Cannabinoids and terpenes

What is CBG?

• Name: Cannabigerol
• Formula: C21H32O2
• IUPAC name: 2-[(2E)-3,7-dimethylocta-2,6-dienyl]-5-pentylbenzene-1,3-diol
• Molecular mass: 316,48 g/mol
• Boiling point: Not available
• Apearance: White powder/crystals

Discovered by Gaoni and Mechoulam in 1964, CBG or cannabigerol is one of the cannabinoids exclusively produced by the cannabis plant, which is stored in the trichome heads with the rest of cannabinoids and terpenes. While the CBG content in most plants is often low or very low – in most cases lower than 1% – this particular compound is crucial for cannabinoid synthesis, as we have known for the past 4 decades ( (Shoyama, Yagi and Nishioka, Phytochemistry Journal, October 1975). As a general rule, hemp contains higher amounts of CBG than commercial, narcotic cannabis strains.

CBG is a non-psychoactive phytocannabinoid, which means it is produced by plants and does not “get you high”. It is believed that it has multiple medicinal properties which can be used to treat different conditions, and is also precursor – its acid form, to be exact – to the main cannabinoids (THCA, CBDA, CBCA) secreted in the trichome heads, which in turn explains the low percentage of CBG found in mature plants when compared to their THC or CBD content.

CBG (cannabigerol) molecule

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What is the entourage effect?

The so-called entourage effect (sometimes referred to as the ensemble effect) is a term used for the first time in a study on the interaction between various compounds present in cannabis, published in the July 1998 issue of the European Journal of Pharmacology. This text (An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity) was written by researchers and scientists including Professor Raphael Mechoulam and Shimon Ben-Shabat among others, and demonstrates the increase in activity of a given cannabinoid thanks to the presence of another compound, in this case the esters of a fatty acid. However, as research has progressed over the years, this term has been coined to refer to the interaction, or synergy between the various cannabinoids, terpenes and flavonoids present in the plant that define the effects of cannabis.

Cannabinoids, terpenes and other compounds act in synergy (Photo: Don Goofy )

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What is Pinene?

• Name: Pinene, alpha-pinene, beta-pinene
• Formula: C10 H16
• IUPAC name: (1S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
• Molar mass: 136.24 g/mol
• Boiling point: 155-156ºC
• Appearance at room temperature: Liquid, almost insoluble in water

Pinene is a bicyclic monoterpene widely found in the resin of many plant species, from conifers (pine trees, spruces) to non-conifer plants like wormwood, rosemary, sage, heterotheca or cannabis. Two isomers are found in Nature, called alpha-pinene (?-pinene) and beta-pinene (?-pinene), which can be found in substances like pine resin, turpentine or camphene and are also used by many insects to communicate. Pinene is also a common terpene in a large number of cannabis strains, being highly appreciated by many users for its beneficial properties.

Molecule of alpha-pinene

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What is Cannabicyclol?

• Name: Cannabicyclol
• Formula: C21 H30 O2
• IUPAC Name: (1aR- (1a alpha, 3a alpha, 8b alpha, 8c alpha)) – 1a, 2, 3, 3a, 8b, 8c-hexahydro-1,1,3a-trimethyl-6-pentyl-1H- 4-oxabenzo (f) cyclobut (cd) inden-8-ol
• Molar mass: 314.469 g/mol

Cannabicyclol, also called CBL, is one of the least known and studied cannabinoids in the cannabis plant. Although it is commonly found in many varieties, in particular those with a higher content of CBC (Cannabichromene), the amount of CBL produced in trichomes is always very low, so it doesn’t usually receive the attention given to other, more plentiful compounds of the plant with a much more noticeable presence, such as THC, CBD or CBN.

CBL or cannabicyclic molecule (Photo: Wiki Commons)

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What is THC?

• Name: Tetrahydrocannabinol or delta-9-tetrahydrocannabinol
• Formula: C21H30O2
• IUPAC Name: Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzene [b, d] pyran-1-ol
• Molecular weight: 314.45 g / mol
• Boiling point: 157ºC
• Presence at room temperature: crystalline solid at low temperature, viscous when heated
• Not soluble in water, highly soluble in lipids, alcohols and hydrocarbons such as butane

Without a doubt, THC (often called delta-9-THC) is the most widely known cannabinoid of the cannabis plant. Although it is almost completely absent in some – usually hemp – varieties, that barely reach 1%, the drug varieties of cannabis show a high content (up to 30%) of what is the main psychotropic compound produced in the trichomes of the marijuana. Indeed, THC is the most important psychoactive component of cannabis, responsible for the “high” sensation commonly associated with the consumption of this plant and which has made it illegal in most countries of the world.

THC molecule (delta-9-tetrahydrocannabinol)

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What is Limonene?

• Name: Limonene, d-limonene
• Formula: C10H16
• IUPAC Name: 1-methyl-4-(1-methylethenyl)-cyclohexene
• Density: 841.1 kg/m3
• Molar mass: 136.23 g/mol
• Boiling point: 176ºC/348.8ºF
• Presence at room temperature: Colourless liquid, very low solubility in water

Limonene is one of the most widely used monoterpenes – aromatic molecules produced by a large number of plants – in the industry, either to make food or as constituents of perfumes, medicines or detergents, also to manufacture biodegradable solvents or to replace toxic solvents. It is a terpene commonly related to cannabis, since many of the existing cannabis strains contain limonene to a greater or lesser degree. Citrus fruits also contain high amounts of limonene, especially in the peel, as well as other plants like mint, rosemary or juniper.

It is usually classed among limonoids along with other terpenes like pinene or eucalyptol, which are often found together in the same fruits. The D-isomer (also called R or alpha) has intense citric aroma, reminiscent of oranges or lemons, while the L-isomer (also called S or beta) is closer to pine trees. Limonene is used in the industry to mask other odours or flavours, and – along with camphene – can be obtained by catalysing another well known aromatic compound, pinene. The most widely used methods to extract limonene – and other terpenes – from fruits are steam distillation or centrifugal force.

Limonene molecule

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What is CBN?

• Name: Cannabinol
• Formula: C21H26O2
• IUPAC name: 6,6,9-trimethyl-3-pentylbenzo [c] chromen-1-ol
• Molecular mass: 310.4319 g / mol
• Melting point: 77 ° C
• Boiling point: 185 ° C
• Presence at room temperature: Solid, crystalline and colorless

CBN or cannabinol is one of the most important compounds found in cannabis, along with THC or CBD. Although the proportion of CBN is usually quite low (no more than 1%), especially when compared to the main psychoactive component of the plant, THC (which can reach almost 30%), this cannabinoid has a number of therapeutic properties of great value for a multitude of medicinal users, which has led to studies and tests on the possible applications of CBN becoming increasingly numerous.

CBN is a cannabinoid produced exclusively by the cannabis plant, and it can not be found in any other plant species. Its psychoactivity is low, which for many medicinal users represents a great advantage, and it is believed to be the cause of the sedative and narcotic effect of some varieties of cannabis, in addition to being a partial agonist of the CB1 and CB2 receptors, being somewhat more linked with the CB2 receptor (inhibits adenylate cyclase). It is a molecule that is readily dissolved in fats or the various solvents used to make cannabis resin extractions, being hydrophobic (water repellent) and lipophilic (having affinity for lipids).

CBN molecule (cannabinol)

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What is CBC?

• Name: Cannabichromene
• Formula: C21H30O2
• IUPAC name: 2-methyl-2- (4-methylpent-3-enyl) -7-pentylchromen-5-ol
• Molecular weight: 314.469 g/mol
• Boiling point: 220 ° C

Although the amount of cannabichromene that’s normally found in analysis of modern cannabis flower or resin samples is relatively small, indeed significantly lower than that of THC, or even CBD (in many cases), CBC is still classified as a major phytocannabinoid produced by the cannabis plant, sharing as it does structural similarities with some of the most important cannabinoids (THC, CBD, CBN or THCV) and in fact sharing a formula with the much better known THC and CBD.

Cannabichromene was discovered in 1966 by Gaoni and Mechoulam on one hand and almost simultaneously by Claussen on the other, although since then little research has been carried out on this cannabinoid, with THC and CBD being the protagonists of the majority of subsequent studies. However, as we will see below, today there is a growing body of evidence demonstrating the tremendous therapeutic potential of this cannabinoid, especially in combination with other compounds in what is often referred to as an ?ensemble? effect.

Cannabichromene molecule (CBC)

Synthesis of cannabichromene (CBC)

CBC is a non-psychoactive compound produced, as we saw in our article on cannabigerol (CBG) and the synthesis of cannabinoids, from the action of the enzyme CBCA-synthase, which transforms into CBGA in cannabichromenic acid or CBCA, the non-decarboxylated acid form of CBC. This, as with other cannabinoids, is decarboxylated and “activated? by losing a molecule of CO2, converting from CBCA to CBC. This can happen gradually with the passing of time (weeks or months) or when applying heat, in this case almost immediately.

While studies in the 1970s pointed to CBC as the second most abundant cannabinoid in cannabis plants, today it is highly doubtful that this remains the case, as hundreds of breeders from around the world have been selecting and crossing for decades seeking plants high in THC, and more recently CBD, or both. The 1970s studies used pure varieties available at that time, probably strains originating from the tropics, which tend to have a higher concentration of CBC, and have very little resemblance to modern commercial hybrids.

What we do know, as we saw in our article on the properties of CBN, is that in the same way that THC degrades to CBN when subjected to heat or UV rays, CBC will degrade to cannabicyclol (CBL) when subjected to such conditions.

Timewreck from TGA Subcool has a higher than average CBC content

Properties and effects of cannabichromene (CBC)

Although further studies are needed to confirm that, like the rest of cannabinoids, CBC acts on CB1 and CB2 receptors in our nervous system, in this particular case we are aware of the interaction between cannabichromene and TRPV1 and TRPA1 receptors, which would explain its multiple medicinal properties and the increase in levels of endocannabinoids in the body, such as anandamide. Some studies on mice have shown that the administration of THC with CBC modulates the anti-inflammatory activity of the latter, suggesting a strong interaction between these two compounds.

Now let’s take a look at some of the most important medicinal properties of CBC, which can be used as:

• Anti-inflammatory (a greater anti-inflammatory effect has been observed when THC and CBC are administered together, thus being more effective in treating conditions such as edema or inflammations of the intestinal tract)
• Antidepressant (as seen in recent studies, its antidepressant effect is far greater than CBD, although once again it seems that the “entourage effect” achieved by combining several compounds is much more effective than the isolated cannabinoid)
• Antinociceptive (reduction of pain caused by nerve damage)
• Analgesic/Reduction of pain (CBC acts in synergy with THC, so amplifying properties to relieve the pain of both cannabinoids)
• Neuroprotector (a study in mice showed in 2013 that CBC increases the survival rate of progenitor stem cells, increasing neurogenesis)
• Antibacterial and antifungal (as early as the 80’s showed excellent antibacterial properties and moderate antifungal properties)
• Acne (as recently as 2016, the great advantages of CBC to treat this common disease have been analysed, as it reduces both the production of sebum by the sebaceous glands and the effects of arachidonic acid)
• Gastrointestinal and inflammatory disorders (possessing antidiarrheal properties and possibly very useful in the treatment of inflammatory bowel disease)
• It inhibits the absorption of anandamide, an endocannabinoid produced by our body (this has been linked to a reduction in various types of cancer, such as colorectal or breast cancer. It is thought that the indirect action of CBC upo the CB2 receptor could partly explain these properties)
• Migraines (studies for the reduction of migraines with CBC have yielded very promising results)

Cannabichromene (CBC) can be very useful for treating acne

As can be seen, scientific research has already demonstrated a number of properties of CBC with huge therapeutic potential, although there is a lack of laboratory work and clinical trials to determine its applications in humans. It is certain that the research will continue, given the enormous potential shown by this cannabinoid, which is attracting more and more attention of researchers, breeders and seed banks every day.

The Future of CBC

Given the positive results obtained in the early studies into cannabichromene, new research projects are in fact increasingly numerous. Its multiple medicinal properties and its interaction with some of the most important cannabinoids, such as THC, have focused part of the attention of the scientific community on this interesting compound and its role in the so-called entourage or ensemble effect. Therefore it is not unrealistic to predict that soon we will be able to buy products containing CBC, as well as products with other non-psychoactive cannabinoids useful to treat certain ailments.

The growing interest in this cannabinoid and its relevance to the therapeutic sector will undoubtedly see the development of new CBC-rich varieties with a higher percentage of this cannabinoid. Current varieties like Williams Wonder or Psycho Crack from Sick Meds have a higher than average cannabichromene content, as does Timewreck from TGA Subcool.

Happy smoking!

Bibliography of studies and publications on CBC consulted for this article:

• Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Ethan B. Russo
• Biosynthesis of cannabinoid acids. Yukihiro Shoyama, Masahiro Yagi, Itsuo Nishioka
• Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M, Smith E, Rahman MM
• Cannabinoids stimulate fibroblastic colony formation by bone marrow cells indirectly via CB2 receptors. Scutt A, Williamson EM
• Constituents of Cannabis sativa L. XI: Cannabidiol and Cannabichromene in Samples of Known Geographical Origin. Janis HenryHolley, Kathy W.Hadley, Carlton E.Turner
• The Inheritance of Chemical Phenotype in Cannabis sativa L. Etienne P. M. de Meijer, Manuela Bagatta, Andrea Carboni, Paola Crucitti, V. M. Cristiana Moliterni, Paolo Ranalli, Giuseppe Mandolino
• Hashish components. Photochemical production of cannabicyclol from cannabichromene. Crombie L , Ponsford R , Shani A , Yagnitinsky B , Mechoulam R
• Antidepressant-like effect of ?9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Abir T. El-Alfy, Kelly Ivey, Keisha Robinson, Safwat Ahmed, Mohamed Radwan, Desmond Slade, Ikhlas Khan, Mahmoud ElSohly, Samir Ross
• Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by ?9-tetrahydrocannabinol. Gerald T. DeLong, Carl E. Wolf, Alphonse Poklis, Aron H. Lichtman
• Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice.
  Angelo A Izzo, Raffaele Capasso, Gabriella Aviello, Francesca Borrelli, Barbara Romano, Fabiana Piscitelli, Laura Gallo, Francesco Capasso, Pierangelo Orlando, Vincenzo Di Marzo
• The effect of cannabichromene on adult neural stem/progenitor cells. NorikoShinjyo, VincenzoDi Marzo
• Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. Sabatino Maione, Fabiana Piscitelli, Luisa Gatta, Daniela Vita, Luciano De Petrocellis, Enza Palazzo, Vito de Novellis, Vincenzo Di Marzo

Hashish and terpenes

As we already know, terpenes are responsible for the taste and scent of many of the vegetables that produce them. They are a broad class of organic hydrocarbons derived from isoprene (CH2=C(CH3)CH=CH2) which compose the bulk of resins and essential oils of plants, thus providing unique flavours to each individual as a result of terpene combination. They are also called terpenoids when they have undergone an oxidating or molecular re-combination process. As we also know, most cannabis terpenes have properties of great medicinal value.

As the flowering stage progresses, more and more terpenes are secreted inside the trichome heads, so that the terpene profile of the plant changes as it ripens. The same thing happens when drying and curing buds, the process of oxidation and partial decarboxylation to which buds are exposed makes their terpene range to change over time. Some terpenes will degrade faster than others, so the terpene range of the weed – we must remember that we know of more than 100 terpenes in cannabis – will vary unless it is vacuum-sealed and properly stored. This fact explains why the smell and taste of one sample can evolve throughout the drying and curing process.

Different hashish samples

Probably, any concentrate lover has realized that, many times, the extraction process changes the terpene profile of the weed, so the resulting extract lacks some of the organoleptic features of the buds from which it comes. In this way, cannabis extracts have a common taste and smell – with subtle variations – regardless of the strain used to make them. This happens especially when using dried/cured plant material, since as we have already seen in our posts about Fresh Frozen and Fresh Chilled, these type of concentrates have a smell and taste much closer to those of the fresh plant material. Somehow, isolating and concentrating the resing glands leads us to limit the terpene range, so we can’t properly appreciate the “personality” of each sample. But, why does it happen? Continue reading →

The cannabis plant and phytocannabinoids

THC, CBD, CBN, CBC, CBG and approxiamately 80 more molecules make up the phytocannabinoids family, which are found in varying amounts, depending on environmental conditions, andt the marijuana plant. Some cannabinoids are responsible for the main effects of cannabis and others have important medicinal properties, that the scientific community continues to discover every day.

Some cannabinoids are mainly antidepressants, anti-inflammatory, anti-anxiety, anti emetic, while others may even help protect the nervous system. Actually, we are just beginning to discover the potential of cannabinoids and all their possible applications, mainly in the context of some cancers, as well as other degenerative diseases.

We can classify the cannabinoids into four major groups: natural cannabinoids from plants (phytocannabinoids), natural endogenous cannabinoids (endocannabinoids produced by the human body and securing biological functions), cannabinoids synthesis (potentially dangerous, as there is very little information on its effects), and mimetic or cannabimimetic cannabinoids (naturally occurring molecule or synthetic, replicating the action of cannabinoids on CB1 and / or CB2 receptors).

In this article, we will only discuss the naturally occurring cannabinoids in the marijuana plant, the phytocannabinoids.

Most of the cannabinoids are present in very small amounts (less than 0.01% of total cannabinoids) are not considered psychoactive, and the effect is not significant. Indeed, many are simply homologues or analogues (similar structure or function) of some of the major known cannabinoids.

However, medical research regularly reveals new and surprising discoveries about these cannabinoids present in trace form. Unfortunately, this research and its findings are significantly hampered by the leglisation in many countries.

Different mixtures of cannabinoids and other related molecules (mainly aromatic compounds such as myrcene), largely explain the variations of effects we found between one variety of cannabis and another. The strength of the effect depends mainly on the level of THC, THC / CBD ratio and form of consumption, but this effect can also be modulated in several different ways. Continue reading →