Tetrahydrocannabiphorol Explained

Synonyms:	(-)-Trans-Δ^9-tetrahydrocannabiphorol Δ^9-THCP (C7)-Δ^9-THC THC-Heptyl
Iupac Name:	(6aR,10aR)-3-heptyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol
Cas Number:	54763-99-4
Pubchem:	6453074
Chemspiderid:	4955468
C:	23
H:	34
O:	2
Smiles:	CCCCCCCc3cc2OC(C)(C)[C@@H]1CCC(C)=C[C@H]1c2c(O)c3
Stdinchi:	1S/C23H34O2/c1-5-6-7-8-9-10-17-14-20(24)22-18-13-16(2)11-12-19(18)23(3,4)25-21(22)15-17/h13-15,18-19,24H,5-12H2,1-4H3/t18-,19-/m1/s1
Stdinchikey:	OJTMRZHYTZMJKX-RTBURBONSA-N

Tetrahydrocannabiphorol (THCP) is a potent phytocannabinoid, a CB₁ and CB₂ agonist which was known as a synthetic homologue of THC,^[1] but for the first time in 2019 was isolated as a natural product in trace amounts from Cannabis sativa.^{[2] [3]} It is structurally similar to Δ⁹-THC, the main active component of cannabis, but with the pentyl side chain extended to heptyl. Since it has a longer side chain, its cannabinoid effects are "far higher than Δ⁹-THC itself." Tetrahydrocannabiphorol has a reported binding affinity of 1.2 nM at CB₁, approximately 33 times that of Δ⁹-THC (40 nM at CB₁).^[4]

THCP was studied by Roger Adams as early as 1942.^[5]

Isomers

Delta-3-THCP

The Δ³/Δ^6a(10a) isomer Δ³-THCP was synthesised in 1941, and was found to have around the same potency as Δ³-THC, unlike the hexyl homologue parahexyl which was significantly stronger.^[6]

Delta-8-THCP

The Δ⁸ isomer is also known as a synthetic cannabinoid under the code name JWH-091.^{[7] [8]} It's unconfirmed whether or not Δ⁸-THCP is found naturally in cannabis plants, but likely is due to Δ⁸-THC itself being a degraded form of Δ⁹-THC.^[9] JWH-091 has approximately double the binding affinity at the CB₁ receptor (22 nM ± 3.9 nM) in comparison to Δ⁹-THC (40.7 nM ± 1.7 nM) or Δ⁸-THC (44 nM ± 12 nM), but appears significantly lower in vitro than the binding activity of Δ⁹-THCP (K_i = 1.2 nM)^[4]

Natural occurrence in cannabis

The Δ⁹ isomer of THCP occurs naturally in cannabis, but in small amounts. A 2021 study reported the content of Δ⁹-THCP ranging from 0.0023% to 0.0136% (w/w) (approximately 0.02–0.13 mg/g) without correlation to THC percentage in Δ⁹-THC-dominant strains of cannabis; that study failed to detect THCP in CBD-dominant strains.^{[2] [10]}

See also

• Nabilone
• Hexahydrocannabiphorol
• 1,2-Didehydro-3-oxo-THCO
• Delta-8-THC
• Parahexyl
• Perrottetinene
• Tetrahydrocannabivarin
• Tetrahydrocannabutol
• Tetrahydrocannabihexol
• THCP-O-acetate

Notes and References

1. Harvey DJ . Identification of hepatic metabolites of n-heptyl-delta-1-tetrahydrocannabinol in the mouse . Xenobiotica; the Fate of Foreign Compounds in Biological Systems . 15 . 3 . 187–197 . March 1985 . 2992174 . 10.3109/00498258509045349 .
2. Bueno J, Greenbaum EA . (-)-trans-Δ⁹-Tetrahydrocannabiphorol Content of Cannabis sativa Inflorescence from Various Chemotypes . Journal of Natural Products . 84 . 2 . 531–536 . February 2021 . 33565878 . 10.1021/acs.jnatprod.0c01034 . 231866062 .
3. Linciano P, Russo F, Citti C, Tolomeo F, Paris R, Fulvio F, Pecchioni N, Vandelli MA, Laganà A, Capriotti AL, Biagini G, Carbone L, Gigli G, Cannazza G . The novel heptyl phorolic acid cannabinoids content in different Cannabis sativa L. accessions . Talanta . 235 . 122704 . December 2021 . 34517579 . 10.1016/j.talanta.2021.122704 . free . 11380/1250339 .
4. Citti C, Linciano P, Russo F, Luongo L, Iannotta M, Maione S, Laganà A, Capriotti AL, Forni F, Vandelli MA, Gigli G, Cannazza G . A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ⁹-tetrahydrocannabinol: Δ⁹-Tetrahydrocannabiphorol . Scientific Reports . 9 . 1 . 20335 . December 2019 . 31889124 . 6937300 . 10.1038/s41598-019-56785-1 . 2019NatSR...920335C .
5. Tetrahydrocannabinol Homologs and Analogs with Marihuana Activity. XIII¹ . 10.1021/ja01255a061 . 1942 . Adams R, Loewe S, Smith CM, McPhee WD . Journal of the American Chemical Society . 64 . 3 . 694–697 .
6. Adams R, Loewe S, Jelinek C, Wolff H . Tetrahydrocannabinol Homologs with Marihuana Activity. IX. . Journal of the American Chemical Society . July 1941 . 63 . 7 . 1971–1973 . 10.1021/ja01852a052 .
7. Martin BR, Jefferson R, Winckler R, Wiley JL, Huffman JW, Crocker PJ, Saha B, Razdan RK . Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists . The Journal of Pharmacology and Experimental Therapeutics . 290 . 3 . 1065–1079 . September 1999 . 10454479 .
8. Bow EW, Rimoldi JM . The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation . Perspectives in Medicinal Chemistry . 8 . 17–39 . 2016 . 27398024 . 4927043 . 10.4137/PMC.S32171 .
9. Book: 10.1016/B978-008045382-8.00091-5 . Chemistry of Cannabis . Comprehensive Natural Products II . 2010 . Hazekamp A, Fischedick JT, Díez ML, Lubbe A, Ruhaak RL . 1033–1084 . 978-0-08-045382-8 . https://books.google.com/books?id=ISBN9780080453828&pg=PA1033 .
10. (-)- trans-Δ9-Tetrahydrocannabiphorol Content of Cannabis sativa Inflorescence from Various Chemotypes. 2021 . 33565878 . 19 Feb 2024 . Journal of Natural Products . 84 . 2 . 531–536 . 10.1021/acs.jnatprod.0c01034 . 231866062 . Bueno J, Greenbaum EA .