Cannabinoids are a group of natural substances present and produced in the cannabis plant, and there are other natural occurring plants, with small traces of cannabinoids.
The cannabis plant however, has many of these active ingredients called cannabinoids, which are found in a wide range of concentrations within the flower, leaf, and stem. Researchers have identified over 100 cannabinoids within the Cannabis plant.
These Cannabinoids are a group of various chemical compounds that act on the receptors located on cells which activate certain neurotransmitters in the brain and body.
We are born with the ability to generate our own endogenous “cannabis molecule”, i.e. a neurotransmitter which stimulates the cannabinoid receptor as part of a regular biological function. Anandamide, a name taken from the Sanskrit word “ananda“, which denotes inner peace and amide, which is in turn a chemical concept. It acts on hormonal processes, but also plays a role in the regulation of feeding behaviour and sleep-wake cycles, also affecting the regulation of pain and pleasure.
Cannabinoids act as a bio regulatory mechanism, which explains why they have been recommended as a treatment for many diseases and ailments in anecdotal reports and scientific literature. Common prescribed ailments include: Depression, bipolar disorder (particularly depression-manic-normal), multiple sclerosis, menstrual cramps, Pain, arthritic conditions, migraine headaches, anxiety, epileptic seizures, insomnia, loss of appetite, nausea, glaucoma, AIDS wasting syndrome, Parkinson’s, trigeminal neuralgia, high blood pressure, irritable bowel syndrome, and bladder incontinence.
If we go into more detail regarding the role of cannabinoid receptors, their significant action in our body can be observed acting on the central nervous system, the brain, the limbic system, as well as the striated muscles and the immune system.
As such, the mechanisms of phytocannabinoids’ biological impact are multidimensional.
CB1 endocannabinoid receptor:
They are found throughout the body and the most prevalent neurotransmitter system in the brain, specifically in the basal ganglia and in the limbic system and the hippocampus. They are also found in the cerebellum and in both male and female reproductive systems.
It is also present in:
- Striated muscles (16.92%)
- Lymph nodes (15.36%)Adrenal gland (7.78%)
- Vascular tissue (arteries and veins) (5.03%)
- Thymus (3.21%)
- Mammary glands (3.07%)
- Uterus (2.52%)
- Pancreas (1.74%)
- Ciliary body and cornea of the eye (1.54%)
- Liver (1.53%)
- Peripheral nerves (peripheral nervous system, SNP)
All these points of action explain why CB1 stimulation has been associated with analgesia, decreased anxiety, increased appetite and production of fat reserves. It is also responsible for the psychedelic effects of cannabis.
CB2 endocannabinoid receptor:
They are found most exclusively in the immune system, with the greatest density in the spleen. CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis. CB2 receptors appear in any tissue when there is pathology.
It can also be found in:
- Lymph nodes (70.86%)
- Bone marrow (9.2%)
- Other tissues (10.13%)
- Liver (2.36%)
- Placenta (1.96%)
As said above, these receptors are stimulated by a particular molecular structure with a particular form, so that the stimulus and its receptor fit like puzzle pieces.
When using the whole plant, these cannabinoids work together in a synergistic manner that provides more therapeutic benefits to us. In addition to the cannabinoids, cannabis also contains terpenoids and flavonoids that have therapeutic value. We will go into this a little later.
Delta-9-THC is the primary psychoactive cannabinoid found in the cannabis plant, but researchers have identified close to one hundred phytocannabinoids. The array of cannabinoids in the plant varies among its diverse strains. Most of the research on cannabis has been conducted on THC rather than the whole plant or its other cannabinoids.
Much has been learned about the pharmacologic actions of some of the other non-psychoactive cannabinoids. Cannabidiol, or CBD, is a very promising cannabinoid that has a wide range of effects including anti-emetic, analgesic, anti-inflammatory, anxiolytic, neuro-protective, antipsychotic, anticancer, and bone stimulation.
Other cannabinoids of interest include:
While in no way a complete list, the following cannabinoids are known to have medicinal benefits. In total there are over 100 known cannabinoids in cannabis, and there is still much research that needs to be done. As research continues, we expect to find that many other cannabinoids have medicinal applications.
Cannabidiolic Acid (CBDA)
CBDA, similar to THCA, is the main constituent in cannabis that has elevated CBD levels. CBDA selectively inhibits the COX-2 enzyme contributing to the anti-inflammatory properties that cannabis has to offer.
With respect to the medical potential of the Cannabis plant, CBD holds tremendous potential to treat many types of disease and disorder, especially when the correct ratio of CBD:THC is identified for the particular condition. CBD acts as an antagonist at both the CB1 and CB2 receptors yet it has a low binding affinity for both. This suggests that CBD’s mechanism of action is mediated by other receptors in the brain and body.
A mildly psychoactive cannabinoid that comes about from the degradation of THC, there is usually very little to no CBN in a fresh plant. CBN acts as a weak agonist at both the CB1 & CB2 receptors having greater affinity for CB2 over CB1. The degradation of THC, into CBN, is often described as creating a “couch lock” and sedative effect and potentiates the effects of THC.
Tetrahydrocannabinolic Acid (THCA)
THCA is the main constituent in raw cannabis. THCA converts to Δ9-THC when burned, vaporized, or heated for a period of time at a certain temperature. THCA, CBDA, CBGA and other acidic cannabinoids hold the most COX-1 and COX-2 inhibition for the anti-inflammatory properties that cannabis has to offer. This cannabinoid also acts as an anti-proliferative and anti-spasmodic.
The most abundant and widely known cannabinoid in marijuana, THC is the cannabinoid responsible for the main psychoactive effects patients are familiar with. This compound acts as a partial agonist at the CB1 & CB2 receptors. The compound is a mild analgesic and cellular research has shown the compound has antioxidant activity.
A nonpsychoactive cannabinoid, CBG has antibacterial effects and can alter the overall effects of Cannabis. CBG may kills or slow bacterial growth, reduces inflammation (particulartly in its acidic CBGA form,) inhibits cell growth in tumor/cancer cells, and promotes bone growth. CBG pharmacological activity at the CB2 receptor is currently unknown and acts as a low affinity antagonist at the CB1 receptor.
More common in tropical cannabis varieties. Effects include anti-inflamatory and analgesic. CBC is known to relieve pain (analgesic), reduce inflammation, inhibits cell growth in tumor/cancer cells (anti-proliferative), and promotes bone growth (bone stimulant). The effects of CBC appear to be mediated through non-cannabinoid receptor interactions.
THCV is a minor cannabinoid found in only some strains of cannabis. The only structural difference from THC is the presence of a propyl (3 carbon) instead of a pentyl (5 carbon) group on the molecule. Though this difference is subtle it causes THCV to produce very different effects from THC. Some of these effects include a reduction in panic attacks, suppression of appetite, and the promotion bone growth. THCV acts as an antagonist at the CB1 receptor and a partial agonist at the CB2 receptor.
Like THCV, CBDV differs from CBD only by the substitution of a pentyl (5 carbon) for a propyl (3 carbon) sidechain. Its mechanism of action has not yet been fully elucidated however recent studies have shown promise for its use in the management of epilepsy due to its action at TRPV1 receptors and modulation of gene expression.