Chemistry

of Cannabis & classification of Cannabinoids

Science uses 3 classifications of cannabinoids

  1. Endogenous Cannabinoids – produced naturally in the body
  2. Phyto/Plant Cannabinoids  – cannabinoids found in the cannabis plant
  3. Synthetic Cannabionoids – chemically produced and distributed by the medical industry

Endogenous cannabinoids – produced naturally in the body

Cells in our body naturally produce endocannabinoids (ANA and 2AG are the best-studied endocannabinoids). The endocannabinoids are molecules that, like the plant’s cannabinoid CBD, bind to and activate cannabinoid receptors.

These endocannabinoids are made from fat-like molecules within cell membranes and created as needed. This means that they are produced and used exactly when needed, rather than packaged and stored for later use like many other biological molecules.

  • 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 but the endocannabinoid can also help control appetite and fertility.
  • 2AG: the endocannabinoid is present at high levels 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.

Phytocannabinoids – produced by the cannabis plant

Today, 113 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 other flanking compounds – consisting of other cannabinoids and terpenes. . Like the cannabinoid of interest, other compounds can also interact with one or more cannabinoid receptors, causing a change in the effect that the cannabinoid of interest has.

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.

The vast majority of these interactions are modulatory in nature and follow a bell-shaped activation curve. In addition, cannabinoid-receptor interactions have a high degree of cooperativity. These have three important implications:

  • Cannabinoid-controlled processes are hardly ever binary or ‘on-off’ but rather graded and subtle.
  • Finding the right dose is crucial, especially for THC, where under- or overdose can result in unwanted or even opposite effects.
  • Instead of focusing on the effects of one cannabinoid or receptor, any physiological or therapeutic effect is more likely produced by a specific combination of cannabinoids and receptors and their web of interactions.

Below is an overview of the most important known cannabinoids, as well as the therapeutic value of each cannabinoid in the table on the right.

Donut Cbd 1200px
1. 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
→ Contractions
→ Reduces Vomiting And Nausea
→ Relieves Pain
→ Relieves Anxiety
→ Slows Bacterial Growth
→ Suppresses Muscle Spasms
→ Treats Psoriasis

2. THCV

→ Reduces Convulsions & Seizures
→ Promotes Bone Growth

3. ∆ 8-THC

→ Relieves Pain

4. ∆ 9-THC

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

5. ∆ 9-THCA

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

6. CBC

→ Relieves Pain
→ Reduces Inflammation
→ Promotes Bone Growth
→ Inhibits Cancer Cell Growth

7. CBN

→ Relieves Pain
→ Antibacterial
→ Appetite Booster
→ Sedative

8. CBG

→ Anti convulsant
→ Improves ASD Behavior
→ Improves ASD Communication
→ Improves Muscle Functions

9. CBD-V

→ Aids Sleep
→ Inhibits Cell Growth
→ Promotes Bone Growth
→ Slows Bacterial Growth

Synthetic cannabionoids – chemically produced and distributed by the medical industry

In principle, 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. Natural cannabinoids do not pose a public threat and have been used worldwide for many years.

Entourage effect
Synthetic cannabinoids are usually not supplemented with .flanking compounds. , something often seen for natural cannabinoids (phytocannabinoids).  The entourage effect is thus not present in synthetic cannabinoids, meaning that the natural cannabinoids are often preferred over synthetic cannabinoids in medical 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 medical treatment.  For instance, mapping the distribution of CB1 receptors can only be valid when the used probe is highly specific for CB1 and does not cross-react with any other receptor in the body (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, the natural cannabinoid is far safer to use in treatment than synthetic cannabinoids.