Tetrahydrocannabutol Explained

Verifiedfields:	changed
Watchedfields:	changed
Verifiedrevid:	448003399
Iupac Name:	(−)-(6aR,10aR)-6,6,9-trimethyl-3-butyl-6a,7,8,10a-tetrahydro-6H-benzo[''c'']chromen-1-ol
Drug Name:	Δ^9-Tetrahydrocannabinol-C4
Cas Number:	60008-00-6
Unii:	LIC9QAS59U
Atc Prefix:	none
Pubchem:	6453891
Chemspiderid:	4956237
Chembl:	4437290
C:	20
H:	28
O:	2
Smiles:	CCCCC1=CC2=C([C@@H]3C=C(CC[C@H]3C(O2)(C)C)C)C(=C1)O
Stdinchi:	1S/C20H28O2/c1-5-6-7-14-11-17(21)19-15-10-13(2)8-9-16(15)20(3,4)22-18(19)12-14/h10-12,15-16,21H,5-9H2,1-4H3/t15-,16-/m1/s1
Stdinchikey:	QHCQSGYWGBDSIY-HZPDHXFCSA-N

Δ⁹-Tetrahydrocannabutol (tetrahydrocannabinol-C4, THC-C4, Δ⁹-THCB, (C4)-Δ⁹-THC, butyl-THC) is a phytocannabinoid found in cannabis that is a homologue of tetrahydrocannabinol (THC), the main active component of Cannabis.^[1] Structurally, they are only different by the pentyl side chain being replaced by a butyl side chain. THCB was studied by Roger Adams as early as 1942 ^[2]

Pharmacology

Δ⁹-THCB, showed an affinity for the human CB₁ (Ki = 15 nM) and CB₂ receptors (Ki = 51 nM) comparable to that of Δ⁹-THC. The formalin test in vivo was performed on Δ⁹-THCB in order to reveal possible analgesic and anti-inflammatory properties. The tetrad test in mice showed a partial agonistic activity of Δ⁹-THCB toward the CB₁ receptor. THCB has rarely been isolated from cannabis samples,^[3] but appears to be less commonly present than THC or THCV. It is metabolized in a similar manner to THC.^[4]

In an analysis by the University of Rhode Island on phytocannabinoids it was found that THC-Butyl had the highest 3C-like protease inhibitor activity against COVID-19 out of all the phytocannabinoids tested within that study but not as high as the antiviral drug GC376 (81% THCB vs. 100% GC376).^[5]

Chemistry

Similarly to THC, it has 7 double bond isomers and 30 stereoisomers.^[6] The Δ⁸ isomer is known as a synthetic cannabinoid under the code name JWH-130,^[7] and the ring-opened analogue cannibidibutol (CBDB) is also known.^[8] THC-Butyl can be synthesized from 4-butylresorcinol.

Legality

THCB is not scheduled internationally under the Convention on Psychotropic Substances, but may be controlled under analogue law in some individual jurisdictions as a homologue of THC.

See also

• Cannabis
• Cannabinoid
• Hexahydrocannabutol
• Parahexyl
• Perrottetinene
• Tetrahydrocannabihexol
• Tetrahydrocannabiphorol

Notes and References

1. Linciano P, Citti C, Luongo L, Belardo C, Maione S, Vandelli MA, Forni F, Gigli G, Laganà A, Montone CM, Cannazza G . Isolation of a High-Affinity Cannabinoid for the Human CB1 Receptor from a Medicinal Cannabis sativa Variety: Δ⁹-Tetrahydrocannabutol, the Butyl Homologue of Δ⁹-Tetrahydrocannabinol . Journal of Natural Products . 83 . 1 . 88–98 . January 2020 . 31891265 . 10.1021/acs.jnatprod.9b00876 . 209519659 .
2. 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 .
3. Harvey DJ . Characterization of the butyl homologues of delta1-tetrahydrocannabinol, cannabinol and cannabidiol in samples of cannabis by combined gas chromatography and mass spectrometry . The Journal of Pharmacy and Pharmacology . 28 . 4 . 280–285 . April 1976 . 6715 . 10.1111/j.2042-7158.1976.tb04153.x . 32734030 .
4. Brown NK, Harvey DJ . In vivo metabolism of the n-butyl-homologues of delta 9-tetrahydrocannabinol and delta 8-tetrahydrocannabinol by the mouse . Xenobiotica; the Fate of Foreign Compounds in Biological Systems . 18 . 4 . 417–427 . April 1988 . 2840781 . 10.3109/00498258809041678 .
5. Liu C, Puopolo T, Li H, Cai A, Seeram NP, Ma H . Identification of SARS-CoV-2 Main Protease Inhibitors from a Library of Minor Cannabinoids by Biochemical Inhibition Assay and Surface Plasmon Resonance Characterized Binding Affinity . Molecules . 27 . 18 . 6127 . September 2022 . 36144858 . 10.3390/molecules27186127 . 9502466 . free .
6. Web site: Verschil THC Olie, CBD olie, wietolie, hennepolie en cannabisolie? . Dutch-Headshop.com . 19 November 2016 .
7. 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 .
8. Hanuš LO, Meyer SM, Muñoz E, Taglialatela-Scafati O, Appendino G . Phytocannabinoids: a unified critical inventory . Natural Product Reports . 33 . 12 . 1357–1392 . November 2016 . 27722705 . 10.1039/c6np00074f . free .