Psychopharmacological activity of the active constituents of hashish and some related cannabinoids


  1. 1.

    The psychopharmacological activity of Δ 1-tetrahydrocannabinol, (I); Δ 1(6)-tetrahydrocannabinol (4′ hexyl), (II); Δ 1(6)-tetrahydrocannabinol, (III); 1-ethoxyhexahydrocannabinol, (IV); 8-ethoxy-iso-hexahydrocannabinol, (V); Δ 1(6)-tetrahydrocannabinolic acid Me ester, Isomer I, (VI); Δ 1(6)-tetrahydrocannabinolic acid Me ester, Isomer II, (VII); cannabigerol, (VIII); Δ 1(6)-tetrahydrocannabinol (3′ hexyl), (IX); cannabichromene, (X); has been examined in a variety of animal species.

  2. 2.

    Compounds (I) and (III) caused severe motor disturbances and a stuporous state in dogs and ptosis, “tameness” and peculiar postural changes in monkeys. In the latter animal, compound (II) elicited similar effects.

  3. 3.

    Compounds (I) and (III) after intraperitoneal but not subcutaneous administration, suppressed the gerbil digging activity; reduced the rat conditioned avoidance response and induced a cataleptoid reaction in mice, rats and gerbils. In addition, compound (I) reduced the performance of mice on the rotating-rod. Both compounds, administered subcutaneously, induced a measurable ataxic gait in rats.

  4. 4.

    Amphetamine reversed the behavioural changes elicited by compounds (I) and (III) in monkeys, as well as the cataleptoid reaction in rats.

  5. 5.

    None of the other compounds provoked observable changes in any of the species studied.

  6. 6.

    It is suggested that Rhesus monkeys might serve as a suitable model for assessing the psychopharmacological activity of active cannabinoids.

This is a preview of subscription content, access via your institution.


  1. Bovet, D., G. L. Gatti, and M. Frank: An automatic device for the study of conditioned escape reactions in the rat. I. A programming and recording method for establishing learning, retention and deconditioning curves. Sci. Repts. Ist. Super. Sanità 1, 127–138 (1961).

    Google Scholar 

  2. Dunham, N. W., and T. S. Miya: A note on a simple apparatus for detecting neurological deficit in rats and mice. J. Amer. pharm. Ass., sci. Ed. 46, 208 (1957).

    Google Scholar 

  3. Gaoni, Y., and R. Mechoulam: Isolation, structure and partial synthesis of an active constituent of hashish. J. Amer. chem. Soc. 86, 1646 (1964).

    Google Scholar 

  4. — —: Hashish. VI. The isomerization of cannabidiol to tetrahydrocannabinols. Tetrahedron 22, 1481–1488 (1966).

    Article  Google Scholar 

  5. Garattini, S.: Effects of a cannabis extract on gross behaviour. In: Hashish: its chemistry and pharmacology. CIBA Foundation Study Group No. 21, pp. 70–78. Eds.: G. E. W. Wolstenholme and J. Knight. London: J. & A. Churchill 1965.

    Google Scholar 

  6. Garriott, J. C., L. J. King, R. B. Forney, and F. W. Hughes: Effects of some tetrahydrocannabinols on hexobarbital sleeping time and amphetamine induced hyperactivity in mice. Life Sci. 6, 2119–2128 (1967).

    Article  PubMed  Google Scholar 

  7. Grunfeld, Y., and H. Edery: Psychopharmacological activity of some substances extracted from Cannabis sativa L. (Hashish). Abst. Proc. Israel Physiol. Pharmacol. Soc. 16th Scient. Meeting, Jerusalem (1968).

  8. Hively, R. L., W. A. Mosher, and F. W. Hoffmann: Isolation of trans-Δ 6-tetrahydrocannabinol from marijuana. J. Amer. chem. Soc. 88, 1832–1833 (1966).

    Google Scholar 

  9. Hofmann, A.: Psychotomimetic agents. In: Drugs affecting the central nervous system. Medicinal Research, Vol.2, pp. 169–235. Ed.: A. Burger. New York: Dekker 1968.

    Google Scholar 

  10. Isbell, H., C. W. Gorodetzsky, D. Jasinski, U. Claussen, F. V. Spulak, and F. Korte: Effects of (−)-Δ9-trans-tetrahydrocannabinol in man. Psychopharmacologia (Berl.) 11, 184–188 (1967).

    Google Scholar 

  11. Joachimoglu, G.: Natural and smoked hashish. In: Hashish: its chemistry and pharmacology. CIBA Foundation Study Group No. 21, pp. 2–11. Eds.: G. E. W. Wolstenholme and J. Knight. London: J. & A. Churchill 1965.

    Google Scholar 

  12. Kalir, A., D. Baldermann, H. Edery, and G. Porath: 7-methoxyindole and its derivatives. Israel J. Chem. 5, 129–136 (1967).

    Google Scholar 

  13. H. Edery, Z. Pelah, D. Balderman, and G. Porath: 1-phenylcycloalkylamine derivatives. Part II. Synthesis and pharmacological activity. J. med. Chem. (in press) (1969).

  14. Loewe, S.: Pharmacological study. In: The marihuana problem in the city of New York. Mayors Committee on Marihuana, pp. 149–212. Lancaster, Pennsylvania: Jacques Cattell Press 1944.

    Google Scholar 

  15. —: Studies on the pharmacology and acute toxicity of compounds with marihuana activity. J. Pharmacol. exp. Ther. 88, 154–161 (1946).

    Google Scholar 

  16. —: Cannabiswirkstoffe und Pharmakologie der Cannabinole. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 211, 175–193 (1950).

    Google Scholar 

  17. Mechoulam, R., and Y. Gaoni: Recent advances in the chemistry of hashish. Fortschr. Chem. org. Nat.-Stoffe 25, 175–213 (1967).

    Google Scholar 

  18. —, B. Yagnitinsky, and Y. Gaoni: Stereoelectronic factor in the chloranil dehydrogenation of cannabinoids. Total synthesis of dl-cannabichromene. J. Amer. chem. Soc. 90, 2418–2420 (1968).

    Google Scholar 

  19. Naftali, J., and J. Wolf: Notes on breeding experiments with the albino strain of meriones tristrami Thomas 1829. Bull. Res. Coun. Israel 5 B, 189–191 (1955).

    Google Scholar 

  20. Norton, S.: Behavioural patterns as a technique for studying psychotropic drugs. In: Psychotropic drugs, pp. 73–82. Eds.: S. Garattini and V. Ghetti. Amsterdam: Elsevier 1957.

    Google Scholar 

  21. Porath, G., and H. Edery: Psychopharmacological actions and effects on smooth muscle of some substituted indolealkylamines. Proc. Israel Physiol. Pharmacol. Soc. 1, 9 (1965).

    Google Scholar 

  22. Rushton, R., H. Steinberg, and C. Tinson: Effects of a single experience on subsequent reactions to drugs. Brit. J. Pharmacol. 20, 90–105 (1963).

    Google Scholar 

  23. Walton, R. P., L. F. Martin, and J. H. Keller: The relative activity of various purified products obtained from american grown hashish. J. Pharmacol. exp. Ther. 62, 239–251 (1938).

    Google Scholar 

  24. Wolstenholme, G. E. W., and J. Knight: Hashish: its chemistry and pharmacology. CIBA Foundation Study Group No. 21. London: J. & A. Churchill 1965.

    Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Grunfeld, Y., Edery, H. Psychopharmacological activity of the active constituents of hashish and some related cannabinoids. Psychopharmacologia 14, 200–210 (1969).

Download citation


  • Psychopharmacology
  • Hashish
  • Cannabinoids
  • Monkeys Amphetamine