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Cannabis Chemistry: Exploring the Entourage

It has been known for many centuries that the psychoactive chemicals in the cannabis plant are produced mainly in the resin of the female buds. In this blog we explore the chemical compounds in cannabis now known to have either a psychoactive or a potentially medicinal effect. In the last few years, several of these “minor” cannabinoids have become the increasing focus of research and marketing in the cannabis world.

The Compounds in Cannabis

Since the 1960s, every few years chemical compounds are newly being discovered in the cannabis plant. By 2014, the number of constituent compounds identified in cannabis had risen to 545. Of these, 104 are what is known as phytocannabinoids (“phyto” means “plant”), which are chemicals deriving specifically from the cannabis plant. These phytocannabinoids have been classified into eleven types (ElSohly and Gul 2016:3–4).

Chemical ClassNumber of Compounds
Delta-9-trans-tetrahydocannabinol (∆9-THC)18
Delta-8-trans-tetrahydrocannabinol (∆8-THC)2
Cannabichromene (CBC)8
Cannabidiol (CBD)    8
Cannabielsoin (CBE) 5
Cannabigerol (CBG)17
Cannabicyclol (CBL)3
Cannabinol (CBN)     10
Cannabitriol (CBT)9
Total cannabinoids     104
Total non-cannabinoids441
Total compounds       545

Most people who are interested in cannabis are nowadays aware of the different effects of THC and CBD. However, the additional effects of many other compounds in cannabis, which are sometimes subtle, and often referred to as the “entourage effect,” are increasingly being understood. The “entourage effect”— a phrase coined by Raphael Mechoulam in the 1960s—of various cannabinoids has been scientifically demonstrated (McPartland and Russo 2016). The chemical compounds in different strains of cannabis vary widely. Nowadays it is possible, through companies like Seedsman, to obtain seeds of various strains of cannabis that have higher proportions of particular chemical compounds.

9-THC (Delta-9-trans-tetrahydocannabinol)

In 1963, Raphael Mechoulam and his colleagues at Hebrew University first published their discovery of ∆9-THC in cannabis, this compound now well known for being chiefly responsible for the psychoactive “high” in cannabis. Mechoulam’s team subsequently reported on cannabidiol, cannabigerol, cannabichromene and some cannabinoid carboxylic acids (Pertwee 2020).

The cannabis plant does not in fact produce either THC or CBD. These compounds actually derive from unstable phenolic acids, which are produced by the plant. Phenolic acids break down to produce, through a process known as decarboxylation, not only THC and CBD but also other compounds in the plant, such as CBN (Bialer 2019).

8-THC (Delta-8-trans-tetrahydrocannabinol)

There are two ∆8-THC-type cannabinoids in cannabis, namely delta-8-trans-tetrahydrocannabinol (∆8-THC, 19) and delta-8-trans-tetrahydrocannabinolic acid (∆8-THC acid, 20), which were first isolated in 1966 (ElSohly and Gul 2016:5). ∆8-THC has been little studied compared to ∆9-THC. ∆8-THC is psychoactive, but is considerably weaker in effect than ∆9-THC (Pertwee and Cascio 2016:124). A fifty-year-old old study (Hollister and Gillespie 1973) found ∆8-THC to be two-thirds as potent as ∆9-THC. However, more recent reports indicates that ∆8-THC is weaker than that (see the blog

8-THC is generally found in cannabis plants in lower concentrations than ∆9-THC, but it is also present in hemp varieties, making extraction from industrial hemp viable. Because the Farm Bill of 2018 legalised hemp at a federal level, and owing to legal restrictions in some places on the sale of ∆9-THC, in the last few years there has been a surge of sales of ∆8-THC products. In a small trial of ∆8-THC, most consumers reported relaxation, euphoria, pain relief, and cognitive alterations similar to those induced by ∆9-THC, but with fewer adverse effects (Kruger and Kruger 2022). ∆8-THC has been combined with CBN to help sleeping (3BC 2022). However, legislation in the USA may close the ∆8-THC loop-hole in states where ∆9-THC is still illegal.

THCV (Tetrahydrocannabivarin)

There are several kinds of THC, one of recent scientific interest being THCV, which is a homolog of  ∆9-THC(see the blog: A few varieties of cannabis, including Durban Poison (from South Africa) and some high-altitude Himalayan plants contain THCV, which may be found in trace amounts in some other varieties. This chemical inhibits appetite (Abioye et al. 2020; Cristino and Di Marzo 2016:464) and pain (Costa and Comelli 2016:479). THCV provides a distinctive, clear, smooth high, an effect is well-known by connoisseurs of high-grade charas. It has been found that THCV may be used effectively against obesity, without any negative side-effects (Rzepa et al. 2016).

CBC (Cannabichromene)

Together with ∆9-THC, cannabidiol and cannabinol, cannabichromene (CBC) is the most abundant, naturally occuring cannabinoid. CBC is not psychoactive, though it may possibly increase the effect of THC, via the entourage effect. CBC is particularly abundant in freshly harvested, dry cannabis and is the second most abundant cannabinoid is some strains of cannabis growing in the USA (Izzo et al. 2012). CBC has been shown to have antimicrobial, anti-inflammatory, analgesic and antidepressant-like effects in rodents. Izzo et al. (2012) demonstrated the anti-inflammatory potential of CBC. During the Covid pandemic, CBC was successfully tested in mice, as an inhalant, for acute respiratory distress syndrome (ARDS) (Khodadadi et al. 2021), one of the most serious effects of Covid (see the blog:

CBD (Cannabidiol)

Although CBD was first isolated in the 1930s by Roger Adams in the USA and by Alexander Todd, the chemical structure was first revealed by Raphael Mechoulam only in the 1960s (Bialer 2019). In the last decade or so, as we know, CBD products have entered mainstream markets globally.

More recently, in 2020, Mechoulam isolated cannabidiolic acid methyl ester (EPM301), a new patented compound. This acid is more potent than naturally produced cannabinoids—such as THC and CBD—has no side effects, and has been shown to be highly effective in suppressing anxiety, nausea and irritable bowel syndrome. It promises to be an alternative to opioids (Hasse 2020).


CBDA (A = acid) is the acidic precursor of CBD, while CBDVA (cannabidivarinic acid) is the acidic precursor to CBDV. CBDA has received little attention until recently, though

some researchers are currently exploring whether or not it has anti-cancer properties.

CBDV has been investigated for the treatment of autism, seizures, nausea, muscular dystrophy, and Rett syndrome, symptoms of which include stunted growth and social and cognitive impairment (Iannotti et al. 2019; Straiker et al. 2021; see also the blog: Although it is still not fully understood how CBDV effects the brain, it has shown potential for treating autism spectrum disorder (ASD), for which there are currently no effective pharmacological treatments (Pretzsch et al. 2019).

CBE (Cannabielsoin)

First detected in 1973 in Lebanese hashish (ElSohly and Gul 2016:11), this compound derives naturally from the oxidation of CBD and appears to have similar effects to those of CBD. Very little scientific work has so far been undertaken on CBE.

CBG (Cannabigerol)

CBG is another cannabinoid that has been more studied in recent years (see the blogs: As CBG is the precursor of other chemicals in the cannabis plant, including THC, CBD and several other cannabinoids, CBG is sometimes defined as “the mother of cannabinoids” (Valeri et al. 2022). Pharmacologically, CBG resides between ∆9-THC and CBD(Nachnani et al. 2021). During the early phase of flowering, CBGA (cannabigerol acid) is converted into THCA, CBDA and CBCA. So, there is far more CBG in the plant before the final flowering. CBG, which is not psychoactive, has been explored for use for several medical conditions, including colon cancer, inflammatory bowel disorder (Borrelli et al. 2013), glaucoma, MRSA (Methicillin-resistant Staphylococcus aureus) infection, pain relief and neuro-protection for conditions such as Huntington’s disease (Nachnani et al. 2021; Valdeolivas et al. 2015). CBG may also help neurogeneration after a spinal cord injury (Valeri et al. 2022). Both CBG and CBD appear to have neuro-protective effects, particularly when combined together (Echeverry et al. 2021; Mammana et al. 2019). So far, these tests have been almost entirely on animals, though human trials are expected to follow. CBG is usually present in relatively low quantities in plants, but Seedsman supplies seeds of plants with higher CBG

CBL (Cannabicyclol)

Although first detected in 1964 [26], CBL has been little studied. It is non-psychoactive and formed from CBC degradation due to heat and sunlight [27]. It is found only in low concentrations in the cannabis plant.

It is assumed that CBL has an “entourage effect”, but substantial tests have yet to confirm this.

CBN (Cannabinol)

In fresh cannabis buds there is very little CBN, a compound first isolated in 1896 (ElSohly and Gul 2016:12). But aged by sunlight and heat, THCA breaks down into CBNA. CBN, which has a very mild psychoactive effect, is then formed by the decarbyloxation of CBNA. So, old weed usually has a much higher CBN content.

Tests of CBN on mice indicated that it may deepen sleep and appears to influence the effects of other cannabinoids (Yoshida et al. 1995). More recently, it has been discovered that CBN may protect nerve cells from oxidative damage, which can cause neuro-degenerative diseases such as Alzheimer’s disease (Liang et al. 2022).

In psychedelic cannabis therapy, the addition of high-CBN weed to a sativa/indica mix is said (McQueen 2021:57) to enrich visions and allow the voyager to go deeper, perhaps by allowing more THC to be absorbed. Interestingly, it has been discovered that CBN can also assist sleeping. On its own, CBN has only a slight effect, but when combined with ∆8-THC, it helps induces sleep. Companies such as 3BC (3BC 2022) sell CBN formulas to aid sleep.

CBND (Cannabinodiol)

First isolated from Lebanese hashish in 1977, as was CBE (ElSohly and Gul 2016:10), CBND is an aromatized derivative of CBD. It is found only in small amounts in cannabis plants. Little is currently known about the pharmacological effects of CBND.

CBT (Cannabitriol)

Cannabitriol (CBT) has received much less attention than some of the other cannabinoids. Cannabicitran (which is CBT-C, a subset of CBT) is currently being marketed as CBT by Bay Medica, though there is very little information available on this compound, which, anecdotally, is only to be found is some strains of cannabis. One report on CBT indicated that it may be useful for glaucoma, as it reduced eye pressure in rabbits (Agboola 2020).


There are around twenty flavonoids and around a hundred terpenes/terpenoids in the cannabis plant. Flavonoids and terpenes are the aromatic oils that provide the distinctive aromas and tastes of different varieties of cannabis. Flavonoids also influence the colour of the plant. Many of these flavonoids and terpenes are found also in other plants; some of them have been found to have useful medicinal properties. Similarly to the cannabinoids discussed above, terpenes also contribute to the entourage effect of cannabis.

Several Seedsman blogs have explored some of the important terpenes. Beta-caryophyllene and myrcene are the most prevalent.


This terpene is also present in hops, black pepper, cloves and cinnamon; it has a spicy, peppery flavour. Some strains of cannabis, such as OG Kush and Sour Diesel have high concentrations of beta-caryophyllene. This terpene has anti-inflammatory properties and may reduce stress.

Read more about beta-caryophyllene here.


Also present in citrus fruits, such as oranges and lemons, limonene is usually only found in trace amounts in most strains of cannabis. However, it is in higher concentrations in Super Lemon Haze, Banana Kush and Wedding Cake. One study found that limonene may reduce anxiety in mice. Other studies (mostly on mice) indicated that limonene may be effective in the treatment of morning sickness and for breast, lung and skin cancers, and may aid tissue healing and neuropathic pain.

Read more about limonene here.


Myrcene is the most abundant terpene in cannabis, comprising about 20% of the plant’s overall terpene profile. It is also present in numerous other plants, including verbena, wild thyme, lemon grass, the West Indian bay tree, cardamom, hops and mangoes. It is used in the perfume industry. Several studies have indicated that myrcene may be effective against several kinds of cancer and arthritis. It has sedative effects and may also reduce pain.

It is commonly assumed that the sedative effects of cannabis are due mainly to CBD. However, Russo (Piomelli and Russo 2016:46) comments that he believes that this is mistaken, as the sedative effects of cannabis are not primarily due to CBD, but rather to myrcene, which has the highest levels in Cannabis ruderalis (Casano et al. 2011:117; Lynch et al. 2017:359; McPartland and Small 2020:359–360).

Read more about myrcene here.


Pinene is the most abundant terpene in plants, responsible for the “pine” aroma that comes from pine trees, and noticeable in the aromas of cannabis varieties such as Jack Herer, Blue Dream and Harlequin. It has been reported that pinene may reduce the uncomfortable, anxious, “spikey” effect of high THC that some people occasionally experience. It may also assist with memory loss that may be experienced in such states. Similarly to some other terpenes, the effect of pinene has been explored for treatments for cancers, bacterial infection, bronchitis and inflammation.

Read more about pinene here.


There is currently a great deal of both popular and scientific interest in the “minor” cannabinoids and terpenes. Companies such as 3BC, Bay Medica, FloraWorks and InMed Pharmaceuticals now market CBC, CBDV, CBN, CBG, CBT, THCV and ∆8-THC products for health and sleep purposes. This trend seems set to continue as we find out more about the multiple properties of the cannabis plant. We should be very grateful to all the mice who have pioneered so much cannabis research.


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Cultivation information, and media is given for those of our clients who live in countries where cannabis cultivation is decriminalised or legal, or to those that operate within a licensed model. We encourage all readers to be aware of their local laws and to ensure they do not break them.

Matthew Clark

Since 2004, Dr. Matthew Clark has been a Research Associate at the School of Oriental and African Studies (University of London), where he taught courses on Hinduism between 1999 and 2004. He has spent many years in India, which he first visited in 1977, visiting nearly all important (several hundred) pilgrimage sites and trekking around 2,000 miles in the Himalayas. He first engaged with yoga in the mid-1970s and began regularly practicing Ashtanga Yoga in 1990. Since 2006 has been lecturing worldwide on yoga, philosophy, and psychedelics. He is one of the editors of the Journal of Yoga Studies and is one of the administrators of the SOAS Centre of Yoga Studies. His publications include The Daśanāmī-Saṃnyāsīs: The Integration of Ascetic Lineages into an Order (2006), which is a study of a sect of sādhus; an exploration of the use of psychedelic plant concoctions in ancient Asia and Greece, The Tawny One: Soma, Haoma, and Ayahuasca (2017); and a short book on yoga, The Origins and Practices of Yoga: A Weeny Introduction (revised edition) (2018).