47 papers in the library · 78 citations · publishing 2020-2026
medRxiv Preprint Server April 28, 2023 Theresa R. Lii, Ashleigh E. Smith, Josephine R. Flohr et al. 28 citations preprint
Ketamine may have antidepressant properties, but its acute psychoactive effects make it difficult to successfully mask in placebo-controlled trials, complicating the interpretation of study results.
medRxiv Preprint Server May 25, 2022 S. Parker Singleton, Julie B. Wang, Michael Mithoefer et al. 9 citations preprint
In nine veterans and first-responders with chronic PTSD, MDMA-assisted therapy did not significantly increase amygdala-hippocampus resting-state functional connectivity as hypothesized, only showing a trend. After treatment, activation in the cuneus decreased when recalling traumatic versus neutral memories. The amount of PTSD recovery correlated with changes in four functional connections during autobiographical memory recall: left amygdala with left and right posterior cingulate cortex and left insula, and left isthmus cingulate with left posterior hippocampus. These findings suggest that MDMA-AT may alter functional connectivity in brain regions involved in memory and fear processing, but more research is needed to determine if these effects are specific to MDMA-AT compared to other PTSD treatments.
medRxiv Preprint Server December 7, 2020 Vasileia Kotoula, Argyris Stringaris, Nuria Mackes et al. 9 citations preprint
Ketamine, an antidepressant, can alter activity in brain reward areas within two hours of a single infusion, even in people who are not currently depressed. In a study of 37 remitted depression patients, ketamine increased brain responses in the nucleus accumbens and putamen during anticipation and receipt of small rewards, and the level of a ketamine metabolite (2R,6R)-HNK correlated with activation in the ventral tegmental area. These changes occurred without any changes in mood symptoms, suggesting ketamine may improve anhedonia by directly modulating how the brain processes reward feedback.
medRxiv Preprint Server July 7, 2021 Or Duek, Yutong Li, Ben Kelmendi et al. 8 citations preprint
A single low-dose infusion of ketamine, an NMDA receptor antagonist, given after recalling a traumatic memory can weaken the fear response associated with post-traumatic stress disorder. In the study, people who received ketamine showed lower activity in the amygdala and hippocampus when re-exposed to trauma memories, compared to those who received midazolam. Ketamine also reduced communication between the amygdala and hippocampus, without affecting connections to the prefrontal cortex. These changes lasted at least 30 days after treatment, suggesting that human traumatic memories can be altered during a reconsolidation window, potentially offering a new approach to treating PTSD.
medRxiv Preprint Server November 26, 2020 Giulia Bommarito, Anjali Tarun, Younes Farouj et al. 7 citations preprint
In people with progressive multiple sclerosis, brain function changes are not well understood, but studying them could reveal more about how the disease works at this stage.
medRxiv Preprint Server September 10, 2024 Kristin Dawson, Athena May Jean M. Carangan, Jessica Klunder et al. 4 citations preprint
Depression and PTSD are linked to poor health outcomes similar to aging. Ketamine infusions rapidly reduce symptoms of treatment-resistant depression and PTSD. In 20 participants with moderate to severe depression or trauma, a 2-3 week course of 0.5 mg/kg ketamine infusions reduced depression and PTSD scores. Epigenetic age, measured by OMICmAge, GrimAge V2, and PhenoAge biomarkers, decreased after treatment. Changes in underlying epigenetic biomarker proxies and surrogate protein markers were also observed. The findings align with prior research on ketamine's epigenetic effects and suggest these biomarkers capture signals related to clinical improvement and biological aging.
medRxiv Preprint Server January 3, 2023 Bessel A. van der Kolk, Julie B. Wang, Rachel Yehuda et al. 2 citations preprint
A Phase 3 clinical trial tested MDMA-assisted therapy (MDMA-AT) against placebo with therapy for severe PTSD. 85% of participants reported early childhood trauma, linked to deficits in emotional coping. MDMA-AT significantly improved alexithymia, self-compassion, and altered self-capacities compared to therapy alone. These changes address transdiagnostic mental processes that often hinder treatment response.
medRxiv Preprint Server April 23, 2022 Alexia G. Aguilar, Burke A. Beauregard, Christopher P. Conroy et al. 2 citations preprint
Ketamine and esketamine effectively treat treatment-resistant depression without the therapeutic delay typical of other antidepressants and do not increase suicidal thoughts or behaviors in adolescents and young adults. Esketamine received FDA approval in March 2019.
medRxiv Preprint Server March 31, 2026 Maia Mallevays, Louise Fuet, Michel Danon et al. 1 citation preprint
In patients with treatment-resistant depression receiving esketamine, mystical experiences—similar to those induced by classic psychedelics—occurred in 58% of patients, with high variability across sessions. Higher mean and peak scores on the Mystical Experience Questionnaire (MEQ-30) were associated with greater improvement in depression severity, while dissociative or other non-mystical effects were not. Positive mood and mystical dimensions of the MEQ predicted therapeutic outcomes, and baseline spirituality predicted both treatment response and peak MEQ scores in the first week. These findings suggest that psychedelic-like mystical experiences may contribute to esketamine's therapeutic efficacy.
medRxiv Preprint Server June 2, 2025 Mario Bogdanov, Jason N. Scott, Shiba M. Esfand et al. 1 citation preprint
A single, subanesthetic dose of ketamine improved reward responsiveness in both humans with treatment-resistant depression and chronically-stressed rats, measured using functionally identical tasks. The finding suggests that ketamine's rapid antidepressant effects may involve enhancing reward processing, a core feature of anhedonia. The work provides translational evidence linking preclinical and clinical observations, though the mechanisms remain unclear.
medRxiv Preprint Server March 21, 2025 Leo R. Silberbauer, Benjamin Eggerstorfer, Paul Michenthaler et al. 1 citation preprint
Oral ketamine may offer a more accessible alternative to intravenous and intranasal routes for treating depression, as it is easier to administer and has established safety and efficacy for chronic pain patients at home. The text suggests that current delivery methods limit ketamine's availability to specialized centers, but oral administration could expand access to antidepressant therapy.
medRxiv Preprint Server February 25, 2025 J Cohen, AC Reichelt, R Zamyadi et al. 1 citation preprint
A male patient in his late 30s with generalized anxiety disorder and depressive symptoms received ketamine-assisted psychotherapy (KAP) and underwent magnetoencephalography (MEG) scans before and after four of six KAP sessions plus two integration sessions. Functional connectivity increased in four of five brain networks measured (default mode, attention, central executive, motor, and visual), alongside increased cortical beta activity, decreased theta oscillations, reduced scores on anxiety and depression scales, and improved attention. These results suggest that resting-state MEG can detect KAP-related brain network changes and may help monitor therapeutic outcomes.
medRxiv Preprint Server November 26, 2024 Bonnie L. Quigley, Adem T. Can, Megan Dutton et al. 1 citation preprint
A weekly low-dose oral ketamine treatment for six weeks significantly reduced PTSD symptoms in adults with PTSD, many of whom also had depression. PTSD Checklist scores dropped from an average of 40 before treatment to 17 after treatment, and remained reduced at 21 one month later. 73% of participants showed at least a 50% reduction in symptoms after treatment, and 59% maintained that improvement at follow-up. The results suggest oral ketamine is a feasible and tolerable treatment option, comparable to intravenous ketamine, and may overcome limitations of IV administration.
medRxiv Preprint Server January 29, 2024 Ariela S. Buxbaum Grice, Laura Sloofman, Tess Levy et al. 1 citation preprint
A single low-dose intravenous ketamine infusion (0.5 mg/kg) triggers immediate and profound changes in gene expression in the blood of 10 individuals with ADNP syndrome, a rare neurodevelopmental disorder causing intellectual disability, developmental delay, and autism spectrum disorder. The alterations are enriched in monocyte-related patterns, with up-regulation of immune and inflammatory processes and down-regulation of RNA processing and metabolism. These changes are transient, returning to baseline within 24 hours to one week after treatment. The findings clarify ketamine's molecular effects and may guide therapeutic development for ADNP syndrome and possibly autism spectrum disorder.
medRxiv Preprint Server December 1, 2023 Brandon Taraku, Joana R. Loureiro, Ashish K. Sahib et al. 1 citation preprint
In major depressive disorder, ketamine infusions alter brain connectivity in networks involving the habenula and nucleus accumbens, regions central to reward processing. After four subanesthetic ketamine infusions given to 58 adults with depression, resting-state fMRI scans showed specific changes in static and dynamic functional connectivity between these regions and visual, parietal, and cerebellar areas. Decreased variability in connectivity between the left habenula and right precuneus and visual cortex, and between the right nucleus accumbens and right visual cortex, correlated with reduced depression severity. Reduced connectivity between the left habenula and visual/parietal cortices, and increased connectivity between the left nucleus accumbens and visual/parietal cortices, correlated with improvements in anhedonia. Ketamine appears to modulate overlapping habenula and nucleus accumbens functional pathways related to therapeutic response.
medRxiv Preprint Server April 10, 2021 Agnes Norbury, Sarah B. Rutter, Abigail B. Collins et al. 1 citation preprint
In a small randomized clinical trial, repeated doses of ketamine improved PTSD symptoms more than midazolam. Brain scans showed that symptom improvement was linked to increased communication between the ventromedial prefrontal cortex and amygdala when viewing emotional faces, especially in those who received ketamine. Ketamine-related improvement was also predicted by decreased activity in the dorsal anterior cingulate during emotional conflict and increased resting-state connectivity between the ventromedial prefrontal cortex and anterior insula. Further analysis indicated that ketamine specifically strengthened the prefrontal cortex's ability to inhibit amygdala responses to threatening social cues, suggesting a normalization of brain circuits involved in fear regulation.
medRxiv Preprint Server April 10, 2020 Chadi G. Abdallah, Kyung-Heup Ahn, Lynnette A. Averill et al. 1 citation preprint
A robust and reproducible brain connectivity fingerprint (CFP) was identified during ketamine infusion in healthy participants, characterized by reduced connectivity within primary cortices and the executive network, but increased connectivity between the executive network and the rest of the brain. This same CFP measured one week after treatment in major depressive disorder patients predicted response to eight weeks of sertraline, but not placebo. The findings suggest a brain network biomarker that links ketamine's acute effects to the mechanisms of conventional antidepressants.
medRxiv Preprint Server May 31, 2026 Yves Martins Varela, Patrícia Cavalcanti-Ribeiro, Geovan Menezes de Sousa et al. preprint
Ketamine rapidly reduces depression symptoms in treatment-resistant depression, but its effects may be enhanced by combining it with psychotherapy. The drug induces neuroplasticity and psychological openness, which could help patients process emotions, restructure thoughts, and maintain improvements. However, research has not yet thoroughly examined whether adding structured psychotherapy to ketamine treatment provides additional benefits.
medRxiv Preprint Server May 31, 2026 Madeline V. Stein, Matt Butler, Sarah Chapman et al. preprint
Context alone can produce psychedelic-like effects, even without an active drug. In a placebo experiment, 78 healthy participants inhaled inert medical air. When told it was nitrous oxide, they reported increased altered states of consciousness, ego dissolution, dissociation, and side effects, compared to when the gas was correctly identified as air. Time perception was not significantly affected. The strength of placebo-induced effects was predicted by individual traits of responsiveness to verbal suggestion and absorption. These results demonstrate that the context of drug administration plays a causal role in shaping psychedelic experiences.
medRxiv Preprint Server May 23, 2026 Lisa Maria Jöbstl, Bente Lubahn, Ebru Kaya et al. preprint
A subset of individuals who use classic psychedelics outside clinical settings reports persisting adverse effects, including hallucinogen persisting perception disorder, depersonalization/derealization disorder, anxiety, and depression. Despite growing non-clinical use, few medical services are equipped to address these complications. The authors highlight a delay in attention to these persisting adverse effects relative to enthusiasm for therapeutic potential.
medRxiv Preprint Server May 5, 2026 Nicholas C. Borgogna, D. Drew Whittington, Tyler Owen et al. preprint
MDMA-assisted therapy (MDMA-AT) shows a moderate-to-large reduction in psychological symptoms compared to control conditions, based on a meta-analysis of eight controlled trials with 295 participants. The effect was larger against inert placebos than active controls. Trauma symptoms improved strongly, while depression showed a smaller, non-significant effect. Only 23% of publications met high-quality standards for reporting harms. Small samples and mediocre harm reporting underscore the need for larger, more transparent trials.
medRxiv Preprint Server May 5, 2026 Tom Quinn, Feng Li, Becky Wheeler et al. preprint
A first-in-human Phase 0 intratarget microdosing study shows that delivering a tiny dose of a new inflammasome inhibitor directly into the lungs of patients with interstitial lung disease is feasible. A 100 microgram microdose of ADS032, a dual NLRP1/NLRP3 inhibitor, was administered to distal airways via bronchoscopy. The drug was detected in plasma, bronchoalveolar lavage fluid, distal airway micro-aspirates, and recovered cells without cross-contamination. Fluorescent labeling allowed direct visualization of alveolar drug uptake in ex vivo human lung tissue. This intrapulmonary microdosing approach offers a human-relevant platform for early pharmacological evaluation of lung therapeutics before Phase 1 trials.
medRxiv Preprint Server April 28, 2026 Sandeep M. Nayak, Nathan D. Sepeda, Matthew Nielsen Dick et al. preprint
Psilocybin is being studied as a treatment for psychiatric and neurologic conditions, but there is limited comprehensive data on its cardiovascular safety. Current clinical trials typically exclude people with blood pressure of 140/90 mmHg or higher, a cutoff set conservatively without strong empirical evidence.
medRxiv Preprint Server April 23, 2026 Willys Cantenys, Zeynep Yoldas, Luc Masset et al. preprint
Ketamine works quickly as an antidepressant but also causes temporary dissociative symptoms. In everyday clinical settings, it is unclear how much of the antidepressant effect comes from patients' expectations versus from the dissociative experience itself, and how these factors relate to changes in depression over time.
medRxiv Preprint Server April 23, 2026 Giada Lombardi, Grace Blest-Hopley, Martina Maria Tarantini et al. preprint
Regular cannabis users show altered brain responses during reward anticipation and outcome processing, but their actual task performance does not differ from non-users. Using the Monetary Incentive Delay Task, the study found that cannabis users had reduced neural activity in reward-related brain regions during anticipation of potential gains and losses, yet their reaction times and accuracy were comparable to non-users. These findings suggest that regular cannabis use is associated with changes in reward-related brain function without corresponding behavioral deficits.