The tetrahydrocannabinoids (THCs) are arguably the best- known cannabinoids but did you know that there are two main classes of THCs and each of these classes has, so far at least, two or more members? Did you know that there are differences in the level of psychoactivity between the two main classes, Δ-8-THC and Δ-9-THC, sometimes written as delta-8-THC or delta-9-THC? These two forms of THC differ in where one double bond is located, yet there are significant differences in how people respond to these two forms of THC.

About the Different Forms of THC

There are two main forms of THC: Δ-8 and the Δ-9 THC. Both the Δ-8 and the Δ-9 forms of THC bind primarily to the CB1 receptors found mainly in the brain and spinal cord.

Δ-8-tetrahydrocannabinols

There are two types of Δ-8-THC:

• Δ-8-tetrahydrocannabinol (Δ8-THC)
• Δ-8-tetrahydrocannabinolic acid (Δ8-THCA)

The acidic form of Δ8-THC is Δ8-THCA. It is found in both C. indica and C. sativa in variable quantities. It is also found in hemp, though at much lower levels. Δ8-THCA is diminished because of decarboxylation which occurs during drying. Heating also causes decarboxylation. This compound is often found at higher levels in dabs, resins, hashish and hash oils.

To give you an idea of how important Δ-8-THCs may be, there is already a synthetic analog of Δ-8-THC, Anabasum. Anabasum is being studied due to its potential to serve as a potent anti-inflammatory agent [1]. It has shown an ability to lower pain and inflammation in the eyes. [2], [3] Anabasum, also known as ajulemic acid, is currently in human trials as a possible treatment for systemic sclerosis (SSc), cystic fibrosis, and dermatomyositis (DM). [4]

Δ -8-THC appears to act as an antagonist to Δ -9-THC. It reduces the actions of Δ -9-THC. [5]

According to the National Cancer Institute (NCI), Δ8-THC exhibits the following actions:

• Anti-nausea
• Anti-anxiety
• Appetite-stimulating
• Analgesic
• Protects the nervous system
• Has less of a psychoactive effect than does Δ9-THC

Δ-9-tetrahydrocannabinols

The NCI reports similar actions for synthetic Δ-9-THC which has been assigned the generic name Dronabinol. It is sold under the brand names Marinol and Syndros:

• Anti-nausea
• Analgesic
• Appetite-stimulating

The difference here may be in degree. There is some anecdotal evidence that Δ8-THC is a better anti-nausea agent as compared to Δ9-THC, but no clinical studies are available.

Currently, there is a clinical trial devoted to examining the effect of dronabinol on the dose of opiates needed in breast cancer patients.

There are quite a few known members of the Δ-9-THC class. These include:

• Δ -9-tetrahydrocannabinol (THC)
• Δ -9-tetrahydrocannabinol-C4 (THC-C4)
• Δ -9-tetrahydrocannabinolic acid A (THCA-A)
• Δ -9-tetrahydrocannabinolic acid B (THCA-B)
• Δ -9-tetrahydrocannabinolic acid-C4 (THCA-C4)
• Δ -9-tetrahydrocannabiorcol (THC-C1)
• Δ -9-tetrahydrocannabiorcolic acid (THCA-C1)
• Δ -9-tetrahydrocannabivarin (THCV)
• Δ -9-tetrahydrocannabivarinic acid (THCVA)

There is some information published about these other Δ-9THCs.

For example, Δ -9-tetrahydrocannabivarin (THCV) acts as an antagonist to Δ -9-THC along with Δ -8-THC. [5] The overall effect is to reduce the psychoactive or intoxicating effects of Δ -9-THC. THCV has no intoxicating effects but it has also been found to decrease appetite, increase a sense of fullness (satiety) and tends to “rev-up” the metabolism. [6] All these properties may indicate that THCV may be useful in the management of diabetes and obesity. [6]

Δ -9-tetrahydrocannabiorcol or THC-C1 appears to be an analgesic, exerting an effect via the TRPA1 (transient receptor potential ankyrin 1) receptors rather than the CB-1 receptors. [7]

Potential Medical Benefits of THCs

Synthetic THCs like dronabinol are used to:

• treat the loss of appetite experienced by AIDs patients.
• treat the nausea and vomiting often encountered by cancer patients.

Common side effects are what you might expect in a synthetic THC and include a sense of elation (high), increased awareness, increased laughter, euphoria and commonly, abnormal thinking and paranoia.

There is great interest in the potential for medicinal application of non-intoxicating forms of THC. THCV, for example, has no intoxicating effects but can be used for:

• Decreasing appetite
• Weight management
• Management of diabetes
• THC-C1 may be useful as an analgesic

Comparing CBD to the THCs

The main difference between CBD and THC is that CBD is non-intoxicating while THC has intoxicating or psychoactive effects. Both CBD and THCs have pain reducing effects, but CBD manifests anti-convulsant effects as well. THCs do not appear to produce any anti-seizure effects.

THCs tend to have a greater effect on the appetite. Here, individual members of the THC family may have opposite effects. For example, THCV tends to decrease appetite while both Δ -8 and Δ -9 THCs tend to stimulate appetite.

Combinations of THC and CBD are being used to treat pain more frequently now. When using this combination therapy, it appears that CBD moderates the effects of the THC. [8] Sativex® for example contains THC and CBD in equal amounts and is used to treat pain experienced by multiple sclerosis and cancer patients.

How are the THCs Made and are They Legal?

CBD is derived from hemp that is low in all THCs. CBD providers must ensure that THC makes up <0.3% of the total composition. Currently, none of these THCs are legal except for research purposes and even that is a bit of a grey area. If you are checking the 3^rd party lab results and there is no THC, or <0.3% THC, it is unlikely that you are ingesting any significant quantities of either Δ-8 or Δ-9 THC. Therefore, you are consuming even less of any of the other THCs.

Watch this video to understand how THC extracted:

References Cited

1. [1] Motwani MP., et al, Potent Anti-Inflammatory and Pro-Resolving Effects of Anabasum in a Human Model of Self-Resolving Acute Inflammation. Clin Pharmacol Ther. 2018 Oct;104(4):675-686. doi: 10.1002/cpt.980. Epub 2018 Jan 30.
2. [2] Thapa, D., et al, Allosteric Cannabinoid Receptor 1 (CB1) Ligands Reduce Ocular Pain and Inflammation. Molecules. 2020 Jan 20;25(2). pii: E417. doi: 10.3390/molecules25020417.
3. [3] Thapa, D. et al, The Cannabinoids Δ8THC, CBD, and HU-308 Act via Distinct Receptors to Reduce Corneal Pain and Inflammation. Cannabis Cannabinoid Res. 2018 Feb 1;3(1):11-20. doi: 10.1089/can.2017.0041. eCollection 2018.
4. [4] Burstein, SH., Ajulemic acid: potential treatment for chronic inflammation. Pharmacol Res Perspect. 2018 Apr;6(2):e00394. doi: 10.1002/prp2.394.
5. [5] Pertwee, RG., et al, The psychoactive plant cannabinoid, delta-9-tetrahydrocannabinol, is antagonized by delta-8- and delta-9-tetrahydrocannabivarin in mice in vivo. Br J Pharmacol. 2007 Mar;150(5):586-94. Epub 2007 Jan 22.
6. [6] Abioye, A., et al, Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes. J Cannabis Res 2, 6 (2020). https://doi.org/10.1186/s42238-020-0016-7.
7. [7] Andersson, DA., et al, TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Δ(9)-tetrahydrocannabiorcol. Nat Commun. 2011 Nov 22;2:551. doi: 10.1038/ncomms1559.
8. [8]Russo, E., Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008 Feb; 4(1): 245–259. Published online 2008 Feb. doi: 10.2147/tcrm.s1928