Abstract: Background and Aims: Understanding the factors that lead to participation in psychedelic clinical trials is essential for assessing potential biases in enrollment and ensuring the generalizability of findings. Psychedelic treatment is thought to impact personality traits, psychological flexibility, and expectations, yet the role of these non-pharmacological variables in the initial...
Serotonergic psychedelics are promising treatments for neuropsychiatric disorders, and their immunomodulatory effects may contribute to their clinical efficacy. However, we lack a systematic review and meta-analysis of these effects across in vitro, in vivo non-human, and human studies. We systematically searched PubMed, EMBASE, Web of Science, PsycINFO, LILACS and ClinicalTrials.gov for all...
This Viewpoint discusses the UMBRAA (unidentifiable multidrug blinding with reduced, authorized awareness) strategy to address the masking problem in psychedelic trials.
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...
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...
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...
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...
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...
INTRODUCTION Ketamine shows promise for treatment-refractory chronic pain and depression, but randomized trials risk unblinding from ketamine's acute dissociative effects. Propofol sedation may mitigate this, though it has not been prospectively tested as a masking strategy outside of surgical contexts. METHODS This protocol describes a single-center, randomized, double-blind,...
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...
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-OncologyNovember 1, 2025Richard 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)...
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...
Background and Aims: Understanding the factors that lead to participation in psychedelic clinical trials is essential for assessing potential biases in enrollment and ensuring the generalizability of findings. Psychedelic treatment is thought to impact personality traits, psychological flexibility, and expectations, however these non-pharmacological variables may also influence the initial...
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
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...
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...
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...
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...
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...
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...
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,...
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...
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...
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...