Abstract
The pharmacological effects of marihuana in man and animals have been attributed to Δ 1 and Δ 6 tetrahydrocannabinol (THC).
Recently, one of the metabolites of THC, 7-OH-THC, has been reported to have intoxicating properties. A comparative study was carried out on the EEG and behavioral effects of cannabinol, cannabidiol, Δ 6-THC, 7-OH-Δ 6-THC and 7-Acetoxy Δ 6-THC acetate in six chronically implanted rabbits bearing cortical and subcortical leads. Drugs were dissolved in polyethyleneglycol and administered i.v. once every 7 days in a crossover experimental design. 7-OH-Δ 6-THC and 7-Acetoxy-Δ 6THC acetate proved to be at least twice as active as Δ 6-THC in inducing EEG changes (disruption of theta waves, appearance of spikes and waves, blockade of the “arousal” reaction) and behavioral alterations (excitation, exophthalmus, mydriasis, corneal arreflexia, ataxia and swaying). Pretreatment with 1 or 2 mg/kg of reserpine, s.c., did not substantially alter the subjects response to THC.
Amphetamine 2 mg/kg, i.v., in animals pretreated with 2 or 4 mg/kg Δ 6-THC, reverses in part the depression induced by THC.
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References
Agurell, S., Nilsson, I. M., Ohlsson, A., Sandberg, F.: Elimination of tritium-labelled cannabinols in the rat with special reference to the development of tests for the identification of cannabis users. Biochem. Pharmacol. 18, 1195 (1969)
Baran, L., Longo, V. G.: Effects de certains hallucinogènes sur l'électroencéphalogramme et le comportement conditionné du Lapin. Thérapie XX, 591–604 (1965).
Barrat, E., Adams, P.: Paper presented at the symposium on Mood, Behavior and Drugs, A. A. A. S. meeting, Chicago, December 27–28, 1970.
Ben-Zvi, Z., Mechoulam, R., Burstein, S. H.: Identification through synthesis of an active Δ 1(6) tetrahydrocannabinol metabolite. J. Amer. chem. Soc. 92, 3468 (1970).
Bicher, H. I., Mechoulam, R.: Pharmacological effects of two active constituents of marihuana. Arch. int. Pharmacodyn. 172, 24 (1968).
Bose, B. C., Saifi, A. Q., Bhagwat, A. W.: Observations on the pharmacological actions of cannabis indica. Part II. Arch. int. Pharmacodyn. 147, 285 (1964).
Boyd, E. S., Meritt, D. A.: Effects of thiopental and tetrahydrocannabinol derivatives on arousal and recruiting in the cat. J. Pharmacol. exp. Ther. 149, 138 (1965).
Burstein, S. H., Menezes, F., Williamson, E., Mechoulam, R.: Metabolism of Δ 1(6) tetrahydrocannabinol, an active marihuana constituent. Nature (Lond.). 225, 87 (1970).
Christensen, H. D., Freudenthal, R. I., Gidley, J. T., Rosenfeld, R., Boegli, G. Testino, L., Brine, D. R., Pitt, C. G., Wall, M. E.: Activity of Δ 8- and Δ 9-tetrahydrocannabinol and related compounds in the mouse. Science 172, 165 (1971).
Dagirmanjian, R., Hodge, H. C.: Are biogenic amines involved in the mechanism of action of tetrahydrocannabinols? Agents and Actions 1, 46 (1970).
Foltz, R. L., Fentiman, A. F., Jr., Leighty, E. G., Walter, J. L., Drewes, H. R., Schwartz, W. E., Page, T. F., Jr., Truitt, E. B., Jr.: Metabolite of (−)-trans-Δ 8-tetrahydrocannabinol: identification and synthesis. Science 168, 844 (1970).
Garriott, J. C., King, L. J., Forney, R. B., Hughes, F. W.: Effects of some tetrahydrocannabinols on hexobarbital sleeping time and amphetamine induced hyperactivity in mice. Life Sci. 6 (2), 2119 (1967).
Hardman, H. F.: Discussion of the paper: Characteristics of tetrahydrocannabinol tolerance, by McMillan et al. Ann. N.Y. Acad. Sci. 191, 99 (1971).
Hockman, C. H., Perrin, R. G., Kalant, H.: Electroencephalographic and behavioural alterations produced by tetrahydrocannabinol. Science 172, 968 (1971).
Kubena, R.: Discussion of the paper: Characteristics of tetrahydrocannabinol tolerance, by McMillan et al. Ann. N.Y. Acad. Sci. 191, 97 (1971).
Lemberger, L., Silberstein, S., Axelrod, J., Kopin, I. J.: Marihuana: Studies on the disposition and metabolism of delta-9-tetrahydrocannabinol in man. Science 170, 1320 (1970).
Lipparini, F., Scotti de Carolis, A., Longo, V. G.: A neuropharmacological investigation of some trans-tetrahydrocannabinol derivatives. Physiol. Behav. 4, 527 (1969).
Loewe, S.: Marihuana activity of cannabinol. Science 102, (2659), 615 (1945).
Martinez, J. L., Jr., Stadnicki, S. W., Schaeppi, U. H.: Δ 9-tetrahydrocannabinol: Effects of i.v. infusion upon EEG and behavior of unrestrained Rhesus monkeys. Pharmacologist 13, 246 (1971).
Masur, J., Khazan, N.: Induction by cannabis sativa (marihuana) of rhythmic spike discharges overriding REM sleep electrocorticogram in the rat. Life Sci. 9 (1), 1275 (1970).
Mechoulam, R.: Marihuana chemistry. Science 168, 1159 (1970).
Moreton, J. E., Davis, W. M.: Electroencephalographic study of effects of Δ 9- and Δ 8-tetrahydrocannabinol and cannabis extract on sleep in the rat. Pharmacologist 13, 246 (1971).
Nilsson, I. M., Agurell, S., Nilsson, J. L. G., Ohlsson, A., Sandberg, F., Wahlqvist, M.: Δ 1-Tetrahydrocannabinol: structure of a major metabolite. Science 168, 1228 (1970).
Pirch, J. H., Cohn, R. A., Barnes, P. R., Barratt, E. S.: Effects of acute and chronic administration of marijuana extract on the rat electrocorticogram. Neuropharmacol. 11, 231 (1972).
Welch, B. L., Welch, A. S., Messiha, F. S., Berger, H. J.: Rapid depletion of adrenal epinephrine and elevation of telencephalic serotonin by (−) trans-Δ 9-tetrahydrocannabinol in mice. Res. Comm. chem. Path. Pharmacol. 2, 382 (1971).
Willinsky, M. D.: Pharmacological studies on Δ 1 trans-tetrahydrocannabinol. Thesis Ph. D., University of Toronto, Toronto 1971.
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Willinsky, M.D., Scotti de Carolis, A. & Longo, V.G. EEG and behavioral effects of natural, synthetic and biosynthetic cannabinoids. Psychopharmacologia 31, 365–374 (1973). https://doi.org/10.1007/BF00421280
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DOI: https://doi.org/10.1007/BF00421280