Investigating the Role of Serotonin in Visual Orientation Processing Using an ‘Ecstasy’ (MDMA)-Based Research Model

Abstract

Aims/Objectives:A growing body of evidence suggests that regular ‘ecstasy’ (3,4-methylenedioxymethamphetamine) use causes lasting changes to central serotonergic functioning in humans, including in the occipital lobe. Serotonin may play a role in visual orientation processing, mediated in the occipital lobe, via lateral inhibition. The tilt aftereffect is an illusion apparent following adaptation to stimuli angled 5–50° from vertical and thought to be affected by lateral inhibition between occipital neurons. A recent study identified an enhanced tilt aftereffect among ecstasy users, but only in a subset that were recently abstinent from amphetamines. The current study examined the effects of ecstasy use, cannabis use and their interacting effect on the magnitude of the tilt aftereffect among participants with no recent history of amphetamine consumption. Materials and Methods: Eleven ecstasy users, 15 cannabis users, 15 ecstasy plus cannabis users and 15 drug-naïve controls were compared on the magnitude of the tilt aftereffect elicited following adaptation to stimuli angled 15, 30, 40 or 60° from vertical. Results:At a 40° adaptation condition, ecstasy users had a greater magnitude of the tilt aftereffect compared to those that had not taken the drug. Additionally, the extent of ecstasy use was positively associated with the magnitude of the tilt aftereffect generated following 15, 30 and 40° adaptation conditions, but not at 60°. Conclusions:Given that lateral inhibition mediates the tilt aftereffect following adaptation to 5–50°, the findings of a relationship between ecstasy use and tilt magnitude at the 15–40° but not 60° adaptation conditions support a role for serotonin in visual orientation processing via lateral inhibition.

The Role of Serotonin in Low Level Visual Processes, as Revealed by Using an “Ecstasy” (MDMA)-Based Research Model

“…This effect was apparent following an adaptation angle of 40° but not 15°, and was interpreted in terms of lateral inhibition. This finding has been subsequently replicated and extended by Dickson, Bruno and Brown [2], who found the effect at 15°, 30° and 40° but not 60°, and that the magnitude of this effect was related to ecstasy use and was unaffected by cannabis use. In an as yet unpublished study, White, Tran, Brown and Edwards (in preparation) further supported the original theory by showing that the tuning bandwidths of orientation sensitive V1 neurons in ecstasy users were broader than that of non-drug using controls (as determined by a orientation detection masking study).…”

Residual effects of ecstasy (3,4‐methylenedioxymethamphetamine) on low level visual processes

“…Although the current study maintained much stricter inclusion criteria (i.e. minimum lifetime occasions of target drug and amount in the last 6 months) than previous research in the area (Brown et al ., ; Dickson et al ., ), methodologically controlled for the confounding effects of cannabis and amphetamines and statistically controlled for the confounding effects of group differences in other drug use variables, it is still possible that the results may be partially confounded by effects of other substances. Methodological problems also arise in ecstasy studies in estimating the intake of MDMA, based on the reliability of self‐report data and the purity of tablet content.…”

Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans

“…While not previously reported with MDA, there have been previous reports of residual effects of MDMA in the closely related tilt aftereffect [112], [113] as well as evidence of lasting changes in occipital cortex excitability measured with TMS or fMRI [114], [115]. In addition, some MDMA users report persisting visual percepts [116], [117].…”