A Guide to THC-O: A Psychoactive Cannabinoid Derived from Hemp

Quick key facts about THC-O:

• THC-O is short for THC-O-acetate, a semi-synthetic analog of Delta-9 THC that is derived from industrial hemp.
• THC-O doesn’t occur naturally in cannabis. It’s synthesized using acetic anhydride and other solvents in a laboratory setting.
• Currently, there’s no clinical research exploring the safety or effects of THC-O.
• Anecdotal reports suggest that THC-O is three times as potent as Delta-9 THC.
• Users have also reported that higher doses of THC-O can impart mild psychedelic effects.
• Due to the toxicity of the solvents commonly used to formulate THC-O, there are concerns about its safety.
• Although THC-O is generally derived from industrial hemp, it’s legality is still questionable as it is an analog of Delta-9 THC.

THC-O (sometimes spelled THCo or ATHC) is short for THC-O-acetate, a semi-synthetic cannabinoid derived from industrial hemp.This ultra-psychoactive cannabinoid has seen some commentators refer to it as a mild psychedelic due to its hallucinogenic effects.

As one of several synthetic cannabinoids currently making waves in the cannabis industry, many consumers are curious about THC-O. The cannabinoid may hold particular appeal for cannabis consumers who live in states where Delta-9 THC is illegal. Given that much is still unknown about THC-O, however, is it safe for consumers to use? And is it really legal?

Leafreport spoke to Dr. Jordan Tishler MD, leading cannabis therapeutics expert at InhaleMD, and Kelly McLoughlin, CEO of FlowerChild CBD, to learn more about THC-O and find out the answers to these questions.

What is THC-O?

Hemp enthusiasts have been experimenting with synthetic cannabis variations since the passing of the 2018 Farm Bill, which saw the legalization of industrial hemp. THC-O is derived from federally legal hemp, but formulated in a laboratory as it isn’t found naturally in the cannabis plant. THC-O is slightly different in its molecular structure to Delta-9 THC.

“THC-O-acetate is a version of Delta-9 THC in which the zero position on the first ring has an acetate group substituted,” says Tishler. “This is not a naturally-occurring variant and it must be synthesized by chemists.”

Although THC-O has only recently come into public consciousness, research into THC-O has been occurring for decades. The US military first began studying THC-O as a non-lethal incapacitating agent in the late forties at Edgewood Arsenal in Maryland. The experiments conducted on dogs revealed that this acetate version of THC temporarily impaired the dogs’ muscle function, balance, and coordination.

How is THC-O made?

THC-O is generally made from Delta-8 THC, which is found in industrial hemp. Hemp-derived CBD is refluxed (boiled) in an organic solvent, such as toluene or heptane, with p-Toluenesulfonic acid (or another acid) that helps to convert CBD to Delta-8 THC.

Once the Delta-8 extract is ready, it can then be converted to THC-O by adding the acetic anhydride. A process called acetylation then takes place, which adds an acetyl group to the THC molecule–making it an acetate. Some experts say the hardest part of the process is cleaning the end product to remove all the solvents and contaminants.

The process appears fairly straightforward, but is very hazardous and risky due to the toxic, volatile chemicals that are used. The acetylation process should only ever be carried out in a lab environment with the appropriate safety and technical equipment. Acetic anhydride is flammable, and is explosive as gasoline.

THC-O Vs. THC

THC-O has gained momentum among consumers on the quest for an ever more potent high. The mission to find more potent strains of THC is nothing new, however. What many consumers don’t realize is that increased potency doesn’t necessarily equate to better results.

In a recent interview, renowned cannabis researcher Dr. Ethan Russo expressed that the sheer potency of THC-O may bombard the body’s endocannabinoid system. When it comes to cannabis, less is often more.

“Potent sounds good. But this is a system in the body—the endogenous cannabinoid system—that works with a great deal of subtlety. In other words, what is needed when you’re using a drug to stimulate the system is a gentle nudge, not a violent push that comes from something that is a lot stronger than THC itself. So, potent is not necessarily better.”

According to McLoughlin, there is already an abundance of potent THC strains available to consumers. THC-O is simply pushing the envelope even further.

“THC-O is supposedly 3 times stronger than regular THC. With THC strains already so strong this is a recipe for disaster, especially for novice THC users,”says McLoughlin. “The only obvious reason a person would use this product is to get very high.”

McLoughlin also points out that while there’s a repository of knowledge regarding THC and its effects, THC-O is effectively an unknown entity.

“No one has ever died of a cannabis overdose, but with these synthetic, altered compounds who knows what could happen. What are the long term effects on health? Your liver? Your lungs?” asks McLoughlin. “It is hard to say whether these compounds have any therapeutic uses–but we know that THC-O will knock your lights out.”

Some also suggest that THC-O may behave as a pro-drug when consumed as an edible. This simply means it may convert into another form of THC, like Delta-9 THC, once metabolized by the liver.

Is THC-O safe?

A lack of research, coupled with insufficient regulation, means there are significant risks associated with purchasing and consuming THC-O.

Tishler points out that presently, there is a scarcity of clinical data on THC-O and its effects.

“Searching in Pubmed reveals exactly zero studies on THC-O,” he says. “There are a bunch of lay articles, however, claiming that THC-O is ‘3x more potent’ than THC and ‘nearly hallucinogenic’.”

Tishler also adds that at present, there’s no evidence suggesting the compound is safe.

“Since THC is quite hallucinogenic at high doses, I don’t doubt that THC-O may be as well,”, he says. “However, except perhaps for getting stoned, there is little that this characteristic would offer to patients. I doubt that there would be much medical benefit, and until a significant number of safety and efficacy studies are done, I would strongly urge people to stay away.”

McLoughlin also emphasizes that the safety profile of THC-O is sketchy at best.

“From the research I have done on THC-O, I would be very cautious about consuming or using this synthetic compound”, she reflects. “It’s manufactured using some very toxic chemicals–the fact that manufacturers are using volatile, flammable chemicals scares the living daylights out of me. No one knows how safe these new “frankenstein” compounds actually are, and testing labs claim they are seeing a lot of residual chemicals showing up in these products.”

Dosing THC-O: How much THC are you getting?

THC-O is an isolate–so what you see is what you get. Unlike whole plant cannabis extracts, no other terpenes, cannabinoids, or flavonoids come with THC-O. This means that although you don’t receive the benefits of the entourage effect, dosing is more straightforward because the compound is pure.

One milligram of THC-O isolate equates to exactly one milligram of cannabinoid. As a point of comparison, in a whole plant extract, there might be 0.4 grams of THC, 0.3 grams of CBD, and 0.3 grams of other phytocompounds–which can make dosing a little more complicated.

Another factor to bear in mind when calculating dosage for THC-O is that the cannabinoid is perceived to be approximately three times as potent as Delta-9 THC (although this hasn’t been clinically substantiated). Based on this calculation, a single dose of THC-O should be a third of a Delta-9 THC dose for comparable potency.

Companies that produce THC-O products will also likely have a recommended dosage chart on their packaging. These guidelines can be helpful in knowing how much to take. But like all cannabinoids, an individual’s personal tolerance, height/weight ratio, and metabolism will also influence the dose.

THC-O dosing charts online suggest the following ranges as rough guidelines:

• A threshold dose (the minimum dose needed to produce psychoactive effects): Approximately 2 mg oral or 0.5 mg inhaled.
• A standard psychoactive dose: Between 1 and 3 mg when inhaled, and 3 and 10 mg when taken as tincture or gummy.
• A heavy, ‘psychedelic’ dose: 10 mg or more when consumed orally, and 5mg or more when inhaled. Doses this high should only be taken if the user is already familiar with the effects of THC-O at lower doses.

As is the case with all cannabis products, experts often recommend the old adage of “start low, and go slow”. By beginning with the threshold dose, you can see how it affects you before moving to higher doses.

The possible benefits of THC-O

The apparent (though questionable) legality of THC-O represents its main source of appeal. In US states where Delta-9 THC is illegal, THC-O is an option for those looking to experience a psychoactive, intoxicating high without going out-of-state.

THC-O may also appeal to certain individuals seeking stronger, more potent cannabis kicks. There has always been a sector of the cannabis market with a mission to experience ever more potent highs–which is how the cannabis concentrates market arose.

Anecdotal reports additionally suggest that THC-O users experience a mild psychedelic high that is both spiritual and introspective. There’s long been debate about whether cannabis constitutes a psychedelic, and for the psychedelic curious, THC-O may represent an enticing entry point. Similarly, the mild psychedelic status of THC-O may be appealing to those in states where psychedelic compounds are illegal (practically all of the US, with the exception of Oregon, Washington D.C., and certain cities in California, Michigan, and Massachusetts.)

Finally, there may be therapeutic applications for THC-O in the future. In cases where the potency of Delta-9 THC doesn’t deliver the desired therapeutic effects, more potent analogs such as THC-O may have benefits to offer certain patients. Until there’s research into this, however, it’s impossible to speculate.

The possible side effects of THC-O

At the moment, there’s a lack of research unpacking the pharmacology, toxicology, and safety of synthetic cannabis compounds in general. There’s a lot we don’t know–but research suggests an association between synthetic cannabinoid use and impaired executive function.

This research resonates with the findings from the military experiments mentioned earlier, where the research carried out on dogs at Edgewood Arsenal in Maryland was found to physically incapacitate the dogs, temporarily impairing their muscle function and coordination. That being said, research on dogs is not the same as research on people.

Most of what we know about the effects of THC-O on humans is derived from anecdotal reports. In some THC-O forums on Reddit, redditors have reported coughing after vaping the cannabinoid. While coughing isn’t necessarily a source of concern, there may be long-term effects that aren’t immediately evident.

Some commentators have compared THC-O-acetate with Vitamin E acetate. Vitamin E acetate is a compound present in black market vape carts that has been linked to the EVALI respiratory illness. EVALI can cause long-term lung scarring, damage, or even death. While there is no evidence yet that THC-O can cause the same harm as vitamin E acetate, gummies or tinctures may represent a safer bet than vape carts until more is known.

There are also reports of users feeling panicked when the THC-O high hits. Dr. Ethan Russo points out that Delta-9 THC overdoses can result in paranoia, anxiety, panic, temporary psychosis, and even vasovagal syncope–a sudden drop in heart rate and blood pressure. Given that THC-O is two to three times more potent than THC, it’s feasible that there’s the potential for similar–if not exacerbated–side effects.

Another potential adverse effect is toxicity. The synthesis of THC-O involves acetic anhydride and sulfuric acid, which are both toxic solvents. McLoughlin also points out that there is a possibility of residual contamination in THC-O formulations that are not prepared properly. Solvents such as sulfuric acid must be totally cleared from the final product lest they leave potentially harmful residues.

Dr. Ethan Russo has also called attention to unknown effects of THC-O on the body. There’s no data about whether THC-O is fully metabolized by the liver when taken orally, or if it can accumulate (causing toxicity). THC-O may also have a mechanism of action that we don’t know about, leading to ‘off-target effects’. These unexpected effects could occur after use, or accumulate and present one day as an illness or condition.

Finally, the increased potency of THC-O may push the boundaries of safety. To date, there’s no evidence that cannabis has ever been responsible for a death from overdose, unlike opioids. However, with more potent variants, such as THC-O, experts like Tishler and Russo have concerns about the potential for overdose-related harm to occur.

Is THC-O legal?

The legality of THC-O is questionable, to say the least. The cannabinoid is derived from CBD found in industrial hemp (which is legal at a federal level), but is an analog of THC (not legal at a federal level).

Producers of THC-O products often argue that since the 2018 Farm Bill legalized industrial hemp, its isomers, and derivatives, THC-O derived from hemp is legal too. However, legislation that pre-dates the Farm Bill suggests otherwise. The 1986 Federal Analogue Act declares that substances that are an analog of a Schedule I drug also qualify as Schedule I drugs. THC-O, which is an analog of THC, would therefore be classified as a Schedule I drug.

“Talking about legality, I feel that it is just a matter of time before the government bans all ‘frankenstein’ compounds,” says McLoughlin. “Already a number of states have deemed Delta-8 THC illegal, and it’s just time before THC-O and others join the ranks.” States such as Alaska, Arizona, Colorado, and Montana have already made blanket bans on any synthetic isomers of THC.

There’s also a widespread consensus among many in the industry that semi-synthetic compounds like THC-O keep emerging because of cannabis prohibition.

“If the government would just legalize THC cannabis across the board, then we wouldn’t have all of these dangerous synthetics hitting the market and jeopardizing people’s health,” reflects McLoughlin.

Where can I buy THC-O?

There are currently a handful of brands manufacturing products containing this super-potent cannabinoid. Binoid CBD, Bearly Legal Hemp, and Delta Extrax all sell THC-O products. The websites of these brands all link to third-party purity testing on their THC-O products.

It’s important to note, however, that determining THC-O potency is difficult, and there is presently a lack of verified laboratories with a reliable method for testing THC-O concentrations. As a result, the actual quantity of THC-O in these formulations could vary dramatically.

When it comes to shipping, none of the brands above mention any restrictions on shipping THC-O products across state lines. Delta Extrax and Bearly Legal Hemp, however, both explicitly state that they observe shipping restrictions in states where Delta-8, another synthetic cannabinoid, is banned.

The future of THC-O

At present, experts such as Tishler and McLoughlin are voicing serious concerns regarding the safety and legality of THC-O. There are a number of unknown variables surrounding its short and long-term effects. Experts also point out that testing for THC-O potency is essential before products go to market, and leading independent laboratories must create verifiable reference standards to ensure THC-O purity and potency.

There are a number of ‘ifs’ surrounding the future of this ultra-potent cannabinoid. In time, the safety profile of THC-O may change as industry experts are working on creating safe formulations of THC-O. If THC-O can be formulated safely and research suggests it holds therapeutic applications, then it’s possible that THC-O may become more integrated into mainstream cannabis culture. For cannabis patients who have to ingest extremely high concentrations of THC to ease pain or soothe symptoms, a more potent iteration such as THC-O may be useful.

Such scenarios are very hypothetical, however. Until studies exploring its safety emerge, THC-O is likely to hold a tenuous place in the cannabis world, with its prevalence determined by consumer demand and legal status.

The final word

It’s vital to take precautions if you’re thinking about experimenting with the THC-O. Before purchasing any products, check the Certificate of Analysis (CoA) associated with the product’s batch number and ensure the CoA number matches that of the batch.

Purchase only from trusted manufacturers with impeccable safety records. Use caution when dosing THC-O by following the adage of start low, and go slow.