Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signalling
Swiss Medical Weekly January 11, 2015 Matthias Liechti 188 citations
Novel psychoactive substances, often sold as 'legal highs' or 'research chemicals', pose health risks similar to classic illicit drugs. They are chemically diverse, including phenethylamines, synthetic cathinones, and tryptamines, and act on monoamine neurotransmitter systems. Stimulants like pipradrols and pyrovalerone cathinones block dopamine and noradrenaline reuptake, while entactogens such as MDMA-like cathinones enhance serotonin release. Hallucinogens, including tryptamines, directly activate 5-HT2A serotonin receptors. Synthetic cannabinoids act on CB1 receptors like THC. The ratio of serotonergic to dopaminergic activity helps predict a substance's psychotropic effects, toxicity, and addiction potential. Most poisonings are mild to moderate, but serotonergic drugs can cause serotonin syndrome, hyperthermia, and seizures; dopaminergic drugs are highly addictive and linked to psychosis; synthetic cannabinoids may cause agitation, hypertension, and renal failure. Treatment is supportive.