THC-O-acetate

THC acetate ester (THC-O-acetate, THC acetate, O-acetyl-THC, THC-O, ATHC) is the acetate ester of THC.

THC-O-acetate
THC-O-acetate.svg
THC-O-acetate 3D BS.png
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)

Physical data, chemistry, and propertiesEdit

 
O-acetyl-Δ8-THC [1], CAS# 23050-54-6

THC acetate ester (THC-O or THCOA) can be synthesized from THC,[1][2] 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 delta-9-THC is the best studied, the acetate esters of other isomers, especially delta-8-THC but also delta-10-THC are also known, as are other esters such as THC-O-phosphate, THC hemisuccinate and THC morpholinylbutyrate.

HistoryEdit

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.[3]

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).[4] 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.[5]

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.[6]

Following legal changes in the USA 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 USA 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.[7][8][9]

ToxicityEdit

According to researchers at Portland State University who screened for the presence of reacted ketene as N-benzylacetamide reported that THC-O-acetate may break down to release ketene gas when heated at 240 °C (464 °F). [10] Ketene gas is potentially lethal at 5 parts per million[11]

Legal statusEdit

United KingdomEdit

THC-O-acetate is a Class B drug in the United Kingdom.[12]

United StatesEdit

THC-O-acetate is not scheduled at the federal level in the United States,[13] but it could be considered an analog of THC, in which case purchase, sale, or possession could be prosecuted under the Federal Analog Act.

ReferencesEdit

  1. ^ a b Gold D (1974). Cannabis Alchemy: Art of Modern Hashmaking. Ronin Publishing (2010). ISBN 978-1-5795-1095-4.
  2. ^ Starks M (1990). Marijuana Chemistry: Genetics, Processing, Potency. Ronin Publishing. ISBN 978-0-9141-7139-3.
  3. ^ 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.
  4. ^ Cooper DA. "Future Synthetic Drugs of Abuse". Drug Enforcement Administration. McLean, Virginia.
  5. ^ Brown DT (2003). Cannabis: The Genus Cannabis. Hardwood Academic Publishers. p. 82. ISBN 90-5702-291-5.
  6. ^ 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.
  7. ^ Drotleff L (3 August 2021). "THC-O-acetate safety concerns: Q&A with scientist James Stephens". MJBizDaily.
  8. ^ Schmidt E (5 August 2021). "THC-O Acetate: Everything you need to know about safety, purity and effects". ACS Laboratory.
  9. ^ Erickson BE (30 August 2021). "Delta-8-THC craze concerns chemists". Chemical & Engineering News. 99 (31).
  10. ^ Munger, Kaelas R.; Jensen, Robert P.; Strongin, Robert M. (18 July 2022). "Vaping Cannabinoid Acetates Leads to Ketene Formation". Chemical Research in Toxicology. 35 (7): 1202–1205. doi:10.1021/acs.chemrestox.2c00170. PMID 35801872. S2CID 250358198.
  11. ^ Ketene. National Academies Press (US). 21 March 2014.
  12. ^ "The Misuse of Drugs Act 1971 (Amendment) Order 2008". Office of Public Sector Information. Retrieved 15 June 2009.
  13. ^ "§1308.11 Schedule I." Archived from the original on 2009-08-27. Retrieved 2014-12-19.