Stimulant and hallucinogenic novel psychoactive substances; an update

The renewed interest in considering a range of stimulants, psychedelics and dissociatives as therapeutics emphasizes the need to draft an updated overview of these drugs' clinical and pharmacological issues.

The focus here was on: stimulants (e.g. amphetamines, methamphetamine, and pseudoephedrine; phenethylamines; synthetic cathinones; benzofurans; piperazines; aminoindanes; aminorex derivatives; phenmetrazine derivatives; phenidates); classical (e.g. ergolines; tryptamines; psychedelic phenethylamines), and atypical (e.g. PCP/ketamine-like dissociatives) psychedelics.Stimulant and psychedelics are associated with: a) increased central DA levels (psychedelic phenethylamines, synthetic cathinones and stimulants); b) 5-HT receptor subtypes' activation (psychedelic phenethylamines; recent tryptamine and lysergamide derivatives); and c) antagonist activity at NMDA receptors, (phencyclidine-like dissociatives).

Clinicians should be regularly informed about the range of NPS and their medical, psychobiological and psychopathological risks both in the acute and long term. Future research should focus on an integrative model in which pro-drug websites' analyses are combined with advanced research approaches, including computational chemistry studies so that in vitro and in vivo preclinical studies of index novel psychoactives can be organized. The future of psychedelic research should focus on identifying robust study designs to convincingly assess the potential therapeutic benefits of psychedelics, molecules likely to present with limited dependence liability levels.