Effect of cannabinoids on neurotransmitter uptake, atpase activity and morphology of mouse brain synaptosomes

Abstract

Δ 1-Tetrahydrocannabinol (Δ 1-THC) and cannabidiol (CBD), a psychoactive and a nonpsychoactive constituent of marijuana respectively, inhibit the uptake of 3H-labelled norepinephrine (NE), dopamine (DA), γ-aminobutyric acid (GABA) and serotonin (5-HT), by mouse brain synaptosomes. CBD is more effective than Δ 1-THC in the inhibition of neurotransmitter uptake. At 5 × 10 −5 M both CBD and Δ 1-THC inhibit uptake by 60–100%. The one exception to the above is the differential effect of Δ 1-THC and CBD on 5-HT uptake. At 10 −6 M of Δ 1-THC the uptake is twice that of the control value and at 5 × 10 −5 M uptake is still equal to control value. At the former concentration CBD has no effect on 5-HT uptake whereas at the latter concentration a 50 per cent inhibition is observed. Both Δ 1-THC and CBD inhibit Na +-K +-ATPase and Mg-ATPase activities; at 5 × 10 −5 M inhibition amounts to 40 per cent. Electron microscopy reveals that synaptosomal preparations are highly damaged at 5 × 10 −5 M. Thus inhibition of uptake could stem from either failure of ATPase activity, from disruption of synaptosomes, or from both.