Psychiatry Research
January 2, 2020
Simon B. Goldberg, Brian T. Pace, Christopher R. Nicholas et al.
234 citations
A meta-analysis of four studies (three randomized, placebo-controlled; one uncontrolled) with 117 participants found that psilocybin combined with behavioral interventions produced large reductions in anxiety and depression among people with elevated symptoms. Within-group effects from before treatment to after treatment and at follow-up were large (Hedges' g = 1.16 to 1.47) and statistically significant. Across the placebo-controlled studies, the pre-post effects compared to placebo were also large (g = 0.82 to 0.83) and statistically significant. No serious adverse events were reported. The results tentatively support further research on psilocybin for anxiety and depression, though the small number of studies and potential bias limit confidence.
Psychiatry Research
January 14, 2020
Clemens Bauer, Kana Okano, Satrajit Ghosh et al.
87 citations
Auditory hallucinations in schizophrenia are linked to overactivity and hyperconnectivity in the default mode network and reduced anticorrelation with the central executive network. Patients were trained with real-time fMRI neurofeedback and meditation strategies to modulate these networks. The intervention reduced default mode network hyperconnectivity and increased anticorrelation between the default mode and central executive networks. Changes in individual default mode network connectivity correlated with reductions in auditory hallucination frequency and severity. This provides the first empirical evidence that meditation-enhanced neurofeedback can directly alter resting state network activity and reduce auditory hallucinations.
Psychiatry Research
April 4, 2018
Alba Franquesa, Alberto Sainz-Cort, Sam Gandy et al.
58 citations
Ayahuasca, a psychedelic brew from Amazonia, may support mental health and boost mindfulness, but the psychological mechanisms behind its therapeutic effects are unclear. Comparing 81 ayahuasca users with 41 non-users, users scored higher on Decentering and Positive self, but not on Valued living, Life fulfillment, or measures of self in social or close relations. More experienced users (over 15 sessions) showed higher Decentering scores than less experienced ones. These findings suggest that psychological processes like Decentering could help explain ayahuasca's benefits in psychotherapy, warranting their inclusion in future studies.
Psychiatry Research
July 29, 2023
Mauro Pettorruso, Roberto Guidotti, Giacomo D’andrea et al.
56 citations
Machine learning models predicted which patients with treatment-resistant depression would respond to esketamine nasal spray. In a retrospective study of 149 patients, three random forest classifiers achieved 68.53% accuracy for response at one month and 66.26% at three months, and 68.60% accuracy for remission at three months. Features such as severe anhedonia, anxious distress, mixed symptoms, and bipolarity positively predicted response and remission, while benzodiazepine use and depression severity were linked to delayed responses. The findings suggest machine learning may aid personalized treatment decisions for treatment-resistant depression.
Psychiatry Research
March 5, 2023
Kevork Danayan, Noah Chisamore, Nelson B Rodrigues et al.
36 citations
Intravenous ketamine reduced symptoms of depression, borderline personality, suicidality, and anxiety in people with treatment-resistant depression and comorbid borderline personality disorder. In a retrospective analysis of 100 participants, those with borderline personality disorder showed significant improvement, with a reduction of 5.95 points on the Quick Inventory of Depressive Symptomatology and a reduction of 0.64 on the Borderline Symptom List. Both groups with and without borderline personality disorder improved similarly on depression, anxiety, and functionality measures, with no significant difference between groups.
Psychiatry Research
October 1, 2021
Tuyen T. Le, Joshua D. Di Vincenzo, K. Teopiz et al.
26 citations
Psychotic depression, a severe form of major depression with hallucinations or delusions, affects 0.35-1% of people over a lifetime. Current treatments, such as antidepressants combined with antipsychotics or electroconvulsive therapy, often lead to relapse and side effects like tardive dyskinesia. Some case studies suggest ketamine may improve both mood and psychotic symptoms in treatment-resistant patients, but its safety is debated because ketamine can induce psychotomimetic effects. Most clinical trials have excluded these patients, so it remains unknown whether ketamine would worsen psychosis. Future research should include people with psychotic features to determine ketamine's safety and effectiveness.
Psychiatry Research
November 1, 2019
Jun Dong, S. Min, H. Qiu et al.
26 citations
For patients with major depressive disorder, adding a low dose of ketamine to electroconvulsive therapy (ECT) once a week improved remission rates and reduced psychiatric complications compared with giving ketamine before every ECT session. In a randomized trial of 134 patients, those receiving intermittent ketamine had a complication rate of 4.35%, far lower than the 20.93% rate in the repeated-ketamine group and similar to the 0% rate in the routine ECT group. Both ketamine regimens led to higher remission than ECT alone. Intermittent low-dose ketamine appears to boost ECT's effectiveness while minimizing side effects.
Psychiatry Research
July 23, 2023
Otto Simonsson, Per Carlbring, Robin Carhart-Harris et al.
24 citations
In a meta-analysis of three psilocybin trials for depression involving 102 participants, clinically significant symptom worsening occurred for a minority of those receiving psilocybin or escitalopram (about 10%) and for a majority of those in the waitlist condition (63.6%). The psilocybin arm showed a lower likelihood of symptom worsening compared to waitlist and no difference compared to escitalopram. The authors note the limitation of a relatively small sample size.
Psychiatry Research
July 16, 2022
Thomas D. Meyer, Priel Meir, Claudia Lex et al.
23 citations
Mental health professionals' attitudes toward psilocybin were neutral, but their self-rated knowledge of the substance was low. Whether the survey used the term 'Psilocybin' or 'Magic Mushrooms' did not significantly affect responses. Gender, attitudes toward medical cannabis, and personal history of psychedelic use were associated with ratings of psilocybin. These findings offer a baseline of mental health professionals' views on psilocybin, which may inform considerations if it receives FDA approval.
Psychiatry Research
June 4, 2020
W. L. Toh, N. Thomas, Y. Hollander et al.
22 citations
Auditory verbal hallucinations (AVHs) show more similarities than differences across diagnoses of bipolar disorder, major depressive disorder, schizophrenia, and schizoaffective disorder. Among 34 AVH characteristics, significant differences emerged only for frequency, number of voices, form of address, perceived location, level of conviction, beliefs about origin, and functional interference. Distress and functional impairment were best predicted by specific AVH variables, and these predictors differed between affective and non-affective psychosis. A qualitative thematic analysis identified four themes: content, form, function, and non-voice experiences. The findings suggest important implications for diagnosis and treatment.
Psychiatry Research
July 26, 2025
G. D’andrea, C. Cavallotto, M. Pettorruso et al.
16 citations
Anhedonia, the reduced ability to experience pleasure, is a core symptom of both unipolar and bipolar depression that often responds poorly to standard antidepressants. In a real-world observational study of 253 treatment-resistant patients (199 with unipolar depression, 54 with bipolar depression), repeated doses of esketamine nasal spray added to ongoing medication significantly reduced anhedonia over three months. The effect was distinct from overall mood improvement. At three months, 51.92% of bipolar and 38% of unipolar patients showed at least a 50% reduction in anhedonia scores. Dropout rates were low (around 13–14%), and manic switches were rare. The findings suggest esketamine has a targeted, transdiagnostic anti-anhedonic effect.
Psychiatry Research
April 25, 2022
Hartej Gill, Parnian Puramat, Pankti Patel et al.
16 citations
Psilocybin shows promise as a treatment for major depressive disorder (MDD), potentially offering an alternative to conventional therapies. A systematic review of neuroimaging studies found that psilocybin administration decreased amygdala activity and reduced depressive symptoms in two studies involving MDD participants. In healthy populations, changes in functional connectivity and activation of prefrontal limbic structures, particularly the ventral medial prefrontal cortex and amygdala, were observed. However, high methodological heterogeneity across the thirteen included studies—ten in healthy populations and three in MDD participants—limits conclusions. Longitudinal research is needed to clarify psilocybin's long-term effects and sustained therapeutic potential for MDD.
Psychiatry Research
March 6, 2020
Jianjing Zhang, H. Tian, Jie Li et al.
13 citations
Adding ketamine to propofol-electroconvulsive therapy (ECT) improves outcomes for patients with depression resistant to ECT alone. In 28 patients, six alternating sessions of ketamine and propofol-ECT over two weeks increased global functional connectivity density in the left temporal and subgenual anterior cingulate cortex and decreased functional connectivity strength within the default mode network. Although the functional brain changes lasted 10 days, the clinical benefit—measured by the Hamilton Depression Scale—lasted only 7 days, indicating a disconnect between brain alterations and symptom relief. The combination offers a short-term improvement, but its effect is limited to one week.
Psychiatry Research
January 29, 2025
Felix Müller, Thomas Sauer, Corina Hänny et al.
11 citations
A 60-year-old man with recurrent depression and a history of delusions died after psilocybin-assisted therapy. Psilocybin-triggered delusions and emotional dysregulation may have contributed to the death. A weak therapeutic alliance hindered assessment of the patient's internal state. Delusional symptoms may contraindicate psychedelic interventions. The case emphasizes the need for thorough assessment and close follow-up in complex cases.
Psychiatry Research
August 15, 2025
Sipan Haikazian, Roger S. McIntyre, Shakila Meshkat et al.
7 citations
Ketamine infusions, given intravenously at sub-anesthetic doses, reduced depression and suicidality scores in patients with treatment-resistant major depressive disorder and treatment-resistant bipolar depression. Improvements from an acute course persisted during maintenance infusions over weeks and months, with no cases of suicidal behavior or addiction. One bipolar patient (4%) experienced an affective switch that stabilized. These results provide preliminary support for the long-term use of maintenance ketamine infusions.
Psychiatry Research
May 8, 2025
Noah Chisamore, Lee Phan, Roger S McIntyre et al.
7 citations
A review of pre-clinical and clinical studies on non-hallucinatory psychedelics (NHPs) for mood and anxiety disorders found five animal studies showing antidepressant-like effects, assessed via forced swim test and open field test, without the head-twitch response that indicates hallucination. One case report described a patient who inadvertently combined trazodone and psilocybin and experienced potent antidepressant effects without psychedelic effects. These preliminary findings suggest that antidepressant benefits of psychedelics may be separable from hallucinatory effects, providing impetus for rigorous clinical trials in humans.
Psychiatry Research
August 18, 2025
Ilenia Rosa, L. Padula, Francesco Semeraro et al.
2 citations
Treatment-resistant depression (TRD) challenges standard approaches, prompting a shift toward non-monoaminergic interventions like neuromodulation and glutamatergic agents. This narrative review examines the endocannabinoid system (ECS) as a potential common pathway for these treatments. Evidence indicates that repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) increase endocannabinoids anandamide and 2-arachidonoylglycerol, correlating with clinical improvement. Ketamine and esketamine modulate CB1 receptors, while psilocybin restores 2-AG and enhances CB1 expression in mood-related brain regions. These findings suggest ECS modulation may unify diverse antidepressant mechanisms in TRD, offering a promising target for novel therapies.
Psychiatry Research
February 13, 2026
Sean P. Goldy, Nathan D. Sepeda, Samantha Hilbert et al.
1 citation
The acute subjective effects of psychedelics are known to predict therapeutic benefits like reduced depression and anxiety. Session facilitators—who support participants before, during, and after dosing—are a key part of the setting, but their influence on subjective effects was unclear. Analyzing data from 9 psilocybin studies with 298 participants, 670 sessions, and 60 facilitators, multilevel models showed facilitators accounted for negligible variance (0.8%) in healthy volunteers but greater variance in clinical samples (13.6%), after controlling for study and participant differences. This suggests facilitators may play a clinically meaningful role in shaping outcomes for patient populations, comparable to or exceeding therapist effects in traditional psychotherapy (~8%).
Psychiatry Research
December 29, 2025
Omer A. Syed, Sean M. Nestor, M.ishrat Husain et al.
1 citation
Adverse event reports for classic psychedelics and MDMA in the WHO global pharmacovigilance database VigiBase show that most reports were for MDMA (1,573) and LSD (394), with fewer for psilocybin (56), DMT (18), and mescaline (15). The most common adverse events were psychiatric, particularly substance abuse and dependence. Overdose reports made up 1.1 to 1.7% of total adverse events. Pregnancy-related and congenital disorders were rare. Compared to acetaminophen, LSD and MDMA were associated with significantly greater odds of reported alcohol abuse, substance use disorder, and substance dependence, and these odds were also greater than those for oxycodone. This exploratory analysis provides a first look at real-world safety data, though findings are limited by potential underreporting and co-use of other substances.
Psychiatry Research
February 19, 2026
Trisha Menon, Andy Lu, Akhilan Arulmozhi et al.
Ketamine, esketamine, repetitive transcranial magnetic stimulation (rTMS), and electroconvulsive therapy (ECT) are associated with reductions in suicidal ideation in people with major depressive disorder. The strongest evidence from randomized controlled trials supports rapid, short-term effects, particularly for ketamine and esketamine. Further research is needed to characterize the durability of these antisuicidal effects and to determine whether reductions in suicidal ideation translate into reduced severity of suicidal behavior.
Psychiatry Research
November 1, 2023
J. Groening, Emma Denton, Rimsha Parvaiz et al.
Cannabis use is associated with psychotic-like experiences and schizotypal traits in healthy people, and with earlier onset and relapse of psychosis in patients with psychotic disorder. However, an association with clinical-high-risk states, attenuated symptoms, or transition to psychosis in high-risk populations could not be confirmed. Whether these associations are causal has not been adequately addressed in the evidence synthesis to date. This umbrella review evaluated 32 systematic reviews and meta-analyses, assessing their quality with the AMSTAR-2 tool.
Psychiatry Research
January 1, 2023
Xuexiao Shao, Danfeng Yan, Wenwen Kong et al.
In patients with treatment-resistant depression, a single 1-hour inhalation of nitrous oxide improved depressive symptoms more than a placebo, as measured by the 17-Hamilton Depression Rating Scale. The treatment altered brain function, shown by changes in event-related potential components (N1, P1, N2, P2) and increased functional connectivity networks. These brain changes correlated with symptom reduction, suggesting nitrous oxide works by modifying brain function.
Psychiatry Research
January 1, 2023
Ricci Valerio, C. França, Di Carlo Francesco et al.
Psychoses linked to natural cannabis and synthetic cannabinoids present distinct symptom profiles and outcomes compared to psychoses without cannabis use. In a sample of 61 first-episode psychosis patients, those using natural cannabis, and especially synthetic cannabinoids, had more severe positive symptoms, while non-users had more negative symptoms. After nine months, non-users recovered better in global functioning than synthetic cannabinoid users. Dissociative symptoms were greater among substance users, and suicidal ideation was highest in synthetic cannabinoid users. These differences may guide specific drug treatments.
Psychiatry Research
August 23, 2020
Chloé de Vos, K. Leopold, Elisabeth S. Blanke et al.
Among 89 people diagnosed with first-episode psychosis, 61 were lifetime cannabis users (at least three times per week for four weeks) and 28 were non-users. Cannabis users were more likely to be male and had more positive symptoms, while non-users had more negative symptoms. No differences were found between the groups on tests of verbal memory, verbal fluency, and attention. The authors conclude that cannabis use showed no association with cognitive impairments in this population.