Parahexyl, also known as synhexyl, is a synthetic homologue of tetrahydrocannabinol (THC) which was invented in 1941 during attempts to elucidate the structure of Δ9-THC, one of the active components of cannabis.[2][3][4]
Parahexyl is similar in both structure and activity to THC, differing only in the position of one double bond and the lengthening of the 3-pentyl chain by one CH2 group to n-hexyl.[5] Parahexyl produces effects typical of other cannabinoid receptor agonists in animals. It has a somewhat higher oral bioavailability than THC itself but is otherwise very similar.[6] Presumably, it acts as a CB1 receptoragonist in the same way as THC, but as there has been no research published using parahexyl since the discovery of the CB1 receptor, this has not been definitively confirmed.
Parahexyl was occasionally used as an anxiolytic in the mid-20th century, the dosage ranging from 5 mg to 90 mg.[7][8]
Parahexyl was made illegal under UN convention in 1971 on the basis of its structural similarity and similar effects profile to THC. Parahexyl was placed into the most restrictive Schedule I[9] as a compound with no medical use.
Isomerism
At least three isomers of parahexyl have been studied and are known to be active as cannabinoids. Parahexyl itself (i.e. the Δ6a(10a) isomer) has not had any significant use in scientific research since it was banned internationally in the early 1980s; however, the Δ8 and Δ9 isomers are both known to be cannabinoid receptor agonists, and Δ8-parahexyl has the code number JWH-124,[10][11] while Δ9-parahexyl has been isolated from Cannabis plant material and assigned the name tetrahydrocannabihexol (THCH).[12]
Dibenzopyran and monoterpenoid numbering of tetrahydrocannabinol derivatives
7 double bond isomers of parahexyl and their 30 stereoisomers
^Adams R, Loewe S, Jelinek C, Wolff H (July 1941). "Tetrahydrocannabinol Homologs with Marihuana Activity. IX1". Journal of the American Chemical Society. 63 (7): 1971–1973. doi:10.1021/ja01852a052.
^Adams R, Harfenist M, Loewe S (1949). "New Analogs of Tetrahydrocannabinol. XIX". Journal of the American Chemical Society. 71 (5): 1624–1628. doi:10.1021/ja01173a023.
^Ono M, Shimamine M, Takahashi K, Inoue T (1974). "[Studies on hallucinogens. VII Synthesis of parahexyl]". Eisei Shikenjo Hokoku. Bulletin of National Institute of Hygienic Sciences (in Japanese). 49 (92): 46–50. PMID4477495.
^Fairchild MD, Jenden DJ, Mickey MR, Yale C (January 1980). "EEG effects of hallucinogens and cannabinoids using sleep-waking behavior as baseline". Pharmacology, Biochemistry, and Behavior. 12 (1): 99–105. doi:10.1016/0091-3057(80)90422-0. PMID6102770. S2CID24865915.
^Supniewski J (1950). Farmakologia. Warsaw: PZWL. p. 89.
^Report of the Technical Committee on Schedules I, II, III and I at the United Nations Conference for the adoption of a Protocol on Psychotropic Substances. 15 February 1971. E/CONF.58/L.47
^Martin BR, Jefferson R, Winckler R, Wiley JL, Huffman JW, Crocker PJ, et al. (September 1999). "Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists". The Journal of Pharmacology and Experimental Therapeutics. 290 (3): 1065–79. PMID10454479.
