Even with a majority of states legalizing cannabis for medical use, and a growing number of states expanding that legalization to include adult-use, the federal prohibition of THC continues to make things difficult for both the industry and the consumer.

While federal legalization of hemp through the 2018 Farm Bill was a step forward for cannabis as a whole, the legal divide between hemp and cannabis has led to a whole lot of legal gray areas when it comes to compounds.

Here, we’ll look at the rise of Delta-8, what that has to do with THC-O, and what you need to know to consume these products safely.

Delta-8 and the rise of THC alternatives

One of the ways this federal disparity between hemp and cannabis is playing out is through the rise of THC alternatives.

Take Delta-8-THC, for example. Delta-8-THC is a close cousin to Delta-9-THC, the naturally occurring and intoxicating compound we all know and love from cannabis. Delta-8-THC is what we call an “isomer,” a compound with a similar, though not identical, structure to Delta-9-THC. 

And while the structural differences between isomers can be quite small, they can lead to significant differences when it comes to how our bodies process and experience the compounds. Delta-8-THC seems to have comparable therapeutic effects to Delta-9-THC with less intoxication, which could make it an attractive and valuable option for folks who would benefit from or enjoy a milder high.

Delta-8-THC is a naturally occurring cannabinoid in hemp and cannabis plants, but in very small quantities — so small that it’s economically infeasible to extract it from the plants for the sole purpose of making Delta-8 dominant products. 

Dr. Christopher Hudalla, chemist, founder, and Chief Science Officer at ProVerde Laboratories  has examined the naturally occurring Delta-8-THC concentrations in thousands of samples and estimates that it would take about 55,000 kilograms (about 121,000 pounds) of plant biomass to extract one kilogram of Delta-8-THC from natural sources. This would mean an unfathomable price tag of about $500,000,000 per kilo.

So instead, Delta-8 is most often synthesized in a lab from the more abundant and readily available CBD molecule found in hemp. And since the 2018 Farm Bill specifically includes hemp “derivatives” and “isomers” (among others), the argument has been made that Delta-8-THC synthesized from hemp CBD is lawful. This is a complex and ongoing debate in the hemp and cannabis industries. 

And while Delta-8-THC seems to be a safe and beneficial compound with potential therapeutic and commercial applications, the unregulated synthesis of Delta-8 from hemp sources is raising concerns for consumer health and safety.

“When Delta-8-THC is synthesized, it involves the use of some very toxic chemicals and catalysts to effect the transformation of CBD to THC. Not all producers are equally adept at removing or neutralizing these toxic reagents and nobody is testing these residuals in final consumer products. There is literally zero oversight in the production or distribution of these products,” explained Hudalla.

Delta-8’s questionable legal status, it’s intoxicating properties, and the absence of regulation to protect the public’s health and safety, has made the Delta-8 landscape complicated indeed. 

So far, individual states have been left to address how they want to deal with, or ignore, the issue. Several states have elected to ban Delta-8 altogether, while some have allowed for Delta-8 to be produced from cannabis-derived Delta-9-THC under their own legal cannabis programs. Most, however, have taken no official stance on Delta-8-THC.

Regardless, the popularity of Delta-8-THC continues to grow rapidly in states where consumers don’t have access to legal, state-licensed Delta-9-THC products.

What is THC-O?

Enter THC-O-Acetate — or THC-O — one of the newest THC alternatives on the block.

Like Delta-8-THC synthesized from CBD, THC-O is a semi-synthetic analog of Delta-9-THC. It begins with either a Delta-9- or Delta-8-THC molecule that is then altered, using strong chemical reactions, to replace the THC hydroxyl group with an Acetyl group. 

Without getting too deep into the chemistry, this change increases the resulting THC-O-Acetate molecule’s fat solubility and membrane permeability, which means it is easier for our bodies to absorb and use. This, in turn, makes it a more potent form of THC than Delta-9-THC. Though there isn’t enough research to say for certain, one review suggested that THC-O is twice as potent as Delta-9-THC. Others hypothesize that it might be even more potent than that.

In addition, THC-O is believed to be a “prodrug” which means that it needs to be metabolized before it produces effects. 

According to Minchul An, PharmD and founder of the cannabis patient and medication management platform Pattern Health, prodrugs are essentially precursors of a drug. “The parent drug, or the drug in its ingested form (in this case THC-O-Acetate), is inactive,” he told Weedmaps. 

“By definition, if THC-O-Acetate is truly a prodrug, it has no pharmacological activity and must be metabolized into the active compound responsible for the effects. After it’s metabolized it is able to bind to and activate the CB1 receptor to produce neuro-intoxicating effects,” he added. 

This means that, akin to Delta-9-THC edibles, there is a delayed onset before one will feel the effects of THC-O. People who have tried THC-O also report psychedelic effects that are distinctly different from the euphoria and intoxication that are common with Delta-9-THC.

Ultimately, we don’t know much about THC-O. Even though it is available for purchase, there has been no appreciable research carried out to understand its effects or how it works in the body.

Is THC-O safe?

The THC-O-Acetate compound has been known to scientists since the 1940s, when some research was conducted looking at its potency and effects in dogs, but no research has been done looking at THC-O for human consumption. 

In addition, no research has been done to evaluate the safety of THC-O or any of the byproducts in THC-O products, in animals or humans, and there isn’t any research evaluating its efficacy or safety for medicinal applications.

We do know that, like Delta-8-THC, THC-O is synthesized in a process that utilizes highly dangerous chemicals, and it should only be done by trained professionals in properly equipped labs. It also requires highly skilled chemists using high-quality chemical inputs.

Once the conversion process is complete, there are several possible sources of contaminants that can show up in the final product: synthetic byproducts, unnatural isomers created unintentionally during the chemical conversion process, or other residuals from toxic solvents, acids, or bleaching clays. 

“When producers are creating analogs in this semi-synthetic manner, the result is a mixture of unnatural isomers with additional synthetic reaction byproducts. All of these are not found in nature, and to date, we have no information on their toxicity,” explained Hudalla.

As mentioned, since the hemp market is largely unregulated we have no oversight for testing and reporting the presence of these contaminants in THC-O products.

THC-O’s delayed onset, coupled with its higher potency, could also lead to unpleasant experiences if folks don’t exercise caution. We’ve all heard about bad experiences with edibles, and these experiences could be amplified with THC-O’s higher potency. So if you try THC-O, be sure to start low and go slow — start with a small amount and wait at least an hour or two before consuming more.

“As a pharmacist, I’d consult my patients to stay away from THC-O. We know nothing about the actual safety of this particular compound. The industry is unregulated and we’ve seen how unsafe it can get with the EVALI crisis,” added An.

Is THC-O legal?

Cannabis lawyer Rod Kight of Kight Law Offices told Weedmaps that THC-O’s legality is questionable. 

“Certainly, it does not have the safety data studies necessary to be approved by the FDA as a new dietary ingredient in food products. More importantly, it is likely a controlled substance under federal law since, unlike Delta-8 and other forms of THC, it is not produced by the hemp plant,” he explained, “It is different from other forms of THC since it is not a naturally occurring cannabis compound.”

The bottom line

THC-O, and other Delta-9-THC alternatives like Delta-8-THC or Delta-10-THC, are new and potentially beneficial innovations for both consumers and patients alike. However, because they are so new, there is little research around their safety and efficacy. 

The synthesis of THC-O from hemp sources and the resulting products are not regulated, meaning that, at present, there is no way for consumers to be sure of the safety or purity of products.

If you want to try THC-O products, be aware that THC-O seems to be significantly more potent than Delta-9-THC and proceed with caution.

Featured image by Gina Coleman/Weedmaps





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