MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor

Abstract

Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol), which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg), combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg). Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS) 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations). Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA.

A First-in-Man Study with 4-Fluoroamphetamine Demonstrates it Produces a Mild Psychedelic State

“…While the subjective experience after 4-FA was rated substantially higher than placebo one hour after intake, these ratings decreased in a linear fashion over time. The ratings of depersonalization and derealization during the peak experience were comparable to those previously assessed after administration of MDMA (75-100 mg) and cocaine (300 mg) (Puxty et al 2017;van Heugten-Van der Kloet et al 2015;van Wel et al 2015), though lower than those of after ketamine (0.5 mg/kg, IV) (Krystal, Karper, and Seibyl et al 1994). While the 5D-ASC assesses the subjective experience of depersonalization and derealization in combination, these two concepts are assessed separately by the B-VAS and CADSS.…”

“…While hallucinations only seldom occur, amphetamine (10-20 mg) and MDMA (75-125 mg) have been shown to induce alterations in mood, perception, thinking, body awareness, and self-control as demonstrated on the hallucinogenic rating scale (HRS) (Johanson et al 2006), and the clinician-administered dissociative rating scale in the case of MDMA (Puxty et al 2017;van Heugten-Van der Kloet et al 2015). The change in consciousness produced by both substances seemed to be comparable, affecting the rating scales in the same direction, as shown by a discrimination study, with the most pronounced effects for MDMA (1.5 mg/kg) and smaller effects for d-amphetamine (20 mg) (Johanson et al 2006).…”

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

“…Results differ in intensity from other psychedelics probably because in this study subjects self-administered low to moderate doses of the substance. Additionally, 2C-E produced higher increases in sociability (VESPA SOC subscale) and augmented ratings on change perceptions, effects widely related to MDMA and LSD (Papaseit et al, 2016;Dolder et al, 2017;Puxty et al, 2017). Overall, the subjective effects induced by 2C-E appear to be closely related to psychedelic drugs indicating that it produces mind-altering and hallucinogenic effects which could be primarily mediated by the 5HT 2A receptor.…”

‘I Get High With a Little Help From My Friends’ - How Raves Can Invoke Identity Fusion and Lasting Co-operation via Transformative Experiences

“…Often classed as an ‘empathogen’, rather than a psychedelic, it is more popular though less associated with ‘mystical’ experiences ( Lyvers and Meester, 2012 ). The altered state of consciousness associated with MDMA does not appear to be associated with the 5-HT 2 A receptor ( Puxty et al, 2017 ). Instead, increased heart rate associated with a moderate dose of MDMA in clinical settings has been associated with disassociation.…”