2-Phenylethylamine as a possible mediator for Δ⁹-tetrahydrocannabinol-induced stimulation

Abstract

IF neuroamines modulate perception and affect, as implied in much of the literature, the behavioural effects of marihuana may be mediated by alterations of brain amine mechanisms, Even in large doses (5–500 mg kg⁻¹), Δ⁹-tetra-hydrocannabinol (Δ⁹-THC) produces only relatively small changes in the brain levels and turnover of serotonin^1–3, catecholamines^2–4 and acetylcholine⁵. We report here biochemical and behavioural experiments suggesting a role for endogenous 2-phenylethylamine (PEA) in the action of Δ⁹-THC. PEA may be one of the neuromodulators involved in wakefulness, arousal and excitement^6,7, and it is the precursor of phenylethanolamine, a putative neurotransmitter⁸. PEA is present in human⁸ and animal⁹ brain; monoamine oxidase B plays a major role in the metabolism of PEA whereas monoamine oxidase A is responsible for the deamination of noradrenaline and serotonin¹⁰. The observations that the urinary excretion of PEA is decreased in patients with endogenous depression^11–13 and that in animals brain levels of PEA are increased by antidepressive treatments [monoamine oxidase inhibitors (MAOIs), imipramine, electroshock^7,9,14] suggest that this amine is important in modulating affect.