THC vs THC-O: What's the difference?

In our latest question and answer, the pharmacist discusses the differences between THC and THC-O.
THC vs THC-O: What's the difference?

TyJil Asked

What is the difference between THC and THC-O?


THC or delta-9-tetrahydrocannabinol is the main psychoactive compound in cannabis responsible for a majority of the drug's effects.
THC-O or "THC-acetate" is a chemical analog of THC. An analog is just a chemical with a similar structure that's different in one or more components.
THC-O is dangerous to produce, is being sold with little (if any) regulatory oversight, and lacks research on its safety. For those reasons, I'd suggest avoiding THC-O products altogether.


Delta-9-tetrahydrocannabinol (THC) and THC-acetate ester (THC-O) are both cannabinoids that bind to the cannabinoid type 1 receptor (CB1) in the brain and central nervous system. However, there are some important differences between the two. First and foremost, THC naturally occurs in the cannabis plant whereas THC-O can only be synthetically produced. THC is an active ingredient in an approved prescription drug (Marinol) and has been used safely for many years. THC-O has almost no scientific evidence supporting safe use in humans.

Synthetic cannabinoids like THC-O have been associated with increased calls to poison control and emergency room visits

What are Synthetic Cannabinoids?

Synthetic cannabinoids are man-made research chemicals that structurally resemble THC, as is the case with THC-O, and mimic the drug's pharmacologic effects. Here's the CDC's definition:

 "Various manmade chemicals that some people may use as an alternative to marijuana." - Centers for Disease Control

Synthetic cannabinoids include, but are not limited to: 

  • Synthetic marijuana
  • Spice
  • K2

The word "synthetic" just means that the compound is made by man, usually by chemical synthesis in a lab, as opposed to a natural chemical that exists in nature. 

What is THC-O?

THC-O is a chemical derivative of THC that can be produced from cannabidiol (CBD) or other cannabinoids such as THC. See below to compare the structures of THC vs THC-O.

THC Acetate (THC-O) Chemical Structure


THC Chemical Structure

The main difference between THC and THC-O is the addition of an acetate ester which is the chemical functional group highlighted in red above. This small change might not seem like much, but it can result in big changes in how the drug interacts with the CB1 receptor. 


Is THC-O Synthetic?

Yes. THC-O is commonly synthesized by converting THC into THC-O via a chemical reaction that involves a chemical called acetic anhydride. Acetic anhydride is very toxic and dangerous if not handled appropriately. Since THC-O can be made by starting with natural cannabinoids like THC and CBD,  some people consider THC-O to be semi-synthetic.


How do the Effects of THC-O differ from that of THC?

THC-O is supposedly 2-3x more potent than THC at the CB1 receptor, but this is based on animal studies. In all honesty, we don’t know that much about how the effects of THC-O differ from THC because there are no well-controlled studies in humans. Anything you've heard or read online about the drug's effects is likely anecdotal at best. 

Is THC-O Safe?

No. Synthetic and semi-synthetic cannabinoids such as THC-O should not be considered safe. THC-O can be very dangerous to produce due to the dangerous nature of the chemicals that are used to synthesize it. 

Is THC-O Legal?

No, but many companies claim that THC-O is legal based on the 2018 Farm Bill which legalized hemp (cannabis with THC<0.3% by weight) and its derivatives. Their argument is based on the fact that THCO- can be synthetically produced from legal hemp-derived THC or CBD (making is a derivative). But in February of this year, the DEA issued a letter clarifying their view on the THC acetate esters like THC-O stating the following:

"Delta-9-THCO and delta-8-THCO do not occur naturally in the cannabis plant and can only be obtained synthetically, and therefore do not fall under the definition of hemp. Delta-9-THCO and delta-8-THCO are tetrahydrocannabinols having similar chemical structures and pharmacological activities to those contained in the cannabis plant. Thus, delta-9-THCO and delta-8-THCO meet the definition of “tetrahydrocannabinols,” and they (and products containing delta-9-THCO and delta-8- THCO) are controlled in schedule I by 21 U.S.C. § 812(c) Schedule I, and 21 CFR § 1308.11(d)."

In Conclusion

To summarize, THC is natural and somewhat safe. Whereas, THC-O is synthetically produced using a dangerous chemical and has very little research available about its effects. THC-O might bind to the CB1 receptor with a greater affinity than THC due to the substitution of an acetate ester functional group on the aryl ring of its chemical structure. More research is needed on THC-O, and until then, it's best to avoid using THC-O products. 

  1. ∆8-THC, THC-O Acetates and CBD-di-O Acetate: Emerging Synthetic Cannabinoids Found in Commercially Sold Plant Material and Gummy Edibles [Article].
  2. Vaping THC-O Acetate: Potential for Another EVALI Epidemic (PubMed).
  3. THCO Don't Go There (Expert Q & A).
  4. THCO is a Schedule I Controlled Substance (Link).

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