National Institute on Drug Abuse, National Institutes of Health
59 papers in the library · 2,859 citations · publishing 1995-2026
ACS Omega June 23, 2026 Elena Bray, Grant C. Glatfelter, Alexander D. Maitland et al.
-dimethyltryptamine (DMT). Overall, the data indicate that 4-Br-DMT has a serotonergic profile without psychedelic-like effects in mice but has a reduced safety profile compared to psilocin and DMT.
ACS Chemical Neuroscience May 27, 2026 Grant C. Glatfelter, Serena S. Schalk, Donna Walther et al.
High Resolution Image Download MS PowerPoint Slide Tryptamine psychedelics induce psychoactive effects via agonist actions at serotonin 2A receptors (5-HT 2A ), but the compounds are generally nonselective. 4-Methoxy- N -methyl- N -isopropyltryptamine (4-MeO-MiPT) is a 5-HT 2A agonist which also blocks the 5-HT transporter (SERT) and has blunted visual and other psychedelic effects in humans....
bioRxiv : the preprint server for biology April 21, 2026 Jeanine Yacoub, Elena Bray, Jude Bayyat et al.
Serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) and 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin) show therapeutic promise for psychiatric and neurodegenerative disorders but may be limited by liabilities from serotonin (5-HT)-2A mediated psychoactive effects and potential cardiotoxicity via 5-HT2B activation. To address these limitations, we designed and synthesized...
Journal of the American Chemical Society December 26, 2025 Christopher Hwu, Václav Havel, Xavier Westergaard et al. 2 citations
) that has a unique therapeutic potential across multiple indications, including opioid dependence, substance use disorders, depression, anxiety, posttraumatic stress disorder (PTSD), and traumatic brain injury (TBI). We systematically examined the effects of ibogaine, its main metabolite noribogaine, and a series of iboga analogs at monoamine neurotransmitter transporters, some of which have...
Psychopharmacology November 15, 2025 Michael H. Baumann, Grant C. Glatfelter, Sara E Walton et al. 1 citation
There is growing interest in the therapeutic utility of psychedelic compounds that act as serotonin-2 A receptor (5-HT2A) agonists. N,N-dimethyltryptamine (DMT) is a 5-HT2A agonist that produces intense and short-lived psychedelic subjective effects, but the compound requires non-oral routes of administration that bypass gastrointestinal metabolism. Intranasal (IN) delivery of DMT represents...
Molecular Psychiatry November 5, 2025 Dino Luethi, Grant C. Glatfelter, Eline Pottie et al. 1 citation
Abstract Various ring-substituted α-methylphenethylamines (i.e., amphetamines) produce psychedelic-like effects that are primarily mediated by activity at 5-hydroxytryptamine 2A (5-HT 2A ) receptors. Small lipophilic substituents at the 4-position of the 2,5-dimethoxyamphetamine core structure can greatly enhance the clinical potency of such derivatives. Here, we studied the effects of various...
Journal of Analytical Toxicology May 26, 2025 Malik Schoffner, Vamshikrishna Reddy Sammeta, Marilyn Naeem et al. 2 citations
Abstract 4-Phosporyloxy-N, N-dimethyltryptamine (psilocybin) is a psychedelic tryptamine found in certain mushroom species that has shown efficacy in the treatment of various psychiatric disorders. In conjunction with the renewed interest in therapeutic effects of psychedelics, there has been an increase in psilocybin-like designer tryptamines appearing in non-medical drug markets. The present...
Psychopharmacology May 17, 2025 Shelby A. McGriff, Jacquelin C Hecker, Alexander D. Maitland et al. 12 citations
The head twitch response (HTR) is a spontaneously occurring behavior in mice that is increased in frequency by serotonergic psychedelics. The mouse HTR is often used as a proxy for psychedelic-like drug effects, but limited information is available about sex differences in HTRs evoked by various classes of psychedelics (i.e., phenethylamines, lysergamides, tryptamines). To examine potential sex...
bioRxiv Preprint Server April 28, 2025 Alexander D. Maitland, Nicholas R. Gonzalez, Donna Walther et al. 1 citation preprint
Serotonergic psychedelics induce the head twitch response (HTR) in mice, an index of serotonin (5-HT) 2A receptor (5-HT2A) agonism and a behavioral proxy for psychedelic effects in humans. Existing methods for detecting HTRs include time-consuming visual scoring, magnetometer-based approaches, and analysis of videos using semi-automated commercial software. Here, we present a new automated...
Journal of Analytical Toxicology January 27, 2025 Melissa F. Fogarty, Sara E Walton, Michael T Truver et al. 6 citations
Identification of N,N-dimethylpentylone (DMP) in counterfeit "Ecstasy" and "Molly" tablets poses risk to public health due to its adverse effects. Little information is available regarding the pharmacological activity or relevant blood or tissue concentrations of DMP, and even less is known about other structurally related beta-keto methylenedioxyamphetamine analogs on recreational drug...
ACS Chemical Neuroscience December 18, 2024 Grant C. Glatfelter, Allison A Clark, Natalie G. Cavalco et al. 14 citations
5-methoxy-N,N-dimethyltrytpamine (5-MeO-DMT) analogs are used as recreational drugs, but they are also being developed as potential medicines, warranting further investigation into their pharmacology. Here, we investigated the neuropharmacology of 5-MeO-DMT and several of its N-alkyl, N-allyl, and 2-methyl analogs, with three major aims: 1) to determine in vitro receptor profiles for the...
Emerging Trends in Drugs, Addictions, and Health December 14, 2024 Eline Pottie, Grant C. Glatfelter, Michael H. Baumann et al.
Introduction: Serotonergic psychedelics induce their characteristic subjective effects via activation of the serotonin 2A receptor (5-HT2AR). This structurally diverse class of drugs includes ergolines (e.g., LSD), phenethylamines (e.g., mescaline), and tryptamines (e.g., psilocin), all of which have NPS analogues that have emerged on recreational drug markets. Importantly, certain ergolines...
The Journal of pharmacology and experimental therapeutics September 18, 2024 Candace B Johnson, Donna Walther, Matthew J. Baggott et al. 5 citations
3,4-Methylenedioxymethamphetamine (MDMA) has shown efficacy as a medication adjunct for treating post-traumatic stress disorder (PTSD). However, MDMA is also used in nonmedical contexts that pose risk for cardiovascular and neurologic complications. It is well established that MDMA exerts its effects by stimulating transporter-mediated release of the monoamines 5-hydroxytryptamine (5-HT),...
ACS Pharmacology & Translational Science March 8, 2024 Grant C. Glatfelter, Eline Pottie, John S. Partilla et al. 28 citations
Lisuride is a non-psychedelic serotonin (5-HT) 2A receptor (5-HT2A) agonist and analogue of the psychedelic lysergic acid diethylamide (LSD). Lisuride also acts as an agonist at the serotonin 1A receptor (5-HT1A), a property known to counter psychedelic effects. Here, we tested whether lisuride lacks psychedelic activity due to a dual mechanism: (1) partial agonism at 5-HT2A and (2) potent...
ACS Chemical Neuroscience January 8, 2024 Alexander M. Sherwood, Elise K. Burkhartzmeyer, Samuel E. Williamson et al. 18 citations
Primary metabolites of mushroom tryptamines, psilocybin and baeocystin (i.e., psilocin and norpsilocin), exhibit potent agonist activity at the serotonin 2A receptor (5-HT2A) in vitro but differ in their 5-HT2A-mediated effects in vivo. In particular, psilocin produces centrally mediated psychedelic effects in vivo, whereas norpsilocin, differing only by the loss of an N-methyl group, is devoid...
ACS Chemical Neuroscience October 17, 2023 Hideaki Yano, Rezvan Chitsazi, Christopher Lucaj et al. 12 citations
The emergence of synthetic cannabinoid receptor agonists (SCRAs) as illicit psychoactive substances has posed considerable public health risks, including fatalities. Many SCRAs exhibit much higher efficacy and potency compared with the phytocannabinoid Δ 9 -tetrahydrocannabinol (THC) at the cannabinoid receptor 1 (CB1R), leading to dramatic differences in signaling levels that can be toxic. In...
Neuropharmacology April 2, 2023 Farah Z Zia, Michael H. Baumann, Sean J Belouin et al. 28 citations
Chronic pain is a leading cause of disability, reduced productivity, healthcare seeking behavior, and a contributor to opioid overdose in the United States. For many people, pain can be satisfactorily managed by existing medicines and comprehensive psychosocial treatments. For others, available treatments are either ineffective or not acceptable, due to side effects and concerns about risks....
ACS Pharmacology & Translational Science March 10, 2023 Marilyn Naeem, Grant C. Glatfelter, Duyen N. K. Pham et al. 25 citations
Analogues of 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin) are being sold on recreational drug markets and developed as potential medications for psychedelic-assisted therapies. Many of these tryptamine-based psilocybin analogues produce psychedelic-like effects in rodents and humans primarily by agonist activity at serotonin 2A receptors (5-HT2A). However, the comprehensive...
ACS Pharmacology & Translational Science November 2, 2022 Eline Pottie, Marilyn Naeem, Vamshikrishna Reddy Sammeta et al. 91 citations
4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug for 4-hydroxy-N,N-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT2A). Several other 4-position ring-substituted tryptamines are present in psilocybin-containing...
ACS Omega July 5, 2022 Grant C. Glatfelter, Duyen N. K. Pham, Donna Walther et al. 14 citations
Aeruginascin (4-phosphoryloxy-N,N,N-trimethyltryptammonium) is an analogue of psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) that has been identified in several species of psilocybin-containing mushrooms. Our team previously reported the synthesis, structural characterization, and biological activity of the putative metabolite of aeruginascin (4-hydroxy-N,N,N-trimethyltryptammonium;...
The FASEB Journal May 1, 2022 Grant C. Glatfelter, David R. Manke, Andrew R. Chadayne et al. 1 citation
4‐phosphorloxy‐ N,N ‐dimethyltryptamine (psilocybin) is a naturally occurring psychedelic compound that is being investigated in clinical studies in conjunction with psychotherapy for treatment of several psychiatric disorders. It is well established that 4‐hydroxy‐ N,N ‐dimethyltryptamine (psilocin) is the bioactive metabolite of psilocybin which mediates its in vivo psychedelic activity in...
ACS Pharmacology & Translational Science April 8, 2022 Grant C. Glatfelter, Michael R. Chojnacki, Shelby A. McGriff et al. 18 citations
Psychedelics are a class of drugs that produce unique subjective effects via agonist actions at the 5-hydroxytryptamine 2A receptor (5-HT2A). The 5-HT2A-mediated head twitch response (HTR) in rodents is used as a reliable proxy for psychedelic drug activity in humans, but existing methods for measuring HTRs require surgery or time-consuming visual scoring. In the present work, we validated a...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology March 1, 2022 Deborah Rudin, John D. Mccorvy, Grant C. Glatfelter et al. 18 citations
Derivatives of (2-aminopropyl)indole (API) and (2-aminopropyl)benzofuran (APB) are new psychoactive substances which produce stimulant effects in vivo. (2-Aminopropyl)benzo[β]thiophene (APBT) is a novel sulfur-based analog of API and APB that has not been pharmacologically characterized. In the current study, we assessed the pharmacological effects of six APBT positional isomers in vitro, and...
ACS Chemical Neuroscience March 9, 2021 Grant C. Glatfelter, Donna Walther, Michael Evans‐brown et al. 29 citations
Synthetic cathinones are a class of new psychoactive substances that induce psychostimulant effects and pose risk for hospitalizations, overdose, and death. At the present time, derivatives of the synthetic cathinone, methylone, are being confiscated in nonmedical (i.e., recreational) drug markets worldwide. In particular, eutylone is a newly emerging methylone analog that possesses ethyl...
Addiction Biology February 3, 2021 Bree A. Humburg, Chloe J. Jordan, Hai‐Ying Zhang et al. 30 citations
Abstract Despite extensive research, the rewarding effects of cannabinoids are still debated. Here, we used a newly established animal procedure called optogenetic intracranial self‐stimulation (ICSS) (oICSS) to re‐examine the abuse potential of cannabinoids in mice. A specific adeno‐associated viral vector carrying a channelrhodopsin gene was microinjected into the ventral tegmental area (VTA)...