Neuropsychopharmacology
July 20, 2026
Noam Goldway, Itamar Jalon, Yara Agbaria et al.
Abstract Ketamine produces both analgesic and dissociative effects, but whether analgesia depends on dissociation remains debated. This question is part of a broader discussion on whether the subjective experiences elicited by psychoactive drugs are necessary for their therapeutic benefits. Here, we tested whether ketamine-induced analgesia and dissociation show separable behavioral and neural...
Neuropsychopharmacology
July 18, 2026
James J Gattuso, Ahmed Kamal, Jennyfer M. Payet et al.
Abstract Psilocybin is a serotonergic psychedelic drug with emerging therapeutic applications, yet its actions under glutamatergic dysfunction, and relevance to schizophrenia and associated psychiatric disorders, remain unclear. We examined the acute and long-lasting effects of psilocybin (1 mg/kg, intraperitoneal) on behavioral and neural outcomes in the metabotropic glutamate receptor 5...
Neuropsychopharmacology
July 10, 2026
Christopher W. Thomas, Kayleigh S. Lamalfa, Tobias P. Whelan et al.
Anhedonia, the blunted responsiveness to previously rewarding stimuli, is a core symptom of several psychiatric disorders. Ketamine and psilocybin have shown promising evidence in ameliorating anhedonic symptoms in clinical trials. The Probabilistic Reward Task (PRT) was developed to objectively quantify reward responsiveness in clinical populations and laboratory animals. Here, the PRT was...
Neuropsychopharmacology
July 7, 2026
Wojciech Pasławski, Daniel Doyon, Carl Johan Ekman et al.
Psilocybin is a rapid-acting antidepressant, but its mechanism of action in major depressive disorder remains unclear. In this secondary analysis of randomized, placebo-controlled trial with multimodal CSF and blood biomarker measurements, psilocybin selectively reduced CSF galanin and noradrenaline, implicating that normalization of these co-transmitters is a key pharmacodynamic signature.
Neuropsychopharmacology
June 18, 2026
Abigail E. Calder, Vincent J Diehl, Morten P. Lietz et al.
Preclinical studies suggest that lysergic acid diethylamide (LSD) may induce lasting changes in brain function and learning ability, but evidence in humans is uncertain. Motor learning, in particular, has clinical relevance but has not been investigated in human studies of psychedelics. Forty-five healthy subjects (24 women) participated in this randomized crossover trial comparing 100 µg LSD...
Neuropsychopharmacology
June 1, 2026
correction
“Adapted from Mian et al. (2025), with permission.” needs to be added to Fig. 1 caption. Thus, the correct Fig. 1 caption reads: Fig. 1 Thereapeutic Intent, legality and structure. Adapted from Mian et al. (2025), with permission. For instance, a medication that is approved by the FDA for prescription by physicians for a specific condition, manufactured under supervision, and dispensed by a...
Neuropsychopharmacology
February 18, 2026
Itishree Sahoo, Sairam Masadi, Ashwath Maheswari et al.
3 citations
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. We hypothesized psilocybin given during adolescence, a time of heightened neuroplasticity, particularly in the forebrain, would affect emotional behavior and the associated underlying neuroanatomy, neurocircuitry, and epigenetics. Female and male mice...
Neuropsychopharmacology
February 13, 2026
Fabrizio Ascone, Valeria Buzzelli, Francesca Mottarlini et al.
2 citations
Fragile X Syndrome (FXS) is the most common inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). As a synaptic disorder, FXS involves the loss of Fragile X messenger ribonucleoprotein 1 (FMRP), leading to abnormal dendrite development and immature dendritic spines. Serotonergic signaling, essential for neuronal development and circuit remodeling,...
Neuropsychopharmacology
January 16, 2026
Philip D. Harvey, Charles B. Nemeroff
2 citations
Interest in psychedelic therapies is booming, with hundreds of studies in process. Despite the interest, there are no approved psychedelic treatments for any psychiatric condition. Further, the one large-scale development program using MDMA that reached the FDA was disapproved by the agency for reasons that could apply to clinical trials for classical psychedelics. We review the definitions of...
Neuropsychopharmacology
November 12, 2025
Hannah M. Kramer, Meghan Hibicke, Jason W. Middleton et al.
7 citations
Activation of serotonin 2A (5-HT2A) receptors is thought to underly the long-lasting antidepressant effects of psychedelics such as psilocybin, but beyond that, the molecular and cellular mechanisms involved are not well understood. Recent preclinical studies using mice have primarily examined relatively short time points after psychedelic administration, which does not address the long-lasting...
Neuropsychopharmacology
October 31, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
1 citation
Lysergic acid diethylamide (LSD) and 3,4-Methylenedioxymethamphetamine (MDMA) are widely used psychoactive drugs and their potential use in psychiatric medicine is currently generating interest. The mechanism by which these drugs may assist recovery in various disorders such as addiction and post-traumatic stress disorder (PTSD) is still not well understood. Most investigations of the effects...
Neuropsychopharmacology
September 12, 2025
Jakub Vohryzek, Andrea I. Luppi, Selen Atasoy et al.
2 citations
Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome...
Neuropsychopharmacology
December 19, 2024
Livio Erne, Severin B Vogt, Lorenz Müller et al.
14 citations
Abstract N,N -dimethyltryptamine (DMT) is a serotonergic psychedelic that is known for its short-lasting effects when administered intravenously. Several studies have investigated the administration of intravenous boluses or combinations of a bolus and a subsequent continuous infusion. However, data on dose-dependent acute effects and pharmacokinetics of continuous DMT infusions are lacking. We...
Neuropsychopharmacology
July 6, 2024
David Martin, Angel M. Delgado, Donna J. Calu
3 citations
Psychedelics produce lasting therapeutic responses in neuropsychiatric diseases suggesting they may disrupt entrenched associations and catalyze learning. Here, we examine psychedelic 5-HT2A/2C agonist, DOI, effects on dopamine signaling in the nucleus accumbens (NAc) core, a region extensively linked to reward learning, motivation, and drug-seeking. We measure phasic dopamine transients...
Neuropsychopharmacology
May 28, 2024
Natalie Ertl, Tom P. Freeman, Claire Mokrysz et al.
19 citations
Adolescence is a time of rapid neurodevelopment and the endocannabinoid system is particularly prone to change during this time. Cannabis is a commonly used drug with a particularly high prevalence of use among adolescents. The two predominant phytocannabinoids are Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which affect the endocannabinoid system. It is unknown whether this...
Neuropsychopharmacology
May 13, 2024
Conor H. Murray
MDMA-assisted psychotherapy has emerged as a potential treatment for psychiatric illnesses, with findings from clinical trials in the last decade demonstrating safety and efficacy in the treatment of posttraumatic stress disorder (PTSD), among other psychiatric indications. Earlier this year (2024), the Food and Drug Administration in the United States granted priority review for a new drug...
Neuropsychopharmacology
April 23, 2024
Julia Colcott, Olivia Carter, Sally Meikle et al.
37 citations
Abstract Evidence suggests that MDMA-assisted psychotherapy (MDMA-AP) has therapeutic potential for treatment of psychiatric illness. We conducted the first comprehensive systematic review and meta-analysis of the side effects of MDMA-AP across indications. We also assessed the quality of side effects-reporting in published trials of MDMA-AP. PubMed, EMBASE, PsycINFO, MEDLINE and Cochrane...
Neuropsychopharmacology
April 16, 2024
Brett D. M. Jones, Muhammad Ishrat Husain
Neural effects of psychedelics: Complexity the key word.
Neuropsychopharmacology
2024
Ryan H. Gumpper, Bryan L. Roth
Recently, psychedelics have emerged as promising therapeutics for numerous neuropsychiatric disorders. While their potential in the clinic has yet to be fully elucidated, understanding their molecular and biological mechanisms is imperative as these compounds are becoming widely used both in therapeutic and recreational contexts. This review examines the current understanding of basic biology,...
Neuropsychopharmacology
2024
Tobias Haeusermann, Winston Chiong
New treatment modalities for mental illness are deeply needed, and emerging therapeutic agents such as psychedelics, ketamine, and neuromodulatory technologies have been welcomed by many researchers and patients. These treatment approaches have also been observed to raise novel ethical questions, and to pose new and different versions of familiar ethical questions in clinical treatment and...
Neuropsychopharmacology
2024
Joshua A. Gordon, Nora D. Volkow, George F. Koob
The vast majority of treatments for psychiatric and substance use disorders take weeks to work. Notable exceptions to this rule exist, with some treatments such as intravenous ketamine resolving symptoms in minutes to hours. Current research is focused on identifying novel approaches to rapid-acting psychotherapeutics. Promising results from studies of novel classes of drugs and innovative...
Neuropsychopharmacology
July 24, 2023
John H. Krystal, Ege T Kavalali, Lisa M Monteggia
229 citations
Ketamine is an open channel blocker of ionotropic glutamatergic N -Methyl- D -Aspartate (NMDA) receptors. The discovery of its rapid antidepressant effects in patients with depression and treatment-resistant depression fostered novel effective treatments for mood disorders. This discovery not only provided new insight into the neurobiology of mood disorders but also uncovered fundamental...
Neuropsychopharmacology
July 24, 2023
Boris D. Heifets, David E. Olson
66 citations
Recent clinical and preclinical evidence suggests that psychedelics and entactogens may produce both rapid and sustained therapeutic effects across several indications. Currently, there is a disconnect between how these compounds are used in the clinic and how they are studied in preclinical species, which has led to a gap in our mechanistic understanding of how these compounds might positively...
Neuropsychopharmacology
July 21, 2023
Jennifer Mitchell, Brian T Anderson
47 citations
The clinical investigation of psychedelic medicines has blossomed over the last 5 years. Data from a Phase 3 industry trial and a multicenter Phase 2 industry trial, in addition to multiple early phase investigator-initiated and industry trials, have now been published in peer-reviewed journals. This narrative review summarizes both the recent data and the current clinical trials that are being...
Neuropsychopharmacology
May 12, 2023
Naim Zaki, Li Chen, Rosanne Lane et al.
122 citations
Patients with treatment-resistant depression (TRD) have higher rates of relapse and pronounced decreases in daily functioning and health-related quality of life compared to patients with major depressive disorder who are not treatment-resistant, underscoring the need for treatment choices with sustained efficacy and long-term tolerability. Adults with TRD who participated in ≥1 of 6 phase 3...