Preprints.org
March 24, 2021
Lehel Balogh, Masaru Tanaka, Nóra Török et al.
22 citations
preprint
Existential phenomenological psychotherapy (EPP) helps people with mood and anxiety disorders find meaning and purpose in life. This narrative review describes EPP's development from the works of Heidegger, Binswanger, Boss, and Frankl, its therapeutic methods, and evidence for its effectiveness. The authors argue that EPP can work synergistically with medication-based treatments for these disorders. They also discuss how neuroscience currently understands mood and anxiety disorders and propose a path to integrate meaning-centered psychotherapy with neuroscience, despite the two fields remaining polarized.
Preprints.org
July 21, 2023
Fran Hancock, Fernando E. Rosas, Mengsen Zhang et al.
16 citations
preprint
Healthy brain function requires a balance between stable integration across brain areas for coordinated activity and brief periods of desynchronization that allow subsystems to reconfigure and express specialized functions. Metastability, a concept from statistical physics and dynamical systems theory, has been proposed as a key signature of this balance. Neuroscience research has used markers of metastability to study cognitive performance, healthy aging, meditation, sleep, responses to drugs, and to characterize psychiatric conditions and disorders of consciousness. However, the term is often used heuristically or inaccurately, making the literature difficult to navigate. This paper provides a comprehensive review of metastability in neuroscience, covering its scientific and historical foundations, practical estimators, and a critical analysis of recent theoretical developments to clarify misconceptions.
Preprints.org
January 24, 2019
Genís Ona, José Carlos Bouso
8 citations
preprint
The current crisis in psychopharmacology has deep historical roots and requires innovative approaches. The therapeutic use of psychedelic drugs offers a promising and integrative treatment with enduring effects for mental health problems.
Preprints.org
November 28, 2025
Ngo Cheung
6 citations
preprint
An oral glutamatergic regimen combining dextromethorphan, a CYP2D6 inhibitor, piracetam, and l-glutamine shows promise for treating refractory mood and anxiety disorders, with case reports and small open series describing sudden, occasionally dramatic recoveries in depression, PTSD, chronic pain, and functional somatic syndromes. However, the pharmacokinetics require careful handling because the CYP2D6 blocker that maintains dextromethorphan levels can also push the drug or co-prescribed psychotropics into toxic territory, limiting the regimen's accessibility despite its potential to bring rapid-acting biology to outpatient clinics.
Preprints.org
November 25, 2025
Ngo Cheung
6 citations
preprint
Rapid-acting antidepressants can lift mood within hours by shifting glutamatergic circuits from an NMDA-dominant to an AMPA-dominant state. Intravenous ketamine achieves this but has dissociative side effects and logistical challenges; the oral combination dextromethorphan + bupropion (Auvelity) only provides initial NMDA blockade, yielding slower, less durable benefit. A proposed fully oral, low-cost, four-component regimen aims to replicate ketamine's plasticity cascade: dextromethorphan for fast NMDA antagonism, a strong CYP2D6 inhibitor to prolong DXM exposure, the AMPA positive allosteric modulator piracetam to amplify downstream glutamate burst, and micronized L-glutamine to restore presynaptic glutamate pools and buffer against excitotoxicity. Preclinical evidence suggests each element synergizes along the same mechanistic axis, potentially democratizing ketamine-level efficacy with inexpensive medications.
Preprints.org
November 10, 2021
Enzo Tagliazucchi
5 citations
preprint
Psychedelics profoundly alter subjective experience, often with lasting effects, yet their impact on language production is underexplored. This review examines how acute psychedelic effects disrupt speech organization regardless of semantic content, and how analyzing the semantic content of written retrospective reports can characterize subjective effects. Computational analysis of language production is an emerging tool to predict therapeutic outcomes, relate psychedelic effects to other altered states, compare them to psychiatric disorder symptoms, and investigate neurochemical profiles and mechanisms of different psychedelics. Researchers can expand scientific conclusions by analyzing brief interviews before, during, and after acute effects. Several open questions remain to consolidate this approach.
Preprints.org
January 13, 2026
Jaba Tkemaladze
3 citations
preprint
The brain may operate like a biological version of the double-slit experiment, maintaining multiple possible interpretations of reality in a state of active interference, analogous to quantum superposition. Sensory input, actions, and social context act as 'which-path' information that collapses this ambiguity into a single, coherent perception and decision. Sleep functions as a periodic quantum eraser, degrading this which-path information to restore cognitive flexibility and prevent rigid, maladaptive thinking. This framework links quantum decoherence, Bayesian inference, and sleep neurobiology, offering a model for disorders like psychosis and PTSD as dysregulations of this interference-localization cycle. The brain does not merely observe quantum reality but instantiates its core logic as a continuous process of resolving ambiguity.
Preprints.org
January 15, 2021
Laura C. Sánchez-Sánchez, María Fernanda Valderrama Rodríguez, José M. García‐Montes et al.
3 citations
preprint
People who practice Mindfulness report higher body awareness, sexual satisfaction, sexual activity, and more intimate erotic fantasies compared to those who do not practice Mindfulness. The study compared 106 Spanish-speaking adults (32 men, 72 women) who either practiced Mindfulness or were naïve to it, using online surveys. Mindfulness practitioners scored significantly higher on measures of body awareness, personal and partner-related sexual satisfaction, desire, arousal, orgasm, and intimate fantasy types. The findings suggest Mindfulness may benefit sexuality in both clinical and non-clinical populations.
Preprints.org
May 10, 2024
Nicolas Deperrois, Mihai A. Petrovici, Jakob Jordan et al.
2 citations
preprint
Dreams during rapid-eye-movement (REM) sleep may help learning and creativity through an adversarial process inspired by artificial intelligence, where a discriminator network classifies internally generated sensory activity as real. This process facilitates the emergence of real-world semantic representations in higher cortical areas and balances fantastic with realistic dream elements to promote creative insights. Non-REM (NREM) dreams, which replay single hippocampal memories, serve a complementary role by improving cortical representations' robustness to environmental perturbations. Subjects can become aware of adversarial REM dreams more easily than NREM dreams, and this awareness relates to wake, dream, and lucid dreaming phenomena.
Preprints.org
Enzo Tagliazucchi
2 citations
preprint
Serotonergic psychedelics alter conscious awareness, perception, mood, emotion, and cognition, but their effects resist simple classification like stimulant or sedative. Their defining feature is temporarily inducing an altered state of consciousness. Because only humans can explicitly report conscious experiences, studying these compounds requires non-invasive neuroimaging techniques in healthy subjects. This review examines how neuroimaging has been applied to investigate the neural correlates of altered consciousness caused by serotonergic psychedelics.
Preprints.org
December 22, 2025
Ngo Cheung
1 citation
preprint
Obsessive-compulsive disorder remains treatment-resistant in 40–60% of patients despite optimized serotonin-reuptake inhibitor therapy and antipsychotic augmentation. Emerging evidence points to glutamatergic dysregulation in cortico-striato-thalamo-cortical circuits as a core driver of rigid, maladaptive synaptic patterns. The Cheung Glutamatergic Regimen—a fully oral, low-cost combination of dextromethorphan, a CYP2D6 inhibitor, piracetam, and optional L-glutamine—aims to replicate the rapid neuroplastic cascade triggered by intravenous ketamine.
Preprints.org
December 2, 2025
Ngo Cheung
1 citation
preprint
A 48-year-old man with treatment-resistant depression experienced dramatic mood improvement and elimination of suicidal thoughts after a single dose of intranasal esketamine, but the high cost (HK $6,000 per session) forced him to stop treatment. Over two years, his condition evolved into severe obsessive-compulsive disorder with violent intrusive images. In 2025, he was switched to an oral regimen designed to mimic ketamine's mechanism: dextromethorphan 120 mg/day, fluoxetine 20–40 mg/day, and piracetam 1.2 g/day. Within four weeks, intrusive imagery became sporadic, his PHQ-9 score dropped from 17 to 5–6, suicidal ideation disappeared, and he returned to full work productivity. Gains persisted for over eight months at a monthly cost of HK $400–600, less than one-tenth the cost of maintenance esketamine.
Preprints.org
August 29, 2025
Alessandro Gonçalves Campolina, Marco Aurélio Tuena De Oliveira
1 citation
preprint
A narrative review synthesizes evidence on ketamine-assisted psychotherapy (KAP) for palliative care patients, who often suffer existential distress, loss of meaning, and emotional pain beyond physical symptoms. The authors present a novel, time-limited KAP model tailored to end-of-life settings, integrating neurobiological, psychological, and experiential effects. The model includes preparatory and integrative psychotherapy, two ketamine dosing sessions (one low-dose and one moderate-dose), concurrent psychotherapy, goals of care discussion, and optional pharmacological optimization. It leverages ketamine's effects on self-processing networks—the Salience Network (embodied self-awareness) and Default Mode Network (narrative self-construction)—to address bodily and narrative dimensions of distress. The approach emphasizes psychological safety, meaning-making, and patient-centered care to enhance quality of life at the end of life.
Preprints.org
June 19, 2025
Danial Daroui, Andrea Mastrostefano, Flavio Davini et al.
1 citation
preprint
Psilocybin, when paired with psychotherapy, reduces heavy drinking days and alcohol-related and mental problems in people with Alcohol Use Disorder (AUD), according to a scoping review of 12 studies published between 1968 and 2025. The review included 7 randomized controlled trials, 4 open-label studies, and 1 case report. Early Polish studies suggested long-term remission of alcohol cravings, while recent U.S.-based RCTs confirmed reductions in heavy drinking and associated problems. Limitations include small sample sizes and short follow-up periods, especially for patients with comorbidities. Most studies were conducted in hospital and university psychiatry departments. Psilocybin remains an experimental treatment requiring further rigorous research on efficacy and safety.
Preprints.org
June 17, 2025
Latha Poonamallee
1 citation
preprint
Mindfulness can foster pro-environmental behaviors by enhancing ecological awareness and emotional regulation, offering an alternative to fear-based climate narratives that often cause disengagement and eco-anxiety. Drawing on empirical studies and theoretical frameworks, the paper explores mechanisms such as intrinsic motivation, connectedness to nature, and cognitive flexibility. Applications in organizational and educational settings are discussed, along with barriers to sustained change. Future research directions and strategies for integrating mindfulness into systemic environmental initiatives are identified, positioning it as a critical tool for addressing the global climate crisis.
Preprints.org
October 17, 2024
Tamara Valdez, Valbhi Patel, Dally Senesombath et al.
1 citation
preprint
Psychedelics are being reconsidered as treatments for substance use disorders (SUDs) such as alcohol and opioid use disorders, following early 20th-century anecdotal reports and pilot studies that suggested their potential. Legal restrictions and stigma had halted research, but rising rates of SUDs have renewed interest in these compounds. This review examines emerging evidence for psilocybin, ketamine, LSD, MDMA, ayahuasca, ibogaine, and peyote in treating SUDs, focusing on novel pharmacological targets and holistic approaches to improve adherence and efficacy.
Preprints.org
August 7, 2024
Maria Margariti, Ilias I. Vlachos, Dimitra Mpourazana et al.
1 citation
preprint
Psychotic arousal is a proposed emotional state during acute psychosis, characterized by abnormal experiential feelings. A new scale, the Psychotic Arousal Scale (PAS), was tested in 55 patients with acute schizophrenia. The scale showed good internal reliability and correlated with measures of delusion conviction, anxiety, and depression. Psychotic arousal decreased with antipsychotic treatment in the first weeks. The findings suggest that emotional arousal with abnormal feelings is present in acute psychosis but often overlooked.
Preprints.org
June 27, 2024
Konstantinos Zorbas
1 citation
preprint
In Tuva Republic, South Siberia, accusations of magical assault and vampirism commonly explain misfortune. Based on fieldwork in an Association of Shamans, this article examines countercursing rituals against antagonists under Russian political domination. It argues that shamanic healing gains efficacy by appropriating hunting symbols and animal spirits from Indigenous Siberian cosmologies. The analysis shows that playing with risk during countercursing structures symbolic resolution. The article concludes that indigenous perceptions of a cursed landscape become a field where agencies of darkness—and their political sponsors—are confronted by an emancipating Buddhist religious mindset.
Preprints.org
May 7, 2024
Gianluca Ficca, Oreste De Rosa, Davide Giangrande et al.
1 citation
preprint
People with schizophrenia spectrum disorders report fewer and shorter dreams than healthy controls, with fewer characters, settings, and emotions. The reduction in emotional content in dreams correlates with greater symptom severity, suggesting that dreaming plays a role in emotion regulation during wakefulness—a function that may be impaired in psychosis.
Preprints.org
October 12, 2023
Mi Hyang Hwang, Leslie Bunt, Catherine Warner
1 citation
preprint
An 8-week programme combining Zen meditation and music listening enhanced mindfulness and happiness among university music therapy students. Participants reported positive responses to daily stressors such as exam anxiety, financial difficulties, and emotional distress during the COVID-19 pandemic. The qualitative study used surveys and semi-structured interviews, analyzed through thematic analysis, to explore the effects of the meditation and music intervention. The findings suggest that integrating these practices can support mental health and well-being in higher education, offering coping strategies and expanding the potential for combined music and meditation interventions.
Preprints.org
June 6, 2023
Sanah Malomile Nkadimeng, Christiaan M.l. Steinmann, J.n. Eloff
1 citation
preprint
Extracts from four psilocybin-containing mushrooms—Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis, and Psilocybe cubensis leucistic A+ strain—did not worsen angiotensin II-induced cardiac hypertrophy in rat heart cells and instead showed protective effects against oxidative stress. Angiotensin II reduced cell viability, increased cell width, and raised reactive oxygen species levels. The mushroom extracts, prepared with ethanol, cold water, or hot water, did not exacerbate these changes; they exhibited cardio-protective activity. Losartan, an angiotensin receptor blocker, served as a positive control. Phytochemical analysis detected known antioxidant and anti-inflammatory compounds in the extracts.
Preprints.org
July 5, 2022
Ravi Philip Rajkumar
1 citation
preprint
Suicidal behavior is a growing public health problem. Existing treatments have limited effectiveness for people who have already attempted suicide, so new approaches are needed. Research on the neurobiology of social pain—the distress from social rejection or loss—identifies it as a key risk factor and suggests several promising drug targets. This paper reviews evidence on those targets and examines how recently approved treatments like ketamine and psilocybin may reduce suicidal ideation and behavior in the short term, especially when social pain is a contributing factor. These pharmacological strategies may work regardless of whether a person has a specific psychiatric diagnosis.
Preprints.org
September 7, 2021
S. Amigó
1 citation
preprint
A brief psychological intervention called Self-Regulation Therapy (SRT), which uses suggestion and classical conditioning to reproduce the positive effects of illegal drugs (cannabis, cocaine, ecstasy), improved coping with stress and emotionality. Fifteen volunteers (average age 24.67) showed superior coping strategies and positive emotionality, with reduced negative emotionality, compared to no intervention. Improvements persisted during a 4-week follow-up. The findings suggest that reproducing the positive effects of such drugs via SRT can enhance young people's coping and emotional regulation.
Preprints.org
June 28, 2021
Maurizio Coppola, Francesco Bevione, Raffaella Mondola
1 citation
preprint
Psychedelics from plants have been used for millennia in religious and spiritual practices. In 1957, Dr. Hofmann identified and synthesized psilocybin, a prodrug found in over 200 species of psychedelic mushrooms. Despite limitations in study design, clinical observations from the 1950s and 1960s suggested psilocybin had potential therapeutic effects for depressive symptoms, anxiety, and conversion disorder. Classified as a Schedule I substance in 1970, scientific interest revived in the 1990s. Recent studies provide further evidence supporting the hypothesis that psilocybin may be useful for treating psychiatric disorders such as pathological anxiety, mood depressive disorder, and addiction.
Preprints.org
Kainat Riaz, Sejal Suneel, Mohammad Hamza Bin Abdul Malik et al.
1 citation
preprint
Half of patients with post-traumatic stress disorder (PTSD) do not respond to standard pharmacotherapy or psychotherapy. A review of six phase II randomized controlled trials indicates that MDMA-assisted psychotherapy can reduce PTSD symptoms, even in treatment-resistant cases, by increasing neurohormones such as dopamine, serotonin, norepinephrine, and oxytocin and by modulating brain regions involved in fear and anxiety. The FDA has granted MDMA-assisted psychotherapy a "Breakthrough Therapy" designation. Further research is needed to determine whether the benefits outweigh the risks and whether this approach can be integrated into existing treatment options.