Harman Brar
Virtual reality is used as a therapeutic tool for anxiety, PTSD, and depression through exposure therapy and simulated environments, but its potential to mimic psychedelic experiences has not been examined. Research suggests individuals in VR simulated psychedelic experiences undergo effects similar to those from psychedelic drugs, though the physiological impact on the brain and mind is largely unexplored. To determine whether VR can mimic psychedelics, targeting 5-HT receptor activity in the frontal lobe is proposed as a hypothesis. This paper examines drug mechanisms of psychedelics, the theoretical application of VR-based psychedelic therapy, and postulates a method to measure the effectiveness of psychedelic simulations for psychopathology.
Stephen Bright, Eyal Gringart, Emily Blatchford et al.
preprint
People who microdose psychedelics report similar improvements in psychological wellbeing, openness, and absorption as people who practice yoga. In a survey of 339 adults, both the yoga-only and microdose-only groups scored higher on wellbeing and absorption than a control group. Those who both microdosed and practiced yoga had the lowest depression scores (lower than the microdose-only group) and the lowest anxiety scores (lower than the yoga-only group), and they also had the highest absorption scores. The control group scored significantly lower on openness than all other groups. The findings suggest that microdosing and yoga may have comparable subjective effects and that combining both could be especially beneficial, although the study cannot establish causation.
Matthias Forstmann, Christina Sagioglou
preprint
After a long period of stagnation, research on psychedelic substances like LSD, psilocybin, and DMT has revived over the last decade, with major programs in Europe and the United States. This review summarizes recent insights into their potential for treating mental health disorders, effects on recreational users, and underlying neurological and cognitive processes. It covers the history of psychedelic research, objective and subjective effects, prevalence and correlates of use, and potential for harm. The review examines clinical benefits for major depression, anxiety, and substance use disorders, along with proposed neural and cognitive mechanisms. It also discusses effects on healthy subjects, including psychological wellbeing, personality changes, nature relatedness, and creativity, and concludes with long-term effects of single experiences.
Nestor Girala
The efficacy of hallucinogenic drugs (ayahuasca, psilocybin, LSD, ketamine) in treating depression and addictions is accompanied by intense emotional states and mystical-type experiences, including feelings of oneness, transcendence, ineffability, and awe. These common psychopathological elements may mediate the drugs' therapeutic action. The paper reviews literature on subjective experiences during such treatments and compares them with other life-changing experiences, discussing the evolutionary value of these emotions for group cohesiveness and the recalibration of cognitions and emotions.
Samuel Kohtala, Wiebke Theilmann, Marko Rosenholm et al.
preprint
Nitrous oxide (laughing gas), a dissociative anesthetic that blocks NMDA receptors, produces rapid antidepressant effects in animals through a mechanism that emerges after the drug is withdrawn, not during its peak action. The gas induces rebound slow EEG oscillations, a brain state also seen with ketamine and electroconvulsive therapy, that is characterized by sedation and drowsiness. During this withdrawal phase, signaling changes in TrkB and GSK3β proteins gradually appear, suggesting that the antidepressant effect relies on cortical excitability triggered by the drug's offset rather than its acute presence.
Khush Jain, Fariah Rizwani, Nisarg Sawant et al.
In a mouse model of depression induced by chronic unpredictable mild stress, harmaline, a monoamine oxidase inhibitor from Peganum harmala, reversed depression-like behaviors. Mice given daily oral doses of harmaline (15 mg/kg) for 21 days showed improved performance in behavioral tests and, compared to stressed controls, had lower serum corticosterone and higher brain levels of serotonin, norepinephrine, and dopamine. Harmaline also reduced oxidative stress markers and pro-inflammatory cytokines. These effects were comparable to those of the standard antidepressant imipramine (30 mg/kg). The findings suggest harmaline may mitigate stress-induced depressive disorders by modulating monoamines, oxidative stress, and neuroinflammation.
Tyler Maxwell Moore, Kathryn Walker, Emma Tung et al.
preprint
Adding psychotherapy to ketamine treatment does not significantly improve depression or PTSD symptoms more than ketamine alone over 30 days. Both approaches produced substantial, rapid symptom improvement that stabilized after 11-15 days. The study analyzed 202 help-seeking individuals (60% female, mean age 41.3 years) who received either ketamine alone or ketamine plus psychotherapy across six sessions. No significant differences in symptom trajectories emerged between the groups, though exploratory analyses suggested younger females might benefit more from combined treatment and older males from ketamine alone. The findings indicate ketamine's effects may be robust enough that concurrent psychotherapy does not enhance short-term outcomes, but longer-term and demographic-specific effects require further study.
Amanda Timek, Catherine Daniels-Brady, Stephen Ferrando
A 33-year-old woman with severe and enduring anorexia nervosa and major depressive disorder, who had not improved with numerous prior treatments including antidepressants, mood stabilizers, antipsychotics, electroconvulsive therapy, and various therapies, received seven sessions of intravenous ketamine combined with acceptance and commitment therapy in a hospital setting. She showed increased cognitive flexibility, disappearance of suicidal ideation, and reduction in Beck Depression Inventory scores. Her body mass index was profoundly low at 13, whereas the lowest previously documented in the literature was 16.9. Ketamine-assisted psychotherapy may be a promising treatment for patients with anorexia nervosa and comorbid depression who have failed other interventions.
Çağrı Özkurt
preprint
A re-analysis of 12 randomized controlled trials on psilocybin for depression found moderate evidence of publication bias, with a bias-corrected effect size about 41% smaller than originally reported. The original analysis reported a large effect (g = 0.90), but after accounting for selective reporting using Robust Bayesian Meta-Analysis, the effect dropped to about 0.53, with a credible interval that includes zero. This evidence of bias disappeared when open-label studies were excluded, suggesting expectancy-driven effects rather than suppressed negative results. The findings do not overturn the original conclusions but indicate greater uncertainty than previously thought.
Milind Raskar
A multidisciplinary investigation combining textual analysis, fieldwork in India's Kutch region, and comparative ethnobotany identifies Vernonia cinerascens Sch. Bip. as a strong candidate for the sacred Soma plant of the Rigveda and its Iranian counterpart Haoma. The plant's woody stems, arrow-like shoots, tawny color, and leafy sprigs match ancient descriptions. Pressing its branches yielded a golden-tawny juice with a crackling sound noted in hymns. Experiential trials reported psychoactive and healing effects—relaxation, enhanced concentration, pain relief, calm joy—similar to those praised in the texts. The plant's known medicinal uses in African ethnobotany for mental disorders and depression further support the identification. Comparisons with Assyrian sacred tree iconography and Zoroastrian Barsom ritual suggest a broader Near Eastern continuity of sacred plant traditions.