Category Archives: Cannabis Research

An Overview of the Main Cannabinoids

All molecules in nature are heavily affected by their surroundings and are in a continuous state of chemical equilibrium. Due to this equilibrium a large variety of chemicals occur under different conditions and environmental factors. There are many cannabinoids, we will walk you through the basics.

Cannabigerolic Acid (CBGA) is the first cannabinoid formed from a biosynthetic reaction, and is the precursor to all other natural phytocannabinoids.

CBGA is produced by the trichomes and converted to THCA,CBDA and CBCA using enzymes.

Cannabinoids like THCA can decarboxylate to THC with heat because the bond between the THC and acid cannot hold. 

Cannabinoids can react with molecules to form new cannabinoids, such as CBGM (cannabigerol monomethyl ether).

Cannabinoids may fold and interact with themselves to form other cannabinoids. 

Presently, there are 146 natural cannabinoids catalogued. It is true that they all exist under certain conditions with certain isolating methods. 

Though each cannabinoid has the potential for breakthroughs in research, most of them have neither been isolated nor characterized. It is often confusing and needs to be simplified. 

THC (tetrahydrocannabinol)

The most well known and studied cannabinoid. Until recently even studying this compound was highly discouraged and supervised. Discovered by Raphael Mechoulam and Yechiel Gaoni in Israel 1964.

THCA (tetrahydrocannabinolic acid)

THCA will play a pivotal role in cannabis medicine. THCA is found in variable quantities in fresh, undried cannabis, but is progressively decarboxylated to THC with drying. THCA is produced from CBGA by THCA synthase.

CBDA (cannabidiolic acid)

CBDA degrades to CBD over time. CBDA is the predecessor to CBD.  Produced from CBGA by CBDA synthase

CBD (cannabidiol)

It is the second most prevalent of the active ingredients of cannabis. CBD exhibits no effects indicative of any abuse or dependence potential. Obtained by a non-enzymatic decarboxylation of CBDA, which is produced by an enzyme from CBGA 

CBN (cannabinol)

CBN is a non-intoxicating, mildly psychoactive, compound that occurs when THC decarboxylated, this cannabinoid created when THC ages. 

CBG (cannabigerol)

Cannabigerol is the non-acidic form of CBGA, the parent molecule from which other cannabinoids are synthesized. Cannabigerol is a minor constituent of cannabis.

CBC (cannabichromene)

Appears in smaller amountsTHC and CBD. It is not scheduled by the convention on psychotropic substances. It is produced from CBCA under thermodynamic conditions.

CBL (cannabicyclol)

CBL differ mainly in the absence of double bond in the second molecule. recent studies have shown promising conclusions, especially regarding the anti-inflammatory potential and anti-tumor effect of CBL. 

CBV (cannabivarin)

Cannabivarin (CBV), also known as cannabivarol, is a non-psychoactive cannabinoid found in minor amounts in the hemp plant.It has no double bond isomers or stereoisomers.

THCV (tetrahydrocannabivarin)

THCV is a cannabinoid receptor type 1 antagonist and cannabinoid receptor type 2 partial agonist.  Δ8-THCV has also been shown to be a CB1 antagonist.

THCV is a new potential treatment against obesity-associated glucose intolerance

CBDV (cannabidivarin)

CBDV is structurally similar to CBD. Like CBD. CBDV is not intoxicating when isolated.

because of a demonstrated neurochemical pathway for previously-observed anti-epileptic and anti-convulsive action. Phase 2 trial for adult epilepsy are being conducted. CBDV is the non-acidic form of CBDVA,

CBCV (cannabichromevarin)

CBCV typically exists in cannabis strains at low levels. CBCV is related to CBC. CBCV has a similar but shorter chemical structure than CBC. It is a propyl cannabinoid, which means it has a propyl chain in its molecular structure rather than a pentyl chain that branches off once again to include a propyl chain. Formed from when heat is applied to CBDVA. 

CBGV (cannabigerovarin)

These agents are able to interfere with the development of cancerous cells, stopping them and preventing them from growing. Using specific dosage patterns, they can destroy cancer cells on their own. Significantly, these compounds are inexpensive to produce could result in much more cost effective anti-cancer drugs

CBGM (cannabigerol monomethyl ether)

Beyond the molecular structure, no clear difference has been identified between the CBGM and other cannabinoids in the CBG group. 

CBE (cannabielsoin)

Cannabielsoin (CBE) was identified as a novel metabolite of CBD.Promotes prolonged pentobarbital-induced sleep.

CBT (cannabicitran)

CBT is a trace cannabinoid..Discovered by Obata and Ishikawa in1966, and determined in 1976. There are nine known types of CBT. CBT is structurally similar to THC. Its psychoactive activities are unknown, but may mitigate the psychoactive components of THC. 

Below is a diagram indicating the basic Cannabinoid synthesis flow.

Water Soluble Terpenes

Terpene Properties 

Terpenes are oils. While some blend with alcohol and chloroform, they do not mix well with water. As you may already know, water molecules are strongly attracted to other water molecules, so they will instantly and tightly bond to one another. Oil molecules are also attracted to water molecules, but because of the water molecule’s tight bond, the oil molecules are unable to mix with the water molecule. 

Emulsification 

To emulsify is to force two immiscible liquids to combine in a suspension causing substances, like terpenes and water, which cannot dissolve in each other to form a uniform, homogenous solution.

There are two main types of emulsions, water in oil and oil in water. An emulsion happens when small droplets of one solution (dispersed solution) are dispersed throughout another (continuous solution)

Although terpenes and water don’t mix, we can break oil down into tiny droplets that can remain suspended in the water. 

The emulsifier coats the terpenes, keeping them separate from each other. When untreated, the droplets will clump together, causing the emulsion to separate. 

Emulsifiers are molecules with a fat-soluble part and a water-soluble part. The emulsifier creates an effective barrier around the terpene droplets. 

Glycosylation 

Glycosylation happens naturally in the body as it metabolizes different foods. The process of glycosylation transforms naturally lipophilic cannabinoid or terpene molecules into hydrophilic (water-soluble) molecules that can be more readily absorbed into the body.

In this process, a sugar molecule is attached to the terpene. Glycosylation improves the water solubility, but may also enable selective delivery, augment side effects and change bioavailability of the terpene.

Application

Water Soluble Terpenes have many applications. These terpenes can mix with water-based products and can be used in water-based foods, beverages,creams, lotions and perfumes. These same terpenes can represent a new class of terpene pharmaceuticals.

Safety 

There are many emulsifiers being used today. Some natural examples include casein and lecithin. Safety of emulsifiers is carefully regulated and tested by the U.S. Food and Drug Administration. The FDA does not take into account new developing applications for these emulsifiers. 

Further research has to be conducted on changing metabolic pathways using glycosylation, however the results look promising.  

Regulation

Regulation is still behind in many fields. Before creating a product make sure you perform the necessary tests on the proper scientific channels, backed by academia. Do not leave it up to the regulator who up until recently, did not even let us conduct research on these life saving compounds.

What Is Limonene

Limonene takes its name from the lemon peel, but can be found in various fruits and flowers including cannabis. Its popularity stems from being the top 5 terpenes found in cannabis and has proven valuable in various applications.

Limonene exists in two  isomeric forms, D-Limonene and L-limonene. Both have different ouders and behave differently. Both forms of Limonene are classified as a monoterpenes, and degrade to produce other terpenes such as  carveol, carvone.

D-Limonene

D-Limonene has a sweet citrusy cent make it a common edible additive and can be found in many food items .Limonene is common as a dietary supplements known to promote weight loss, prevent cancer and treat bronchitis

L-Limonene

L-Limonene has a more piney, lemony, clean, turpentine-like scent. L-Limonene is a popular  ingredient in water-free hand soaps as it cleanses and leave the hands smelling fresh. 

Limonene Uses

Limonene scent characteristics makes it popular in perfumery, cosmetic and scented products 

In manufacturing, limonene is considered an effective, naturally occurring, biodegradable solvent and degreaser. It is 100% natural, environmentally friendly, non-toxic and renewable product . 

Producing Limonene

Manufacturers Extract it from the skin of citrus fruits by two methods: by spinning liquefied citrus rind (centrifugal separation) or by ‘cooking’ the rind (steam distillation). 

Limonene Toxicity

Generally Recognized As Safe (GRAS) by the FDA. D-Limonene can be used safely and effectively in a wide range of products and medications. 
Limonene itself has low toxicity, which is why it is used so widely in food-grade products. When applied to skin may sometimes cause irritation, but otherwise appears to be safe for human use.

Limonene Dermal Absorption

D-limonene can enhance Skin Absorption. It is evident that D-limonene is important factors for promoting the percutaneous absorption of indomethacin. As a possible mechanism for enhancement action of d-limonene may change the barrier structure of the stratum corneum and can help produce effective dermal drug delivery methods for  liniments, lotions, ointments, creams, dusting powders, aerosols, and transdermal patches.

Limonene Mechanism

Limone works on the endocannabinoid system and helps regulate cannabinoid uptake by the receptors CB1 and CB2. It is one of the active terpenes in the Entourage Effect 

Limonene has demonstrated the ability to reduce inflammation. One way limonene reduces inflammation is through the inhibition of angiogenesis. Angiogenesis is the formation of new blood vessels, which is an inherent component of inflammation. Thus, by inhibiting this process, limonene can help to reduce inflammation and also improve wound healing.

Studies have also shown that limonene have anti-cancer effects. Limonene increase the levels of liver enzymes involved in detoxifying carcinogens. The Glutathione S-transferase (GST) is a system which eliminates carcinogens. In addition, anti-inflammatory, antioxidant, antinociceptive, antidiabetic, antihyperalgesic and antiviral properties of limonene have been observed.

New research is uncovering how valuable Limonene is. Like limonene, there are many useful terpenes. Studying the various terpenes give us knowledge that we are eager to spread.

Chemical Properties 

Formula: C10H16

Molar mass: 136.24 g/mol

Density: 841 kg/m³

Boiling point: 176 °C

Chemical Structure 

Limonene chemical structure
Limonene