THC-O-acetate

THC acetate ester (THC-O-acetate, THC acetate, O-acetyl-THC, THC-O, ATHC) is the acetate ester of THC. It is a metabolic pro-drug, with its subjective effects being felt around 30 minutes after ingestion.[1][2][3]

THC-O-acetate
Legal status
Legal status
Identifiers
  • (6aR,10aR)-6,6,9-Trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-yl acetate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H32O3
Molar mass356.506 g·mol−1
3D model (JSmol)
  • O=C(Oc2cc(cc1OC([C@@H]3CC/C(=C\[C@H]3c12)C)(C)C)CCCCC)C
  • InChI=1S/C23H32O3/c1-6-7-8-9-17-13-20(25-16(3)24)22-18-12-15(2)10-11-19(18)23(4,5)26-21(22)14-17/h12-14,18-19H,6-11H2,1-5H3/t18-,19-/m1/s1 checkY
  • Key:DEWSJDIJFWQLOA-RTBURBONSA-N checkY
 ☒NcheckY (what is this?)  (verify)

The term THC-O-acetate and its variations are commonly used for two types of the substance, dependent on which cannabinoid it is synthesized from. The difference between Δ8-THC derivatives (shown on the left image) and Δ9-THC derivatives (shown on the right image) is bond placement on the top-left cyclohexene ring. Regardless of the derivative used, both are significantly more potent than THC.[4]

Physical data, chemistry, and properties
O-acetyl-Δ8-THC , CAS# 23050-54-6

THC acetate ester (THC-O or THCOA) can be synthesized from THC,[1][5] or from THCA. The acetylation of THC does not change the properties of the compound to the same extent as with other acetate esters, as the parent compound (THC) is already highly lipophilic, but potency is nonetheless increased to some extent. While the acetate ester of Δ9-THC is the best studied, the acetate esters of other isomers, especially Δ8-THC but also Δ10-THC are also known, as are other esters such as THC-O-phosphate, THC hemisuccinate and THC morpholinylbutyrate.

History

THC acetate ester was investigated as a possible non-lethal incapacitating agent as part of the Edgewood Arsenal experiments at some point between 1949 and 1975. It was noted to have about twice the capacity to produce ataxia (lack of voluntary coordination of muscle movements) as did THC when administered to dogs.[6]

Author D. Gold provided synthesis instructions for this compound (calling it "THC acetate") in his 1974 book Cannabis Alchemy: Art of Modern Hashmaking, in which it is described as follows;[1]

"The effect of the acetate 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."

The U.S. DEA first encountered THC-O-acetate as an apparent controlled substance analogue of THC in 1978. It was made in an analogous manner to how aspirin (acetylsalicylic acid) is made from willow bark (salicylic acid).[7] The incident was described by Donald A. Cooper of the DEA thus:

"Given the world wide ready availability of marijuana, it is somewhat difficult to produce a viable argument for making [controlled substance analogs (CsA's)] of cannabinoids. However, ten years ago (1978) an attempt to produce CsA's from cannabis extracts was encountered in the Jacksonville, Florida area. In this case a concentrated extract of cannabis had been obtained by a soxhlet extraction. The extract had been acetylated with acetic anhydride, and in the final step, the excess acetic anhydride removed by distillation (reference is unretrievable due to its appearance in an underground periodical). The product contained neither quantities of nonderivatized cannabinoid nor any identifiable plant fragments. Since this single instance, no acetalaced cannabinoid samples have been reported by a DEA laboratory. Therefore, this instance is assumed to represent an isolated occurrence and as such, will serve to terminate our discussion of cannabinoid CsA's."

A similar case reported in June 1995 in the United Kingdom, and THC-O-acetate was ruled to be a Class A drug in that case. The description of that case appears to indicate the convicted manufacturer was using D. Gold's book Cannabis Alchemy as a guide.[8]

THC acetate was also reported to have been found by New Zealand police in 1995, again made by acetylation of purified cannabis extracts with acetic anhydride.[9]

Following legal changes in the United States since around 2018, especially the legalisation of cannabis in an increasing number of states and the passage of the 2018 Farm Bill which eased restrictions on the cultivation of industrial hemp, THC-O-acetate has become increasingly available as a recreational drug, initially in the United States[10] but subsequently in other countries also. It may be produced from extracts of psychoactive strains of cannabis in states where this is permitted, in which case the product will be primarily O-acetyl-Δ9-THC, but it is also commonly produced from Delta-8-THC which is synthesised from cannabidiol extracted from hemp, in which case the product will be primarily O-acetyl-Δ8-THC. Since Δ9-THC and Δ8-THC are quite different in potency, the corresponding acetylated derivatives also will be, which may pose risks to consumers who are unaware of which isomer is in commercial products.

Concerns have also been raised about the lack of safety data or quality control testing given the limited history of human use and potentially toxic chemical reagents used during manufacture. The legal issue of whether purified THC-O-acetate is considered legal in jurisdictions where cannabis is legal is also complex and varies between jurisdictions.[11][12][13]

Toxicity

In 2022, researchers at Portland State University who screened for the presence of reacted ketene as N-benzylacetamide reported that Vitamin E acetate, CBD-acetate, CBN-acetate and THC-O-acetate may break down to release ketene gas when heated at 340 °C (644 °F). Ketene gas is potentially lethal at 5 parts per million[14]

United Kingdom

THC-O-acetate is a Class B drug in the United Kingdom.[15]

United States

THC-O-acetate is not directly listed under the Controlled Substances Act but is designated as a federally prohibited Schedule I controlled substance in the United States.[16][17] Despite not being listed in the federal controlled substance act directly by name, Terrence Boos the DEAs Chief Drug & Chemical Evaluation Section Diversion Control Division released a legal opinion in response to a letter asking to clarify legality.

"The CSA classifies tetrahydrocannabinols (THC) as controlled in schedule I. 21 U.S.C. § 812, Schedule I(c)(17); 21 CFR 1308.11(d)(31). Subject to limited exceptions, for the purposes of the CSA, the term "tetrahydrocannabinols" means those "naturally contained in a plant of the genus Cannabis (cannabis plant), as well as synthetic equivalents of the substances contained in the cannabis plant and/or synthetic substances, derivatives, and their isomers with similar chemical structure and pharmacological activity to those substances contained in the plant." 21 CFR §(d)(31).

"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. Δ9-THC-O and Δ8-THC-O are tetrahydrocannabinols having similar chemical structures and pharmacological activities to those contained in the cannabis plant. Thus, Δ9-THC-O and Δ8-THC-O meet the definition of "tetrahydrocannabinols," and they (and products containing Δ9-THC-O and Δ8-THC-O) are controlled in schedule I by 21 U.S.C. § 812(c) Schedule I, and 21 CFR § 1308.11(d). The Controlled Substances Code Number (CSCN) assigned to these substances are 7370, which is that of tetrahydrocannabinols, and the conversion factors (CF) are 1.00. Because Δ9-THC-O and Δ8-THC-O are controlled substances, they do not meet the definition of controlled substance analogues under 21 U.S.C. § 813."[18][19][20][21][22][23][24]

Although this may conflict with the federal definition of hemp which includes "(1) HEMP.—The term 'hemp' means the plant Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a Δ9-THC concentration of not more than 0.3 percent on a dry weight basis."[25]

Its sudden status in the early 2020s as both a Schedule I and widely commercially distributed chemical is a heavily debated topic, most notably by the United States Ninth Circuit Court of Appeals, which made an opinion post that stated; products containing hemp-derived Δ8-THC may be lawfully used in commerce and eligible for trademark protection under the Lanham Act. Significantly, the court decided that downstream hemp-derived Δ8-THC products can fit within the legal definition of “hemp” under the Agricultural Improvement Act of 2018 so long as they consist of less than 0.3% Δ9-THC and are derived from hemp itself consisting of less than 0.3% Δ9-THC. Under the Controlled Substances Act and the 2018 Farm Bill, this would hypothetically make every hemp-derived product fully legal so long as it contained 0.3% or less of Δ9-THC in total, including Δ8-THC-O.[26]

See also

References
  1. Gold D (1974). Cannabis Alchemy: Art of Modern Hashmaking. Ronin Publishing (2010). ISBN 978-1-5795-1095-4.
  2. Starks M (1977). "Marijuana Potency". Google Books. And/Or Press. p. 174. Retrieved 3 April 2023.
  3. Levenson M (19 August 2021). "Meet THC-O acetate, a hemp-derived compound three times stronger than THC". Leafly. Retrieved 3 April 2023.
  4. Sabaghi D (2023). "Δ8 And Δ9 THC-O Are Controlled Substances, DEA Says". Forbes.
  5. Starks M (1990). Marijuana Chemistry: Genetics, Processing, Potency. Ronin Publishing. ISBN 978-0-9141-7139-3.
  6. Committee on Toxicology, National Research Council (1984). Possible Long-Term Health Effects of Short-Term Exposure To Chemical Agents, Volume 2: Cholinesterase Reactivators, Psychochemicals and Irritants and Vesicants. The National Academies Press. p. 79. ISBN 978-0-309-07772-9.
  7. Cooper DA. "Future Synthetic Drugs of Abuse". Drug Enforcement Administration. McLean, Virginia.
  8. Brown DT (2003). Cannabis: The Genus Cannabis. Hardwood Academic Publishers. p. 82. ISBN 90-5702-291-5.
  9. Valentine MD (1995). "Δ9-THC acetate from acetylation of cannabis oil". Science and Justice. 36 (3): 195–197. doi:10.1016/S1355-0306(96)72595-9.
  10. Holt AK, Poklis JL, Peace MR (October 2022). "∆8-THC, THC-O Acetates and CBD-di-O Acetate: Emerging Synthetic Cannabinoids Found in Commercially Sold Plant Material and Gummy Edibles". Journal of Analytical Toxicology. 46 (8): 940–948. PMID 35674405.
  11. Drotleff L (3 August 2021). "THC-O-acetate safety concerns: Q&A with scientist James Stephens". MJBizDaily.
  12. Schmidt E (5 August 2021). "THC-O Acetate: Everything you need to know about safety, purity and effects". ACS Laboratory.
  13. Erickson BE (30 August 2021). "Delta-8-THC craze concerns chemists". Chemical & Engineering News. 99 (31).
  14. Ketene. National Academies Press (US). 21 March 2014.
  15. "The Misuse of Drugs Act 1971 (Amendment) Order 2008". Office of Public Sector Information. Retrieved 15 June 2009.
  16. Sabaghi D (2023). "Δ8 And Δ9-THC-O Are Controlled Substances, DEA Says". Forbes.
  17. "DEA-THCO-response-to-Kight" (PDF). cannabusiness.law. Kight, Rod.
  18. Sabaghi D (16 February 2023). "Δ8 And Δ9-THC-O Are Controlled Substances, DEA Says". Forbes.
  19. Roberts C (15 February 2023). "THC-O is not hemp and is illegal under Farm Bill, DEA says". MJBiz.
  20. "THCO is a Schedule 1 Controlled Substnace Says DEA". cannabusiness.law.
  21. Potter N (13 February 2023). "DEA States that Δ9-THC-O, Δ8-THC-O Are Not Hemp". hightimes.co.
  22. Paxhia M (17 February 2023). "Δ8 and Δ9-THC-O Classified as Schedule I Drugs: This Week in Cannabis Investing". Kiplinger.
  23. Long J (15 February 2023). "DEA finds two synthetic cannabinoids are controlled substances—not hemp". Natural Products Insider.
  24. "Controlled Substances" (PDF). Diversion Control Division, Drug Enforcement Agency. U.S. Department of Justice.
  25. "S.2667 - Hemp Farming Act of 2018". 115th Congress (2017-2018).
  26. Fisher DM. "AK FUTURES LLC, v. BOYD STREET DISTRO, LLC Appeal from the United States District Court for the Central District of California; Case opinion publication" (PDF). cdn.ca9.uscourts.gov. UNITED STATES COURT OF APPEALS FOR THE NINTH CIRCUIT. Retrieved 5 March 2023.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.