The term “cannabinoids” has undergone a certain change in meaning over the years.
While previously only the substances that occur naturally in the hemp plant (phytocannabinoids) were referred to as such, today messenger substances that occur in the human body (endocannabinoids) as well as artificially produced compounds (synthetic and semi-synthetic cannabinoids) are also included in this group. Although the endocannabinoids and synthetic substances are often chemically very different from the plant cannabinoids such as Δ9-terahydrocannabinol (THC) and cannabidiol (CBD), they also interact with the so-called endocannabinoid system (ECS) of the human body, resulting in a variety of pharmacological effects.
In the following, we want to take a closer look at the cannabinoids of the hemp plant:
Phytocannabinoids – cannabinoids of the hemp plant
Phytocannabinoids are a group of substances that currently includes over 120 different compounds. Chemically speaking, these are so-called terpene phenols that are produced and stored in the glandular hairs (trichomes) of the hemp plant. Since the inflorescences of the female plants in particular are densely covered with these glandular hairs, they also have the highest cannabinoid concentrations. It is assumed that these substances serve the plants to defend themselves against predators and harmful microorganisms (bacteria and fungi).
In addition to the more well-known representatives that are usually present as main components, such as THC and CBD, there is a wide range of other phytocannabinoids. Although they often only occur in trace amounts, they modify the effects of the main components and thus make a decisive contribution to the overall pharmacological profile of the respective cannabis strains.
We offer you the quantitative determination of the 11 most important phytocannabinoids as a complete package! (Link to cannabinoid analysis)
What is the difference between THC and THCA or CBD and CBDA?
Cannabinoids marked with the suffix A (acid) are so-called acidic cannabinoids, which are the precursors for the more commonly known neutral cannabinoids. These substances, also known as cannabinoid carboxylic acids (or cannabinoid acids for short), are the components originally formed by the plant and make up the majority of the cannabinoid fraction contained in fresh flowers, for example.
Over time, the cannabinoid acids are converted into their neutral forms by releasing carbon dioxide; For example, THCA is broken down into THC and CBDA into CBD.
This process, known as decarboxylation, usually takes place gradually, but can be accelerated considerably by the effects of heat. For example, in cannabis extracts that were produced using heat, the original acid forms are often only found in trace amounts. When cannabis products are smoked, they are also immediately and completely converted into their neutral analogues.
Although neutral cannabinoids generally have a much stronger cannabinoid effect than acidic forms, acidic cannabinoids also have unique effects. CBDA and CBGA in particular are repeatedly the focus of scientific interest due to their anti-inflammatory and antiviral properties.
As part of our quantitative cannabinoid analysis, acidic and neutral cannabinoids are recorded both separately and together. As a result, the information “Total THC”, for example, represents the sum of acidic and neutral THC in your sample material.
How does the biosynthesis of cannabinoids occur in the hemp plant?
The starting point for most other cannabinoids in the plant is cannabigerolic acid (CBGA), which is converted into other cannabinoid acids by certain enzymes, the so-called synthases. THCA synthase catalyzes the conversion of CBGA into THCA, while CBDA synthase and CBCA synthase are responsible for the formation of CBDA and CBCA respectively.
As already mentioned in the previous section, these cannabinoid acids can be converted into their neutral forms through decarboxylation. This process is non-enzymatic and can therefore also take place outside of the living plants, as is the case, for example, when storing dried flowers. A similar thing is also the case with cannabinol (CBN), which is only formed from THC long after harvest through oxidative degradation.
Through targeted, artificial selection and crossing of cannabis plants with favored characteristics, it has been possible in recent decades to generate a large number of new genetics that differ drastically from one another in their cannabinoid profile (so-called chemotypes). The reason for this can be found at the molecular level: in CBD hemp varieties that are virtually THC-free, for example, the gene that codes for THCA synthase is defective, so that this enzyme can no longer be produced properly by the plant. In THC-rich varieties, on the other hand, the CBDA synthase is missing, which shifts the ratio in favor of the psychoactive THC.
What are synthetic and semi-synthetic cannabinoids?
The term „synthetic“ basically means that a substance has not been obtained from natural resources, but has been artificially produced in a chemical laboratory. Naturally occurring cannabinoids such as CBD and Δ9-THC can not only be extracted from the hemp plant, but can also be chemically „reproduced“, i.e. synthesized. The „nature-identical“ cannabinoids generated in this way do not differ in any way – neither chemically nor pharmacologically – from their natural analogues.
Synthetic cannabinoids in the narrower sense are primarily substances that have similar pharmacological effects to phytocannabinoids, but are neither chemically similar to them nor occur naturally. An example of this would be the exclusively synthetically available cannabinoid JWH-018, which was legally available in the form of herbal mixtures (“spice”) for many years and gained notoriety due to several deaths.
Semi-synthetic cannabinoids are also produced in the laboratory. In contrast to (fully) synthetic cannabinoids such as JWH-018, naturally occurring cannabinoids such as CBD and THC are always used as starting materials, which are then chemically modified. In semi-synthetic cannabinoids, the basic structure of the phytocannabinoids and thus the chemical affiliation to this group of substances is usually still evident. An example would be hexahydrocannabinol (HHC), a psychoactive cannabinoid that only occurs naturally in trace amounts, but is easily accessible synthetically by hydrogenating THC.
What is the human endocannabinoid system (ECS)?
The fact that the cannabinoids of the hemp plant trigger various pharmacological effects in humans suggested early on that the human body also has its own messenger substances (endogenous cannabinoids or endocannabinoids) with corresponding effects. Furthermore, there must also be receptors through which these messenger substances can develop their specific effects.
In fact, anandamide (N-arachidonylethanolamide, AEA) and related substances were subsequently identified as endogenous ligands, as well as two subtypes of cannabinoid receptors (CB1 and CB2). The interaction of these biochemical factors is referred to as the human endocannabinoid system.
While the CB1 receptors are primarily located in the nervous system and are involved in the regulation of physiological processes such as pain transmission, hunger and sleep induction, the CB2 receptors present in bone tissue and immune cells, for example, influence important functions of the human immune system.
If plant-based or synthetic cannabinoids are administered to the body, the body’s own regulatory circuits can be influenced in different ways. For example, the intoxicating effect of THC is primarily mediated via the CB1 receptors in nerve cells, while the non-psychoactive CBD exerts its immunomodulatory effect via the CB2 receptors, among others. In addition to influencing the ECS, the complex effect profile of the various cannabinoids results from a variety of other interactions with other, different receptor systems in the human body.
Which cannabinoids are detected during quantitative determination?
The fact that the cannabinoids of the hemp plant trigger various pharmacological effects in humans suggested early on that the human body also has its own messenger substances (endogenous cannabinoids or endocannabinoids) with corresponding effects. Furthermore, there must also be receptors through which these messenger substances can develop their specific effects.
In fact, anandamide (N-arachidonylethanolamide, AEA) and related substances were subsequently identified as endogenous ligands, as well as two subtypes of cannabinoid receptors (CB1 and CB2). The interaction of these biochemical factors is referred to as the human endocannabinoid system.
While the CB1 receptors are primarily located in the nervous system and are involved in the regulation of physiological processes such as pain transmission, hunger and sleep induction, the CB2 receptors present in bone tissue and immune cells, for example, influence important functions of the human immune system.
If plant-based or synthetic cannabinoids are administered to the body, the body’s own regulatory circuits can be influenced in different ways. For example, the intoxicating effect of THC is primarily mediated via the CB1 receptors in nerve cells, while the non-psychoactive CBD exerts its immunomodulatory effect via the CB2 receptors, among others. In addition to influencing the ECS, the complex effect profile of the various cannabinoids results from a variety of other interactions with other, different receptor systems in the human body.
We can routinely test your samples for the 11 most relevant cannabinoids: Δ9-THC, Δ9-THCA, Δ8-THC, CBD, CBDA, CBG, CBGA, Δ9-THCV, CBDV, CBN and CBC. On request – especially for customers from Germany – we also offer stereoselective determinations of the semi-synthetic hexahydrocannabinol (HHC)! All of our analyses are quantitative and recorded as a percentage (in weight%).
We are able to test a wide variety of sample materials: hemp flowers, oils, cannabis extracts, „water-soluble“ formulations (micro and nano emulsions), cannabis resins (hashish), cosmetics, vapes and isolates (purified cannabinoids). If your product is not on this list, please feel free to contact us! Please also note our instructions for sampling! (Link to instructions for sampling cannabinoids)
In the following, we would like to take a closer look at the cannabinoids we analyzed in the form of short portraits:
Δ9-tetrahydrocannabinol (Δ9-THC) and Δ9-tetrahydrocannabinolic acid (Δ9-THCA)
Besides CBD, Δ9-THC is probably the best-known cannabinoid and is primarily responsible for the psychoactive effect of corresponding hemp varieties and products. Unfortunately, the current legal situation in Austria still makes the medical use of THC-rich varieties difficult, so that only the purified cannabinoid (under the name Dronabinol®) can be prescribed after a strict indication. In some other EU countries, the THC-CBD combination preparation Sativex® is used as a mouth spray to treat spasticity in multiple sclerosis. In particular, the antiemetic (nausea-suppressing), appetite-stimulating and pain-relieving effects can contribute significantly to improving the general condition of cancer patients and can also be used for a variety of other ailments.
The typical effects of THC result mainly from the binding of the active ingredient to the CB1 receptors of the human endocannabinoid system. Since the Δ9-tetrahydrocannabinolic acid (Δ9-THCA) originally formed by the plant has a much lower affinity for these receptors, it is important to convert it as completely as possible into the neutral and more potent Δ9-THC before use. While this is easily achieved when smoking, for example, it is recommended to heat the respective non-temperature-treated cannabis product to at least 100 °C for some time before consumption.
Since the manufacture, possession and distribution of products with more than 0.3% THC by weight is prohibited in Austria and can result in criminal consequences, the quantitative determination of THC in the context of cannabinoid analysis is of particular importance. We are happy to take on this responsible task for you!
Δ8-Tetrahydrocannabinol (Δ8-THC)
This cannabinoid is an isomer of the previously discussed Δ9-THC. Isomers are substances that differ only slightly from one another in terms of their chemical structure. It is thanks to this chemical similarity that Δ8-THC and Δ9-THC share almost identical pharmacological effects, although the effect of the former is slightly weaker. Therefore – just like Δ9-THC – the manufacture, possession and distribution of products with more than 0.3% by weight of Δ8-THC are prohibited in Austria under current law.
Although Δ8-THC can be formed from the Δ9-isomer by rearrangement, it is usually only present in trace amounts in natural cannabis products. In contrast, the synthetic production of THC produces varying amounts of Δ8-THC in addition to the actual Δ9-THC. Therefore, unusually high concentrations of Δ8-THC in the sample material suggest that it has been mixed with synthetic THC or contaminated.
Cannabidiol (CBD) and cannabidiolic acid (CBDA)
Going into all the positive pharmacological effects and medical applications of these two non-psychoactive cannabinoids in more detail would go far beyond the scope of this portrait. Examples of these are the calming, antispasmodic, anti-inflammatory, pain-relieving, antioxidant and immunomodulatory effects, which are reflected in an almost unmanageable variety of CBD products available on the market. Although these are pharmacologically valuable active ingredients with very low potential for side effects, the preparation Epidyolex® for the treatment of childhood epilepsy is the only CBD-based medicine approved throughout the EU. In addition, the THC-CBD combination preparation Sativex® is used in some other EU countries as a mouth spray to treat spastic disorders in multiple sclerosis.
As already explained in the section on the biosynthesis of cannabinoids, targeted selection has made it possible to breed hemp varieties that have high concentrations of CBD and at the same time low, legally compliant THC concentrations (less than 0.3% by weight). The best known of these varieties is the EU hemp variety Fedora 17, from which countless other genetics have been derived.
It should be noted at this point that the cannabinoid profile of hemp plants is subject to significant fluctuations, especially during the flowering phase. Therefore, cannabis cultivation requires regular in-process checks of the still living plants in order to determine the appropriate harvest time and to ensure maximum CBD yield with minimal THC concentration. We are happy to support and advise you in this task!
In contrast to THC, it is not recommended to convert the CBDA, which is mainly present in the fresh material, into CBD by heat treatment, as CBDA has unique anti-inflammatory effects. Furthermore, it has been shown that CBD products in which part of the CBD is present as an acid are generally more effective than pure CBD. This is also one of the reasons for the popularity of so-called full-spectrum products, which attempt to reproduce the natural cannabinoid profile of the hemp plant.
Cannabigerol (CBG) and cannabigerolic acid (CBGA)
Cannabigerolic acid is, in a sense, the „primal cannabinoid“ of the hemp plant, from which most other cannabinoids can be derived through enzymatic and non-enzymatic processes. Through the targeted selection of cannabis varieties with a „defective enzyme apparatus“, it has recently been possible to produce breeds with a very high content of CBGA and CBG. Both cannabinoids are not psychoactive and only occur in small quantities in conventional breeds.
Like cannabidiolic acid (CBDA), CBGA also has a strong anti-inflammatory effect and appears to be effective in certain forms of epilepsy. In addition, it has been found that CBGA can actively prevent coronaviruses from penetrating host cells. Neutral CBG is also the subject of current pharmacological research.
Δ9-Tetrahydrocannabivarin (Δ9-THCV)
This is a cannabinoid that is somewhat unique in terms of both biosynthesis and pharmacology. While the previously discussed compounds all have their biochemical origin in cannabigerolic acid (CBGA), Δ9-tetrahydrocannabivarinic acid (Δ9-THCVA) is derived from cannabigerovanic acid (CBGVA). From this acid form, the chemically pH-neutral Δ9-THCV is formed through decarboxylation – just like the other cannabinoids.
Δ9-THCV is structurally closely related to Δ9-THC. The only chemical difference is that the alkyl side chain in the former only has three carbon atoms instead of six. This is also the reason why these two substances share certain pharmacological properties. Δ9-THCV is also in principle a psychoactive cannabinoid – albeit a weaker one. This fact means that Δ9-THCV/A has been categorized as a „new psychotropic substance“ since June 2020 and has been subject to the Austrian Narcotics Act since then.
Interestingly, the main pharmacological differences between Δ9-THCV and Δ9-THC only become apparent upon closer inspection: In lower doses, Δ9-THCV proves to be an antagonist (counterpart) at the CB1 cannabinoid receptors, through which the typical THC effects are mediated. This means that when Δ9-THCV and Δ9-THC are present at the same time, the former can displace the latter from the common receptor, which results in a weakening or change in the THC effect. Only at higher doses of Δ9-THCV do the actual, sometimes psychoactive effects of this cannabinoid become more apparent.
Apart from that, Δ9-THCV has proven to be a very promising pharmacological model substance. Various studies indicate a positive effect on glucose metabolism in diabetics as well as anti-epileptic and antipsychotic efficacy.
Cannabidivarin (CBDV)
Like the previous Δ9-THCV, CBDV is biochemically derived from cannabigerovanic acid (CBGVA), which – chemically speaking – is illustrated by the propyl side chain consisting of only three carbon atoms.
Analogous to the previous comparison between Δ9-THCV and Δ9-THC, pharmacological similarities between CBDV and CBD can also be seen here: Both are non-psychoactive cannabinoids which, according to recent studies, are characterized primarily by their anticonvulsant (ie anti-epileptic) effects.
Cannabinol (CBN)
Cannabinol is an oxidative degradation product of THC, which is only found in relevant quantities in older samples and is hardly detectable in fresh hemp flowers. The conversion of THC to CBN is promoted by ultraviolet radiation (e.g. sunlight).
CBN is considered – depending on the source – to be a weakly or non-psychoactive cannabinoid, which is why it is not subject to Austrian drug law. On a pharmacological level, it is particularly worth noting its hypnotic (sleep-inducing) effect.
Cannabichromene (CBC)
Like most others, this cannabinoid is derived from our “original cannabinoid”, cannabigerolic acid (CBGA). From this, cannabichromenic acid (CBCA) is first formed by the enzyme CBCA synthase, which is then converted into the neutral (and more potent) cannabichromene by decarboxylation.
Interestingly, young hemp plants usually have higher CBC levels than older plants in full bloom, which are at the end of their life cycle. This is because cannabichromene is a light-sensitive molecule that is gradually broken down into what is known as cannabicyclol (CBL) by the light as the plant ages.
Although CBC itself has no pain-relieving effects, it can support the analgesic effects of THC. Therefore, medical cannabis varieties with high CBC and THC levels are considered particularly suitable for pain therapy. In addition, various studies indicate antibiotic properties against resistant bacterial strains and anti-epileptic effects.
Hexahydrocannabinol (HHC)
Although this semi-synthetic cannabinoid has already been detected in trace amounts in the hemp plant, economically significant quantities have been and are only produced artificially – for example by hydrogenation of THC.
Like the chemically very similar THC, HHC has a strong psychoactive effect. In contrast to THC, however, it was not explicitly listed in the Austrian Narcotics Act until March 2023, which enabled legal marketing and led to a real hype about HHC products as a „legal high“.
With effect from March 23, 2023, HHC was included in the regulation on “new psychotropic substances”, which resulted in an immediate ban on the manufacture and sale of HHC and products containing HHC in Austria. However, possession and consumption of HHC remained exempt from punishment until further notice. In Germany, HHC is still not subject to any legal restrictions.
Semi-synthetically produced HHC is usually present as a mixture of two stereo isomers (9R-HHC and 9S-HHC), whereby the percentage weighting of the two can differ considerably depending on the method used. Stereo isomers are variants of a chemical substance that differ only in the spatial orientation of partial structures within the molecule (the so-called stereochemistry).
Despite this chemical similarity, these two stereo isomers differ drastically in terms of their pharmacological effectiveness: It was found that the 9R derivative has an approximately 10-fold stronger psychoactive effect than the 9S derivative.
Therefore, the differentiation between these two stereo isomers is of particular importance in the analysis of HHC products. On request, we will therefore examine your samples stereoselectively for the presence of 9R-HHC and 9S-HHC!