Trifluoromethylphenyl piperazine (TFMPP) is an active constituent of a relatively new group of recreational drugs known as 'party pills'. TFMPP has been anecdotally reported to induce mild psychedelic effects similar to lysergic acid diethylamide and psilocybin. There has been no research about the subjective effects of TFMPP in humans. This study aimed to investigate the subjective effects of...
Studies in laboratory animals strongly suggest reciprocal modulation of the opioidergic and endocannabinoid systems, a relationship that has not been demonstrated in humans. This study sought to clarify this interaction by assessing how a range of naltrexone doses altered the subjective, cognitive, and cardiovascular effects of marijuana. Daily marijuana smokers (n = 29) participated in this...
Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats.
Disruptions in perception and cognition are characteristic of psychiatric conditions such as schizophrenia. Studies of pharmacological agents that alter perception and cognition in humans might provide a better understanding of the brain substrates of these complex processes. One way to study these states in rodents is with tests that require attention and visual perception for correct...
Salvinorin A, the primary psychoactive derivative of the hallucinogenic herb Salvia divinorum, is a potent and highly selective kappa-opioid receptor (KOR) agonist. Several recent studies, however, have suggested endocannabinoid system mediation of some of its effects. This study represents a systematic examination of this hypothesis. Salvinorin A was isolated from S. divinorum and was...
The widely available hallucinogen salvinorin A is a unique example of a plant-derived compound selective for kappa-opioid receptors and may produce effects distinct from those of other compounds with classic hallucinogenic or dissociative properties which are also abused in humans. The objective of this study is to characterize the salvinorin A discriminative cue in nonhuman primates with high...
PsychopharmacologyJune 2010Hugo A Tejeda, Vladimir I Chefer, Agustin Zapata et al.
Kappa-opioid receptor (KOR) agonists produce dysphoria and psychotomimesis in humans. KORs are enriched in the prefrontal cortex and other brain regions that regulate mood and cognitive function. Dysregulation of the dynorphin/KOR system has been implicated in the pathogenesis of schizophrenia, depression, and bipolar disorder. Prepulse inhibition of the acoustic startle reflex (PPI), a...
PsychopharmacologyMay 2010Robert A Battisti, Steven Roodenrys, Stuart J Johnstone et al.
The endogenous cannabinoid system is sensitive to the introduction of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, which are known to impact upon memory functioning. We sought to examine the impact of chronic cannabis use upon memory-related brain function via examination of the subsequent memory effect (SME) of the event-related potential (ERP). The SME is predictive of recall...
The effectiveness of MDMA and its enantiomers to reinstate responding previously maintained by drug self-administration has not been thoroughly investigated. The present study was designed to compare the reinstatement effects of amphetamine, the piperazine-analog BZP, SR(+/-)-MDMA, S(+)-MDMA, R(-)-MDMA, and fenfluramine on behavior maintained under a second-order schedule of intravenous...
PsychopharmacologyMay 2010Pierre Pouget, Nicolas Wattiez, Sophie Rivaud-Péchoux et al.
Ketamine, a non-competitive N-methyl-D: -aspartic acid antagonist, has been widely used for anaesthetic purposes. At sub-anaesthetic dosage, it induces a dissociative state similar to schizophrenia. The discovery of this effect on dissociative state has led to its use as a pharmacological model of schizophrenia and has also been responsible for its illegal use as a recreational drug. Whereas...
Depressive-like effects of the kappa opioid receptor agonist salvinorin A are associated with decreased phasic dopamine release in the nucleus accumbens.
Although delta-9-tetreahydrocannabinol (THC)-induced elevations in accumbal dopamine levels are believed to play an important role in the abuse-related effects of cannabis, little direct evidence has been provided that the dopaminergic system is involved in the psychotropic effects of THC. The objective of this study is to investigate whether drugs activating or blocking the dopaminergic system...
RationaleHallucinogenic serotonin 2A (5-HT2A) receptor partial agonists, such as (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), induce a frontal cortex-dependent head-twitch response (HTR) in rodents, a behavioral proxy of a hallucinogenic response that is blocked by 5-HT2A receptor antagonists. In addition to 5-HT2A receptors, DOI and most other serotonin-like...
INTRODUCTION: 3,4-methylenedioxymethamphetamine (MDMA) is known to improve psychomotor function and mood when measured during daytime. However, MDMA users tend to take this drug at dance parties while staying awake for prolonged periods of time. SUBJECTS AND METHODS: This study was designed to assess dose-related residual effects of MDMA on psychomotor function and mood after a night without...
RATIONALE: Compounds that activate the 5-HT(2A) receptor, such as lysergic acid diethylamide (LSD), act as hallucinogens in humans. One notable exception is the LSD congener lisuride, which does not have hallucinogenic effects in humans even though it is a potent 5-HT(2A) agonist. LSD and other hallucinogens have been shown to disrupt prepulse inhibition (PPI), an operational measure of...
PsychopharmacologyNovember 1, 2009C B Willmore, D M Krall, F M Spears et al.
Deficits in memory and attention are broadly acknowledged during psychosis; however, experiments on modeled psychosis often test working memory without systematic manipulation of attentional demands. The major research goal was discovering which neurobehavioral processes, attention, or memory contributed more to drug-provoked performance deficits. Rats were trained to perform operant ratio...
Model psychosis is characterised by experimentally induced symptoms of withdrawal from reality, frequently accompanied by perceptual disturbances, thought disorders, delusional ideas and sometimes by hallucinations. These "altered states of consciousness" provide a long-standing and valid approach to enhance our understanding of certain aspects of schizophrenia. Targeting the endocannabinoid...
There is evidence demonstrating changes in dopamine (DA) transmission in the nucleus accumbens (NAc) related to contingent versus non-contingent drug administration. The aim of this study was to evaluate basal and 3,4-methylenedioxymethamphetamine (MDMA)-stimulated DA levels in the NAc of mice that had previously received contingent and non-contingent infusions of MDMA. Contingent mice were...
Introduction: This study sought to test the association between 3,4-methylenedioxymethamphetamine use, serotonergic function and sleep. Materials and methods: Ambulatory polysomnography was used to measure three nights sleep in 12 ecstasy users and 12 controls after screening (no intervention), a tryptophan-free amino acid mixture (acute tryptophan depletion (ATD)) and a tryptophan-supplemented...
Rationale There has been increased recreational use of dimethyltryptamine (DMT), but little is known of its discriminative stimulus effects. Objectives The present study assessed the similarity of the discriminative stimulus effects of DMT to other types of hallucinogens and to psychostimulants. Methods Rats were trained to discriminate DMT from saline. To test the similarity of DMT to known...
We have previously shown that (+/-)-3,4-methylenedioxymethamphetamine (MDMA) treatment from postnatal days (P)11 to P20 leads to learning and memory deficits when the animals are tested as adults. Recently, the club drug 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) has gained popularity. Due to the similarities between MDMA and 5-MeO-DIPT and the substitution of 5-MeO-DIPT for MDMA, the...
INTRODUCTION: Various experimental manipulations, usually involving drug administration, have been used to produce symptoms of psychosis in healthy volunteers. Different drugs produce both common and distinct symptoms. A challenge is to understand how apparently different manipulations can produce overlapping symptoms. We suggest that current Bayesian formulations of information processing in...