Phytocannabionoids are natural terpenophenolic compounds with 21 carbons, present in Cannabis Sativa. The cannabinoids are lipophilic molecules and thus are stored in the body in fat tissue. While numerous cannabinoids have been identifies thus far, their function and activity is yet to be elucidated. Hence, only a handful of the identified cannabinoids are currently studied, with the vital three being THC, CBD and CBN.

The Cannabinoid Receptors – CB1 and CB2 have been identified.  While CB1 is mostly expressed in the central nervous system it can be found in lungs, liver and kidneys. The CB2 receptor is predominantly expressed in the immune system.

Delta-9-tetrahydrocannabinol (Δ9THC)

is the predominant cannabinoid and possesses a broad spectrum of physiological activities, among which analgesia, anti-spasm, anti-nausea, appetite stimulation and anti-inflammatory activities are included. THC is the primary psychoactive cannabinoid present is cannabis. The structure of THC was elucidated in 1964 by Mechoulam and colleagues at the Hebrew University of Jerusalem, Israel. This opened the door for major advances in THC research. THC is a CB1 and CB2 agonist.

Δ9-THC Acid (THCA)

THCA is the acidic precursor form of Δ9-THC. In the plant most of the THC is present in its acidic form and only upon decarboxylation is transformed to the active compound.  THCA is proposed to  possess immune modulating activities as well as exert anti proliferative and anti-spasmodic effects.

Cannabidiol (CBD)

CBD is the major non-psychoactive cannabinoid that has  been recognized for its potential therapeutic effects. CBD has been shown to possess anti-inflammatory, anti-spasm, anti-oxidation, anti-psychotic, neuroprotection and anxiolytic effects. It is also suggested for diabetic and epilepsy treatments. Furthermore, CBD has the ability to reduce some of the THC psychoactive effects.  CBD is a CB1 and CB2 antagonist.

Cannabidiol Acid (CBDA)

CBDA is the precursor of CBD and is suggested to exerts anti proliferative, anti microbial and anti inflammatory activities.

Cannabinol (CBN)

CBN is the oxidation product of THC and is usually only detected at low levels in the cannabis plant. However, as the plant ages this cannabinoid levels in the plant increase. Nevertheless, CBN possesses about 10% of THC activities.

Tetrahydrocannabivirin (THCV)

THCV has dual biochemical activity as at low concentrations it acts as a CB1 antagonist while at high doses it functions as a CB1 agonist.  In vivo studies in mice demonstrated the inhibitory effect of THCV on neurotransmission release and decreased food consumption, thus it may be a therapeutic candidate against epilepsyand obesity.

Cannabichromene (CBC)

Very little research has been conducted with CBC thus far. It is suggested though, to possess anti-inflammatory, anti-microbial and some analgesic activities. More recent studies have also demonstrated the role of CBC in stimulation of bone formation.

Cannabigerol (CBG)

CBG is suggested to possess anti proliferative, anti-bacterial and anti oxidation activities as well as the ability to reduce intra ocular pressure.

Cannabigerol acid (CBGA)

CBGA is the parental cannabinoid from which three main pathways are synthesized, the THCA channel, the CBDA channel and CBCA channel.


Other isomers and degradation products of central cannabinoids, include:
Δ8-THC, a thermally stable isomer of Δ9-THC
CBL, produced by UV-radiation of CBC


Generally, the acidic form of the cannabinoids predominates in the wild plant. However, upon decarboxylation the non-acidic form of the cannabinoid is produced. While the rate of this process at room temperature is very slow, it is highly accelerated with high temperatures. CBGA is synthesized in the plant as a precursor cannabinoid and via enzymatic processing is converted into either THC-acid (THCA), CBD-acid (CBDA) or CBC-acid (CBCA).

Cannabinoids are produced in the trichome of the female plant. They are secreted in the form of resin that is composed of cannabinoids, terpenoids and flavonoids. Although cannabinoids accumulate in the flowers, they can be present at low levels in other plant parts excluding seeds. Cannabinoids concentrations are highly dependent on cultivation conditions and elevated levels are usually reached by indoor cultivation in comparison with outdoors cultivation.

Mechanism of Action:

Cannabinoids bind the cannabinoid receptors CB1 and CB2, expressed both in the central nervous system as well as in the periphery. The affinity to the receptors varies between the cannabinoid and while some may bind CB1 or CB2, others have the affinity to bind both. Furthermore, some of the cannabinoids act as agonists to the receptor while others exert antagonistic effects. The endogenous ligands of the receptors (endocannabinoids) are lipophilic signaling molecules, similar to the phytocannabinoids.

CB receptors are G-coupled receptors leading to decreased levels of cyclic AMP and thus to an inhibitory effect. They have been shown to possess a role in various physiological and pathological processes. Thus, the endocannabinoid system participate in neurotransmission, neurogenesis, modulation of insulin metabolism, proliferation and immune system modulation. However, it has been shown that cannabinoids exert some of their effects via a non CB receptor dependent mechanism.

Cannabis Research

The research in cannabis is highly limited as there is lack of standardized methods. Different laboratories use various analytic tools and various extraction methods which hinders the understanding of the precise functions of cannabinoids and cannabis as a medicinal plant.



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