Nature 226, 1265 - 1267 (27 June 1970); doi:10.1038/2261265a0

Pharmacology of some Marijuana Constituents and Two Heterocyclic Analogues

WILLIAM L. DEWEY^*, LOUIS S. HARRIS^*, JOHN F. HOWES^*, J. STEPHEN KENNEDY^*, FELIX E. GRANCHELLI^†, HARRY G. PARS^† & RAJ K. RAZDAN^†

^*Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27514.
^†Arthur D. Little, Inc., Acorn Park, Cambridge, Massachusetts 02140.

THERE have been few reports concerning the chemistry and pharmacology of marijuana and its constituents^1,2, and most investigators have studied the natural product or a crude extract. Mechoulam and co-workers³ isolated ⁹-tetrahydrocannabinol, which is believed to be the most active constituent of marijuana and has been shown to have marijuana-like activity in man⁴. Subsequently, ⁸-tetrahydrocannabinol was purified and now both isomers have been prepared synthetically and are available in small quantities for pharmacological experimentation. These substances are somewhat unique in that there are few agents which have such a profound effect on the central nervous system yet do not contain either a sulphur or nitrogen atom in the molecule. We report here some preliminary pharmacological results with pure synthetic ⁸ and ⁹-tetrahydrocannabinol (⁹-THC), and also describe the effect of the insertion of a heterocyclic atom in ring C on the pharmacology of these agents. The nitrogen analogue of ⁹-THC (I in Fig. 1) was synthesized by Pars and co-workers⁵ and the sulphur analogue (II) by R. K. R. (unpublished data).

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