1.0 2020-03-19 00:35:37 UTC 2020-11-18 16:35:09 UTC CDB000017 Delta-9-tetrahydrocannabinolic acid B Delta-9-tetrahydrocannabinolic acid B or THC acid B, a delta 9-tetrahydrocannabinol, is one of the major non-psychoactive cannabinoid compounds that are found only in the cannabis plant. THC acid B, to a much lesser extent than THC acid A, is a biosynthetic precursor to delta-9-tetrahydrocannabinol, the principal psychoactive constituent of the cannabis plant. The difference between THC acid A and B is the position of the carboxyl functional group. In THC acid A it is on the C-2 whereas in THC acid B it is on the C-4 (PMID: 6991645). THC acid is produced via the following pathway: Geranyl pyrophosphate and olivetolic acid react, catalyzed by an enzyme Geranyl-pyrophosphate—olivetolic acid geranyltransferase to produce cannabigerolic acid which is then cyclized by the enzyme THC acid synthase to give THC acid. Over time, or when heated (via vaping or smoking), THC acid is decarboxylated, producing THC. While some studies showed that delta-9-THC acid binds cannabinoid type one (CB1) receptors with a Ki value of 23.5 nM (PMID: 25311884), others had found a negligible activity (PMID: 18303850). Decarboxylation of THC acid A to THC during storage or under certain experimental conditions may contribute to these contrasting results A recent study showed that freshly prepared and highly pure delta-9-THC acid (98%) has a low binding affinity for CB1 and CB2 receptors (PMID: 28861508). Thus, it seems that the biological activities of delta-9-THC acid are not mediated by interaction with these classical membrane receptors. Delta-9-THC acid exhibited anti-emetic and immune-modulatory activities through CB1-dependent and CB1-in- dependent mechanisms respectively (PMID: 16504929; PMID: 23889598). Delta-9-THC acid shows potent neuroprotective activity, that may aid in the treatment of Huntington's disease and possibly other neurodegenerative and neuroinflammatory diseases (PMID: 28853159). (6AR,10as)-1-hydroxy-6,6,9-trimethyl-3-pentyl-6H,6ah,7H,8H,10ah-benzo[c]isochromene-4-carboxylate C22H30O4 358.48 358.2144 (6aR,10aS)-1-hydroxy-6,6,9-trimethyl-3-pentyl-6H,6aH,7H,8H,10aH-benzo[c]isochromene-4-carboxylic acid (6aR,10aS)-1-hydroxy-6,6,9-trimethyl-3-pentyl-6aH,7H,8H,10aH-benzo[c]isochromene-4-carboxylic acid CCCCCC1=C(C(O)=O)C2=C([C@H]3C=C(C)CC[C@H]3C(C)(C)O2)C(O)=C1 InChI=1S/C22H30O4/c1-5-6-7-8-14-12-17(23)19-15-11-13(2)9-10-16(15)22(3,4)26-20(19)18(14)21(24)25/h11-12,15-16,23H,5-10H2,1-4H3,(H,24,25)/t15-,16+/m0/s1 VITZNDKHSIWPSR-JKSUJKDBSA-N belongs to the class of organic compounds known as 2,2-dimethyl-1-benzopyrans. These are organic compounds containing a 1-benzopyran moiety that carries two methyl groups at the 2-position. 2,2-dimethyl-1-benzopyrans Organic compounds Organoheterocyclic compounds Benzopyrans 1-benzopyrans Aromatic heteropolycyclic compounds 1-hydroxy-2-unsubstituted benzenoids Alkyl aryl ethers Carboxylic acids Hydrocarbon derivatives Hydroxybenzoic acid derivatives Monocarboxylic acids and derivatives Organic oxides Oxacyclic compounds 1-hydroxy-2-unsubstituted benzenoid 2,2-dimethyl-1-benzopyran Alkyl aryl ether Aromatic heteropolycyclic compound Benzenoid Carboxylic acid Carboxylic acid derivative Ether Hydrocarbon derivative Hydroxybenzoic acid Monocarboxylic acid or derivatives Organic oxide Organic oxygen compound Organooxygen compound Oxacycle logp 5.11 ALOGPS logs -4.55 ALOGPS logp 5.6 ChemAxon pka_strongest_acidic 3.83 ChemAxon pka_strongest_basic -5 ChemAxon iupac (6aR,10aS)-1-hydroxy-6,6,9-trimethyl-3-pentyl-6H,6aH,7H,8H,10aH-benzo[c]isochromene-4-carboxylic acid ChemAxon average_mass 358.48 ChemAxon mono_mass 358.2144 ChemAxon smiles CCCCCC1=C(C(O)=O)C2=C([C@H]3C=C(C)CC[C@H]3C(C)(C)O2)C(O)=C1 ChemAxon formula C22H30O4 ChemAxon inchi InChI=1S/C22H30O4/c1-5-6-7-8-14-12-17(23)19-15-11-13(2)9-10-16(15)22(3,4)26-20(19)18(14)21(24)25/h11-12,15-16,23H,5-10H2,1-4H3,(H,24,25)/t15-,16+/m0/s1 ChemAxon inchikey VITZNDKHSIWPSR-JKSUJKDBSA-N ChemAxon polar_surface_area 66.76 ChemAxon refractivity 103.99 ChemAxon polarizability 41.13 ChemAxon rotatable_bond_count 5 ChemAxon acceptor_count 4 ChemAxon donor_count 2 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon number_of_rings 3 ChemAxon bioavailability 1 ChemAxon rule_of_five Yes ChemAxon ghose_filter Yes ChemAxon veber_rule Yes ChemAxon mddr_like_rule Yes ChemAxon 163029426 Turner CE, Elsohly MA, Boeren EG: Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J Nat Prod. 1980 Mar-Apr;43(2):169-234. doi: 10.1021/np50008a001. 6991645 Rosenthaler S, Pohn B, Kolmanz C, Huu CN, Krewenka C, Huber A, Kranner B, Rausch WD, Moldzio R: Differences in receptor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures. Neurotoxicol Teratol. 2014 Nov-Dec;46:49-56. doi: 10.1016/j.ntt.2014.09.003. Epub 2014 Oct 12. 25311884 Ahmed SA, Ross SA, Slade D, Radwan MM, Zulfiqar F, Matsumoto RR, Xu YT, Viard E, Speth RC, Karamyan VT, ElSohly MA: Cannabinoid ester constituents from high-potency Cannabis sativa. J Nat Prod. 2008 Apr;71(4):536-42. doi: 10.1021/np070454a. Epub 2008 Feb 28. 18303850 McPartland JM, MacDonald C, Young M, Grant PS, Furkert DP, Glass M: Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. Cannabis Cannabinoid Res. 2017 May 1;2(1):87-95. doi: 10.1089/can.2016.0032. eCollection 2017. 28861508 Verhoeckx KC, Korthout HA, van Meeteren-Kreikamp AP, Ehlert KA, Wang M, van der Greef J, Rodenburg RJ, Witkamp RF: Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways. Int Immunopharmacol. 2006 Apr;6(4):656-65. doi: 10.1016/j.intimp.2005.10.002. Epub 2005 Nov 7. 16504929 Rock EM, Kopstick RL, Limebeer CL, Parker LA: Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus. Br J Pharmacol. 2013 Oct;170(3):641-8. doi: 10.1111/bph.12316. 23889598 Nadal X, Del Rio C, Casano S, Palomares B, Ferreiro-Vera C, Navarrete C, Sanchez-Carnerero C, Cantarero I, Bellido ML, Meyer S, Morello G, Appendino G, Munoz E: Tetrahydrocannabinolic acid is a potent PPARgamma agonist with neuroprotective activity. Br J Pharmacol. 2017 Dec;174(23):4263-4276. doi: 10.1111/bph.14019. Epub 2017 Nov 2. 28853159