tetrahydrocannabiphorol
{{Short description|Cannabinoid agonist compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{redirect|THCP|the organophosphorus compound|tetrakis(hydroxymethyl)phosphonium chloride}}
{{More citations needed|date=September 2022}}
{{Infobox drug
| synonyms = (-)-Trans-Δ9-tetrahydrocannabiphorol,
Δ9-THCP,
(C7)-Δ9-THC,
THC-Heptyl
| IUPAC_name = (6aR,10aR)-3-heptyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol
| image = THCP 2D skeletal.svg
| image_class = skin-invert-image
| image2 = THCP 3D BS.png
| image_class2 = bg-transparent
| pronounce = /tɛtʃrəhaɪdroʊkənæbɪfoʊrɔːl/
| legal_AU =
| legal_CA =
| legal_DE =
| legal_UK =
| legal_US =
| legal_status =
| IUPHAR_ligand =
| CAS_number = 54763-99-4
| ATC_prefix =
| ATC_suffix =
| PubChem = 6453074
| DrugBank =
| ChemSpiderID = 4955468
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = WTK87HN3LG
| 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
| class = Cannabinoid
}}
Tetrahydrocannabiphorol (THCP) is a potent phytocannabinoid, a CB1 and CB2 receptor agonist which was known as a synthetic homologue of tetrahydrocannabinol (THC),{{cite journal | vauthors = Harvey DJ | title = Identification of hepatic metabolites of n-heptyl-delta-1-tetrahydrocannabinol in the mouse | journal = Xenobiotica; the Fate of Foreign Compounds in Biological Systems | volume = 15 | issue = 3 | pages = 187–197 | date = March 1985 | pmid = 2992174 | doi = 10.3109/00498258509045349 }} but for the first time in 2019 was isolated as a natural product in trace amounts from Cannabis sativa.{{cite journal | vauthors = Bueno J, Greenbaum EA | title = (-)-trans-Δ9-Tetrahydrocannabiphorol Content of Cannabis sativa Inflorescence from Various Chemotypes | journal = Journal of Natural Products | volume = 84 | issue = 2 | pages = 531–536 | date = February 2021 | pmid = 33565878 | doi = 10.1021/acs.jnatprod.0c01034 | s2cid = 231866062 }}{{cite journal | vauthors = 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 | title = The novel heptyl phorolic acid cannabinoids content in different Cannabis sativa L. accessions | journal = Talanta | volume = 235 | pages = 122704 | date = December 2021 | pmid = 34517579 | doi = 10.1016/j.talanta.2021.122704 | hdl-access = free | hdl = 11380/1250339 }}
THCP 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), however this does not mean it's 33x stronger per milligram.{{cite journal | vauthors = Citti C, Linciano P, Russo F, Luongo L, Iannotta M, Maione S, Laganà A, Capriotti AL, Forni F, Vandelli MA, Gigli G, Cannazza G | title = A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ9-tetrahydrocannabinol: Δ9-Tetrahydrocannabiphorol | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 20335 | date = December 2019 | pmid = 31889124 | pmc = 6937300 | doi = 10.1038/s41598-019-56785-1 | bibcode = 2019NatSR...920335C }}
THCP was studied by Roger Adams as early as 1942.{{cite journal | url=https://pubs.acs.org/doi/abs/10.1021/ja01255a061 | doi=10.1021/ja01255a061 | title=Tetrahydrocannabinol Homologs and Analogs with Marihuana Activity. XIII1 | date=1942 | vauthors = Adams R, Loewe S, Smith CM, McPhee WD | journal=Journal of the American Chemical Society | volume=64 | issue=3 | pages=694–697 | url-access=subscription }}
Isomers
=Delta-3-THCP=
{{clear left}}
The Δ3/Δ6a(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.{{cite journal | vauthors = Adams R, Loewe S, Jelinek C, Wolff H | title = Tetrahydrocannabinol Homologs with Marihuana Activity. IX. | journal = Journal of the American Chemical Society | date = July 1941 | volume = 63 | issue = 7 | pages = 1971–1973 | doi = 10.1021/ja01852a052 }}
=Delta-8-THCP=
{{clear left}}
The Δ8 isomer is also known as a synthetic cannabinoid under the code name JWH-091.{{cite journal | vauthors = Martin BR, Jefferson R, Winckler R, Wiley JL, Huffman JW, Crocker PJ, Saha B, Razdan RK | title = Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 290 | issue = 3 | pages = 1065–1079 | date = September 1999 | pmid = 10454479 | url = https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10454479 }}{{cite journal | vauthors = Bow EW, Rimoldi JM | title = The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation | journal = Perspectives in Medicinal Chemistry | volume = 8 | issue = | pages = 17–39 | date = 2016 | pmid = 27398024 | pmc = 4927043 | doi = 10.4137/PMC.S32171 }} 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.{{cite book |doi=10.1016/B978-008045382-8.00091-5 |chapter=Chemistry of Cannabis |title=Comprehensive Natural Products II |date=2010 | vauthors = Hazekamp A, Fischedick JT, Díez ML, Lubbe A, Ruhaak RL |pages=1033–1084 |isbn=978-0-08-045382-8 |chapter-url=https://books.google.com/books?id=ISBN9780080453828&pg=PA1033 }} 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 (Ki = 1.2 nM)
Natural cannabis occurrence
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.{{cite journal|url=https://pubmed.ncbi.nlm.nih.gov/33565878|title=(-)- trans-Δ9-Tetrahydrocannabiphorol Content of Cannabis sativa Inflorescence from Various Chemotypes|date=2021 |pmid=33565878 |access-date=19 Feb 2024 |journal=Journal of Natural Products |volume=84 |issue=2 |pages=531–536 |doi=10.1021/acs.jnatprod.0c01034 |s2cid=231866062 | vauthors = Bueno J, Greenbaum EA }}[https://bestbudscbdstore.com/collections/delta-8-gummies-healing-nation Delta 8 Gummies Guide]