Drugs can function as punishers. However, work on the study of drugs as punishers is limited, as is the range of compounds known to function as punishers. Kappa opioid agonists, which have received much experimental attention as potential therapeutics for drug abuse, reportedly produce aversive effects. However, kappa agonists have yet to be tested as punishers of behavior. The goal of the...
A family history (FH) of alcoholism accounts for approximately 50% of the risk of developing alcohol problems. Several lines of preclinical evidence suggest that brain cannabinoid receptor (CB1R) function may mediate the effects of alcohol and risk for developing alcoholism including the observations that reduced CB1R function decreases alcohol-related behaviors and enhanced CB1R function...
PsychopharmacologyJune 2014Philip L R Gaskin, Stephen P H Alexander, Kevin C F Fone
Schizophrenia is a debilitating disorder comprising positive, negative and cognitive deficits with a poorly defined neurobiological aetiology; therefore, animal models with greater translational reliability are essential to develop improved therapies. This study combines two developmental challenges in rats, neonatal phencyclidine (PCP) injection and subsequent rearing in social isolation from...
±3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) produces “prosocial” effects, such as feelings of empathy and closeness, thought to be important to its abuse and its value in psychotherapy. However, it is not fully understood how MDMA alters basic emotional processes to produce these effects, or whether it produces corresponding changes in actual social behavior. Here, we examined how MDMA...
PsychopharmacologyApril 2014Reagan R Wetherill, Anna Rose Childress, Kanchana Jagannathan et al.
Addiction theories posit that drug-related cues maintain and contribute to drug use and relapse. Indeed, our recent study in cocaine-dependent patients demonstrated that subliminally presented cocaine-related stimuli activate reward neurocircuitry without being consciously perceived. Activation of reward neurocircuitry may provoke craving and perhaps prime an individual for subsequent...
Several laboratories have conducted placebo-controlled drug challenge studies with 3,4-methylenedioxymethamphetamine (MDMA), providing a unique source of data to examine the reliability of the acute effects of the drug across subject samples and settings. We examined the subjective and physiological responses to the drug across three different laboratories and investigated the influence of...
Psychoactive-substituted phenethylamines 2,5-dimethoxy-4-chlorophenethylamine (2C-C); 2,5-dimethoxy-4-methylphenethylamine (2C-D); 2,5-dimethoxy-4-ethylphenethylamine (2C-E); 2,5-dimethoxy-4-iodophenethylamine (2C-I); 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2); and 2,5-dimethoxy-4-chloroamphetamine (DOC) are used recreationally and may have deleterious side effects. This study compares...
The "subjective high" from marijuana ingestion is likely due to Δ(9)-tetrahydrocannabinol (THC) activating the central cannabinoid receptor type 1 (CB1R) of the endocannabinoid signaling system. THC is a weak partial agonist according to in vitro assays, yet THC mimics the behavioral effects induced by more efficacious cannabinergics. This distinction may be important for understanding...
PsychopharmacologyFebruary 2014Lynn Taurah, Chris Chandler, Geoff Sanders
Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a worldwide recreational drug of abuse. Unfortunately, the results from human research investigating its psychological effects have been inconsistent. The present study aimed to be the largest to date in sample size and 5HT-related behaviors; the first to compare present ecstasy users with past users after an abstinence of 4 or more years,...
PsychopharmacologyOctober 1, 2013Katja Clarissa Ward, Halima Zainab Khattak, Louise Richardson et al.
Visual perception is impaired during pathological psychosis, which can be mimicked by NMDA receptor antagonists. However, the underlying mechanisms are poorly understood, partly due to limits of current rodent models for visual integration. The objectives of the study are (1) to develop a rodent task that can differentiate between effects on perception and nonspecific effects on task...
Rationale: Recently, products containing synthetic cannabinoids, collectively referred to as Spice, are increasingly being used recreationally. Objectives: The availability, acute subjective effects-including self-reports posted on Erowid-laboratory detection, addictive potential, and regulatory challenges of the Spice phenomenon are reviewed. Results: Spice is sold under the guise of potpourri...
BackgroundAyahuasca, a South American psychotropic plant tea containing the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine, has been shown to increase regional cerebral blood flow in prefrontal brain regions after acute administration to humans. Despite interactions at this level, neuropsychological studies have not found cognitive deficits in abstinent long-term...
Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the plant Salvia divinorum, which has increased in popularity as a recreational drug over the past decade. Few human studies have examined salvinorin A. This double-blind, placebo-controlled study evaluated the dose-related effects of inhaled salvinorin A in individuals with histories of hallucinogen use. Eight...
Several studies have documented impairments in memory processes as a result of ketamine administration; however, few studies have compared the profile of cognitive effects of ketamine to other drugs. The aim of this study was to compare the cognitive effects of ketamine with those of triazolam in healthy volunteers. Doses of ketamine (0.2, 0.4 mg/kg intramuscular (i.m.)), triazolam (0.2, 0.4...
PsychopharmacologyMarch 2013Ross Zimnisky, Gloria Chang, István Gyertyán et al.
A major challenge in the pharmacological treatment of psychotic disorders is the effective management of the associated cognitive dysfunctions. Novel concepts emphasize a potential benefit of partial agonists acting upon dopamine D(2)-like receptors in ameliorating these cognitive deficits, and pre-clinical studies suggest that D(3)-receptor-preferring compounds can exert pro-cognitive effects....
Serotonergic hallucinogens such as (+)-lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT) produce distinctive visual effects, whereas the synthetic hallucinogen N,N-diisopropyltryptamine (DiPT) is known for its production of auditory distortions. This study compares the discriminative stimulus effects of DiPT to those of visual hallucinogens. Adult male rats were trained to...
PsychopharmacologyMarch 2013Donald M Dougherty, Charles W Mathias, Michael A Dawes et al.
Marijuana is a popular drug of abuse among adolescents, and they may be uniquely vulnerable to resulting cognitive and behavioral impairments. Previous studies have found impairments among adolescent marijuana users. However, the majority of this research has examined measures individually rather than multiple domains in a single cohesive analysis. This study used a logistic regression model...
Behavioral, neurochemical and pharmaco-EEG profiles of a new synthetic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats were examined. Locomotor effects, prepulse inhibition (PPI) of acoustic startle reaction (ASR), dopamine and its metabolite levels in nucleus accumbens (NAc), EEG power spectra and coherence in freely moving rats were analysed. Amphetamine was used as a reference...
The serotonin (5-HT) system is involved in pain modulation, and 5-HT receptor agonists can enhance antinociceptive effects of mu opioid receptor agonists. Less is known about the actions of 5-HT receptor agonists on other effects of opioids. This study examined the effects of non-contingent and contingent administration of the 5-HT(2A) receptor agonists DOM and quipazine on i.v. heroin...
The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a widely abused drug, particularly in adolescent and young adult populations. Although it was shown that MDMA-associated cues reinstate extinguished MDMA seeking in an animal relapse model, there is little information regarding the neural mechanisms underlying this behavior. Because the medial prefrontal cortex...
Cannabinoids have been shown to alter time perception, but existing literature has several limitations. Few studies have included both time estimation and production tasks, few control for subvocal counting, most had small sample sizes, some did not record subjects’ cannabis use, many tested only one dose, and used either oral or inhaled administration of Δ9-tetrahydrocannabinol (THC), leading...
Marijuana is believed to increase impulsivity and risk taking, but the processes whereby it affects such behaviors are not understood. Indeed, either the pharmacologic effect of delta-9-tetrahydrocannabinol (THC) or the expectancy of receiving it may lead to deficits in cognitive processing and increases in risk taking. We examined the relative effects of expecting to receive active marijuana...
Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Single, acute oral doses of DXM (100, 200, 300, 400, 500, 600, 700, and 800 mg/70 kg), triazolam (0.25 and 0.5 mg/70 kg), and placebo were administered to 12 healthy...
The effects of adolescent marijuana use on the developing brain remain unclear, despite its prevalence. Arterial spin labeling (ASL) is a noninvasive imaging technique that characterizes neurovascular status and cerebral blood flow (CBF), potentially revealing contributors to neuropathological alterations. No studies to date have looked at CBF in adolescent marijuana users. This study examined...
In schizophrenia patients, optimal treatment with antipsychotics requires weeks to months of sustained drug therapy. However, single administration of antipsychotic drugs can reverse schizophrenia-like behavioral alterations in rodent models of psychosis. This raises questions about the physiological relevance of such antipsychotic-like activity. This study evaluates the effects of chronic...