Acute Effects of 2C-E in Humans: An Observational Study.

Esther Papaseit,Johannes G Ramaekers,Magí Farré,Clara Pérez-Mañá,Marc Grifell,Mireia Ventura,Elizabeth B De Sousa Fernandes Perna,Eulalia Olesti,Rafael De La Torre,Oscar J Pozo,Marta Torrens

doi:10.3389/fphar.2020.00233

Abstract

2,5-Dimethoxy-4-ethylphenethylamine (2C-E) is psychedelic phenylethylamine, with a chemical structure similar to mescaline, used as new psychoactive substance (NPS). It inhibits norepinephrine and serotonin uptake and, more relevant, acts as a partial agonist of the serotonin 2A (5-HT2A), 2B (5-HT2B), and (5-HT2C) receptors. Consumers have reported that 2C-E induces mild-moderate psychedelic effects, but its pharmacology in humans, including pharmacological effects and pharmacokinetics, have not yet studied. To assess the acute effects of 2C-E on physiological and subjective effects and evaluate its pharmacokinetics, an observational study was carried-out. Ten recreational users of psychedelics self-administered a single oral dose of 2C-E (6.5, 8, 10, 15, or 25 mg). Blood pressure and heart rate were evaluated at baseline, 2, 4, and 6 h post-administration. Three rating scales were administered to evaluate subjective effects: a set of Visual Analog Scales (VAS), the 49-item short form version of the Addiction Research Centre Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 2, 4, and 6 h after self-administration. To assess 2C-E concentrations oral fluid (saliva) was collected during 6 h. 2C-E induced primarily alterations in perceptions, hallucinations, and euphoric-mood. Saliva maximal concentrations were achieved 2 h after self-administration. Administration of oral 2C-E at recreational doses produces a group of psychedelic-like effects such to 2C-B and other serotonin-acting drugs.

Highlights

Classical psychedelics have traditionally been defined as a class of psychoactive substances that induce in humans a wide range of complex physiological, behavioral and psychological effects through serotonin 5-HT2A receptors stimulation (Nichols, 2016)
In the past few years, phenethylamine psychedelics have emerged as a class of new psychoactive substances (NPS) able to induce similar effects to those of controlled psychedelic substances (Vollenweider, 2001; Aarde and Taffe, 2017). 2C-compounds (2C-s) are ringsubstituted phenylethylamines derived from the modification of the mescaline structure with two methoxy groups on the benzene ring (2nd and 5th positions) (Tracy et al, 2017)
Synthesized in 1977 by Alexander Shulgin it is one of the most potent 2C-compounds (Shulgin and Shulgin, 1990). 2C-E is structurally very closely related to other 2C-s and to other well-studied phenethylamine substitutes such as mescaline and MDMA. It first came out the club scene in the mid-1980s as a quick replacement for MDMA which had been banned in the United States. 2C-E remerged on the psychedelic scene and lately has been present as part of the NPS phenomenon

Summary

Introduction

Classical psychedelics (serotonergic psychedelics) have traditionally been defined as a class of psychoactive substances that induce in humans a wide range of complex physiological, behavioral and psychological effects through serotonin 5-HT2A receptors stimulation (Nichols, 2016). 2C-compounds (2C-s) are ringsubstituted phenylethylamines derived from the modification of the mescaline structure with two methoxy groups on the benzene ring (2nd and 5th positions) (Tracy et al, 2017). They are widely considered a family of substances with hallucinogenic/psychedelic and psychostimulant properties, information available on their pharmacology and toxicology in humans is very limited. 2C-E is structurally very closely related to other 2C-s and to other well-studied phenethylamine substitutes such as mescaline and MDMA (ecstasy) It first came out the club scene in the mid-1980s as a quick replacement for MDMA which had been banned in the United States. 2C-E has been documented as being contained in pills sold as ecstasy in America and Europe (United Nations Office on Drugs and Crime [UNODC], 2014), and more recently in Colombia and other Latin American countries, where it is considered an NPS due to its new presence on the drug market (Observatorio de Drogas de Colombia [ODC], 2017)

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