A NEUROPHARMACOLOGICAL INVESTIGATION OF SOME TRANS-TETRAHYDROCANNABINOL DERIVATIVES

A study of the central action of six cannabinoids has been carried out. The compounds studies (see table) were (-)Δ9THC and (-)Δ8THC, the racemic Δ8THC, the α methyl, and α, α dimethyl derivatives of (-)Δ8THC, and (-)cannabidiol. The effects of these drugs have been studied on the cerebral electrical activity and on spontaneous and conditioned behavior of cats, rabbits, and rats with chronically implanted electrodes. In the rabbit and in the rat, (-)Δ9THC, (-)Δ8THC, and the two methylated derivatives of (-)Δ8THC proved to have a similar effect; they induced a flattening of the EEG tracing, the disruption of the theta waves of the hippocampus and they gave rise to trains of high voltage spike-and-waves. These EEG modifications were accompanied by corneal arreflexia and other signs of motor deficit, together with a state of excitation and a reduced response to painful stimuli. The racemic Δ8THC, although provoking the same picture, proved less active. (-)Cannabidiol provoked motor paralysis and corneal arreflexia, these symptoms were accompanied by an EEG synchronization. In the cat, the performance of a conditioned instrumental discrimination exercise was blocked by the administration of 2 mg/kg of Δ9THC; this effect was accompanied by a synchronization of the EEG. These results are discussed also in relation to the human effect of some of these compounds. It is suggested that the flattening of the EEG and the appearance of the spike-and-waves may be the EEG counterpart of the psychodysleptic action of the tetrahydrocannabinols in man. © 1969.