The effect of Δ⁹-tetrahydrocannabinol on the conversion of [³H]tryptophan to 5-[³H]hydroxytryptamine in the mouse brain

The effects of a 30-min pretreatment with varying doses of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) on the synthesis of 5-[³H]hydroxytryptamine (5-[³H]HT) from an intravenous 10 min pulse of L-[³H]tryptophan ([³H]try) were measured in the mouse brain. They also determined the effects of Δ⁹-THC on several parameters believed to influence the synthesis of brain 5-HT including total and free plasma tryptophan and the high-affinity synaptosomal uptake of tryptophan. Δ⁹-THC was found to increase the amount of [³H]try accumulated by the brain as well as the amount of 5-[³H]HT synthesized. This effect was greater at intermediate doses than at the highest dose tested. However, Δ⁹-THC was determined to have no effect on the actual rate of conversion of [³H]try into 5-[³H]HT at any dose tested. Δ⁹-THC decreased total plasma tryptophan at low and intermediate doses, but had no effect at the highest dose tested. Synaptosomal uptake of [³H]try was unaffected by pretreatment with Δ⁹-THC at any dose tested. These data suggest that Δ⁹-THC increases the synthesis of 5-HT, not by altering the actual rate of conversion of tryptophan to 5-HT, but by altering, via an unknown mechanism, the quantity of tryptophan available for conversion to 5-HT.