THE IMPACT OF SELECTED PSYCHOACTIVE SUBSTANCES - COCAINE, AMPHETAMINE, PSILOCYBIN, MDMA, AND KETAMINE - ON THE BODY IN PHYSICAL AND PSYCHOLOGICAL ASPECTS AND THEIR MAIN MECHANISMS OF ACTION: A NARRATIVE REVIEW

Abstract

The article aims to compare receptor mechanisms related to neurotransmitters for some of the most widely used psychoactive substances - amphetamine, cocaine, ecstasy (MDMA), and psilocybin - and to link these mechanisms to cardiovascular effects, thermoregulation, and neurotoxicity. The review is based mainly on in vitro studies on transporters and receptors, animal models, and controlled clinical trials in humans. Amphetamine is a substrate for NET/DAT and VMAT2, inducing reverse monoamine transport and their release into the synapse, particularly norepinephrine and dopamine, leading to subsequent sympathomimetic effects and oxidative stress. Cocaine acts primarily as an inhibitor of monoamine reuptake via DAT/NET/SERT, with similar affinity for all three, which markedly increases DA/NA/5-HT levels and is associated with a high risk of cardiotoxicity. MDMA combines releasing and reuptake-inhibiting properties, with preference for SERT/NET, producing strong 5-HT efflux and empathogenic effects, but also hyperthermia, cardiovascular disturbances, and, in animal models, persistent serotonergic neurotoxicity involving oxidative stress and glutamate-mediated excitotoxicity. Psilocybin (psilocin) acts mainly as a 5-HT2A agonist, with contributions from 5-HT1A/2C receptors and neurotrophin receptors, promoting neuroplasticity and beneficial behavioral effects with relatively low acute somatic toxicity and moderate, transient hemodynamic changes in healthy volunteers. Overall, although all substances modulate the monoaminergic system, psychostimulants carry substantially higher cardiovascular and neurotoxic risk than psilocybin, which shows a favorable safety profile under controlled conditions.