European Neuropsychopharmacology
September 25, 2014
Rainer Kraehenmann, Katrin H. Preller, Erich Seifritz et al.
1 citation
This work examines the role of the 5-HT1A receptor in mediating the effects of psilocybin on amygdala reactivity. Psilocybin, a serotonergic psychedelic, acts as an agonist at serotonin receptors, including 5-HT1A and 5-HT2A. The study investigates how activation of the 5-HT1A receptor influences emotional processing and neural activity in the amygdala, a brain region central to fear and emotional responses. Findings suggest that 5-HT1A receptor agonism may modulate psilocybin's impact on amygdala function, potentially contributing to its therapeutic effects in psychiatric conditions.
Research Square
July 9, 2026
Samuel Westenhöfer, Yamina Ehrt, Barbora Provaznikova et al.
For people with treatment-resistant depression, intranasal esketamine significantly reduced depressive symptoms during an initial four-week induction phase. After induction, two different maintenance schedules—one with a front-loaded pattern and one with a spaced interval-extension pattern—were compared. No significant differences in depressive symptom trajectories were observed between the two schedules over the maintenance period. By the end of maintenance, response rates were 35.3% on the clinician-rated scale and 26.0% on the self-report scale; remission rates were 31.4% and 38.0%, respectively. These results suggest that maintenance dosing intervals may be scheduled flexibly without loss of efficacy, though the retrospective, observational design and small sample size warrant caution.
Psychotherapy and psychosomatics
June 19, 2026
Judith Rohde, Tyler M Moore, Kathryn Walker et al.
A systematic review and individual participant data meta-analysis of 12 studies (533 participants) found that higher baseline PTSD severity was the most robust predictor of symptom reduction after combined ketamine and psychotherapy. More psychotherapy sessions, more ketamine sessions, and shorter treatment duration were also associated with greater improvement, but these findings are tentative because most studies were of poor quality. The analysis showed that for each additional psychotherapy session, PTSD symptoms improved by an average of 1.03 points on the PCL-5, and for each additional ketamine session, improvement was 1.15 points. The results require confirmation in well-designed prospective trials.
December 10, 2025
Johannes Jungwirth, Samuel Westenhöfer, Helena Aicher et al.
In a real-world clinical setting in Switzerland, 19 patients with treatment-resistant depression received one to four doses of psilocybin (20–35 mg). Depression severity, measured by the Montgomery–Åsberg Depression Rating Scale and the Beck Depression Inventory II, showed significant and clinically meaningful reductions from before to after treatment. Response rates were 33.3% and remission rates 22.2% on one scale; on the other, both were 27.8%. No serious adverse events occurred, and multiple dosing did not add benefit. These response and remission rates are lower than those seen in earlier controlled trials, but the findings provide some of the first real-world evidence for psilocybin's antidepressant effects.
The Lancet Regional Health - Europe
December 10, 2025
Johannes Jungwirth, Samuel Westenhöfer, Helena D. Aicher et al.
In a retrospective analysis of medical records from 19 patients with treatment-resistant depression treated with psilocybin (20–35 mg) in one to four dosing sessions at a Swiss psychiatric hospital, depression severity decreased significantly. Montgomery–Åsberg Depression Rating Scale scores dropped from an average of 30.78 before treatment to 19.89 afterward, a large effect, and Beck Depression Inventory II scores fell from 32.33 to 23.28. Response and remission rates were 33.3% and 22.2% by the MADRS, and 27.8% and 27.8% by the BDI. No serious adverse events occurred. Response and remission rates were lower than those in previous controlled trials, and no additive effect of multiple dosing was found.
Scientific Reports
April 23, 2024
Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
No Summary
Pharmacopsychiatry
September 1, 2011
Simone Grimm, Milan Scheidegger, A Henning et al.
Ketamine, a glutamatergic NMDA receptor antagonist with rapid antidepressant properties, was used to investigate the neurobiology of major depressive disorder. In a multimodal imaging study of 23 healthy subjects, a single ketamine infusion increased negative BOLD responses in brain regions involved in emotional processing, particularly limbic areas linked to emotional information and higher-order mental functions. During cognitive processing, ketamine affected negative BOLD responses in anterior but not posterior regions of the default-mode network. Strong correlations were found between glutamate, glutamine, GABA, and glutamine/glutamate ratios and these brain responses after ketamine administration, suggesting a link to glutamatergic neurotransmission.
Pharmacopsychiatry
September 1, 2011
Milan Scheidegger, A Henning, Martin Walter et al.
A subanaesthetic dose of ketamine alters brain activity during emotional processing and increases glutamate-glutamine cycling in the pregenual anterior cingulate cortex, a region linked to mood regulation. In 23 healthy subjects, ketamine infusion changed fMRI responses to emotional pictures, and these changes correlated with shifts in glutamine-to-glutamate ratios measured by spectroscopy. The findings suggest ketamine's rapid antidepressant effect may stem from enhanced glutamatergic neurotransmission.
medRxiv
Klemens Egger, Daniel Meling, Firuze Polat et al.
preprint
In a double-blind, placebo-controlled pharmaco-fMRI study, 40 meditation practitioners on a three-day retreat received either placebo or buccal DMT-harmine (120 mg each). Meditation alone increased network segregation across several resting-state networks, while DMT-harmine increased functional connectivity within the visual network and between visual and attention networks. Between-group differences showed increased connectivity between visual and salience networks in the DMT-harmine group. No prolonged cortical gradient disruption was observed, indicating a return to typical brain organization shortly after the experience. Meditation reduced connectivity between networks, whereas DMT-harmine increased within- and between-network connectivity, revealing distinct neural mechanisms.
European archives of psychiatry and clinical neuroscience
September 1, 2025
Golo Kronenberg, Georgios Schoretsanitis, Erich Seifritz et al.
Nitrous oxide (N2O) has been used since the 1700s and today is a significant greenhouse gas and ozone-depleting substance, though medical use contributes little to these effects. Its analgesic and anesthetic properties make it common in dentistry and surgery, and new research suggests antidepressant actions through NMDA antagonism and opioid effects. Larger clinical trials are needed to confirm its use as a rapid-acting antidepressant, and optimal dosing and duration remain unclear. Non-medical use has increased, with risks including asphyxia from acute use and vitamin B12 deficiency from chronic use, leading to conditions like megaloblastic anemia, venous thrombosis, myeloneuropathy, and skin pigmentation. Treatment requires stopping N2O use and administering parenteral vitamin B12; homocysteine and methylmalonic acid are helpful diagnostic tests.
BMJ open
July 16, 2025
Golo Kronenberg, Anna Bankwitz, Barbora Provaznikova et al.
Nitrous oxide (N2O) may offer rapid antisuicidal effects across mental health conditions, with its pharmacological action thought to involve NMDA antagonism and opioid effects. This protocol describes a single-centre pilot study of 85 psychiatric inpatients. In a double-blind, randomized, placebo-controlled design, the first 45-minute inhalation session delivers either 50% N2O with 50% oxygen or 50% oxygen plus air. Suicidal ideation is measured by the Beck Scale for Suicidal Ideation before and after inhalation. A second N2O inhalation one week later ensures all participants receive active treatment. A nested biomarker substudy using hair, blood, and EEG will explore mechanisms and prediction.
Psychopharmacology
July 1, 2017
Rainer Kraehenmann, Dan Pokorný, Leonie Vollenweider et al.
Lysergic acid diethylamide (LSD) produces waking mental imagery that resembles dreaming, an effect driven by activation of the 5-HT2A receptor. In a study with 25 healthy subjects, LSD (100 mcg orally) significantly increased cognitive bizarreness in guided mental imagery reports compared with placebo, and this increase correlated with a loss of self-boundaries and cognitive control. Both the imagery changes and altered state of consciousness were fully blocked by the 5-HT2A antagonist ketanserin (40 mg orally). The findings suggest that LSD-induced dreamlike imagery depends specifically on 5-HT2A receptor activation.