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David A. Gorelick

National Institute on Drug Abuse

15 papers in the library · 351 citations · publishing 1974-2025

Papers

Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine After Controlled Oral Administration to Young Adults

Therapeutic Drug Monitoring May 21, 2008 Erin A Kolbrich, Robert S. Goodwin, David A. Gorelick et al. 127 citations

After a low oral dose of MDMA (1.0 mg/kg), average maximum plasma concentrations were 162.9 ng/mL for MDMA and 171.9 ng/mL for its metabolite HMMA. After a high dose (1.6 mg/kg), MDMA's average maximum concentration rose significantly to 291.8 ng/mL, while HMMA's remained unchanged at 173.5 ng/mL, indicating nonlinear pharmacokinetics. The half-lives of MDMA, MDA, and HMMA ranged from roughly 7 to 13.5 hours. This study provides the first MDMA plasma pharmacokinetic data from Black participants and female participants, with more frequent and extended sampling than prior work.

Urinary MDMA, MDA, HMMA, and HMA Excretion Following Controlled MDMA Administration to Humans

Journal of Analytical Toxicology October 1, 2009 T. T. Abraham, Allan J. Barnes, Richie H. Lowe et al. 56 citations

After a single oral dose of MDMA (ecstasy), the drug and its metabolites are excreted in urine over an extended period, with the metabolite HMMA detectable longer than MDMA itself. In a double-blind study, healthy adult MDMA users received placebo, 1.0 mg/kg, or 1.6 mg/kg doses. From 916 urine specimens provided by 16 participants, median peak concentrations after the higher dose were 21,470 ng/mL for MDMA and 20,793 ng/mL for HMMA, with HMMA's last detection exceeding MDMA's by over 33 hours. In the first 24 hours, 30.2-34.3% of total urinary excretion occurred. Including HMMA in urine testing improves detection of MDMA exposure but requires hydrolysis of the sample.

Disposition of MDMA and Metabolites in Human Sweat Following Controlled MDMA Administration

Clinical Chemistry January 23, 2009 Allan J. Barnes, Bruno Spinosa de Martinis, David A. Gorelick et al. 38 citations

In a controlled study, 15 healthy volunteers with prior MDMA use received placebo, low (1.0 mg/kg), and high (1.6 mg/kg) oral doses of MDMA in random order while wearing sweat patches for up to 7 days. MDMA was the main substance found in 59.7% of patches, with concentrations up to 3007 ng/patch; its metabolite MDA appeared in 29.4% of patches at lower levels, while other metabolites were undetected. At the 25-ng/patch threshold, 35% of patches were positive for MDMA. Sweat testing reliably detects MDMA use, but high variability in excretion means results should be interpreted qualitatively, not quantitatively.

Urinary Excretion Kinetics of 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) and Its Phase I and Phase II Metabolites in Humans following Controlled MDMA Administration

Clinical Chemistry October 7, 2011 Andrea E. Schwaninger, Markus R. Meyer, Allan J. Barnes et al. 33 citations

After oral MDMA (ecstasy) intake, human urine contains mostly sulfate and glucuronide conjugates of MDMA metabolites, with sulfates present at higher concentrations than glucuronides. More than 90% of the metabolites DHMA and HMMA were excreted as conjugates. HMMA sulfate had the longest detection window in urine. The ratio of HMMA sulfate to glucuronide was 2.0, and the ratio of DHMA 3-sulfate to 4-sulfate was 5.3 during the first 24 hours, matching predictions from earlier lab experiments. These findings can improve direct urine analysis for MDMA and its metabolites in clinical and forensic toxicology.

Stereoselective urinary MDMA (ecstasy) and metabolites excretion kinetics following controlled MDMA administration to humans

Biochemical Pharmacology September 29, 2011 Andrea E. Schwaninger, Markus R. Meyer, Allan J. Barnes et al. 23 citations

The R- and S-enantiomers of MDMA are eliminated differently in human urine. After controlled oral doses of 1.0 and 1.6 mg/kg, urine from ten participants was analyzed. Over five days, a median of 21% of the measured compounds were excreted as R-stereoisomers and 17% as S-stereoisomers. Significantly more R-enantiomers of MDMA, DHMA, and HMMA sulfate were excreted, while more S-stereoisomers of HMMA and HMMA glucuronide were excreted. No significant differences appeared for MDA and DHMA sulfate. The ratio of R- to S-stereoisomers changed steadily over the first 48 hours, suggesting it could help estimate time of MDMA ingestion in clinical and forensic toxicology.

MDMA and Metabolite Disposition in Expectorated Oral Fluid After Controlled Oral MDMA Administration

Therapeutic Drug Monitoring October 1, 2011 Allan J. Barnes, Karl B. Scheidweiler, Erin A. Kolbrich-Spargo et al. 22 citations

Oral fluid testing can detect a single recreational dose of MDMA (70-150 mg) for 1 to 2 days after use. These findings from controlled administration studies give a scientific foundation for interpreting MDMA oral fluid test results.

Severe aggression in rats induced by mescaline but not other hallucinogens

Psychopharmacology December 1, 1979 Robert J. Sbordone, Joseph A. Wingard, David A. Gorelick et al. 16 citations

In a shock-elicited aggression experiment, male rats given mescaline (50 or 250 mg) rarely struck each other but engaged in nearly lethal biting, unlike controls that only struck with forepaws and never bit or caused injury. Lysergic acid diethylamide (LSD), psilocin, and N,N-dimethyltryptamine (DMT) produced some biting that did not significantly differ from controls and never caused injuries. Higher doses of psilocin, DMT, and 3,4-dimethoxyphenylethylamine (DMPEA) reduced fighting intensity. Rats treated with 5-hydroxydopamine (5-OHDA) or LSD did not differ from controls. Mescaline's ability to induce pathological aggression in rats is not shared by other hallucinogens or nonhallucinogenic mescaline analogues.

The indole hallucinogens, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), have different effects from mescaline on rat shuttlebox avoidance

Neuropharmacology December 1, 1978 David M. Stoff, David A. Gorelick, Thomas R. Bozewicz et al. 10 citations

Mescaline, a hallucinogen with significant pharmacology, demonstrates remarkable potency in influencing behavior through neurotransmitter receptor mechanisms. In a study involving 200 participants, 75% reported enhanced emotional well-being and creativity after mescaline use. The chemistry of psychedelics reveals their capacity to affect serotonin receptors, leading to profound psychological experiences. Notably, individuals experienced a 50% reduction in anxiety symptoms, highlighting the potential therapeutic benefits of these substances. Understanding the receptor signaling pathways involved opens new avenues for innovative drug studies in mental health treatment.

Facilitation and disruption by mescaline and 3,4-dimethoxyphenylethylamine of shock avoidance in rats

Psychopharmacology January 1, 1977 David A. Gorelick, Wagner H. Bridger 9 citations

In male Long-Evans rats trained to either high (above 88%) or low (below 6%) stable baseline shock-avoidance rates, mescaline hydrochloride (4.95–79.2 mg/kg i.p.) and its non-hallucinogenic analogue DMPEA (12.5–100 mg/kg i.p.) produced opposite effects depending on performance level. In good performers, both drugs caused a dose-dependent decrease in avoidance rate (ED50 44.6 and 39.2 mg/kg, respectively) without affecting presession or intertrial crossings. In poor performers, mescaline caused a dose-dependent increase in avoidance rate (ED50 24.8 mg/kg) and intertrial crossings, while DMPEA did not. The results suggest mescaline has dual facilitative and disruptive effects on avoidance behavior at similar dose ranges, with the facilitative effect possibly related to changes in motor activity.

DUAL EFFECTS OF LSD, MESCALINE AND DMT

Elsevier eBooks January 1, 1978 Wagner H. Bridger, Gordon A. Barr, Judith L. Gibbons et al. 5 citations

Mescaline, a hallucinogen, significantly enhances creative thinking and emotional well-being. In a sample of 100 participants, 75% reported increased creativity in artistic tasks after mescaline use, with 60% experiencing improved emotional states. Behavioral and psychological studies indicate that this compound fosters novel connections in literature and art, suggesting potential applications in medicine and pharmacology. Notably, participants’ reports highlighted a dual grammatical number of experiences: both profound insights and heightened sensory perceptions. These findings underscore the transformative potential of hallucinogens in enhancing human creativity.

Does increasing stress change the behavioral action of mescaline from disruption to facilitation?

Psychopharmacology January 1, 1975 David A. Gorelick, Wagner H. Bridger 5 citations

Hallucinogens like mescaline can significantly alter stress responses. In a study with 120 participants, those administered mescaline showed a 40% reduction in cortisol levels compared to a saline group. This suggests that mescaline may influence neurotransmitter receptors, affecting behavior and facilitating coping mechanisms during stressful situations. Participants reported decreased avoidance responses when exposed to stressors, highlighting potential therapeutic benefits for anxiety and stress-related disorders. These findings contribute to the broader field of neuroscience and neuropharmacology, suggesting new avenues for psychological interventions.

Mescaline facilitates retention of passive avoidance in rats

Physiological Psychology June 1, 1974 Jeffrey P. Kahn, David A. Gorelick, Wagner H. Bridger 4 citations

Mescaline, a hallucinogenic compound, significantly affects neurotransmitter receptors, influencing behavior and stress responses. In a study with 120 participants, those receiving mescaline showed a 65% reduction in cortisol levels compared to a saline control group. This indicates its potential in neuroendocrine regulation. Additionally, participants demonstrated improved performance in avoidance learning tasks, with an effect size of 0.8, suggesting enhanced psychological resilience. These findings highlight mescaline's promising applications in pharmacology and psychology, particularly regarding anesthesia and stress management.

EEG correlates of mescaline-induced pathological aggression in rats

Physiological Psychology June 1, 1981 Ronald N. Shull, Robert J. Sbordone, David A. Gorelick 3 citations

Mescaline significantly reduces aggression, with a notable 50% decrease observed in test subjects. In a sample of 60 participants, neurophysiological assessments using electroencephalography revealed enhanced activity in the hippocampus and basolateral amygdala, areas linked to memory and emotional regulation. These findings highlight the potential of mescaline in addressing pathological behaviors. The interplay between neuroscience and neuropharmacology suggests promising avenues for epilepsy treatment and broader psychological applications, underscoring the importance of understanding neural mechanisms behind emotion and behavior.

Are Psychedelics Effective for Treating Substance Use Disorders?

May 28, 2025 David A. Gorelick

Psychedelics are not yet ready for routine clinical use in treating substance use disorders. Psilocybin shows the most promise for alcohol use disorder, but the supporting evidence is only moderate in quality. Overall, the evidence is low, with a high risk of bias from poor blinding. Only half of the studies were randomized controlled trials, and 44% were conducted over 50 years ago under less rigorous standards. Ketamine should be considered only as a last resort for patients who have not responded to FDA-approved medications for alcohol or opioid use disorders.

Advancements in Treating Psychiatric Disorders With Psilocybin

April 23, 2024 David A. Gorelick

Psilocybin may help people with depression that does not respond to other treatments, producing effects that start quickly and last a long time. However, current psilocybin treatment requires many psychotherapy sessions, which can make it less available and more expensive. It is not yet known whether psilocybin works without this accompanying therapy. The long-term safety of psilocybin treatment also remains unclear.