Nature Communications
August 3, 2026
Frederik Gudmundsen, Julia Czurylo, Daniel Ryskamp Rijsketic et al.
Serotonergic psychedelics show therapeutic potential across neuropsychiatric disorders despite transient acute effects. These compounds share serotonin 2 A receptor agonism but differ in broader pharmacology, motivating a systematic comparison of their neurobiological effects. Here, we use [18 F]FDG-PET in rats to assess acute and one-week effects of psilocybin, LSD, and 2C-B on brain metabolic...
British Journal of Anaesthesia
August 1, 2026
Pilleriin Sikka, Sherry Hu, Boris D. Heifets
Dreaming during anaesthesia has been documented for over a century, yet it remains poorly understood. This scoping review synthesises evidence on the frequency, phenomenology, predictors, outcomes, and neural correlates of anaesthesia dreaming. We systematically searched multiple databases for studies examining anaesthesia dreaming, including clinical trials, observational studies, and...
The American journal of psychiatry
June 1, 2026
Jason M Tucciarone, Igor D. Bandeira, Christine Blasey et al.
5 citations
Ketamine rapidly reduces suicidal ideation in major depressive disorder (MDD), but its effects are transient. Preclinical and clinical studies suggest that ketamine's antidepressant and antisuicidal effects may be partly mediated by mu-opioid receptor (MOR) modulation. The authors investigated the efficacy and safety of low-dose sublingual buprenorphine, a partial MOR agonist, as a follow-on...
JAMA Psychiatry
June 1, 2026
Ben Deverett, Duan Li, Theresa R. Lii et al.
1 citation
Ketamine has well-known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Considering that specific cortical oscillations have been associated with specific therapeutic effects, modulating selective aspects of ketamine neurophysiology could inform...
ACS Chemical Neuroscience
May 6, 2026
Maxemiliano V. Vargas, Cassandra J. Hatzipantelis, Lee E. Dunlap et al.
Recent clinical evidence suggests that racemic 3,4-methylenedioxymethamphetamine (MDMA) might be useful for treating a range of neuropsychiatric diseases including post-traumatic stress disorder (PTSD) and depression. However, concerns about its abuse potential stemming from its monoamine releasing properties have hampered its clinical development. Thus, safer analogues of racemic MDMA with...
Anesthesiology
February 3, 2026
Pilleriin Sikka, May Ching Ngo, Sherry Hu et al.
1 citation
BACKGROUND: Dreaming during anesthesia is common and may have mental health benefits. However, systematic research on its incidence and outcomes in clinical settings remains limited. This study implemented a standardized propofol-based, electroencephalography (EEG)-guided emergence bundle to facilitate a preemergence state conducive to dreaming, integrating it into routine care to assess...
Nature Communications
January 22, 2026
Nicholas Gregory, Tyler E. Girard, Akila Ram et al.
5 citations
The psychedelic psilocybin may have lasting therapeutic effects for patients with chronic pain syndromes. Some preclinical data suggest these putative benefits derive from direct analgesic effects; however, this possibility has not been comprehensively tested in preclinical models. Here, we evaluated the analgesic properties of a single exposure to psilocybin at acute and chronic time points in...
Neuro-Oncology
November 1, 2025
Richard Drexler, Belgin Yalçın, Rebecca Mancusi et al.
Abstract High-grade gliomas are the most aggressive form of brain tumors, and neuronal activity has emerged as a driver of glioma pathophysiology. Activity-dependent glioma growth results from paracrine factor signaling and bona fide neuron-to-glioma synapses that integrate glioma cells into brain-wide neuronal circuits. Here, we report how glioma cells integrate into serotonergic (5-HT)...
British Journal of Pharmacology
October 21, 2025
Austen B Casey, Boris D. Heifets
3 citations
The illicit drug 3,4-methylenedioxymethamphetamine (MDMA) has recently shown promising efficacy as an adjunct to psychotherapy for posttraumatic stress disorder (PTSD), although the underlying mechanisms are poorly defined. In this review, we contextualize the emergence of MDMA-assisted psychotherapy (MDMA-AT) within 20th century psychiatry and trace its journey from assisting with military...
The International Journal of Neuropsychopharmacology
October 1, 2025
Igor D. Bandeira, Luke A. Jelen, Jason M Tucciarone et al.
4 citations
Igor D Bandeira, MD, PhD, Luke A Jelen, MD, PhD, Jason M Tucciarone, MD, PhD, Boris D Heifets, MD, PhD, Carolyn I Rodriguez, MD, PhD, Alan F Schatzberg, MD
Nature Neuroscience
September 1, 2025
Isak K Aarrestad, Lindsay P. Cameron, Ethan M Fenton et al.
Nonhallucinogenic psychoplastogens, such as tabernanthalog (TBG), are being developed as potentially safer, more scalable alternatives to psychedelics for promoting neuronal growth and treating various brain conditions. Currently, it is unclear whether 5-hydroxytryptamine 2A (5-HT2A) receptors and immediate early gene (IEG) activation have a role in the neuroplasticity-promoting effects of...
medRxiv
August 7, 2025
Ben Deverett, Duan Li, Theresa R. Lii et al.
preprint
Structured Abstract Importance Ketamine has well known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Given prior studies that link specific cortical oscillations with specific therapeutic effects, it is likely that modulating selective aspects...
Journal of Affective Disorders
July 15, 2025
Theresa R. Lii, Josephine R. Flohr, Robin L. Okada et al.
1 citation
The endogenous opioid system is thought to play a role in the placebo antidepressant response. A recent trial comparing the rapid antidepressant effects of ketamine versus placebo in surgical patients, some of whom were on chronic opioid therapy, revealed a substantial placebo effect. This finding provided an opportunity to test the hypothesis that opioid agonist exposure interacts with placebo...
bioRxiv (Cold Spring Harbor Laboratory)
July 7, 2025
Akila Ram, Austen B Casey, Robert C. Malenka et al.
2 citations
preprint
Abstract The psychedelic psilocybin may have lasting therapeutic effects for patients with chronic pain syndromes. Some clinical and preclinical data suggest these putative benefits derive from direct analgesic effects. However, this possibility has not been comprehensively tested in preclinical models. Here, we show that psilocybin is not analgesic over a range of doses across multiple pain...
Biological Psychiatry
May 5, 2025
Matthew B Pomrenze, Sam Vaillancourt, Pierre Llorach et al.
11 citations
Ketamine has anesthetic, analgesic, and antidepressant properties which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. This mechanism may differentiate ketamine from other NMDA receptor antagonists. Animal models that reflect OR-dependent behavioral effects of ketamine may shed light on the...
bioRxiv (Cold Spring Harbor Laboratory)
April 9, 2025
Odilia D Lu, Katrina White, Kendall Raymond et al.
18 citations
preprint
ABSTRACT Studies reporting novel therapeutic effects of psychedelic drugs are rapidly emerging. However, the reproducibility and reliability of these findings could remain uncertain for years. Here, we implemented a multi-institutional collaborative approach to define the robust and replicable effects of the psychedelic drug psilocybin on mouse behavior. Five laboratories performed the same...
JAMA Network Open
April 1, 2025
Xue Zhang, Laura M Hack, Claire Bertrand et al.
10 citations
Rapidly acting therapeutics like 3,4-methylenedioxymethamphetamine (MDMA) are promising treatments for disorders such as posttraumatic stress disorder (PTSD). However, understanding who benefits most and the underlying neural mechanisms remains a critical gap. Stratifying individuals by neural circuit profiles could help differentiate neural, behavioral, and affective responses to MDMA,...
Journal of Psychoactive Drugs
November 22, 2024
Wesley C Ryan, Boris D. Heifets
2 citations
The use of ketamine and ketamine-assisted psychotherapy (KAP) for treatment of depression has grown dramatically, though much of these data are short term. The clinical profile of maintenance treatment remains poorly characterized. We assessed maintenance KAP for efficacy, tolerability, and reasons for dropout. This observational study retrospectively analyzed electronic health records from an...
medRxiv : the preprint server for health sciences
November 2, 2024
Theresa R. Lii, Josephine R. Flohr, Robin L. Okada et al.
preprint
The endogenous opioid system is thought to play a role in the placebo antidepressant response. A recent trial comparing the rapid antidepressant effects of ketamine versus placebo in surgical patients, some of whom were on chronic opioid therapy, revealed a substantial placebo effect. This finding provided an opportunity to test the hypothesis that opioid agonist exposure interacts with placebo...
bioRxiv : the preprint server for biology
October 22, 2024
Matthew B Pomrenze, Sam Vaillancourt, Juliana S Salgado et al.
1 citation
preprint
MDMA is a promising adjunct to psychotherapy and has well-known abuse liability, although less than other amphetamine analogs. While the reinforcing dopamine (DA)-releasing properties of MDMA are on par with methamphetamine (METH), MDMA is a far more potent serotonin (5-HT) releaser, via the 5-HT transporter (SERT). MDMA-mediated 5-HT release in a major reward center, the nucleus accumbens...
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Balázs Szigeti, Boris D. Heifets
62 citations
Clinical trials of psychedelic compounds like psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltrptamine (DMT) have forced a reconsideration of how nondrug factors, such as participant expectations, are measured and controlled in mental health research. As doses of these profoundly psychoactive substances increase, so does the difficulty in concealing the treatment condition in the...
Science Advances
April 26, 2024
Ben Rein, Kendall Raymond, Cali Boustani et al.
37 citations
MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology,...
bioRxiv : the preprint server for biology
March 6, 2024
Matthew B Pomrenze, Sam Vaillancourt, Pierre Llorach et al.
1 citation
preprint
Ketamine has anesthetic, analgesic, and antidepressant properties which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. It is unclear whether naltrexone blocks a direct effect of ketamine at ORs, or whether normal functioning of the OR system is required to realize the full antidepressant...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
November 1, 2023
Daniel Ryskamp Rijsketic, Austen B Casey, Daniel A. N. Barbosa et al.
49 citations
The effects of context on the subjective experience of serotonergic psychedelics have not been fully examined in human neuroimaging studies, partly due to limitations of the imaging environment. Here, we administered saline or psilocybin to mice in their home cage or an enriched environment, immunofluorescently-labeled brain-wide c-Fos, and imaged iDISCO+ cleared tissue with light sheet...
Nature Mental Health
October 19, 2023
Theresa R. Lii, Ashleigh E. Smith, Josephine R. Flohr et al.
94 citations
Ketamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials. Here we present a single-center, parallel-arm, triple-masked, randomized, placebo-controlled trial assessing the antidepressant efficacy of intravenous ketamine masked by surgical anesthesia (ClinicalTrials.gov, NCT03861988). Adult patients (N = 40) with...