesis, motion sickness or other similar conditions. Research shows that it has anti-inflammatory, analgesic and anti-cancer effects and is a more potent inhibitor compared to CBD or other cannabinoids.

Cannabidivarin (CBDV)

Reports indicate that CBDV reduces seizure severity in animals and has therapeutic potential in reducing nausea. CBDV displays anticonvulsant properties in mice and rats. The TRPV1-4 is found to have therapeutic applications regarding the gastrointestinal tract and inflammation.

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Cannabidivarin Acid (CBDVA)

CBDVA may assist the prevention or treatment of neurodegenerative diseases or disorders, such as Alzheimer’s. It may also assist with reverse cholesterol transport activity. 

Cannabinolic Acid (CBN)

Antibacterial properties have been found in CBN.  CBN may also assist with the modulation of the immune system. Studies have also shown that mixing Delta-9 THC with CBN synergized the depressant effects on rabbits that were sleep deprived.

Cannabigerol (CBG)

CBG may inhibit as well as reduce cancer growth in the colon. Antibacterial properties have been found in CBG research. Other studies show that CBG alleviates inflammation in multiple sclerosis and may even assist with other types of neuroinflammatory diseases, including inflammatory bowel disease.

Cannabigerolic Acid (CBGA)

Research studies show that CBGA affects the TRPV1-4 with potential therapeutic applications regarding the gastrointestinal tract and inflammation. THCA is biosynthesized from CBGA. 

Cannabichromene (CBC)

Antibacterial properties have been found in research associated with CBC. Other research shows that CBC has anti-inflammatory properties, as well as antibacterial and antifungal properties. (36) Research indicates that CBC affects the TRPV1-4 with potential therapeutic applications regarding the gastrointestinal tract and inflammation.

Cannabichromic Acid (CBCA)

Research indicates that there is enzymological evidence for CBDA biosynthesis. CBCA has been observed in cannabis seedlings prior to the appearance of THCA. 

Cannabicyclol Acid (CBLA)

More research is needed to analyze potential properties associated with CBLA. CBLA is known to be one of the more stable cannabinoid acids when heated and has a tendency to resist decarboxylation*.

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Synergistic Effects

The Carlini et al study demonstrated that there may be potentiation (a form of synaptic plasticity that is known to be important for learning and memory) of the effects of THC by other substances present in cannabis. The double-blind study found that cannabis with equal or higher levels of CBD and CBN to THC induced effects two to four times greater than expected from THC content alone. The effects of smoking twice as much of a THC-only strain were no different than that of the placebo.

This suggestion was reinforced by a study done by Wilkinson et al to determine whether there is any advantage in using cannabis extracts compared with using isolated THC. A standardized cannabis extract of THC, CBD and CBN (SCE), another with pure THC, and also one with a THC-free extract (CBD) were tested on a mouse model of multiple sclerosis (MS) and a rat brain slice model of epilepsy.

Scientists found that SCE inhibited spasticity in the MS model to a comparable level of THC alone, and caused a more rapid onset of muscle relaxation and a reduction in the time to maximum effect than the THC alone. The CBD caused no inhibition of spasticity. However, in the epilepsy model, SCE was a much more potent and again more rapidly-acting anticonvulsant than isolated THC; however, in this model, the CBD also exhibited anticonvulsant activity. CBD did not inhibit seizures, nor did it modulate the activity of THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. anti-spasticity), THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb is due to the THC content.

Dr. Ethan Russo further supports this theory with scientific evidence by demonstrating that non-cannabinoid plant components such as terpenes serve as inhibitors to THC’s intoxicating effects, thereby increasing THC’s therapeutic index. This “phytocannabinoid-terpenoid synergy,” as Russo calls it, increases the potential of cannabis-based medicinal extracts to treat pain, inflammation, fungal and bacterial infections, depression, anxiety, addiction, epilepsy and even cancer.

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