The “New Kid” Cannabinoid on the Block—Delta-8-THC

An isomer, for those of you who are chemically curious, contains the same number of atoms, the same type of atoms, and has one or two (in this case one) structural differences. Δ-8-THC is a degradation product of Δ-9-THC and can be pretty laboriously extracted from cannabis. Alternatively, CBD can be converted to Δ-8-THC through a patented isomerization process. (U.S. Patent US-7399872-B2.)

The difference (chemically) between the two forms of THC is that in Δ-9-THC, there is a double bond between carbons 9 and 10 while in Δ-8-THC, the double bond is between carbons 8 and 9. There ARE other differences, though. The National Cancer Institute describes Δ-8-THC as “an analogue of tetrahydrocannabinol (THC) with antiemetic, anxiolytic, appetite-stimulating, analgesic, and neuroprotective properties…[that] exhibits a lower psychotropic potency than delta-9-tetrahydrocannibinol (delta-9-THC), the primary form of THC found in cannabis”[1]

How Does Δ-8-THC Differ From Δ-9-THC?

You might think that such a small structural difference between substances may not make a significant difference in how they might behave—but then you may be letting someone else put those toys together for you—you know, the ones where widget A is supposed to fit into slot X…but doesn’t! On a molecular level—when binding to a receptor—it can make a difference.

The main differences between Δ-8-THC and Δ-9-THC is that Δ-8-THC is less psychoactive and chemically more stable than Δ-9-THC. Both the chemical stability of Δ-8-THC and the fact that it is less psychoactive than its more common isomer makes it more attractive to use. This decreased psychoactivity is also attractive to some consumers because they don’t want too much of a high.[2] Δ-8-THC is reportedly 50-75% less psychoactive (potent) than Δ-9-THC.[2]

CB1 and CB2 Receptor Binding

Both Δ-8-THC and Δ-9-THC appear to bind primarily to the CB1 receptor—the receptor found in the brain and other parts of the central nervous system, but Δ-8-THC appears to bind with less affinity ie. with less strength than Δ-9-THC does. This may be part of the reason why Δ-8-THC is less psychoactive than Δ-9-THC and results in a milder “high”. [3] Δ-8-THC (and Δ-9-THC) appear to also inhibit the function of other receptors—the serotonin receptors. [4] These are found throughout the body, but at higher levels in the digestive system and Δ-8-THC has been studied as a potential therapy to reduce nausea and vomiting and to maintain appetite in cancer patients.[5]

Current Research

Much of the research (and there isn’t much) on Δ-8-THC centers around its potential use to reduce nausea and vomiting related to chemotherapy. Δ-8-THC has been used to treat nausea and vomiting in children undergoing chemotherapy with good results. [6] 8 children undergoing chemotherapy for various blood cancers were treated with Δ-8-THC in oil, and in all of them, vomiting was completely stopped.

The other main focus on Δ-8-THC research is to treat glaucoma and other eye conditions to reduce pain and inflammation.[7][8]Δ-8-THC has been directly on or in the eyes of experimental lab animals to reduce swelling, response to pain and to reduce inflammation. [4]

Legal Questions

The legal profession is in some ways as precise as the sciences—if a substance isn’t specifically mentioned in a law, then, at least in the minds of some, it’s not illegal. For many years, “underground” chemists used this “chemical loophole” in developing street drugs that were slightly different from the illegal drug and were able to at least try and argue that these newly synthesized substances were not illegal.

The US agencies in charge of federal drug law regulation—the FDA and the DEA—know this and try to counter it. The DEA has published an “Interim Final Rule” stating that the Agricultural Improvement Act (aka 2018 Farm Bill legalizing CBD) “…does not impact the control status of synthetically derived tetrahydrocannabinols…all synthetically derived tetrahydrocannabinols remain schedule I controlled substances”.[9] This would seem that the DEA intends to leave Δ-8-THC as a Schedule I drug—and that appears to be a valid legal argument that Δ-8-THC may be considered at least in some states and localities to be an illegal substance.[10]

Ultimately, the legal status of Δ-8-THC is uncertain. As with other substances, the FDA and the DEA are currently a bit behind the curve, but this legal uncertainty—as well as the lack of research on Δ-8-THC, is something you need to be aware of and informed on.

Refferences

[1] NCI Drug Dictionary, National Cancer Institute at the National Institutes of Health, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/delta-8-tetrahydrocannabinol?redirect=true.

[2] Chris Dewildt, Delta 8 THC: What Is It And What Does It Do?, Growers Network (Mar. 29, 2019), https://growersnetwork.org/processing/delta-8-thc/.

[3] Madras BK. Cannabinoid and Marijuana Neurobiology. InCannabis in Medicine 2020 (pp. 25-47). Springer, Cham. https://link.springer.com/chapter/10.1007/978-3-030-45968-0_2

[4] Serafimovska T, Darkovska-Serafimovska M, Stefkov G, Arsova-Sarafinovska Z, Balkanov T. Pharmacotherapeutic Considerations for Use of Cannabinoids to Relieve Symptoms of Nausea and Vomiting Induced by Chemotherapy. Folia Medica. 2020 Dec 31;62:668. https://foliamedica.bg/article/51478/download/pdf/

[5] Avraham Y, Ben-Shushan D, Breuer A, Zolotarev O, Okon A, Fink N, Katz V, Berry EM. Very low doses of delta 8-THC increase food consumption and alter neurotransmitter levels following weight loss. Pharmacol Biochem Behav. 2004 Apr;77(4):675-84. doi: 10.1016/j.pbb.2004.01.015. PMID: 15099912. https://pubmed.ncbi.nlm.nih.gov/15099912/

[6] Abrahamov A, Abrahamov A, Mechoulam R. An efficient new cannabinoid antiemetic in pediatric oncology. Life Sci. 1995;56(23-24):2097-102. doi: 10.1016/0024-3205(95)00194-b. PMID: 7776837. https://pubmed.ncbi.nlm.nih.gov/7776837/

[7] Nguyen AX, Wu AY. Cannabis and the Cornea. Ocular immunology and inflammation. 2020 Mar 9:1-6. https://www.tandfonline.com/doi/abs/10.1080/09273948.2020.1726969

[8] Thapa D, Cairns EA, Szczesniak AM, Toguri JT, Caldwell MD, Kelly MEM. 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. PMID: 29450258; PMCID: PMC5812319. https://pubmed.ncbi.nlm.nih.gov/29450258/

[9] Implementation of the Agriculture Improvement Act of 2018, 85 Fed. Reg. 51,639 (Aug. 21, 2020) (to be codified at 21 C.F.R. pt. 1308 and 21 C.F.R. pt. 1312).

[10] Wilson N. New Market Entrants and Uncertain Drug Policy in the United States. Ohio State Legal Studies Research Paper. 2021 Apr 1(611).