Halogenated derivatives of amphetamine-type stimulants are appearing on the drug market, often with altered pharmacological profile and sometimes different legal status compared to the non-halogenated substances. The aim of the present study was to investigate the pharmacological profile and hepatocellular toxicity of para-halogenated amphetamines and cathinones. The potential of amphetamine,...
NBOMes are N-benzylmethoxy derivatives of the 2C family hallucinogens. 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is one of the commonly used illicit drugs. It exhibits high binding affinity for 5-HT 2A/C and 5-HT 1A serotonin receptors. Activation of 5-HT 2A receptor induces head-twitch response (HTR) in rodents, a behavioral marker of hallucinogen effect in humans....
The serotonin transporter (SERT), a member of the neurotransmitter:sodium symporter family, is responsible for termination of serotonergic signaling by re-uptake of serotonin (5-HT) into the presynaptic neuron. Its key role in synaptic transmission makes it a major drug target, e.g. for the treatment of depression, anxiety and post-traumatic stress. Here, we apply hydrogen-deuterium exchange...
The disruption of the serotonergic (5HT) system has been implicated in causing major depression and the standard view is that a lack of serotonin is to blame for the resulting symptoms. Consequently, pharmacological interventions aim to increase serotonin concentration in its target areas or stimulating excitatory 5HT receptors. A standard approach is to use serotonin reuptake inhibitors...
One of the main limitations of pharmacological fMRI is its inability to provide a molecular insight into the main effect of compounds, leaving an open question about the relationship between drug effects and haemodynamic response. The aim of this study is to investigate the acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on functional connectivity (FC) using a novel multimodal method...
The FASEB JournalApril 1, 2019Melodi Ann Bowman, Melissa Vitela, W. Anthony Owens et al.
Twenty percent of adults are diagnosed with major depressive disorder, which is typically treated with selective serotonin reuptake inhibitors (SSRIs). However, SSRIs take approximately six weeks to produce therapeutic effects. Recently, low doses of ketamine, a noncompetitive N‐methyl‐ D‐aspartate (NMDA) receptor antagonist, have been shown to produce rapid and long‐lasting antidepressant...
The prefrontal cortex (PFC) plays a key role in many high-level cognitive processes. It is densely innervated by serotonergic neurons originating from the dorsal and median raphe nuclei, which profoundly influence PFC activity. Among the 5-HT receptors abundantly expressed in PFC, 5-HT2A receptors located in dendrites of layer V pyramidal neurons control neuronal excitability and mediate the...
Given the recent resurgence of clinical interest in the application of classical serotonergic psychedelics as treatment for various disease states, a comprehensive analysis of the structure‐activity relationship (SAR) is necessary to fully understand the differential expression of behavioral and physiological effects elicited by these compounds. While the field is mostly focused on action...
Serotonin, one of the first neurotransmitters to be identified, is an evolutionarily old molecule that is highly conserved across the animal kingdom, and widely used throughout the brain. Despite this, ascribing a specific set of functions to brain serotonin and its receptors has been difficult and controversial. The 2A subtype of serotonin receptors (5-HT2A receptor) is the major excitatory...
RationaleDepressive syndrome or depression is a debilitating brain disorder affecting numerous people worldwide. Although readily available, current antidepressants have low remission rates and late onset times. Recently, N-methyl-D-aspartate (NMDA) receptor antagonists, like ketamine and methoxetamine (MXE), were found to elicit rapid antidepressant effects. As the search for...
The original version of this article contained an error in the labelling of Figures 2 and 3. While the captions and figures themselves are correct, in order to correspond with the in-text references, they have now been re-numbered in both the PDF and HTML versions of the article.
BMJ Case ReportsMarch 7, 2019Geoffrey Peter Ronan, Nicola Ronan, Siobhan Mcgettigan et al.4 citations
A 26-year-old cachectic man presented with an altered mental status. He was agitated, tremulous, hyperthermic and diaphoretic with largely dilated pupils. Collateral history revealed acute ingestion of 3,4-methylenedioxymethamphetamine on a background of chronic drug abuse. His condition deteriorated requiring sedation and intubation with transfer to the intensive care unit. A diagnosis of...
Graphical abstract Figure. No Caption available. Abstract The 3,4‐methylenedioxymethamphetamine (MDMA) is a popular recreational drug, which ultimately leads to serotonergic (5‐HT) neurotoxicity and psychiatric disorders. Previous in vitro studies have consistently demonstrated that MDMA provokes autophagic activation, as well as damage of 5‐HT axons and nerve fibers. So far, whether autophagy,...
The entactogen MDMA (3,4-methylenedioxy-methamphetamine, “Ecstasy”) exerts its psychotropic effects acting primarily as a substrate of the serotonin transporter (SERT) to induce a non-exocytotic release of serotonin. Nevertheless, the roles of specific positions of the aromatic ring of MDMA associated with the modulation of typical entactogenic effects, using analogs derived from the MDMA...
Background: Recent studies have suggested therapeutic benefits of psychedelics for a variety of mental health conditions. The understanding of how single psychedelic administrations can induce long-lasting effects are, in large, still lacking. However, recent studies in both healthy and clinical populations suggest a role for personality changes. Aim: To test support for some of these plausible...
Background There is evidence that mGlu2/3 receptors regulate 5-HT_2A signaling, interactions that have been theorized to play a role in the antipsychotic-like effects of mGlu2/3 agonists as well as the hallucinogenic effects of 5-HT_2A agonists. One approach to unraveling this interaction is through the chronic administration of agonists at the two receptors, which should influence the...
5-Methoxy-α-methyltryptamine (5-MeO-AMT) is a tryptamine derivative that is used recreationally because of its reported hallucinogenic and mood elevating effects. Studies suggest that the psychopharmacological effects of tryptamines involve serotonin receptor 2a (5-HTR2a) activation in the brain. The head-twitch response (HTR) is widely used as a behavioral correlate for assessing 5-HTR2a...
The main psychedelic component of magic mushrooms is psilocybin, which shows promise as a treatment for depression and other mental disorders. Psychedelic effects are believed to emerge through stimulation of serotonin 2A receptors (5-HT2ARs) by psilocybin's active metabolite, psilocin. We here report for the first time the relationship between intensity of psychedelic effects, cerebral 5-HT2AR...
Abstract Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers in-vestigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of...
Abstract Recent research found lasting increases in personality trait Openness in healthy individuals and patients after administration of the serotonin 2A receptor (5‐HT 2A R) agonist psilocybin. However, no studies have investigated whether 5‐HT 2A R availability as imaged using positron emission tomography (PET) is associated with this trait. In 159 healthy individuals (53 females), the...