What happens when you take the cannabinoids out of cannabis?

By Jillian Jastrzembski

Pure THC and CBD versus cannabis plant extract: is one better than the other?

Intro

Part of the appeal of herbal therapeutics, including cannabis, is that they are more “natural.” The word “natural” has a frustratingly ambiguous definition in both colloquial and regulatory context, but an undeniable appeal.

In Traditional Chinese Medicine, it is said that a perfectly formulated herbal combination should have no side effects. Not only are the herbs consumed in whole plant form, but often the properties of each herb are balanced by the addition of another.

Modern pharmacology views herbalism as a kind of drug pharmacopeia: the traditional formulae tell us where to look. From there, we can often identify single bioactive molecules to be isolated (or synthesized) and consumed in their pure form.

So on one end of the spectrum, we use a relatively intact plant, and on the other end of the spectrum, we use only the bioactive molecules. In the case of cannabis, that means you can consume the plant in its herbal form, or you can consume isolated compounds like THC and CBD. Is one option better than the other? What exactly are we missing out on when we take THC and CBD out of cannabis?

The bioactives: CBD and THC

Cannabis is best known for its cannabinoid content. There exist over 100 cannabinoids in cannabis, the most famous of which are CBD and THC.¹ [Duggan]

Let’s start by looking at CBD and THC in combination; specifically, whether or not it is advantageous to consume a ratio of these molecules that is found in the cannabis plant. Already, we are on tricky ground, as plants can be bred through traditional (read: “natural”) methods to produce a variety of ratios.

THC is best known for its psychoactive effects, and CBD is often touted for its anti-inflammatory effects, though it is important to recognize that this is an over-simplification, and our understanding of the powerful molecules that activate and inhibit the mammalian cannabinoid receptors is still in its infancy. Both THC and CBD are being researched for their therapeutic effects for pain, psycho-emotional disorders, and a variety of diseases, especially autoimmune disorders.

THC is an activator of certain cannabinoid receptors including CB1 and CB2. CBD, on the other hand, acts on a different site of the receptor to change the active site. In this way, CBD helps to mitigate some of the negative or dangerous effects of THC like anxiety and loss of cognitive function, apparently while preserving the therapeutic benefits. [Gado, Lu]

The take-away: It is a good idea not to consume THC in isolation; instead, seek cannabis strains that have a lower THC:CBD ratio.

What else is in cannabis?

Regular cannabis-users have already intuited that the THC:CBD ratio is not the only thing at play. Users have reported different therapeutic effects from cannabis extracts compared to isolated THC/CBD, even when the ratios are the same. To explain this phenomenon, researchers have hypothesized something called “the entourage effect.” [Anand]

The entourage effect is the idea the presence of inactive compounds can somehow enhance or modulate the effect of the bioactives. Compounds of particular interest are terpenes and terpenoids. Terpenes and terpenoids are abundant in plant/flower matrices, often noted for their floral, piney, or hoppy aromas. There is increasing evidence that these compounds may work to enhance and modulate the effects of cannabinoids in cannabis. [Anand]

The potential mechanisms for this are diverse. For example, the inactive compound could affect the ability of an active compound to bind to a receptor; or, it could prevent the degradation of a bioactive compound. Because there is such diverse variation between different cultivars, or “chemovars,” of cannabis, it is difficult to isolate the mechanisms at play behind the entourage effect.

The take-away: There is evidence that consuming cannabis extract can have a different effect compared to consuming THC and CBD in isolation. The presence of non-cannabinoid compounds may also influence the effects of the cannabis plant.

Conclusion

Cannabis is one of the first plants to be cultivated by humans. Even before we had the ability to isolate and purify bioactive compounds, we could use traditional breeding methods to manipulate the components of plants.

Reverse-engineering nature is not a simple game. Choose your cannabinoids – and their entourage – wisely.

References

Anand, Uma et al. “Cannabis-based medicines and pain: a review of potential synergistic and entourage effects.” Pain management vol. 11,4 (2021): 395-403. doi:10.2217/pmt-2020-0110

Duggan, Peter J. “The Chemistry of Cannabis and Cannabinoids.” Australian Journal of Chemistry, vol. 74, no. 6, 2021, pp. 369–387., https://doi.org/10.1071/ch21006.

Gado, Francesca, et al. “Allosteric Modulators Targeting Cannabinoid CB1 and CB2 Receptors: Implications for Drug Discovery.” Future Medicinal Chemistry, vol. 11, no. 15, 2019, pp. 2019–2037., https://doi.org/10.4155/fmc-2019-0005.

Lu, Hui-Chen, and Ken Mackie. “Review of the Endocannabinoid System.” Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, vol. 6, no. 6, 2021, pp. 607–615., https://doi.org/10.1016/j.bpsc.2020.07.016.

 

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