Chemistry of Cannabis

Classification of Cannabinoids

Science Uses

3 Classifications of Cannabinoids

Endogenous Cannabinoids

produced naturally by the body

Synthetic Cannabinoids

chemically produced and distributed by the medical industry

Phyto/Plant Cannabinoids

cannabinoids found in the cannabis plant

Endogenous Cannabinoids

Naturally produced by the body.

Cells in our body naturally produce endocannabinoids. ANA and 2AG are the best- studied and known endocannabinoids.

Endocannabinoids are molecules that, like CBD, can interact with cannabinoid receptors.

Anandamide (ANA)

is derived from the Sanskrit word “ananda” meaning “happiness” or “joy” and is therefore known as “the molecule of happiness”. Anandamide can relieve physical discomfort and pain, at the same time, it can help to control appetite and fertility.

2AG

high levels of the endocannabinoid are found in the central nervous system. 2AG has also been shown to be present in maternal bovine and human milk. This endocannabinoid plays a role in many functions, including emotions, cognition, energy balance, pain sensation and neuroinflammation.

Distance running or other exercises that require stamina can lead to a feeling known as “runners high”, which is linked to decreased anxiety and pain, an increased sense of relaxation, and a feeling of euphoria. The levels of Anandamide and β-endorphin. are found to be abundantly increased in the plasma of humans and mice after long-distance running.

Endogenous Cannabinoids

Produced by the Cannabis plant

Today, 144 cannabinoids have been identified in the cannabis plant. However, the list of known cannabinoids is certain to grow in the future as current research already offers hundreds to thousands of potential cannabinoid-receptor interactions that may provide therapeutic possibilities.

Natural cannabinoids from plants or extracts are supplemented with flanking compounds – consisting of other cannabinoids and terpenes. Other compounds can also interact with one or more cannabinoid receptors, causing a change in the effect of the cannabinoid which may be a part of the interaction.

The influence of the flanking compounds on the cannabinoids and terpenes is called the ‘entourage effect’. To this date, there is a lack of evidence on how the ‘entourage effect’ works. Nevertheless, it is known that the ‘entourage effect’ consistently improves the therapeutic potential of cannabinoids. (Russo & Guy – 2006, Gallily et al. – 2015; Russo, 2011).

To fully understand the cannabinoid-receptor interactions, it is important to know that the biologically active cannabinoids are not present in the raw plant. Instead, the active compounds are formed when the raw plant is heated – leading to decarboxylation – forming, for example, CBD and THC.

Cannabinoid-receptor interactions are modulatory in nature and follow a bell-shaped activation curve. Furthermore, these interactions possess a high degree of cooperativity. These have three crucial implications:

Cannabinoid-controlled processes are hardly ever binary or ‘on-off’. They are rather graded and subtle.
It is vital to find the right dose, especially for THC, where under- or overdose can lead to unwanted or even opposite effects.
A specific combination of cannabinoids and receptors and their web of interactions can more likely produce physiological or therapeutic effects when compared to the effect of one cannabinoid or receptor.

Synthetic Cannabinoids

Chemically produced and distributed by the medical industry

In principle, the synthesis of exact copies of natural cannabinoids can be done, meaning that the synthetic cannabinoids can be similar or even identical to natural cannabinoids. However, in practice, the safety profile of synthetic cannabinoids can be different, meaning that they can lead to adverse effects, which natural cannabinoids do not lead to, as shown by clinical trials and ages of traditional usage.

Entourage Effect

Synthetic cannabinoids are usually not supplemented with flaking compounds something often seen for natural cannabinoids (phytocannabinoids). The entourage effect is thus not present in synthetic cannabinoids, meaning that natural cannabinoids are often preferred over synthetic cannabinoids in treatment.

Specificity

Endocannabinoids, as well as phytocannabinoids, can interact with more than one receptor and exhibit more than one activity which can be beneficial in normal physiology. In contrast, synthetic cannabinoids are specific for the receptor of interest and do not interact with any other receptor. This allows for synthetic cannabinoids to be useful in research but not necessarily in treatment. For example, it is important to have a specific marking compound when mapping the location of the CB1 receptor. If the marking molecule is not specific only for the CB1 receptor, the mapping will be inaccurate due to non CB1 receptors populating the map (Ceccarini et al., 2015).

Efficacy

Another difference is that natural cannabinoids (endo- as well as phytocannabinoids) have a moderate affinity and short-lasting effect for their receptor whereas synthetic cannabinoids are often produced to have a high affinity for their receptor of interest and possess a long-lasting effect.

For Example

The analogy of the receptor CB1 being a lightbulb can help describe the difference between allosteric modulators, a full agonist, an antagonist and a partial agonist. And this works for both natural and synthetic analogs.

When CB1 is introduced to a full agonist like the synthetic cannabinoid Win55232-2, the CB1 lightbulb would light up to its maximum lighting. Oppositely, if introduced to the synthetic cannabinoid SR141716, an antagonist, the CB1 lightbulb would be turned off. However, if instead the CB1 lightbulb was introduced to the phytocannabinoid THC, a partial agonist, the lightbulb would only give dim lighting. If the CB1 lightbulb was introduced to an allosteric modulator, such as the phytocannabinoid CBD, the lightbulb would be provided with a dimmer or on/off switch. In the case of CBD, it does not bind directly to the activation site of CB1 but to another part of the receptor, acting as a modulator of CB1, or as a dimmer for the CB1 lightbulb.

The example above illustrates why treatment with cannabinoids is recommended, as the distinct cannabinoids influence the receptor in four different ways and thereby have different effects. However, since natural cannabis- and cannabinoids have been used globally for over 6.000 years without a single reported fatality, natural cannabinoids have a well-established safety profile and can therefore often be safer to use.

Compounds in the Cannabis Plant

∆ 9-THCA

→ Inhibits Cancer Cell Growth
→ Suppresses Muscle Spams
→ Aids Sleep

∆ 9-THC

→ Reduces Vomiting and Nausea
→ Suppresses Muscle Spasms
→ Stimulates Appetite
→ Relieves Pain

∆ 8-THC

→ Relieves Pain

THCV

→ Reduces Convulsions & Seizures
→ Promotes Bone Growth

CBD

→ Antibacterial
→ Inhibits Cancer Cell Growth
→ Neuro-protective
→ Promotes Bone Growth
→ Reduces Seizures and Convulsions
→ Reduces Blood Sugar Levels
→ Reduces immune system attacks
→ Reduces Risk Of Artery Blockage
→ Reduces Small Intestine
→ Reduces Contractions – Muscle Relaxant
→ Reduces Vomiting And Nausea
→ Relieves Pain
→ Relieves Anxiety
→ Slows Bacterial Growth
→ Suppresses Muscle Spasms
→ Treats Psoriasis