Natural vs Synthetic Cannabinoids

Natural vs Synthetic Cannabinoids

By Dr. Andrea Holmes[1] [2] 

There is a lot of controversy around the “intoxicating synthetic cannabinoids.” The word “synthetic cannabinoids” is typically associated with designer drug molecules that are NOT occurring naturally in a plant or nature but bind to the same receptors as cannabis does. The term first arose with organic chemistry Professor John Huffman at Clemson University who worked on many new molecules and synthesized JWH-018 which later has shown to have very highly potent and negative health effects. Without Huffman’s knowledge, this drug was later introduced on the black market and was given the street name K2/Spice or bath crystals.  It is sold illegally as an herbal incense plant type material and since then underground “cooks” have created hundreds of illegal substances by poaching procedures from publications and patents. These compounds are a big problem and health concern!

However, cannabinoids from federally legal hemp are NOT comparable to this type of synthetic designer drug molecules. They are completely different in chemical structure and the effect they have on the central nervous system. Furthermore, hemp derived THC isomers are prepared from naturally extracted CBD. It is important to distinguish these synthetic cannabinoids like K2/Spice from naturally occurring cannabinoids like delta 8 THC, its isomers, and other minor cannabinoids because the consumption of designer drugs can be dangerous while cannabinoids from cannabis has been consumed for hundreds even thousands of years for spiritual, religious, and health and wellness reasons. Furthermore, surveys have shown that consumers favor hemp derived cannabinoids like delta-8-THC because they can self-treat multiple conditions and have access to inexpensive natural alternatives to pharmaceutical prescription drugs.(1)

Innovations in science and technology are driven by mimicking what is happening in nature and in the case of hemp, chemists have learned how to reproduce chemical conversions that are happening in the plant. Compounds like delta-8-THC can be prepared in the lab by chemists by using legal hemp derived CBD and applying conditions such as heat, catalysts and solvents to isomerize CBD to THC. This is similar to what is happening in the plant in the presence of light, enzymes, and molecules that rearrange in molecular structure and electronic arrangements to achieve different states of stability. This is not novel to hemp. In fact, many naturally occurring compounds are now prepared or processed in the lab, including most vitamins, melatonin, biotin, vanilla flavoring, decaffeinated tea and coffee, aspirin, and much more. These controlled industrial processes are widely used in the pharmaceutical, food, and dietary supplement industry to allow access to pure compounds at high volumes and prices that would otherwise be prohibitive if these compounds were extracted naturally from the source material like hemp.

Insulin to treat diabetes is a perfect example to show how synthesis has improved human life. Diabetes used to be a death sentence. In the early days of discovery, insulin was extracted from the pancreas of dogs, cattle, and pigs. Only small quantities of insulin could be isolated from many animal sacrifices, and it was very expensive to treat patients and caused allergic reactions. Innovation in science allowed chemists at pharmaceutical companies to insert a gene into a gut-flora bacteria called E-Coli and this organism was able to “synthesize” large quantities of human grade insulin at affordable prices.

Whether a cannabinoid is naturally extracted from hemp or prepared in the lab, the result is the same. A molecule is a molecule, and there is no difference between synthetic or naturally derived cannabinoids. To assure consumer safety, CBD derived cannabinoids coming from legal hemp containing should be tested at third party labs to assure that they are compliant (less than 0.3% delta9-THC per g of dry mass), free of solvents, metals, pesticides and microbial contaminants. It is important to source these types of cannabinoids from reputable manufacturers with good manufacturing practices, process controls in place and standardized SoPs.

Research and scientific studies on delta 8 THC, its isomers, and minor cannabinoids are still limited when compared to other cannabinoids like CBD and delta-9 THC. The novelty of these compounds as well as the regulatory uncertainty has stifled academic research in this area. However, we do have some preliminary research that has shown promise of CBD derived synthetic delta-8-THC for nausea in pediatric cancer patients undergoing chemotherapy.(2) Other research has shown that delta-8THC has several therapeutic effects. (3, Table 2, 4) We also know the pharmacology of delta-8-THC. It is a much less potent cannabinoid than delta-9-THC due to a weaker binding to receptors in the brain, making this cannabinoid a preferred choice for some consumers who prefer a milder effect. However, research on delta-8 THC is largely anecdotal, and not many studies do not involve human subjects. (5)

Finally, in my personal experience and as an owner of three hemp dispensaries in Nebraska, I attest to the fact that my customers, many of whom get referred to us by physicians, purchase hemp derived compounds like THC isomers to help with sleep quality, feelings of anxiety, pain, sobriety and mood disorders.

In conclusion, it is my view that reasonable laws and regulations are needed to mitigate the risks of using delta-8 THC, isomers and minor cannabinoids, particularly around the quality of manufacturing practices, testing, packaging, dosages, labeling, marketing and minimum purchase age.

1. https://pmc.ncbi.nlm.nih.gov/articles/PMC8725316/

Kruger JS, Kruger DJ. Delta-8-THC: Delta-9-THC's nicer younger sibling? J Cannabis Res. 2022 Jan 4;4(1):4. doi: 10.1186/s42238-021-00115-8. PMID: 34980292; PMCID: PMC8725316.

2. https://pubmed.ncbi.nlm.nih.gov/7776837/

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.

3. https://pubmed.ncbi.nlm.nih.gov/34797727/

Kruger DJ, Kruger JS. Consumer Experiences with Delta-8-THC: Medical Use, Pharmaceutical Substitution, and Comparisons with Delta-9-THC. Cannabis Cannabinoid Res. 2023 Feb;8(1):166-173. doi: 10.1089/can.2021.0124. Epub 2021 Nov 19. PMID: 34797727.

4. https://pubmed.ncbi.nlm.nih.gov/29450258/

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.

5. https://pubmed.ncbi.nlm.nih.gov/36710464/

LoParco CR, Rossheim ME, Walters ST, Zhou Z, Olsson S, Sussman SY. Delta-8 tetrahydrocannabinol: a scoping review and commentary. Addiction. 2023 Jun;118(6):1011-1028. doi: 10.1111/add.16142. Epub 2023 Feb 13. PMID: 36710464.

Reference terms: Open Learning Academy (OLA), online learning, online course, Natural Cannabinoids, Synthetic Cannabinoids, Intoxicating synthetic cannabinoids, synthetic cannabinoids, organic chemistry,JWH-01, federally legal hemp, THC isomers, naturally extracted CBD, gut-flora bacteria, cannabinoids, Diabetes, insulin, delta 8 THC, delta-9-THC, isomers, minor cannabinoids