Acute Psychological and Neurophysiological Effects of MDMA in Humans (original) (raw)

3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy"): pharmacology and toxicology in animals and humans

Addiction, 1994

(±)3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”), a ring-substituted amphetamine derivative first synthesized in 1914, has emerged as a popular recreational drug of abuse over the last decade. Pharmacological studies indicate that MDMA produces a mixture of central stimulant and psychedelic effects, many of which appear to be mediated by brain monoamines, particularly serotonin and dopamine. In addition to its pharmacologic actions, MDMA has been found to possess toxic activity toward brain serotonin neurones. Serotonergic neurotoxicity after MDMA has been demonstrated in a variety of experimental animals (including non-human primates). In monkeys, the neurotoxic dose of MDMA closely approaches that used by humans. While the possibility that MDMA is also neurotoxic in humans is under investigation, other adverse effects of MDMA in humans have been documented, including various systemic complications and a number of untoward neuropsychiatric sequelae. Notably, many of the adverse neuropsychiatric consequences noted after MDMA involve behavioral domains putatively influenced by brain serotonin (e.g., mood, cognition and anxiety). Given the restricted status of MDMA use, retrospective clinical observations from suspecting clinicians will probably continue to be a primary source of information regarding MDMA's effects in humans. As such, this article is intended to familiarize the reader with the behavioral pharmacology and toxicology of MDMA, with the hope that improved recognition of MDMA-related syndromes will provide insight into the function of serotonin in the human brain, in health as well as disease.

Psychological and Cardiovascular Effects and Short-Term Sequelae of MDMA (“Ecstasy”) in MDMA-Naïve Healthy Volunteers

Neuropsychopharmacology, 1998

4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a recreational drug reported to produce a different psychological profile than that of classic hallucinogens and stimulants. It has, therefore, been tentatively classified into a novel pharmacological class termed entactogens. This double-blind placebo-controlled study examined the effects of a typical recreational dose of MDMA (1.7 mg/kg) in 13 MDMA-naïve healthy volunteers. MDMA produced an affective state of enhanced mood, well-being, and increased emotional sensitiveness, little anxiety, but no hallucinations or panic reactions. Mild depersonalization and derealization phenomena occurred together with moderate thought disorder, first signs of loss of body control, and alterations in the meaning of percepts. Subjects also displayed changes in the sense of space and time, heightened sensory awareness, and increased psychomotor drive. MDMA did not impair selective attention as measured by the Stroop test. MDMA increased blood pressure moderately, with the exception of one subject who showed a transient hypertensive reaction. This severe increase in blood pressure indicates that the hypertensive effects of MDMA, even at recreational doses, should not be underestimated, particularly in subjects with latent cardiovascular problems. Most frequent acute somatic complaints during the MDMA challenge were jaw clenching, lack of appetite, impaired gait, and restless legs. Adverse sequelae during the following 24 hours included lack of energy and appetite, feelings of restlessness, insomnia, jaw clenching, occasional difficulty concentrating, and brooding. The present findings are consistent with the hypothesis that MDMA produces a different psychological profile than classic hallucinogens or psychostimulants.

Neurochemistry and Neurotoxicity of 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy")

Journal of Neurochemistry, 1990

Methylenedioxymethamphetamine (MDMA; also known as "Ecstasy") is a ring-substituted phenylisopropylamine that is related to both amphetamines and hallucinogens, such as mescaline (Fig. 1). Although the drug was patented in 1914, interest in the compound was minimal until the past decade. During this period, MDMA began to be used as an adjunct to psychotherapy by certain therapists due to its purported ability to induce a state of reduced anxiety and lowered defensiveness (Downing, 1986; Greer and Tolbert, 1986). In addition, the recreational use of MDMA, particularly on college campuses, appears to have increased significantly in recent years (Peroutka, 1987).

MDMA: neurohormonal, neurocognitive, and psychobiological aspects of recreational Ecstasy

Open Addiction …, 2009

This Ecstasy/MDMA symposium was held at the Annual Conference of the Australian Psychological Society, Hobart, Tasmania, in September 2008. The Australian government has been funding research into MDMA for many years, and hence there are several Australian groups at the forefront of international research in this field. Included in the studies reported here, were collaborations with universities from other countries. The main focus was on human studies, although animal psychopharmacology findings were also presented. The topics covered within this half-day symposium included Ecstasy dependence, the problems reported by recreational users, the influence of other psychoactive drugs, the Internet as a research tool, the contributory role of neurohormones such as oxytocin and cortisol, and the energetic stress model for recreational Ecstasy/MDMA.

Recreational 3,4-methylenedioxymethamphetamine or 'ecstasy': Current perspective and future research prospects

Journal of psychopharmacology (Oxford, England), 2017

The purpose of this article is to debate current understandings about the psychobiological effects of recreational 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'), and recommend theoretically-driven topics for future research. Recent empirical findings, especially those from novel topic areas were reviewed. Potential causes for the high variance often found in group findings were also examined. The first empirical reports into psychobiological and psychiatric aspects from the early 1990s concluded that regular users demonstrated some selective psychobiological deficits, for instance worse declarative memory, or heightened depression. More recent research has covered a far wider range of psychobiological functions, and deficits have emerged in aspects of vision, higher cognitive skill, neurohormonal functioning, and foetal developmental outcomes. However, variance levels are often high, indicating that while some recreational users develop problems, others are less affe...

Psychological and Cardiovascular Effects and Short-Term Sequelae of MDMA (“Ecstasy”) in MDMA-Naı̈ve Healthy Volunteers

Neuropsychopharmacology, 1998

3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) is a recreational drug reported to produce a different psychological profile than that of classic hallucinogens and stimulants. It has, therefore, been tentatively classified into a novel pharmacological class termed entactogens. This double-blind placebo-controlled study examined the effects of a typical recreational dose of MDMA (1.7 mg/kg) in 13 MDMA-naı̈ve healthy volunteers. MDMA produced an affective state of enhanced mood, well-being, and increased emotional sensitiveness, little anxiety, but no hallucinations or panic reactions. Mild depersonalization and derealization phenomena occurred together with moderate thought disorder, first signs of loss of body control, and alterations in the meaning of percepts. Subjects also displayed changes in the sense of space and time, heightened sensory awareness, and increased psychomotor drive. MDMA did not impair selective attention as measured by the Stroop test. MDMA increased blood pressure moderately, with the exception of one subject who showed a transient hypertensive reaction. This severe increase in blood pressure indicates that the hypertensive effects of MDMA, even at recreational doses, should not be underestimated, particularly in subjects with latent cardiovascular problems. Most frequent acute somatic complaints during the MDMA challenge were jaw clenching, lack of appetite, impaired gait, and restless legs. Adverse sequelae during the following 24 hours included lack of energy and appetite, feelings of restlessness, insomnia, jaw clenching, occasional difficulty concentrating, and brooding. The present findings are consistent with the hypothesis that MDMA produces a different psychological profile than classic hallucinogens or psychostimulants.

A reconsideration and response to Parrott AC (2013) “Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research”

Human Psychopharmacology: Clinical and Experimental, 2014

Parrott recently published a review of literature on MDMA/ecstasy. This commentary is a response to the content and tenor of his review, which mischaracterizes the literature through misstatement and omission of contrary findings, and fails to address the central controversies in the literature. The review makes several erroneous statements concerning MDMA-assisted psychotherapy, such as incorrect statements about research design and other statements that are baseless or contradicted by the literature. Though it critiques an attempt by other authors to characterize the risks of MDMA, the review fails to produce a competing model of risk assessment, and does not discuss potential benefits. Parrott does not represent an even-handed review of the literature, but instead recites dated misconceptions about neurotoxicity concerns involving the recreational drug ecstasy, which do not relate directly to the use of pure MDMA in a therapeutic setting. Unchallenged, Parrott's report may deter researchers from further investigating an innovative treatment that in early clinical trials has demonstrated lasting benefits for people with chronic, treatment-resistant posttraumatic stress disorder.