Journal of affective disorders • November 1, 2026 • Carlton M Kelly, Mathieu Fradet, Catherine M Bostian et al.
A single 25-mg dose of psilocybin with psychological support was associated with sustained improvements in anxiety, quality of life, functioning, and PTSD symptoms in 15 veterans with treatment-resistant depression. Anxiety scores dropped 59% from baseline at three weeks and remained lower through 12 months. Quality of life increased 24% and functional impairment decreased 46% at three weeks, though these effects were no longer statistically significant after accounting for concurrent improvements in depression. PTSD symptom reductions were observed at all timepoints. Acute subjective experiences did not correlate with treatment response. The study is limited by its small sample and open-label design.
Neuropsychopharmacol Rep • September 1, 2026
In a mouse model of social defeat stress, the serotonin 5-HT2A receptor mediates the ability of psilocin to restore deficits in social behavior. Mice repeatedly subjected to social defeat stress showed reduced social interaction, and treatment with psilocin reversed this impairment. The therapeutic effect of psilocin was blocked by a 5-HT2A receptor antagonist and absent in mice lacking the 5-HT2A receptor, indicating that this receptor is necessary for the prosocial action of psilocin. These findings suggest that the 5-HT2A receptor is a key target for psilocin's effects on social behavior deficits caused by chronic stress.
Hearing research • August 1, 2026 • Shuhan Lu, Zhixin Zhang, Xinmiao Xue et al.
Tinnitus, the perception of sound without an external source, lacks effective treatments. Psilocybin, a psychedelic, shows promise by activating 5-HT2A receptors, boosting glutamate release, and upregulating BDNF, which increases dendritic spine density and synaptic proteins in the hippocampus and prefrontal cortex, restoring neural plasticity. This review connects these neuroplasticity mechanisms to tinnitus-related neural changes, highlighting psilocybin's regulatory effects on excitatory (glutamate, dopamine) and inhibitory (GABA) neurotransmitters and their receptors, suggesting a novel therapeutic pathway.
Journal of affective disorders • August 1, 2026 • Taro Kishi, Kenji Sakuma, Masakazu Hatano et al.
A systematic review and meta-analysis of six randomized controlled trials examined how psilocybin's effects on major depressive disorder change over time. Standard-dose psilocybin (25 mg/session or 20-30 mg/70 kg/session) was superior to control conditions (placebo, waiting-list, niacin, or 1 mg psilocybin) in reducing depressive symptoms. Sensitivity analyses excluding waiting-list controls confirmed this benefit with reduced heterogeneity. Standard-dose psilocybin also produced higher response and remission rates at 2-3 weeks and sustained response at 6-12 weeks, and lower all-cause discontinuation. However, it was associated with more headaches and nausea within 1-9 days, which resolved. Low-dose psilocybin showed no superior efficacy. The authors suggest standard-dose psilocybin is a promising treatment but note considerable methodological heterogeneity across trials.
Journal of affective disorders • August 1, 2026 • Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al. • 2 citations
In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.
BMJ open • July 13, 2026 • Thomas D Meyer, Lauren N Vale, Maya Ibrahim et al.
A protocol describes an upcoming feasibility study testing psilocybin-assisted therapy in 10 outpatients with bipolar II disorder who have mild to moderate passive suicidal thoughts. Participants may receive two oral doses of 25 mg psilocybin about four weeks apart, combined with a structured mindfulness-based cognitive-behavioral therapy protocol. The study aims to assess the acceptability and safety of this approach, measuring changes in suicidality and depressive symptoms, and to gather preliminary data for a future randomized trial. Individuals with bipolar disorder and suicidality have typically been excluded from psilocybin trials due to safety concerns.
bioRxiv (Cold Spring Harbor Laboratory) • July 13, 2026 • Natasha L. Mason, Eline Chm Haijen-bongers, Kim P. C. Kuypers et al.
Female participants reported more intense subjective effects from psilocybin, 2C-B, and LSD than male participants, including feeling more strongly under the drug's influence, reduced vigilance, and impaired control and cognition, with medium-to-large effects consistent across the three drugs. No sex differences were found in empathy measures or peak drug concentrations in blood. These findings suggest pharmacodynamic mechanisms—how the body responds to the drug—rather than pharmacokinetic differences in drug exposure explain the sex differences. The results have implications for dosing, informed consent, and safety monitoring in psychedelic research.
Journal of Psychedelic Studies • July 13, 2026 • Nils Hörnqvist
A review of psilocybin-assisted therapy trials for major depressive disorder and treatment-resistant depression found that reporting practices are inconsistent in several key areas. Overrepresentation of participants with prior psychedelic experiences (22.4% of participants) was noted. Trials often failed to report blinding success for therapists (10%) and participants (16.7%), therapist fidelity (6.7%), and expectancy (6.7%). Preparatory and integration sessions were reported as hours rather than number of sessions. Some standardization was observed, such as increased use of the MADRS depression scale and consistent dosing (25 mg for intervention, 1 and 0 mg for control groups). The review calls for future research to better assess blinding, therapist fidelity, expectancy, and to include more psychedelic-naïve participants.
Journal of neurogenetics • July 12, 2026 • Albert M Dong, Yi Han, Zheng Xu et al.
Psilocybin, a psychedelic compound, rapidly inhibited mouse locomotor activity, with effects resolving within about one hour. In the nucleus accumbens, a brain region involved in reward and emotion, psilocybin increased expression of the immediate early gene c-Fos in neurons around six hours after treatment and in non-neuronal cells around 1.5 hours. Blocking serotonin 2A receptors reduced psilocybin-induced c-Fos only in neurons, while blocking serotonin 2B receptors reduced it in both neurons and non-neuronal cells. These findings suggest that serotonin 2B receptors and non-neuronal cells may play important roles in the neural circuits underlying mood disorders.
Universitätsbibliothek der LMU • July 9, 2026 • Sowmya Narayan
Exposure to stress during brain development is a known risk factor for adult mental illness, which often differs by sex and responds poorly to current treatments. Using a mouse model, this work examined how early-life stress alters the adult brain across multiple levels—transcriptomics, network connectivity, resting-state activity, and behavior—and tested whether the psychedelic psilocybin could reverse these effects. Many adulthood differences caused by developmental stress were distinct and even opposing between sexes, driven by changes in processes active during neurodevelopment. Psilocybin broadly shifted behavior in a direction opposite to the effects of developmental stress, but through different behavioral domains in males and females. The findings highlight the need to consider sex as a biological variable and to improve translational validity in preclinical research.
The New England journal of medicine • November 3, 2022 • Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al. • 1,095 citations
A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.
New England Journal of Medicine • April 14, 2021 • Robin Carhart‐Harris, Bruna Giribaldi, Rosalind Watts et al. • 1,372 citations
In a selected group of patients, psilocybin did not show a significantly greater antidepressant effect than escitalopram based on depression scores at week 6. Secondary outcomes generally favored psilocybin, but these analyses were not corrected for multiple comparisons. The authors call for larger and longer trials to compare psilocybin with established antidepressants.
JAMA Psychiatry • November 4, 2020 • Mary P Cosimano, Alan K. Davis, Frederick S. Barrett et al. • 1,269 citations
Two doses of psilocybin (20 and 30 mg per 70 kg) combined with supportive psychotherapy produced large, rapid antidepressant effects in adults with major depressive disorder who were not taking other antidepressants. In a randomized waiting list-controlled trial with 24 completers, depression scores on the GRID-Hamilton scale dropped from a mean of 22.8 at baseline to 8.0 one week after the second session, compared with 23.8 at the same time point in the delayed-treatment group. Seventy-one percent of participants showed a clinically significant response at week 1, and 58% met remission criteria. Effects persisted through the four-week follow-up.
Pharmacological Reviews • June 20, 2019 • Robin Carhart‐Harris, Karl Friston • 1,163 citations
Psychedelics work by relaxing the precision of deeply held beliefs (high-level priors) in the brain, allowing more bottom-up information flow from intrinsic sources like the limbic system. This process, called REBUS (Relaxed Beliefs Under Psychedelics) and the anarchic brain, integrates the free-energy principle with the entropic brain hypothesis. The model explains how psychedelics can revise pathologically over-weighted priors underlying mental illness, and also potentially alter strongly held priors related to political, religious, or philosophical perspectives. The authors propose that this relaxation and sensitization of priors to bottom-up signaling enables therapeutic revision, especially when combined with appropriate intention, care, and context.
Psychopharmacology (Berl) • November 8, 2017 • 978 citations
In an open-label trial, twenty patients with severe, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, one week apart) in a supportive setting. Depressive symptoms dropped markedly within the first five weeks, with large effect sizes (Cohen's d = 2.2 at week 1 and 2.3 at week 5). Nine patients responded and four achieved remission at week 5. Improvements remained significant at three and six months (Cohen's d = 1.5 and 1.4). No one sought conventional antidepressants within five weeks. The quality of the acute psychedelic experience predicted symptom reductions at five weeks. Tolerability was good, and psilocybin appears promising for unresponsive depression, though double-blind trials are needed.
Journal of Psychopharmacology • November 30, 2016 • Stephen Ross, Anthony Bossis, Jeffrey Guss et al. • 1,699 citations
A single moderate dose of psilocybin (0.3 mg/kg), combined with psychotherapy, produced immediate and sustained improvements in anxiety and depression among 29 patients with cancer-related psychological distress. At the 6.5-month follow-up, approximately 60–80% of participants continued to show clinically significant reductions in depression or anxiety. Psilocybin also decreased demoralization and hopelessness, improved spiritual wellbeing, quality of life, and attitudes toward death. The therapeutic effects on anxiety and depression were mediated by the psilocybin-induced mystical experience.
Journal of Psychopharmacology • November 30, 2016 • Annie Umbricht, Mary P Cosimano, Roland R. Griffiths et al. • 2,174 citations
In cancer patients with life-threatening diagnoses and symptoms of depression or anxiety, a high dose of psilocybin (22 or 30 mg/70 kg) produced large decreases in depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety, compared with a very low placebo-like dose (1 or 3 mg/70 kg). At 6-month follow-up, about 80% of participants continued to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life, mood, relationships, and spirituality to the high-dose experience, with over 80% endorsing moderately or greater increased well-being or life satisfaction. The mystical-type experience during the session mediated the effect of dose on therapeutic outcomes.
Lancet Psychiatry • May 17, 2016 • 1,546 citations
In an open-label trial, 12 patients with moderate-to-severe treatment-resistant depression received two doses of psilocybin (10 mg and 25 mg, one week apart) in a supportive setting. The psychedelic effects peaked 2-3 hours after dosing and subsided within 6 hours. No serious adverse events occurred; transient anxiety, confusion, nausea, and headache were noted. Depressive symptoms, measured with the Quick Inventory of Depressive Symptoms, were markedly reduced one week after the high dose (mean reduction of 11.8 points) and remained lower at three months (mean reduction of 9.2 points). Improvements in anxiety and anhedonia were also observed. The results provide preliminary support for psilocybin's safety and efficacy in treatment-resistant depression, warranting further controlled trials.
Journal of Psychopharmacology • January 13, 2015 • Michael P. Bogenschutz, Alyssa A. Forcehimes, Jessica A. Pommy et al. • 1,164 citations
In a small proof-of-concept study, ten volunteers with alcohol dependence received one or two supervised doses of psilocybin alongside therapy. Abstinence did not increase during the first four weeks of treatment but increased significantly after psilocybin administration, with gains largely maintained up to 36 weeks. The intensity of effects during the first psilocybin session strongly predicted reduced drinking and craving and increased abstinence self-efficacy in the following weeks. No serious adverse events occurred. These preliminary findings support larger controlled trials to test efficacy and mechanisms.
Journal of Psychopharmacology • September 11, 2014 • Mary P Cosimano, Matthew W. Johnson, Albert Garcia‐romeu et al. • 910 citations
In an open-label pilot study, 15 nicotine-dependent smokers received moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin as part of a structured 15-week smoking cessation program. At 6-month follow-up, 12 of 15 participants (80%) showed seven-day point prevalence abstinence, a rate substantially exceeding the typical 35% or less reported for other behavioral or pharmacological therapies. The authors note the open-label design prevents definitive conclusions about efficacy, but the findings suggest psilocybin may be a potentially useful adjunct to smoking cessation treatment.
Proceedings of the National Academy of Sciences • January 23, 2012 • Alessandro Colasanti, Robin J. Tyacke, Robert Leech et al. • 1,191 citations
Psychedelic drugs like psilocybin, found in magic mushrooms, produce profound changes in consciousness by decreasing activity and connectivity in key brain hub regions. Using functional MRI, researchers observed that psilocybin reduced cerebral blood flow and BOLD signal, especially in the thalamus, anterior cingulate cortex (ACC), and posterior cingulate cortex (PCC). Decreased activity in the ACC and medial prefrontal cortex (mPFC) predicted the intensity of subjective psychedelic effects. Psilocybin also reduced positive coupling between the mPFC and PCC. These findings suggest that psychedelics work by dampening the brain's connector hubs, leading to a state of unconstrained cognition.
Psychopharmacology • December 1, 2011 • Roland R Griffiths, Matthew W Johnson, William A Richards et al. • 938 citations
Psilocybin can produce mystical-type experiences that lead to lasting positive changes in attitudes, mood, and behavior. In a double-blind study, 18 adults (17 with no prior hallucinogen use) received 0, 5, 10, 20, or 30 mg/70 kg psilocybin in five sessions under supportive conditions. At the two highest doses, 72% of volunteers reported a mystical-type experience, and 39% experienced extreme anxiety or fear. One month later, participants rated these sessions as having substantial personal and spiritual significance, with the ascending dose sequence showing greater positive effects. At 14 months, these positive ratings remained undiminished and were consistent with observer reports. The effects generally increased with dose.
Journal of Psychopharmacology • September 28, 2011 • Katherine A. Maclean, Matthew W. Johnson, Roland R. Griffiths • 907 citations
Core personality traits are generally stable after age 30, but a high dose of the hallucinogen psilocybin can increase Openness to experience in healthy adults. In a double-blind controlled study, participants who had a mystical experience during their psilocybin session showed significantly higher Openness than baseline, and this increase persisted for more than a year. The findings suggest that psilocybin and mystical-type experiences can produce lasting personality change in adults.
Archives of General Psychiatry • September 7, 2010 • Gurpreet S Chopra, Marycie Hagerty, Charles S. Grob et al. • 1,220 citations
In a double-blind, placebo-controlled study, twelve adults with advanced-stage cancer and anxiety received a moderate dose (0.2 mg/kg) of psilocybin. Safe physiological and psychological responses were documented, with no clinically significant adverse events. The State-Trait Anxiety Inventory trait anxiety subscale showed a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory indicated improved mood that reached significance at 6 months; the Profile of Mood States showed mood improvement that approached but did not reach significance. The results support the need for more research into psilocybin for cancer-related anxiety.