Article by Travis Cesarone, Cannabis Life Network
New marvel cannabinoids have been discovered within cannabis decades after Dr. Roger Adams first found CBD in 1942 and then later synthesized THC from CBD. (1) So, wonderous discoveries into new phytocannabinoids clearly take numerous steps to achieve. And thankfully, new potent forms of THCo and CBDo ents, have now been created from dirt-cheap and natural terpenes that are derived from the essential oils of cannabis. (2)
This means that, as a step in the process, synthetic cannabinoids can be used as reference tools for breeders. This can unlock higher evolutions of natural cannabis plants. These novel cannabinoids are also useful reference bases for clinicians formulating viable cannabimimetic solutions for pain, epilepsy, cancer, and many other ailments. (3)
New novel cannabinoids from NMSU
New research from Maio Laboratories in New Mexico State University elucidated octo-CBD. Their team also focused on CBD variants that are a thousand percent stronger than regular CBD at cannabinoid receptor sites. (2) But, potency (affinity) does not translate to what happens when a cannabinoid binds to a receptor (efficacy). In other words, we still don’t know what these cannabinoids do to the body. (5)
What are ent and octo-cannabinoids?
Pentyl-CBD has a five-carbon chain and is simply referred to as CBD since it is the common variation. Phorol THC (THCp) has a seven-carbon side chain and is thirty times stronger than THC (affinity).
Octyl instead regards the eight-carbon side-chain group of cannabinoids. To extend their definition, all of the aforementioned cannabinoids have regarded different homologues of the D9 isomer.
Enantiomers of different cannabinoids are also possible, which we explained for the THC molecule in a previous document. Ent simply stands for enantiomer, which is a chiral (mirror) of an identical molecule. The potent enantiomer, (+)-ent-CBD, does exist within natural strains of cannabis plants. And, most of the ingredients for octo-cannabinoids can also be derived from the plant. This means that highly potent THCo and CBDo, and other ents, might be natural substances we have yet to find in the wild.
Maio Lab’s plans to assess ent-octo-CBD on Epilepsy
Conventional synthesis of CBD ents by Professor Mechoulam in 2005 used synthetic and expensive starting agents. (6) Professor Maio from New Mexico State University (NMSU) recently found a novel route to these variations of CBD by oxidizing and modifying an organic terpene product, carvone. His team’s achievement ultimately circumvented the need for more costly artificial compounds priced at $1000 per gram.
Dr. William Maio is an Associate Professor at NMSU with a Ph.D. in organic chemistry from John Hopkins and the lead of Maio Labs. His lab will be exploring effects within their growing catalogue of different CBD molecules in greater detail.
I sent Professor Maio an email and asked if he was willing to leave any further comments for publication, to which he happily replied.
We are hopeful that our improved synthesis of enantiomers of CBD, which can also be applied to the synthesis of the natural stereoisomers of CBD simply by switching the enantiomer of carvone (which is a terpene natural product) that you use as starting material, will lead to the increased synthesis of novel derivatives. As an example, our laboratory is already preparing another library of derivatives.
In terms of future plans, we have already tested our derivatives into a mouse model for epilepsy and the results have been exciting! We submitted these preliminary findings to the NIH and recently received funding for that part of the project. We hope to publish some of these results later this year. While I can’t disclose specifics at this time, the ent-CBD-oct is a clear winner.
Professor William Maio
How terpenes make carvone and novel CBD molecules
In nature, carvone is an oxidation product of the cannabis terpene, limonene. It is otherwise extracted from caraway oil and costs 0.15/g USD. During CBDo synthesis, carvone is intricately oxidized even further into an intermediate terpenoid. This resulting intermediate (hydrazone) can be transformed into specific orientations of itself (an enantioselective reaction).
The reaction from carvone to the intermediate terpenoid is partially initiated with acetic acid, which is the main ingredient in tabletop vinegar. The modified terpenoid then completes the four technical steps required to build minor forms of CBD that are found in cannabis plants from a natural terpene. Otherwise, the team found a means to use carvone to create other novel cannabinoids, including a few non-natural variations.
What do potent new THCo and CBDo mean for the future?
Higher side-chain groups (homologues) such as the natural octyl cannabinoids are known to possess stronger affinities towards cannabinoid receptors. This occurs for CBDo, so perhaps THC-oct is even stronger than the super-potent new cannabinoid, THCp. Enantiomers (ents) are also known to possess high affinities than their standard cannabinoid counterpart.
We asked Dr. Maio if he is interested in discovering more about unusual forms of THC.
While we are able to work with CBD derivatives here at NMSU, we are not permitted to work on THC derivatives at this time. So, we have no plans to prepare these derivatives… Using our method it is indeed possible to synthesize the ent-THC-oct, simply by modifying the reaction conditions slightly.
New Mexico passed the Controlled Substances and Therapeutic Research Act in 1978, (7) and yet, Professor Maio is still not permitted to study THC. At the very least, the discovery at Maio Labs will give researchers reference data on CBDo. So, labs can start identifying the substance in cannabis plants and extracts. And, before the breeders succeed in their efforts, clinicians can get a jumpstart on their work by validating some of the cannabinoid’s (like THCo and CBDo) medicinal properties.
A niche need for synthesis in the cannabis space
To prove any viability in epilepsy research for CBDv, we first had to discover the propyl-cannabinoid. Some cannabinoids exist within the plant but they are not yet clinically viable. Even CBD was trapped in an unfunded position before science discovered its importance. Oftentimes, pharmaceutical industries rather fund synthetic cannabinoids to override the need for natural ones – and fail. Does this misguided mindset disvalue the true need for organic synthesis in the cannabis space? (8)