3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is neurotoxic upon central serotonin systems in experimental animals and probably also in humans. Serotonin is involved in the habituation, sensitization and prepulse inhibition (PPI) of the startle reflex. To study the plasticity of startle reflex in currently abstinent MDMA users. Electromyographic responses to acoustic startle stimuli (pulse...
The issue of ecstasy-related fatalities has extensively attracted the attention of both the media and the general public, but less so of the scientific literature. The aim of the present review is to focus on the epidemiological, clinical and pharmacological issues related to ecstasy fatalities. Possibly due to a number of different reasons, the rates of ecstasy-related deaths seem to have...
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is increasingly used by young people for its euphoric and empathic effects. MDMA presents non-linear pharmacokinetics, probably by inhibition of cytochrome P450 isoform 2D6. Users are known to often take more than one dose per session. This practice could have serious implications for the toxicity of MDMA. To evaluate the pharmacological...
3,4-Methylenedioxymethamphetamine (MDMA) administration to rats produces an acute hyperthermic response and induces localised neuronal activation, which can be visualised via expression of immediate-early genes. The pharmacological and anatomical basis of these effects are unclear. At high doses, MDMA also causes selective neurotoxicity at serotonergic nerve terminals. We investigated the...
It has been suggested that 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) causes damage to the serotonergic system, and that this damage results in cognitive and mood impairments. To examine the effect of chronic MDMA usage on a wide battery of cognitive tests and psychological abilities and processes. In the present study, the performance of 17 participants with a history of MDMA use was...
RationaleDuring binocular rivalry, two incompatible images are presented to each eye and these monocular stimuli compete for perceptual dominance, with one pattern temporarily suppressed from awareness. One variant of stimulus presentation in binocular rivalry experiments is dichoptic stimulus alternation (DSA), when stimuli are applied to the eyes in rapid reversals. There is preliminary...
RationaleSerotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT(2A) agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness.ObjectiveInvestigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters.MethodsEight...
Salvinorin A is the active component of the hallucinogenic plant Salvia divinorum. The potential mode of action of this hallucinogen was unknown until recently. A recent in vitro study detected high affinity and efficacy of salvinorin A at kappa-opioid receptors. It was postulated that salvinorin A would produce discriminative stimulus effects similar to those of a high efficacy kappa-agonist...
Interest in therapeutic activities of cannabinoids has been restrained by the fact that they are most often mediated through activation of cannabinoid CB1 receptors, the same receptors that mediate the effects of delta9-tetrahydrocannabinol (THC) and are responsible for the abuse liability of marijuana. Persistent intravenous self-administration of THC by animals was first demonstrated in...
Phencyclidine (PCP) binds with high affinity to a site located within the ionophore of N-methyl- D-aspartate (NMDA) receptors. Previous studies have demonstrated that PCP and other high-affinity NMDA channel blockers reliably disrupt prepulse inhibition (PPI) of acoustic startle, an animal model of sensorimotor gating used to study attentional deficits associated with schizophrenia. Recently, a...
Studies in non-human animals suggest that opioid antagonists block the reinforcing effects of cannabinoids. The present studies in humans investigated how naltrexone modulates (1) the subjective and physiological effects of oral THC in comparison to methadone, (2) the reinforcing effects of oral THC, and (3) plasma levels of oral THC. In study 1, marijuana smokers (n=9) received naltrexone (0,...
The drug discrimination procedure has proven to be a valuable tool for studying the mechanism of action of psychoactive drugs. Recently, mice with targeted gene mutations have been developed that may also prove useful in evaluating the role of specific receptors in mediating the actions of drugs. We were interested in studying the effects of hallucinogens in genetically modified mice using the...
Symptoms of marijuana withdrawal include increased irritability, depression and anxiety, and decreased sleep quality. Nefazodone, which is an antidepressant with sedative properties, may attenuate symptoms of marijuana withdrawal. The present within-subject, placebo-controlled study investigated the effects of nefazodone during marijuana withdrawal. Marijuana smokers [ n=7; averaging 6.0...
RationaleAyahuasca, a South American psychotropic plant tea, combines the psychedelic agent and 5-HT(2A/2C) agonist N, N-dimethyltryptamine (DMT) with beta-carboline alkaloids showing monoamine oxidase-inhibiting properties. Current human research with psychedelics and entactogens has explored the possibility that drugs displaying agonist activity at the 5-HT(2A/2C) sites temporally disrupt...
There is substantial evidence that lisuride can produce effects linked to 5-HT(1A) receptor occupancy. Nevertheless, this action has generally been ignored in the mechanism of action of lisuride, in favor of an exclusive role for dopamine receptors in considering its antiparkinsonian effects, or an exclusive role of 5-HT(2A/2C) receptor activation in hallucinogenesis. These conclusions are...
PsychopharmacologyJuly 2002Jeffrey A Vivian, Courtney A Waters, Kendall T Szeliga et al.
The current study was designed to extend our knowledge of the N-methyl- D-aspartate (NMDA) glutamate receptor system in mediating the discriminative stimulus effects of ethanol in non-human primates. To characterize the discriminative stimulus effects of the NMDA uncompetitive antagonists dizocilpine, phencyclidine (PCP) and ketamine in male and female monkeys under different ethanol training...
RationaleResearch with animals suggests that central 5-hydroxytryptamine (5-HT) function may be attenuated for a period following a single dose of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). If the same is true in humans, then functions thought to be modulated by 5-HT may differ in MDMA users compared with non-users a few days after the drug is taken.AimsThe present study therefore...
(R)-methanandamide (AM-356), a metabolically more stable chiral analog of the endocannabinoid ligand anandamide, was used as a representative of fatty acid ethanolamide CB1 receptor ligands to characterize the discriminative stimulus functions of anandamides. Rats discriminated between 10 mg/kg (R)-methanandamide and vehicle administered IP 15 min prior to session onset. Another group of rats...
The neurochemical, behavioral, and cognitive effects of the benzodiazepine receptor partial inverse agonist beta-carboline FG 7142 (FG), a drug traditionally described as exhibiting 'anxiogenic' effects, are proposed to model core components of present theories of the neuronal mechanisms of schizophrenia. FG activates the mesolimbic dopaminergic system and, via increases in dopaminergic...
Rationale3.4-Methylenedioxymethamphetamine (MDMA) mainly releases serotonin (5-HT) and is contained in the recreational drug Ecstasy. 5-HT is known to play an important role in mood and anxiety disorders, for which there is a female preponderance. To date, there are no systematic data on gender differences in the subjective effects of MDMA.ObjectivesThe present work analyzed the pooled data...
RationaleAyahuasca is a South American psychoactive beverage that contains the naturally occurring psychedelic agent N,N-dimethyltryptamine (DMT). This "tea" has been used for centuries in religious and medicinal contexts in the rain forest areas of South America and is presently gaining the attention of psychedelic users in North America and Europe.ObjectivesIn the present study, the...
The long-term neurochemical effects produced by the repeated administration of methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) are well documented; however, the functional consequences have not been clearly defined. The present study was designed to investigate whether rats treated with a monoamine-depleting regimen of MA or MDMA exhibit disturbances in locomotor activity...
PsychopharmacologyJanuary 1, 2001R J Verkes, H J Gijsman, M S Pieters et al.
(+/-) 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to cause long term damage to serotonergic cerebral neurons in animals. The neurotoxic effects in humans are less clear and little is known about the functional consequences, although some studies suggest memory impairment. Given the widespread use of MDMA, our lack of knowledge raises concerns. We investigated, in...
Abstract. Rationale: Recreational use of "ecstasy" (3,4-methylenedioxymethamphetamine; MDMA) has become increasingly widespread. Until recently, however, little was known about the possible persistent psychological effects of extensive use of this drug. Objective: The aim of the present review is to evaluate recent empirical evidence concerning the persistent psychological sequelae of...
The phenomenon of sensitization has been theoretically implicated in mediating various aspects of drug addiction. Recent dose-response studies demonstrated that pretreatment with the putative antiaddictive agent, ibogaine (IBO), and a synthetic iboga alkaloid congener, 18-methoxycoronaridine (18-MC), increase the potency of cocaine to elicit behavioral sensitization, an effect proposed to...