Editorial: Pharmacology of new psychoactive substances

Abstract

Pharmacology of new psychoactive substancesSeveral classes of novel psychoactive substances have been introduced in illicit markets throughout the world and more are being developed.They present major law enforcement challenges and global public health threats.However, there is limited information on their harmful effects on the central nervous, cardiovascular, respiratory, and gastrointestinal systems.In particular, some phenethylamine derivatives are very potent psychedelic substances and may exert toxic effects at very low doses.Vorovbyeva and Kozlova reviewed three natural psychedelic drugs, psilocybin, ibogaine and N, N-dimethyltryptamine (DMT), in terms of their pharmacological properties and their therapeutic potential.Psilocybin primarily produces its psychedelic effects by acting as a partial agonist at serotonin 2A (5-HT2Ar), whereas DMT acts at a number of serotonin receptor subtypes.Ibogaine has a complicated pharmacology, interacting with a number of different neurotransmitter systems, including N-methyl-D-aspartate receptors, kappa-and mu-opioid receptors, sigma-2 receptors and nicotinic cholinergic receptors.Both psilocybin and DMT are relatively safe in humans, but ibogaine can decrease heart rate and cause lifethreatening cardiac arrhythmias.All three drugs have shown some efficacy in the treatment of anxiety, depression and substance use disorders, but further evidence of safety and efficacy should be obtained.Syrová et al. report the pharmacokinetics and acute behavioural effects of 2C-B-Fly-NBOMe, an analog of popular psychedelic entactogen 2C-B (4-Bromo-2,5dimethoxyphenethylamine), in male adult Wistar rats.Pharmacokinetic data revealed a serum peak concentration at 30 and a brain peak level at 60 min.The compound suppressed locomotor activity and, at a higher dose (5 mg/kg) caused prepulse inhibition, suggesting that it attenuates sensorimotor gating.It is well-known that some 4-substituted analogs of 1-(2,5-dimethoxyphenyl) isopropylamine (2,5-DMA) are serotonergic psychedelic agents that behave as agonists of the human serotonin 5-HT 2A (h5-HT2A) receptor and produce sideeffects such as cardiac vulvulopathy via activation of h5-HT2B receptor.Hemanth et al. demonstrate rat and human 5-HT2A receptor binding data can be utilized for the estimation of affinity, but not the functional activity of phenylisopropylamines for h5-HT2B receptors.In fact, the authors demonstrate that both h5-HT2A and h5-HT 2B receptor affinities for 13 tested analogs of 2,5-DMA parallel their rat 5-HT 2A and 5-HT2B receptor affinities.The rat 5-HT 2 receptor affinity was also related with the increased lipophilicity and electron withdrawing nature of the 4-position substituents of 2,5-DMA.Likewise, the latter properties correlate with their interactions at h5-HT2A and h5-HT2B receptors.In