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Experimental and Clinical Psychopharmacology

ISSN 1064-1297

15 papers in the library · 297 citations · publishing 1997-2025

Papers

Cognitive and subjective acute dose effects of intramuscular ketamine in healthy adults.

Experimental and Clinical Psychopharmacology November 1, 2006 Michelle R Lofwall, Roland R. Griffiths, Miriam Z Mintzer 57 citations

Ketamine, a drug that blocks NMDA receptors, produces selective, temporary, dose- and time-related effects on memory and cognition. In a double-blind, placebo-controlled crossover study, 18 healthy adults received low or moderate doses of ketamine. Ketamine impaired memory encoding (free recall) and working memory speed, but spared retrieval, recognition, source memory, attention, and accuracy on a symbol substitution task. Subjective effects lasted longer than memory or psychomotor impairments, and there were no hallucinations or mystical experiences. The findings help clarify the role of NMDA receptors in different cognitive processes.

Ethnoracial health disparities and the ethnopsychopharmacology of psychedelic-assisted psychotherapies.

Experimental and Clinical Psychopharmacology June 7, 2021 Colleen Fogg, Timothy I. Michaels, Sara de la Salle et al. 53 citations

Psychedelic-assisted psychotherapy (PAP) shows promise for treating substance use disorders, PTSD, depression, and anxiety in randomized, double-blind, placebo-controlled trials, but research has almost exclusively involved White populations in North America and Western Europe, neglecting Black, Indigenous, and People of Color (BIPOC). Ethnoracial differences in the metabolism, safety, and efficacy of psychotropic drugs are known from previous research, yet no studies have directly examined such differences for psychedelic pharmacology. This article argues that failing to include BIPOC in trials limits generalizability and overlooks biological and social factors affecting responses to PAP. It discusses limitations of ethnopsychopharmacology and advocates for expanded funding to address cultural, clinical, and public health needs.

A three-choice discrimination procedure dissociates the discriminative stimulus effects of d-amphetamine and (±)-MDMA in rats.

Experimental and Clinical Psychopharmacology January 1, 2000 A. K. Goodwin, L. E. Baker 44 citations

MDMA produces subjective effects in humans that are similar to, but distinguishable from, those of psychostimulants. In rats trained to discriminate between MDMA and d-amphetamine using a three-choice operant procedure, cocaine fully substituted for d-amphetamine, while LSD dose-dependently increased MDMA-appropriate responding, reaching nearly complete substitution (78%) for MDMA. The hallucinogen 2,5-dimethoxy-4-bromoamphetamine only partially substituted for MDMA and severely disrupted response rate. Fenfluramine and both isomers of MDA fully substituted for MDMA. The serotonin-receptor antagonist pirenpirone only partially blocked MDMA discrimination.

Effects of acute and repeated treatment with serotonin 5-HT2A receptor agonist hallucinogens on intracranial self-stimulation in rats.

Experimental and Clinical Psychopharmacology January 10, 2019 Farhana Sakloth, Elizabeth Leggett, Megan J. Moerke et al. 42 citations

The classic hallucinogens LSD, mescaline, and psilocybin, classified as Schedule 1 drugs, were tested in rats using intracranial self-stimulation (ICSS), a procedure that detects abuse-related effects of other drugs. In acute tests, all three drugs predominantly depressed ICSS, with weak and inconsistent evidence of abuse-related facilitation. Repeated LSD treatment did not alter its own depressant effects or the abuse-related effects of methamphetamine, but it did attenuate ICSS depression caused by the kappa opioid receptor agonist U69,593. These findings suggest that 5-HT2A agonist hallucinogens have weak abuse potential and provide evidence that repeated LSD may reduce depressant-like effects mediated by kappa opioid receptors.

In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys.

Experimental and Clinical Psychopharmacology February 1, 2008 William E Fantegrossi 30 citations

The chiral nature of the MDMA molecule produces two enantiomers, each biologically active. Reviewing the author's research and other publications, no differences between racemic MDMA and its enantiomers in maintaining behavior were noted. Blocking the 5-HT2A receptor shifted the dose-effect function rightward for S(+)-MDMA but insurmountably reduced the reinforcing effects of R(-)-MDMA. Long-term self-administration can lead to chronic tolerance, with S(+)-MDMA somewhat less susceptible than the racemate or R(-)-enantiomer. PET neuroimaging showed negligible dopamine transporter occupancy after R(-)-MDMA but reasonable interaction after S(+)-MDMA. Non-human primate studies caution that results with enantiomers may not inform about the racemate and vice versa.

Call for evidence-based psychedelic integration.

Experimental and Clinical Psychopharmacology November 27, 2023 Jakub Greń, Ingmar Gorman, Anastasia Ruban et al. 27 citations

Psychedelic integration (PI) refers to practices that aim to minimize harms or maximize benefits after psychedelic use. Although PI is considered essential in psychedelic-assisted therapy, existing models lack empirical support and are not evidence-based. With psychedelic use increasing, the article calls for scientific efforts to develop, examine, and evaluate PI methods. It summarizes current literature, suggests research avenues, and discusses limitations and challenges of PI-focused research.

Syllogistic Reasoning Performance in MDMA (Ecstasy) Users.

Experimental and Clinical Psychopharmacology January 1, 2005 Catharine Montgomery, John E. Fisk, Russell Newcombe et al. 22 citations

Recreational use of MDMA (Ecstasy) is linked to impairments in syllogistic reasoning, a form of logical deduction. In a study comparing 22 MDMA users (average age 21.36) with 26 non-users (average age 21.31), users performed significantly worse on reasoning tasks, even after accounting for other drug use. However, this deficit was no longer statistically significant when differences in working memory capacity were considered. The findings suggest that MDMA-related declines in working memory and executive function may underlie the observed reasoning difficulties.

Ibogaine interferes with the establishment of amphetamine place preference learning.

Experimental and Clinical Psychopharmacology May 1, 1997 I Moroz, L A Parker, S Siegel 11 citations

A single injection of ibogaine given 24 hours before amphetamine prevented the formation of a conditioned place preference for amphetamine after one or two conditioning trials, but was less effective after four trials. The reduced effectiveness with more trials appears due to tolerance developing to ibogaine.

Harmine impairs memory performance of treated rats and nontreated cagemates.

Experimental and Clinical Psychopharmacology November 4, 2021 Tânia Cristina Libânio, R. Eufrásio, Suzy S Niigaki et al. 6 citations

Harmine, a component of the psychedelic brew ayahuasca, impairs memory in emotional contexts in rats, and even untreated rats housed with harmine-treated rats show memory deficits. In experiments using contextual and tone fear conditioning and a plus-maze discriminative avoidance task, harmine at 10 mg/kg impaired contextual fear conditioning, and all doses (5, 10, or 15 mg/kg) impaired discriminative avoidance. Untreated rats housed in cages with harmine-treated rats also showed memory deficits across all tasks, suggesting that social context and cohabitation can influence the drug's behavioral effects.

To treat or not to treat? High-potency benzodiazepine use in a case of comorbid hallucinogen persisting perception disorder and alcohol use disorder.

Experimental and Clinical Psychopharmacology September 1, 2022 Julie A E Christensen, David C. Fipps, J Michael Bostwick 4 citations

Hallucinogen persisting perception disorder (HPPD) causes visual disturbances that resemble psychedelic intoxication and persist after drug use stops. A 37-year-old man with a history of alcohol, cannabis, LSD, cocaine, and nicotine use disorders experienced visual distortions—such as halos around objects, moving walls, and cartoonish figures—for over 20 years after his last LSD use. He understood these perceptions were not real. Hospital tests, including head CT and EEG, found no other cause. His symptoms resolved with scheduled clonazepam treatment, though treatment programs were hesitant to accept him while on a benzodiazepine. The case highlights the need to distinguish HPPD from psychosis and to weigh risks and benefits of long-term benzodiazepine use for patients with co-occurring substance use disorders.

Differential effects of repeated fluoxetine and ketamine administration on behavioral and pharmacological stressor-induced depression of digging behavior in mice.

Experimental and Clinical Psychopharmacology October 1, 2024 Kaitlyn J Partridge, Todd M. Hillhouse 1 citation

Digging behavior in mice is a stable and consistent compulsive-like behavior that can be reduced by both behavioral and pharmacological stressors, producing a depression-like state. A single swim stress significantly reduced digging for at least three days, with recovery by day seven. Repeated treatment with fluoxetine (10 mg/kg/day), but not ketamine, partially reversed swim stress-induced digging suppression on days three and seven. The pharmacological stressor yohimbine dose-dependently decreased digging, and repeated ketamine (10 mg/kg/day), but not fluoxetine, reversed yohimbine-induced digging suppression. These results indicate that stress-induced suppression of digging behavior is stimulus- and drug-dependent, requiring further investigation.

Self-reported changes and experiences with substance use among real-world patients treated with medical ketamine.

Experimental and Clinical Psychopharmacology July 24, 2025 Shahar Almog, Maribel Rodriguez Perez, Deepthi S Varma et al.

In a survey of 201 patients receiving medical ketamine for psychiatric or pain conditions, most reported either a positive change (54.7%) or no change (44.3%) in their use of other substances. Those with a past history of problematic substance use showed significantly greater reductions than those with present or no such history. Patients described reduced craving, less need to self-medicate, and increased motivation to quit substances. Ketamine did not appear to induce or increase drug use among those with minimal or no prior use, though some reported risky behaviors such as using other psychedelics or substituting alcohol with recreational ketamine. Further research is needed to identify and protect at-risk patients.

Conditioned anti-immobility by ketamine: A comparison to escitalopram and bupropion.

Experimental and Clinical Psychopharmacology April 1, 2023 Brett Melanson, Michael Wolter, Zion Leatham et al.

Exposure to a context previously paired with the effects of ketamine reduced immobility in the forced-swimming test in male rats, indicating a conditioned antidepressant-like response. This effect was not observed with bupropion, but was comparable to escitalopram. The response was not due to changes in general activity or conditioned incentive or aversive states, as no group differences appeared in a place-conditioning test. The findings suggest that drug-environment interactions may contribute to ketamine's sustained antidepressant effects in clinical settings.

Interoceptive attention or merely distraction? An examination of the effects of brief breath counting training on stress-induced alcohol-seeking behavior.

Experimental and Clinical Psychopharmacology February 1, 2023 Luke Herchenroeder, Eleanor Williams, Emma Wedell et al.

A brief mindfulness exercise (breath counting) and a simple distraction task (cross counting) both reduced stress-induced alcohol cravings to a similar degree in young adult drinkers. The study randomly assigned 278 university students to breath counting, distraction, stress-only, or no-stress conditions. Stress increased preference for alcohol pictures, but both breath counting and distraction attenuated this effect equally, and the difference faded in the second half of the choice test. The authors argue that the therapeutic effect of breath counting on stress-induced alcohol-seeking may stem from distraction or cognitive load rather than a unique state of mindful acceptance.

Effects of NMDA antagonists ketamine, methoxetamine and phencyclidine on the odor span test of working memory in rats

Experimental and Clinical Psychopharmacology February 1, 2018 Michael Mathews, R. N. Mead, M. Galizio

NMDA receptor antagonists impair working memory in rodents, but the effects differ across drugs. In the odor span task, which tests memory for multiple stimuli, phencyclidine (PCP) and methoxetamine (MXE) reduced accuracy only when memory load was high, without affecting simple discrimination. Ketamine (KET) produced less selective impairments. These findings support the glutamate hypothesis, which links NMDA receptor hypofunction to cognitive symptoms of schizophrenia, but suggest that not all NMDA antagonists affect memory identically.