Spinning Around in Circles: Rediscovering THC-O-Acetate and Cannabinoid Stereochemistry

This was initially published in the Fourth Issue of Extraction Magazine published in 2018 and is being shared for educational purposes on this blog. Please cite as Bone, CB “Spinning Around in Circles: Rediscovering THC-O-Acetate and Cannabinoid Stereochemistry.” Extraction Magazine, Sep./Aug. 2018, Volume 1: Issue 4; pp. 46–50.

THC-O-Acetate is a mystical concept in cannabis circles. Depending on who you ask, you can expect to be met with wide-eyed excitement or confusion. And when pressed, most of the excitement tends to come from a conflation between the equally significant but vastly different THC Isolates. This is no surprise as much of what has been written and widely circulated about THC-O-Acetate has been largely redundant. Indeed, the half-dozen articles do a good job of summarizing what we already know about the THC mystery molecule.

For those less familiar with THC-O-Acetate, it is a “metabolic prodrug” of THC, meaning it is less susceptible to the high first-pass metabolism that THC suffers from. This substance is psychoactive, much like THC, yet consumers report a much higher and slightly more “elevated” experience, at least according to experiments by the US Army. These findings, part of the Edgewood Arsenal experiments starting in the 1950s -- when the US government conducted classified chemical experiments on human subjects -- found THC-O-Acetate to be an ineffective “truth serum,” and shelved the substance for further research. Other than three encounters by law enforcement agencies, one in the US, another in the UK, and the most recent in New Zealand, THC-O-Acetate has largely remained out of the public eye, relegated to the back corners of cannabis blogs and cafes.

However, peeling back the curtain and blowing away the smoke reveals a rich history of THC-O-Acetate and some potential avenues for future research and development, largely thanks to one person: cannabis extraction pioneer, D. Gold, known most famously for the book “Cannabis Alchemy: The Art of Modern Hashmaking.” D. Gold, one of the early experts on cannabis technologies, has been a longtime advocate of Isomerization as an accessible method of cannabis refinement. Isomerization was a popular method of turning “bunk” weed into highly potent oils popularized during the 70s. As D. Gold describes:

“... In 1977 I made and marketed a machine called The Isomerizer. It made oils, isomerized CBD to THC, made hash concentrates, etc. [. . .] Sold them thru High Times, head shops, and record stores. The feds sued us to stop after two years because we weren’t shy about saying what it was used for...” [D. Gold Interview, SkunkPharmResearch 2016]

The federal pressure combined with the advent of home cultivation and butane, CO2, and distillation technologies meant that isomerization hype fell to the wayside as the pursuit of better cannabis became the goal. Interestingly, the case against the individual convicted of THC-O-Acetate production in the UK in 1995 relied on evidence that suggested the suspect learned how to process the chemical by following the formula outlined by D. Gold in “Cannabis Alchemy.” This process, known as Acetylation, is a standard practice in pharmaceutical development (ever heard of acetaminophen, or Tylenol?), however, the DEA compared this method of THC-O-Acetate production, in its 1978 prosecution case in Jacksonville, to how heroin is processed from morphine.

HC-O-Acetate, while separately classified in the UK, remains in legal limbo in the United States. According to the Federal Analogue Act, analogs of controlled substances are also illegal. However, as states continue to legalize cannabis, ambiguity grows around THC-O-Acetate. Yet research continues to remain scarce and largely homebrewed. The state of the substance is therefore unlikely to change unless the industry makes its development and research a concern. One way it could do so is by redeveloping isomerization technologies that can take high-quality consumer extracts like isolates a step further. These are certainly within the realm of possibility, just as they were in the 70s, however until then, we find ourselves reliant on the expertise and experiments of alchemists like D. Gold.

In the spirit of D. Gold, the team at the Upward Cannabis Kitchen has begun sharing some of our observations and experiences developing our line of cannabis-fermented Kombucha with the goal of stimulating more conversations about the isomerization of cannabinoids. The Junup line of edibles is a kind of Kombucha -- a lightly fermented tonic beverage -- called Jun that involves the fermentation of green tea with honey by a SCOBY (symbiotic colony of bacterial yeast). Kombucha fermentation is a process that involves the transformation of a sugar-infused liquid, or substrate, into an acidic, slightly carbonated tonic. Our process starts with the infusion of local honey with high-quality cannabis distillate. This honey blend is added to our tea water and cooled to room temperature before the SCOBY is introduced and given about a week to work the magick.

The Magick in this sense is a kind of alchemy, not turning lead into gold per se but water into a kind of wine (or Kombucha at least). Kombucha, as a lactic acid ferment, contains negligible amounts of ethanol, acetic acid, and other organic acids. The process of determining the appropriate balance, or pH, and deciding when to bottle our Junup has been a delicate balance to strike. Like with all brewed beverages, understanding the development of flavor is crucial, and unstable ingredients like volatile terpenes make taste less reliable. Photosensitive and oxidative compounds (like cannabinoids) will shift and change over time when left exposed to certain conditions (sunlight and oxygen). This means that the condition a product goes into a bottle may not always reflect the taste a consumer experiences. This is true even of cannabis flower and extracts as many processors and producers will attest, and why the need for appropriate packaging is critical.

In cannabis flowers or extracts, THC-A decarboxylates to THC, which then slowly transforms into its sleepier and less psychoactive compounded CBN when over-cured or stored improperly. We’ve found that the bottling conditions for our Junup were similar to those necessary for acetalization reactions. To begin with, the proper pH to bottle Jun is around the same as that of acetic anhydride, the chemical utilized to process morphine into heroin as well as THC into THC-O- Acetate. Furthermore, acetaldehyde is created during a partial oxidation state of ethanol and is a key component in the synthesis of THC-O-Acetate from cannabinoids.

While this evidence is purely anecdotal, it points to potential areas for development for cannabis extraction that involve enzymatic and acetalization processes. Indeed, multiple consumers of Junup attest to a similar experience and timeframe to the one D. Gold describes THC-O-Acetate to illustrate, which is “... more spiritual and psychedelic than that of the ordinary product. The most unique property of this material is that there is a delay of about thirty minutes before its effects are felt.” [Cannabis Alchemy; THC Acetate Synthesis]. While some companies are taking this initiative, such as the CBD processor Hemp & Heal who are experimenting with enzymatic interactions with terpenes in their PhytoDrop edible line, much more research and further developments are needed regarding THC-O-Acetate. Whether it is related to acetalization processes, enzymatic approaches, or isomerization technologies, it is up to the extraction industry to continue the work of the alchemists before us if we want to discover the mysteries of THC-O-Acetate.