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Journal ArticleDOI

Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens.

01 Oct 1986-Journal of Psychoactive Drugs (Taylor & Francis Group)-Vol. 18, Iss: 4, pp 305-313
TL;DR: The widc,pre of psychedelic drug • ,>uch a Iy t:rgic acid dit:lh) IJmide (LSD), dunng Ihe 1960's and 1970' led 10 ev re reaclion by govern menIal agencies and pro criplion~ a '.lin~1 Iheir u e.
Abstract: (1986). Differences Between the Mechanism of Action of MDMA, MBDB, and the Classic Hallucinogens. Identification of a New Therapeutic Class: Entactogens. Journal of Psychoactive Drugs: Vol. 18, MDMA: Proceedings of the Conference, pp. 305-313.
Citations
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Journal Article
TL;DR: The available evidence does not yet permit an accurate assessment of the size of the problem presented by the use of these drugs, but a detailed review of the literature has revealed over 87 "ecstasy"-related fatalities.
Abstract: "Ecstasy" (MDMA) and related drugs are amphetamine derivatives that also have some of the pharmacological properties of mescaline. They have become popular with participants in "raves," because they enhance energy, endurance, sociability and sexual arousal. This vogue among teenagers and young adults, together with the widespread belief that "ecstasy" is a safe drug, has led to a thriving illicit traffic in it. But these drugs also have serious toxic effects, both acute and chronic, that resemble those previously seen with other amphetamines and are caused by an excess of the same sympathomimetic actions for which the drugs are valued by the users. Neurotoxicity to the serotonergic system in the brain can also cause permanent physical and psychiatric problems. A detailed review of the literature has revealed over 87 "ecstasy"-related fatalities, caused by hyperpyrexia, rhabdomyolysis, intravascular coagulopathy, hepatic necrosis, cardiac arrhythmias, cerebrovascular accidents, and drug-related accidents or suicide. The toxic or even fatal dose range overlaps the range of recreational dosage. The available evidence does not yet permit an accurate assessment of the size of the problem presented by the use of these drugs.

562 citations

Journal ArticleDOI
TL;DR: The results establish that MDA and MDMA produce structural damage to 5-HT axon terminals followed by lasting denervation of the forebrain, and the selective degeneration of 5- HT axons indicates that these drugs may serve as experimental tools to analyze the organization and function of5-HT projections.
Abstract: The psychotropic amphetamine derivatives 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) have been used for recreational and therapeutic purposes in man. In rats, these drugs cause large reductions in brain levels of serotonin (5-HT). This study employs immunocytochemistry to characterize the neurotoxic effects of these compounds upon monoaminergic neurons in the rat brain. Two weeks after systemic administration of MDA or MDMA (20 mg/kg, s.c., twice daily for 4 d), there is profound loss of serotonergic (5-HT) axons throughout the forebrain; catecholamine axons are completely spared. Regional differences in drug toxicity are exemplified by partial sparing of 5-HT axons in hippocampus, lateral hypothalamus, basal forebrain, and in some areas of neocortex. The terminals of 5-HT axons are selectively ablated, while axons of passage and raphe cell bodies are spared. Thickened preterminal fibers exhibit increased staining due to damming-up of neurotransmitter and other axonal constituents. Fine 5- HT axon terminals are extremely vulnerable to these drugs, whereas terminal-like axons with large varicosities survive, raising the possibility that some 5-HT axons may be resistant to the neurotoxic effects. At short survivals, visualization of greatly swollen, fragmented 5-HT axons provides anatomic evidence for degeneration of 5- HT projections. The results establish that MDA and MDMA produce structural damage to 5-HT axon terminals followed by lasting denervation of the forebrain. Both drugs have similar effects, but MDA produces a greater reduction of 5-HT axons than does MDMA at the same dosage. The selective degeneration of 5-HT axons indicates that these drugs may serve as experimental tools to analyze the organization and function of 5-HT projections. Caution should be exercised until further studies determine whether these compounds may be hazardous in man.

538 citations

Journal ArticleDOI
TL;DR: The research revealed that Ecstasy is primarily used by infrequent recreational drug users for 'fun' at dance parties and social gatherings and tolerance was reported to develop to the positive effects of Ecstasy, while negative effects increased with use.
Abstract: 'Ecstasy' (3,4-methylenedioxymethamphetamine or MDMA) is a recreational drug that is gaining popularity world wide. There is a paucity of research regarding the ways in which Ecstasy is used and the nature of its effects. A 'snowball' peer network technique was used to recruit 100 users who completed anonymous questionnaires. The research revealed that Ecstasy is primarily used by infrequent recreational drug users for 'fun' at dance parties and social gatherings. The primary reported effects of Ecstasy were a 'positive mood state' and feelings of intimacy and closeness to others. The secondary effects of Ecstasy were the stimulant effects of energy and activation, and the psychedelic effects of insight and perceptual and sensual enhancement. Ecstasy was reported to share the properties of both amphetamines and hallucinogens in the nature of its side effects and residual effects which were no more severe than those of the latter two classes of drug. It appeared Ecstasy was not conductive to regular and frequent use, because tolerance was reported to develop to the positive effects of Ecstasy, while negative effects increased with use. Although few problems associated with the recreational use of Ecstasy have surfaced to date, animal research has shown it to be neurotoxic to serotonergic nerve terminals. Caution must be observed until further research can determine the level of hazard in humans.

421 citations

Journal ArticleDOI
TL;DR: The present findings are consistent with the hypothesis that MDMA produces a different psychological profile than classic hallucinogens or psychostimulants.

398 citations


Cites background or result from "Differences between the mechanism o..."

  • ...…and Nichols reported that MDMA produces an “easily controlled altered state of consciousness with emotional and sensual overtones” and suggested that MDMA might be useful as an adjunct in insightoriented psychotherapy (Greer 1985; Downing 1986; Greer and Tolbert 1986; Nichols 1986; Shulgin 1986)....

    [...]

  • ...Hence, the present findings provide further support for the view that MDMA and MDE may constitute a new class of psychoactive substances (Nichols 1986)....

    [...]

Journal ArticleDOI
TL;DR: The lack of linearity of MDMA pharmacokinetics (in a window of doses compatible with its recreational use) is a more general phenomenon as it concerns the whole population independent of their CYP2D6 genotype.
Abstract: Aims 3,4-Methylenedioxymethamphetamine (MDMA, commonly called ecstasy) is a synthetic compound increasingly popular as a recreational drug. Little is known about its pharmacology, including its metabolism and pharmacokinetics, in humans in controlled settings. A clinical trial was designed for the evaluation of MDMA pharmacological effects and pharmacokinetics in healthy volunteers.

362 citations

References
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Journal ArticleDOI
14 Feb 1975-Science
TL;DR: A role in central mediation of reward perception is suggested for dopamine but not for noradrenaline, after low and high doses of a dopamine blocking agent had effects on lever pressing for intravenous amphetamine reward which resembled the effects of reward reduction and reward termination.
Abstract: Low and high doses of a dopamine blocking agent had effects on lever pressing for intravenous amphetamine reward which resembled the effects of reward reduction and reward termination, respectively. Noradrenaline blockade had no such effects. A role in central mediation of reward perception is suggested for dopamine but not for noradrenaline.

528 citations

Journal ArticleDOI
TL;DR: The enantiomers of 3,4-(methylenedioxy)amphetamine (MDA), p-methoxyamphetamine (PMA), and N-Me-MDA (MDMA), along with their alpha, alpha-dimethylated derivatives, were evaluated for an effect on the release of [3H]serotonin from rat whole brain synaptosomes and suggested that transmitter release may play a role in the biological activity of MDMA.
Abstract: The enantiomers of 3,4-(methylenedioxy)amphetamine (MDA), p-methoxyamphetamine (PMA), and N-Me-MDA (MDMA), along with their alpha, alpha-dimethylated derivatives, were evaluated for an effect on the release of [3H]serotonin from rat whole brain synaptosomes. The amphetamine isomers were all potent in inducing the release of [3H]serotonin at bath concentrations of 1 and 10 micrometers but were inactive at 0.1 micrometers. No significant difference in isomer potency was observed at the 10 micrometers concentration. However, at 1 micrometer the (+) isomer of MDMA was more effective in inducing release than was the (-) isomer. Since it is the (+) isomer which is clinically active, this result suggests that transmitter release may play a role in the biological activity of MDMA. By contrast, the alpha, alpha-dimethyl compounds were not effective in releasing serotonin, even at the highest bath concentration.

196 citations

Journal ArticleDOI
TL;DR: The results of this study suggest that the discriminative stimulus effects of DOM, the three hallucinogenic agents to which DOM-stimulus generalization occurred, and quipazine, may involve those sub-populations of serotonin receptors that are labeled by tritiated ketanserin (i.e. 5-HT2 sites).

167 citations

Journal ArticleDOI
TL;DR: It is suggested that this compound is the prototype of a new pharmacologic class that may have value in facilitating psychotherapy and that this class be designated as entactogens.
Abstract: The alpha-ethyl phenethylamine derivative 1-(1,3-benzodioxol-5-yl)-2-butanamine was prepared. An asymmetric synthesis was used to prepare the enantiomers of this compound and the related alpha-methyl homologue (MDA). The racemates and enantiomers of both compounds were evaluated in the two-lever drug discrimination assay in rats trained to discriminate saline from 0.08 mg/kg of LSD tartrate. Stimulus generalization occurred with the racemate and the R-(-) enantiomer of the alpha-methyl homologue and the S-(+) enantiomer of the alpha-ethyl primary amine. No generalization occurred with the other enantiomers or with the N-methyl derivatives of either series. Human psychopharmacology studies revealed that the N-methyl derivative of the title compound was nonhallucinogenic and that it had a new, novel psychoactive effect. It is suggested that this compound is the prototype of a new pharmacologic class that may have value in facilitating psychotherapy and that this class be designated as entactogens.

156 citations

Book ChapterDOI
01 Jan 1978
TL;DR: Amphetamine and a number of pharmacologically related drugs act in the brain to increase alertness, suppress appetite, and reduce sleep and fatigue and acting in the periphery the drugs also have sympathomimetic properties.
Abstract: Amphetamine and a number of pharmacologically related drugs act in the brain to increase alertness, suppress appetite, and reduce sleep and fatigue. In animals these drugs generally facilitate ongoing spontaneous and operant behaviors. High doses of these drugs cause stereotyped behaviors that are characteristic for each species, and in humans they can cause toxic psychoses. Acting in the periphery the drugs also have sympathomimetic properties.

136 citations