The Rise and Risk of New Synthetic Cannabinoids

Walk into a cannabis retailer these days, and it\’s more than likely you\’ll encounter a series of new cannabinoids. Instead of just delta-9 (tetrahydrocannabinol, THC), other intoxicating, lab-made cannabinoids like THC-O, delta-8, and delta-10 are lining store shelves. 


These tweaked cannabinoids, often more psychoactive than natural THC, claim to be legal because they typically start as hemp-derived CBD. Although the Food and Drug Administration (FDA) has confirmed otherwise, these synthetic creations continue to proliferate on retail shelves, especially in places where it\’s more difficult to access legal cannabis.


The Rise of Over-the-counter Cannabinoids: Delta-8, Delta-10, and THC-O


New semi- and fully synthetic cannabinoids are on the rise for two reasons. First, thanks to the decades-long war on drugs, black market producers became increasingly innovative, developing new intoxicating compounds that slipped into legal loopholes. Often labeled K2, or \”Spice,\” these creations were notorious on the street in the 1990s and early 2000s.


But, a second reason why these compounds are much more popular than ever is that the legal sector is getting a tsunami of investment. As a result, more labs and more lab techs are working and experimenting with cannabinoids. As cultivators and extractors look for new ways to profit from a CBD surplus and remediated THC, this has naturally led to new creative cannabinoid endeavors.


Popular and commercially available synthetic cannabinoids include delta-8, delta-10, and THC-O.


Delta-8 (Delta-8-Tetrahydrocannabinol)


Technically speaking, delta-8 is one of the hundred or more cannabinoids naturally produced by cannabis plants. But, in nature, it exists in such low quantities that all of the delta-8 products on the market today come from lab-created chemical transformations.


Most delta-8 begins its life as CBD, or less commonly THC. The chemical conversion requires a solvent, an acid, and a long period of heated agitation. The conversion is simple enough that it\’s possible to complete the transformation in a home setup with the right equipment.


Most consumers report that the effects of delta-8 mirror those of delta-9, except they are less powerful. According to the US Cannabis Council, the effects are roughly 75 percent as potent as regular delta-9. It is widely available in the form of vapes, gummies, and concentrates, both online and off.


As the most popular lab-made synthetic cannabinoids thus far, the FDA has issued a comment on this intoxicating compound. In a post dated September 2021, the FDA stated, \”Delta-8 THC products have not been evaluated or approved by the FDA for safe use and may be marketed in ways that put the public health at risk.\” Many states, like Alaska, New York, and Washington, have legislated outright bans.


Delta-10 (Delta-10-Tetrahydrocannabinol)


Soon after delta-8 began popping up around the country, delta-10 arrived. It\’s another minor cannabinoid naturally produced by cannabis, but only in minuscule amounts. Therefore, it only became commercially viable once it was synthesized from hemp. Delta-10 comes from a slightly different chemical conversion of CBD isolate than the delta-8 process.


It\’s typically produced for edibles and vape cartridges but isn\’t as widely available yet. Although little information exists for delta-10 beyond user reports, most indications suggest delta-10 is even less psychoactive than delta-8. As one consumer put it in an interview for Hemp Grower, \”For me, delta-10 had no psychoactive effects; it was more like a mood enhancer.\”


THC-O (THC-O-Acetate)


THC-O is one of the newest and most controversial semi-synthetic cannabis cannabinoids. This new molecule is a derivative of THC, produced via another chemical conversion. However, many producers start with CBD using a multistep process, taking it into a THC analog, then on to THC-O. This allows producers to (perhaps falsely) claim it comes from legal origins.


Unlike delta-8, which is relatively easy to create in a makeshift laboratory, THC-O requires acetic anhydride, an incredibly toxic chemical.


Because it is reportedly several times more potent than delta-9, THC-O has already earned significant negative attention from regulators and cannabis researchers, like Dr. Ethan B Russo. 


In a recent interview with Hemp Grower, Russo explained, \”So, between the inherent danger of the process to make it, the potential toxicity of the product, and its illegality, I\’ve got to recommend that people forget about it. It\’s just not something that people should be trying.\”


The Unknown Risks of Lab-made Cannabinoids


These new synthetic and semi-synthetic cannabinoids are scientifically exciting for chemists and researchers. However, due to their out-of-lab proliferation within the consumer market, there are rising concerns about their effects and overall safety profile.


At the time of writing, most of the research into delta-8 remained exploratory at best. There are no randomized controlled trials nor robust assessments of its effects in humans. There were also zero results available through PubMed for delta-10 and THC-O. Although consumers may report greater or lesser potency, nobody can confirm what\’s happening when these new compounds interact with the endocannabinoid system.


Thanks to the 2018 Farm Bill, which legalized hemp cultivation and production, many manufacturers of semi-synthetic cannabinoids claim these products are legal. This is a gross misinterpretation of the law, according to both the FDA and legislative changes at the state level.


California is one of the most recent examples of states seeking to clarify cannabinoid legislation. Enacted in the fall of 2021, California law now covers THC and comparable cannabinoids, which includes \”any tetrahydrocannabinol, including, but not limited to, Delta-8-tetrahydrocannabinol, Delta-9-tetrahydrocannabinol, and Delta-10-tetrahydrocannabinol, however derived.\” Essentially, any cannabinoid linked to intoxication, even if it originates from hemp, is now regulated like THC.


Designer Cannabinoids Remain a Risky Alternative Until We Know More


Until researchers better understand how these designer intoxicating cannabinoids affect the endocannabinoid system, both acutely and chronically, they are risky. Although they may be much more available than natural cannabinoids and are often sold as a \’legal alternative\’ to THC, everyone needs to approach these semi-synthetic, hemp-derived analogues with caution. 

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