3,4-methylenedioxymethamphetamine (MDMA) is a substituted amphetamine derivative that is widely abused as the street drug “ecstasy”. Despite its high abuse liability, the neuropharmacology of MDMA remains poorly understood. In the present study, functional magnetic resonance imaging (fMRI) was used in fully conscious rhesus monkeys to characterize the neuroactivational effects of MDMA and its...
Serotonin and the hallucinogenic metabolites of tryptamines, dimethylated tryptamines, activate the serotonin 2A receptor (5‐HT2AR), which is implicated in numerous mental health disorders. We have previously demonstrated that the 5‐HT2AR is differentially regulated by βarrestin2 (βarr2) depending upon the agonist; here we utilized βarr2 knockout mice to compare signaling profiles in vivo, by...
MDMA is a widely used amphetamine derivative that increases dopamine and serotonin transmission via its interaction with monoamine transporters. Compared to other psychostimulants, little is known about the long‐term neurobehavioral effects of MDMA. We conducted a series of studies aimed at elucidating the effects of MDMA administration on behavior, limbic cortico‐striatal neuronal structure,...
Pursuant to the Controlled Substances Act (CSA), DEA collects and reviews scientific, medical and other data for substances with abuse potential for possible placement under the CSA. The administrative process for scheduling is ongoing for indiplon, carisoprodol, dextromethorphan, salvinorin A and several petitions requesting a change in the control status of nabilone, methylphenidate product,...
The FASEB JournalApril 1, 2009Helmut B Gottlieb, Lisa Ji, JT Cunningham
One of active ingredients of Salvia divinorum , Salvinorin A (Sal A), has been shown to be a kappa opioid receptor agonist. The activation of central kappa opioid systems markedly affects renal function (water diuresis) in a manner that is different from any clinically used diuretic to date. The cardiovascular and renal effects produced by central administration of Salvinorin A are yet to be...
PURPOSE: Characterization of the binding sites for ibogaine analogs on the nicotinic acetylcholine receptor (AChR) in the resting and desensitized states. METHODS: [ 3 H]18‐methoxycoronaridine ([ 3 H]18‐MC) Scatchard‐plots using Torpedo AChR membranes, [ 3 H]TCP (a well characterized noncompetitive antagonist) competition binding experiments and Schild‐type analysis, analog‐induced binding...
3,4‐Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative with increasingly widespread abuse. MDMA has been difficult to classify as a stimulant or hallucinogen because it shares effects with both drug classes. Furthermore, racemic MDMA is composed of two isomers that vary in terms of behavioral effects rather than simple potency differences. Specifically, the R(−) isomer of MDMA...
The plant hallucinogen N,N ‐dimethyltryptamine (DMT) has been used for religious and other purposes for many centuries. Over the past few decades, DMT has been reported in human brain, and pharmacological studies have shown that DMT binds to monoamine receptors. Recently, several N,N ‐dialkyltryptamines were reported to modify monoamine uptake and release in rat brain synaptosomes, indicating...
We recently showed that the up-regulation of the glial cell line-derived neurotrophic factor (GDNF) pathway in the midbrain, is the molecular mechanism by which the putative anti-addiction drug Ibogaine mediates its desirable action of reducing alcohol consumption. Human reports and studies in rodents have shown that a single administration of Ibogaine results in a long-lasting reduction of...
The human serotonin 2A receptor (h5‐HT 2A R) plays an essential role in cognition, and is the principal target for serotonergic hallucinogens as well as atypical antipsychotics. Utilizing our in silico ‐activated h5‐HT 2A R homology model, an interaction was predicted between Asn343(6.55) in TM6 and the carbonyl of LSD. Virtual docking simulations of a new class of 5‐HT2 agonists, substituted N...
Schizophrenia is a severe psychiatric disorder whose etiology is unknown; however, disruptions in glutamatergic and dopaminergic transmission may play a role. The NMDAR antagonist, phencyclidine (PCP), has been shown to mimic both the positive and negative symptoms of the disease and is widely used in animal studies as a model of schizophrenia. PCP administration results in increased locomotor...
ABSTRACT 3,4‐Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular drug of abuse. MDMA is pharmacologically classified as an entactogen because of its affinities to classical hallucinogens and stimulants. Oral ingestion of a single dose of the drug is associated with euphoria, elevated self‐confidence, and heightened sensory awareness in humans. Evidence for neurotoxicity in the human...
The widely abused amphetamine analog 3,4‐methylenecdioxymethamphetamine (MDMA, also called “ecstasy”) induces hallucination and psychostimulation, as well as long‐term neuropsychiatric behaviors such as panic and psychosis. In rodents and monkeys, MDMA is cytotoxic to serotonergic neurons, but this is less clear with humans. Herein, MDMA was cytotoxic to human serotonergic JAR cells; it altered...