Journal of psychiatric research
July 1, 2021
Ashley N Siegel, Shakila Meshkat, Katie Benitah et al.
101 citations
A review of clinical trials registered on clinicaltrials.gov as of December 3, 2020, shows that 70 studies are evaluating psychedelics (excluding ketamine) for psychiatric disorders. Most studies focus on MDMA (45.7%) and psilocybin (41.4%), with fewer investigating ayahuasca, LSD, ibogaine, salvia divinorum, 5-MeO-DMT, and DMT fumarate. MDMA and psilocybin are primarily studied for PTSD and major depressive disorder; LSD for depression, anxiety, and severe somatic disorders; ibogaine for substance use disorders; and 5-MeO-DMT and DMT for major depressive disorder. Only 21 of the 70 studies had published results; most are ongoing.
Journal of psychiatric research
May 1, 2022
Timothy D Brewerton, Julie B Wang, Adele Lafrance et al.
81 citations
Among 89 individuals with severe PTSD enrolled in a placebo-controlled trial of MDMA-assisted therapy, 15% had eating disorder symptoms in the clinical range and 31.5% in the high-risk range at baseline, despite no active purging or low weight. After treatment, participants who received MDMA-assisted therapy showed significantly greater reductions in eating disorder symptoms compared to those who received placebo, especially among women with elevated baseline scores. The findings suggest that eating disorder psychopathology is common in severe PTSD and that MDMA-assisted therapy may reduce these co-occurring symptoms.
Journal of psychiatric research
May 1, 2023
Franklin R Schneier, Jamie Feusner, Michael G Wheaton et al.
79 citations
A single 25 mg oral dose of psilocybin, given with psychological support, significantly reduced body dysmorphic disorder (BDD) symptoms in 12 adults whose condition had not responded to at least one prior serotonin reuptake inhibitor. Over 12 weeks of follow-up, scores on a standard BDD severity scale decreased substantially, with a large effect size and improvements evident from week 1 and sustained through week 12. Seven of 12 participants (58%) showed a 30% or greater reduction in symptoms at week 12. No serious adverse events occurred. These preliminary findings suggest psilocybin may be a promising treatment for BDD, warranting further controlled trials.
Journal of psychiatric research
May 1, 2021
Bruno Romeo, Marianne Hermand, Amélie Pétillion et al.
74 citations
A systematic review of 20 studies examined factors predicting response to psychedelic treatments for psychiatric and addictive disorders. The main predictor of a positive response across alcohol and tobacco use disorders, treatment-resistant depression, and anxiety and depressive symptoms in patients with life-threatening cancer was the intensity of the acute psychedelic experience. This factor did not predict response for obsessive-compulsive disorder. Possible mechanisms include modulation of the serotoninergic system via 5-HT2A receptor agonism, disruption and reintegration of the default mode network, or anti-inflammatory effects.
Journal of psychiatric research
November 1, 2024
Benneth Ben-Azu, Aliance R Fokoua, Olajide S Annafi et al.
24 citations
Silymarin, a polyphenolic flavonoid with neuroprotective functions, prevented and reversed schizophrenia-like behaviors in mice given ketamine, an NMDA antagonist that induces neurochemical dysregulation, neuroimmune stress, and oxidative stress. In a preventive-reversal model, silymarin (50 and 100 mg/kg) reduced ketamine-induced increases in dopamine, serotonin, acetylcholinesterase, malondialdehyde, and nitrite in the striatum, prefrontal cortex, and hippocampus. It improved hyperlocomotion, stereotypy, memory, and social impairments without causing catalepsy. Silymarin also lowered inflammatory markers (myeloperoxidase, tumor-necrosis factor-α, interleukin-6) and normalized decreased brain-derived neurotrophic factor, glutathione, catalase, and superoxide-dismutase levels. The antipsychotic effect may involve normalization of neurochemical and neurotrophic changes.
Journal of psychiatric research
May 1, 2024
M Colla, B Offenhammer, H Scheerer et al.
23 citations
A novel oral prolonged-release formulation of racemic ketamine (KET01) was tested as an add-on therapy for treatment-resistant depression. Patients received 160 mg/day, 240 mg/day, or placebo for 14 days. The 240 mg/day group showed a numerically larger but statistically non-significant improvement in depression scores compared to placebo. The trial was terminated early due to poor recruitment during the COVID-19 pandemic, with only 27 patients completing the protocol. Adverse event rates were similar across groups, and no increased risk of suicidality, dissociation, or blood pressure changes was observed. Baseline leukocyte count correlated with response to KET01 in exploratory analysis.
Journal of psychiatric research
October 1, 2024
Mohammad-Ali Samizadeh, Seyedeh-Tabassom Abdollahi-Keyvani, Hamed Fallah et al.
21 citations
In a rat model of schizophrenia induced by five daily injections of ketamine (30 mg/kg), recognition memory was impaired and brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex decreased in both sexes. Ketamine also lowered pain threshold in females, increased rearing behavior in males, and caused greater hyperlocomotion in females. Subsequent treatment with risperidone (2 mg/kg) restored or attenuated all these behavioral effects and BDNF levels. The findings suggest sex differences in how ketamine affects pain perception, locomotion, and rearing behavior in this model.
Journal of psychiatric research
August 1, 2024
Noah Chisamore, Danica Johnson, Margery J Q Chen et al.
21 citations
Psilocybin-assisted psychotherapy shows promise for treating depression and distress in life-threatening illnesses, but a systematic review of 28 clinical trial protocols reveals substantial variability and inconsistency in therapeutic approaches beyond the basic framework of preparatory, dosing, and integration sessions. The review found no validated or universally agreed-upon protocol, with frequent lack of clarity in descriptions of therapy models, duration, and number of sessions. Future studies need to define and report psychotherapeutic components more clearly to identify the safest and most effective approaches.
Journal of psychiatric research
December 1, 2024
Soroush Oraee, Mohammadreza Alinejadfard, Hossein Golsorkh et al.
13 citations
Intranasal esketamine, given alongside an oral antidepressant, leads to higher remission and response rates than a placebo in people with major depressive disorder, including those with treatment-resistant depression. A meta-analysis of nine clinical trials involving 1,752 patients found that esketamine doses ranging from 28 to 84 mg produced significantly greater remission (risk ratio 1.37) and response (risk ratio 1.27). The 84 mg and flexible doses were particularly effective. Adverse events were common but generally tolerable. The drug appears safe and effective in the short term, though more research is needed on long-term effects and specific patient subgroups.
Journal of psychiatric research
November 1, 2023
Hui Kou, Wei Luo, Xinnan Liu et al.
11 citations
Eight weeks of mindfulness training reduced anxiety and depressive symptoms in a non-clinical sample of 80 adults, with effects lasting at least three months. The training also shifted attention: participants became more attentive to happy faces and less attentive to sad faces compared to a control group. The change in attention to sad faces partially explained the reduction in depression immediately after training, but this attentional mechanism played only a limited role in symptom improvement overall. The study suggests mindfulness improves emotional symptoms through multiple pathways, not solely by altering attention to emotional faces.
Journal of psychiatric research
December 1, 2024
Lindsey Marwood, Megan Croal, Sunil Mistry et al.
9 citations
In a phase II randomized controlled trial of 233 participants with treatment-resistant depression, those who discontinued antidepressant drugs before receiving psilocybin showed no worsening of depression severity during the discontinuation period, comparable baseline suicidality, and no compromise in psilocybin's treatment efficacy or subjective psychedelic effects relative to those who entered the trial antidepressant-free. The findings suggest that antidepressant discontinuation does not limit the feasibility of psilocybin treatment for treatment-resistant depression and support the homogeneity of psilocybin's effects as a monotherapy.
Journal of psychiatric research
October 1, 2024
Zixun Wang, Xinyu Hu, Zhongyi Wang et al.
9 citations
Post-traumatic stress disorder affects 3-4% of people globally each year. In a rat model of PTSD induced by single prolonged stress, a single low dose of ketamine (10 mg/kg) prevented anxiety-like behaviors. Ketamine also reversed stress-induced changes in the hippocampus: it increased expression of glucocorticoid receptor, brain-derived neurotrophic factor, phosphorylated GSK-3β, FKBP5, and CRH, while decreasing GSK-3β protein expression, and it improved synaptic structure. A GSK-3β inhibitor produced similar behavioral effects, suggesting ketamine works by regulating GSK-3β/GR signaling to improve synaptic plasticity.
Journal of psychiatric research
August 1, 2024
Eduardo Igor Torquato Cardoso Lopes, Patrícia Cavalcanti-Ribeiro, Fernanda Palhano-Fontes et al.
9 citations
Subcutaneous esketamine injections given weekly for eight weeks produced a rapid and lasting reduction in suicidality among 18 adults with treatment-resistant depression. Suicidal thoughts dropped within 24 hours after the first dose and remained low throughout the eight-week treatment period. At six months after treatment ended, suicidality was still consistently lower. Clinician ratings showed significant improvement only after two sessions, and 61% of patients achieved remission from suicidal ideation. The findings suggest that weekly subcutaneous esketamine may be a cost-effective way to achieve fast and sustained anti-suicide effects, but controlled studies are needed to confirm these initial observations.
Journal of psychiatric research
June 1, 2024
Lior Dvorak, Esther Bloemhof-Bris, Assaf Shelef et al.
9 citations
About 60% of patients with treatment-resistant depression who completed an acute phase of esketamine therapy went on to finish a maintenance phase. Depressive symptoms, measured with the Quick Inventory of Depressive Symptomatology, showed linear improvement during both phases. A sub-analysis of patients with a comorbid personality disorder revealed a similar improvement pattern in the acute phase but milder improvement during maintenance compared to other patients. The findings support the use of esketamine for treatment-resistant depression, including for those with comorbid personality disorder or a history of electroconvulsive therapy.
Journal of psychiatric research
February 1, 2024
Monique Williams, Cynthia Honan, Sarah Skromanis et al.
9 citations
A systematic review and meta-analysis of five controlled trials (277 participants with elevated trait or generalized anxiety) examined the acute effects of a brief audio-based mindfulness induction on state anxiety and attention. Compared with non-therapeutic control conditions, mindfulness induction produced a medium reduction in state anxiety and a large increase in state mindfulness. Two studies comparing mindfulness to therapeutic active controls also showed small-to-moderate anxiety reductions, though results could not be pooled. Evidence for attention improvements was limited, with one study reporting changes in brain activity in the anterior cingulate cortex. State mindfulness partially mediated anxiety reductions. The small number of studies, high risk of bias, and low certainty of evidence qualify confidence in the findings.
Journal of psychiatric research
July 1, 2024
Yecun Liu, Jiguo Yang, Yuanxiang Liu
8 citations
Electroconvulsive therapy (ECT) and ketamine each improve depressive symptoms more than placebo, but ECT appears superior to both ketamine and their combination for reducing depression severity. A network meta-analysis of 17 randomized controlled trials involving 1,370 patients with severe depression found that ECT had the highest probability of being the most effective treatment, followed by the combination of ketamine plus ECT, then ketamine alone, and finally placebo. No significant differences were observed on the Montgomery-Asberg Depression Rating Scale, though rank probabilities again favored ECT. The combination of ketamine and ECT was associated with more adverse reactions, indicating a need for further research on optimal combined use. Individualized treatment decisions remain important.
Journal of psychiatric research
January 1, 2025
Carolina Mariño-narvaez, Borja Romero-Gonzalez, Jose A Puertas-Gonzalez et al.
7 citations
A mindfulness-based stress reduction program for hospital workers during the COVID-19 pandemic reduced symptoms of somatization, depression, and anxiety, and improved mindfulness skills, self-compassion, and body awareness. In a randomized trial with 97 hospital staff, those in the program showed significant improvements compared to a control group in depression, anxiety, somatization, observing, acting with awareness, nonjudging, nonreactivity, self-kindness, mindfulness, self-judgment, isolation, and body awareness. The findings suggest that teaching hospital staff to connect with their feelings and thoughts without judgment and with self-compassion can protect against worsening psychopathological symptoms during crises.
Journal of psychiatric research
July 1, 2024
Yen-Han Lee, Yen-Chang Chang, Mack Shelley et al.
6 citations
Sexual minority adults in the United States—particularly those identifying as lesbian, gay, or bisexual—are more likely than their heterosexual peers to perceive illicit drug use (LSD, heroin, cocaine) as low risk. Analysis of five waves of a national survey (2015–2019) with over 205,000 participants showed that among men, about 11% viewed illicit drug use as moderate risk and 2% as low risk; among women, about 6% viewed it as moderate risk and 1% as low risk. After accounting for sex, identifying as lesbian/gay or bisexual was associated with higher odds of perceiving low risk compared to heterosexual identification. Prevention strategies should address these disparities.
Journal of psychiatric research
August 1, 2025
Lucas F Borkel, Jaime Rojas-Hernández, Domingo J Quintana-Hernández et al.
4 citations
Psychedelic therapy, while physiologically and psychologically safe, can alter users' beliefs, including inducing paranormal beliefs. This paper introduces the concept of epistemic criteria—the principles people use to validate and justify their beliefs—and hypothesizes that psychedelics may change beliefs by modifying these criteria. The authors argue that this potential, under-researched risk highlights ethical and epistemic challenges, vindicating the importance of epistemology in clinical and psychotherapeutic settings. Further research is needed to determine the extent of this risk.
Journal of psychiatric research
August 1, 2025
Elizabeth Wassenaar, Dan V Blalock, Alan Duffy et al.
4 citations
Ketamine is safe for patients with eating disorders who also have treatment-resistant depression or bipolar depression, even when medical or nutritional instability is present due to disordered eating. A retrospective analysis of 104 patients receiving higher levels of care for their eating disorder found no safety concerns with ketamine treatment. The findings indicate that ketamine can be used with medical monitoring in this challenging population, despite the complications of malnutrition and other behaviors that often accompany eating disorders.
Journal of psychiatric research
March 1, 2025
Lőrinc Frivaldszky, Kincső Lőrincz, Jakub Hoferica et al.
4 citations
Perioperative administration of esketamine to women undergoing cesarean section is associated with a lower rate of postpartum depression (PPD) at 3–7 days and 28–42 days after delivery, with odds ratios of 0.43 and 0.59, respectively. Edinburgh Postnatal Depression Scale scores were also significantly lower at 3–7 days postpartum. The analysis, based on 17 eligible trials, suggests that esketamine is safe compared to placebo or standard care. PPD affects 14% of women after childbirth.
Journal of psychiatric research
August 1, 2025
Yaxin Ju, Yuan Liu, Li Tan et al.
3 citations
An analysis of the FDA Adverse Event Reporting System from 2004 to 2023 identified 21 drugs potentially linked to increased suicidal ideation risk in children aged 6–17. Among 4,779 valid cases, montelukast was the most commonly reported drug, and esketamine showed the highest statistical signal. The most common indications were ADHD, depression, acne, and asthma. Cumulative incidence of suicidal ideation within 90 days was 51.6% in males and 58.8% in females; within 360 days it was 76.9% and 85.3%, respectively. The findings suggest specific medications may pose elevated risk, but further research is needed to confirm.
Journal of psychiatric research
April 1, 2025
Kristian Elersič, Anamarija Banjac, Marko Živin et al.
3 citations
Ketamine, a fast-acting antidepressant, is a racemic mixture of R- and S-ketamine. In a preclinical study using Wistar-Kyoto rats (a depression model) and Wistar rats (controls), researchers compared behavioral effects of R- and S-ketamine at 10 mg/kg in a clinically relevant treatment protocol. S-ketamine produced stronger acute psychomotor effects (locomotor stimulation, ataxia, stereotypy) than R-ketamine, and Wistar-Kyoto rats were more sensitive to these effects. After repeated treatment, sensitization to locomotor stimulation and tolerance to ataxic effects of S-ketamine developed. No persistent changes in working memory, anxiety, or behavioral despair were found. Results suggest depressed individuals may be more prone to negative side effects, but tolerance may develop with repeated treatment.
Journal of psychiatric research
April 1, 2024
Lena Vera Danyeli, Zümrüt Duygu Sen, Lejla Colic et al.
3 citations
In healthy men, a thinner posterior cingulate cortex (PCC) is linked to a stronger feeling of disembodiment after a low dose of ketamine, a drug that can rapidly relieve depression. The study measured cortical thickness in two brain regions—the PCC and the pregenual anterior cingulate cortex (pgACC)—and found that only PCC thickness correlated with the altered sense of self (disembodiment). No such link appeared for the pgACC. These results suggest the PCC plays a key role in ketamine's effects on self-experience, a feature shared with other fast-acting antidepressants that also produce psychedelic-like effects.
Journal of psychiatric research
December 1, 2022
Chris R Brewin, Kirsty Phillips, John Morton et al.
2 citations
Voice-hearers typically report about four distinct voices, most perceived as male and with negative content. Child-aged voices are significantly less negative than other voices except those perceived as elderly. Variability in voice characteristics is greater between different voices within an individual than between different utterances of the same voice. These findings are inconsistent with cognitive models that attribute voices to misattributed inner speech and better support a dissociation model of voice-hearing. The results suggest that classifying voices by subtype or dimensional methods may be useful, and that clinical assessment should more systematically evaluate the multiplicity of voices.