Δ⁹-Tetrahydrocannabinol decreases turnover of brain histamine

Histamine (HA) is a neurotransmitter present in the brain. As there is little information on the effect of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) on brain histaminergic activity, the possible Δ⁹-THC-induced changes in brain HA turnover were studied in rats and mice. Whereas various doses of Δ⁹-THC had no influence on the brain HA levels in these species, high doses of Δ⁹-THC reduced the content of tele-methylhistamine (t-MH), a predominant HA metabolite in the brain, in mice. A moderate dose of Δ⁹-THC was effective in decreasing the brain t-MH content in the rats. Pargyline (65 mg/kg i.p.) caused a 101 ng/g accumulation of t-MH in mice and an 80 ng/g accumulation of t-MH in rats 105 min after the injection. Δ⁹-THC significantly suppressed the pargyline-induced t-MH accumulation at 50 mg/kg in mice whereas only 2 mg/kg of this compound was effective in rats, when administered i.v. 15 min after pargyline treatment. Δ⁹-THC (50 mg/kg i.v.) delayed the depletion of neuronal HA in the mouse brain, as induced by treatment with a specific histidine decarboxylase inhibitor α-fluoromethylhistidine (50 mg/kg i.p.). Δ⁹-THC (30 and 100 μM) significantly inhibited the K⁺-induced release of endogenous HA from guinea-pig hypothalamic slices. These results suggest that Δ⁹-THC decreases HA turnover in the brain.