Research Square
June 4, 2025
Isaac N Treves, Ya-Yun Chen, Caitlyn L Wilson et al.
Mindfulness-based interventions produce small-to-medium improvements in self-reported interoceptive awareness, according to a meta-analysis of 29 randomized controlled trials involving 2,191 participants (77.8% female, mean age 32.8 years). The overall effect size was g = 0.31, with mindfulness-based programs showing the largest effects (g = 0.41). Improvements in interoception were similar in size to improvements in self-reported mindfulness and were linked to reductions in psychological distress. No evidence of publication bias was found, and no other moderators—such as practice dosage or clinical sample—were significant. The findings suggest that mindfulness training leads to adaptive changes in how people subjectively experience bodily signals, which may contribute to better mental wellbeing.
Research Square
May 6, 2025
Zitong Wang, Brett Robbins, R. L. Zhuang et al.
In an animal model of treatment-resistant depression, psilocybin produced a significant and lasting reduction in behavioral despair and cognitive impairment. The compound increased thyroid-stimulating hormone levels without altering the hypothalamic-pituitary-adrenal axis, countering stress-induced TSH reductions that may serve as a proxy marker of therapeutic response. Changes in cannabinoid receptor type I after psilocybin administration suggest possible modulation of the endocannabinoid system, though causal links remain unconfirmed. These findings highlight psilocybin's potential to treat treatment-resistant depression through targeting previously unexplored biological pathways.
Research Square
May 6, 2025
Benjamin J. B. Bréant, José Prius-Mengual, Alexander Andrews et al.
Psychedelics like 5-MeO-DMT induce a dissociated state of arousal in mice, combining features of waking and sleep. In freely moving adult male mice, chronic neocortical recordings and pupillometry showed that the drug triggered prominent slow oscillations in the cortex and marked pupil dilation while the animals remained awake and moving. REM sleep was initially suppressed but overcompensated in the following 48 hours. This dissociated brain state, mixing waking and sleep characteristics, may underlie psychedelic effects such as dream-like hallucinations and reopening of the critical period for plasticity.
Research Square
April 28, 2025
Yi Wang, Tianjie Li, Erin S. Reynolds et al.
An enzyme called PcncAAAD, a noncanonical aromatic L-amino acid decarboxylase, is activated by calcium through a specific mechanism. Using computer simulations and lab experiments, researchers identified two calcium-binding sites: site A, at the junction of two enzyme domains, primarily drives activation, while site B within a unique tail domain stabilizes the enzyme's structure. Calcium binding at site A stabilizes a 'lid-rim' structure that maintains the substrate-binding pocket. Mutations disrupting site A or this lid-rim severely distort the active site and reduce or eliminate enzyme activity. These findings clarify how calcium activates this enzyme and may aid in designing enzymes to produce aromatic amino acid derivatives.
Research Square
April 16, 2025
Jino Park, Rufus Banks, Akul Munjal et al.
Among 100 cancer patients undergoing radiation therapy, 43% expressed interest in psychedelic-assisted therapy (PAT), 31% opposed it, and 26% were unsure. Interest was higher among those with prior mood disorders, prior recreational psychedelic use, younger age, and male sex. Patients experiencing more depression, worse spiritual well-being, greater demoralization, poorer quality of life, and more pain were more likely to be receptive. The main reason for hesitancy, cited by 43% of those not interested or unsure, was a lack of information. The findings suggest substantial patient openness to PAT, with education needed to address informational barriers.
Research Square
March 31, 2025
Eirini K. Argyri, F C Fraser, Stefan Schilling et al.
Awe experienced during psychedelic trips is linked to lasting changes in how people perceive boundaries between themselves and the world, and to shifts in their ways of knowing. In a mixed-methods study of 90 participants, awe—especially its connectedness and vastness aspects—was significantly correlated with increased overlap between self and others. Thematic analysis of open-ended responses identified three clusters of epistemic change: dissolving societal and natural boundaries, expanding awareness and openness to complexity, and increasing prosociality, compassion, and acceptance of difference. The findings suggest that psychedelic-induced awe may help foster a more holistic worldview, with potential benefits for prosocial and ecological awareness.
Research Square
March 5, 2025
Expedito Do Nascimento Júnior, Luiz Pereira, Wigínio Lira-Bandeira et al.
Chronic stress during adolescence can shrink neurons in the brain's somatosensory cortex, a region involved in depression. In a study of juvenile monkeys, those isolated to induce chronic stress had significantly smaller neurons than those living in a family group. However, monkeys given the traditional psychoactive brew ayahuasca before and during isolation had neuron volumes similar to the family group, suggesting the brew may protect against stress-induced cortical atrophy. Trends also hinted at preserved cortical structure in the ayahuasca-treated group, though differences in neuron density and overall cortical volume were not statistically confirmed. The findings point to ayahuasca's potential to mitigate stress-related brain changes and support further research into its therapeutic use for adolescent depression.
Research Square
September 26, 2024
Shona G. Allohverdi, Milad Soltanzadeh, André Schmidt et al.
Ketamine and psilocybin affect sensory learning in the brain through different neural mechanisms. By combining computational modeling with EEG data from a previous study, researchers analyzed how these drugs alter the brain's processing of prediction errors during an auditory task. Ketamine produced a larger reduction in sensory precision from 207 to 316 milliseconds after sounds, peaking at 277 milliseconds in frontal central brain regions, while psilocybin showed no significant effect on this measure. Both drugs reduced belief precision between 160 to 184 milliseconds, peaking at 172 milliseconds. For higher-level volatility prediction errors, ketamine reduced expression while psilocybin had no effect at 312 milliseconds. These distinct effects could inform tailored therapies for major depressive disorder.
Research Square
September 18, 2024
Shane Mageean, Anderson Daniel, Sara Tai
Cancer patients often suffer significant psychological distress, and current treatments often fall short. Psilocybin combined with psychotherapy may help, but oncologists, who are key gatekeepers to patient care, have not been well studied. Interviews with nine oncologists in England revealed five themes: their current approaches to distress, attitudes toward psychedelics, the need for quality research, service design, and distress across different patient backgrounds. Oncologists are open to psilocybin-assisted therapy but have concerns about safety and drug interactions with cancer treatments. Future research should explore these issues and include diverse patient groups.
Research Square
August 15, 2024
Paweł Holas, Justyna Kamińska
Around 4% to 8% of Polish adults, or about 2 million people, have tried classic psychedelics like psilocybin or LSD at least once. Men were more likely than women to use these substances, with the largest group of users aged 25–34 and living in urban areas. Curiosity was the most common reason for trying them, and users typically described the experience as a mix of pleasant and unpleasant sensations. Many participants held negative views of psychedelics and psychedelic-assisted therapy, but those with prior psychedelic experience had more positive attitudes.
Research Square
July 15, 2024
Cynthia U Price, Kenneth C Pike, Anna Treadway et al.
Integrating mindfulness-based interoceptive training with medication for opioid use disorder (MOUD) led to significant health improvements. In a study involving 303 participants across six clinics, those receiving Mindful Awareness in Body-oriented Therapy (MABT) alongside MOUD reported enhanced interoceptive awareness, reduced PTSD symptoms, and lower pain severity compared to those on MOUD alone. Although overall substance use levels remained similar between groups, MABT showed promise in addressing mental health and physical symptom challenges, highlighting its potential as an adjunct intervention in treating opioid use disorder.
Research Square
March 14, 2024
Micah Johnson, Ninette Simonian, Nicco Reggente
A novel technique of audiovisual stimulation (AVS) substantially improves self-reported mood by reducing anxiety and depression, and enhances performance on mood-sensitive cognitive tasks. In a randomized, controlled, double-blind experiment with 262 participants, AVS effects were highly similar whether binaural beats were present or not and regardless of session duration. Remarkably, the mood benefits from AVS closely aligned with those from breath-focused meditation, and a brief AVS exposure of about five minutes may be sufficient or even optimal for improving mood to a comparable or greater degree than meditation sessions of 11 or 22 minutes. These findings position AVS as a potentially more accessible alternative to meditation.
Research Square
February 22, 2024
Bettina Habelt, Dzmitry Afanasenkau, Cindy Schwarz et al.
Current treatments for alcohol use disorder (AUD) are often ineffective due to large variability in individual responses and high relapse rates. A precision medicine approach using biomarkers of prefrontal control mechanisms—which are severely disrupted in AUD, reducing inhibitory control and promoting compulsive behavior and relapse—may improve outcomes. In a rat model of alcohol addiction and relapse, a biocompatible neuroprosthesis measured prefrontal neural function during abstinence. Alcohol-dependent rats showed reduced amplitudes of P1N1 and N1P2 event-related potential components and attenuated event-related oscillatory activity. Treatment with psilocybin (a 5-HT2AR agonist) or LY379268 (an mGluR2 agonist) restored these impairments. Psilocybin also counteracted a dominance in higher beta frequencies indicative of hyperarousal prone to relapse. These findings identify prefrontal markers of relapse and treatment response, particularly for psychedelic drugs.
Research Square
January 12, 2024
Erik Kaadt, Rolf Søkilde, Hanne D. Hansen et al.
A single dose of psilocybin alters the expression of specific microRNAs (miRNAs) in the prefrontal cortex and hippocampus of pigs, brain regions central to depression. One day after administration, 12 miRNAs were dysregulated in the prefrontal cortex and 2 in the hippocampus; after one week, only 4 dysregulated miRNAs remained in the hippocampus. Nine of the 18 identified miRNAs have been previously linked to depression. Two miRNAs, miR-212-3p and miR-107, showed robust acute regulation in the prefrontal cortex and are known to exert anti-inflammatory effects, mirroring previously reported effects of psilocybin. These results suggest psilocybin may exert its molecular effects through miRNA regulation.
Research Square
December 13, 2023
David Sjöström, Emma Claesdotter-Knutsson, Petri Kajonius
In a national Swedish sample, people who have used psychedelics at least once report lower depression scores (effect size d = -0.29) but substantially more drug use (d = 1.27) compared to matched non-users. The largest personality difference is openness to experience (d = 1.72), and the lower depression in users is partly explained by lower neuroticism. The findings suggest that personality traits, especially neuroticism and openness, help account for both the mental health differences and the higher drug use seen in psychedelic users.
Research Square
November 20, 2023
Ottone Baccaredda Boy, Giuseppe Pierpaolo Merola, Andrea Patti et al.
Adolescents reported more severe psychotic symptoms on the Positive and Negative Syndrome Scale than adults, while no significant difference was found in cannabis exposure or Aberrant Salience Inventory scores. A hierarchical pattern emerged among adult subgroups, with psychotic patients scoring higher than other psychiatric and neurological patients. The findings suggest that aberrant salience, and to a lesser degree cannabis use, may contribute to psychotic symptom severity, particularly during more at-risk developmental phases. The role of cannabis in this relationship remains unclear.
Research Square
August 16, 2023
Anurag Jayswal, Kabita Devi, Ajanta Deka et al.
A five-minute technique coordinating breathing with thumb movement on finger divisions, performed with eyes closed, calmed participants and induced sleep in a group of 28 people in a classroom setting. EEG results from one participant showed increased low-frequency delta waves and decreased higher-frequency waves during the practice, with the strongest effect in the prefrontal lobe. The technique appears effective for quick rejuvenation and relaxation, and may help those with restlessness and anxiety.
Research Square
June 27, 2023
Louise Hecker, Kosuke Kato, Jennifer Kleinhenz et al.
Psilocybin, the psychoactive substance in hallucinogenic mushrooms, has shown therapeutic effects in over 136 clinical studies for psychiatric, neurodegenerative, and chronic pain conditions, though its molecular mechanisms remain unclear. This study tested whether psilocybin affects cellular aging using a human cell model of replicative senescence. Continuous treatment with psilocybin caused a dose-dependent reduction in cell-cycle arrest markers, increased DNA replication and proliferation markers, lowered senescence-associated secretory phenotype (SASP), and decreased oxidative stress, without killing senescent cells. These results provide the first experimental evidence that psilocybin may slow cellular senescence, suggesting potential as a geroprotective agent for age-related diseases.
Research Square
May 5, 2023
Nargess Rahnama, Gholamreza Malek Zadeh, Mohammad Moshtari
During the coronavirus pandemic, pre-hospital emergency staff who practiced mindfulness were more likely to experience flow states, a sense of full immersion and engagement in their work. This connection was explained by two factors: psychological capital (a positive psychological state including hope, efficacy, resilience, and optimism) and coping competence (the ability to manage stressful situations). The findings suggest that mindfulness supports well-being and optimal functioning in high-stress healthcare roles by strengthening these personal resources.
Research Square
March 20, 2023
Ahmed N. Hassan, Sean Ferkul, Zena Agabani et al.
A virtual Mantram Repetition Program—a brief, mindfulness-based, non-trauma-focused group intervention—was feasible, safe, and acceptable for adults with both posttraumatic stress disorder (PTSD) and substance use disorder (SUD). Of 43 enrolled participants, 35 completed the 8-week program (81.4% retention). Qualitative feedback highlighted the program's acceptability through its delivery method, informative materials, and a practical mindful tool for managing symptoms. Further controlled trials are needed to compare the program with other interventions.
Research Square
March 10, 2023
Xue Chen, Jing Li, Lisa Yu et al.
An enzyme from cane toad (Rhinella marina), named RmNMT, efficiently produces N,N-dimethylated indolethylamines, including psychedelic compounds like N,N-dimethyltryptamine. Unlike similar enzymes in mammals and fungi, RmNMT is highly efficient and promiscuous, enabling the bioproduction of new-to-nature indolethylamine derivatives. N,N-Dimethylated indolethylamines showed reduced binding and activation at 5-HT1A and 5-HT2A receptors compared to primary amines, yet only these tertiary amines induced hallucinogenic behavior in mice, suggesting metabolic stability is key. This discovery establishes a platform for producing and screening novel indolethylamines for potential psychiatric medicines.
Research Square
February 14, 2023
Frank Sánchez-Quijano, Diana Ximena Puerta-Cortés, Julio Eduardo Mazorco-Salas
A pilot study compared mindfulness and holotropic breathwork treatments for female adolescents aged 15–18 in rehabilitation for psychoactive substance use. Eighteen participants from a Colombian treatment center were studied using a mixed methods exploratory design. Heart rate, an indicator of psychological and cardiovascular well-being, decreased in the mindfulness group compared to a control group. Qualitative reports from participants and staff described positive changes in emotional regulation, coping, communication, and reductions in stress, anxiety, and the desire to use substances following both treatments.
Research Square
November 15, 2022
Kennedy Robertson, Ian Gold, Samuel P. L. Veissière et al.
Delusional ideation, or false beliefs, is linked to social factors such as feeling the presence of unseen others, loneliness, social anxiety, and empathy. A survey of 2,200 healthy adults during the COVID-19 pandemic found that all measured aspects of social imagery were positively associated with delusional ideation. The strongest predictor was felt presence, followed by loneliness, social fear, and empathic concern. The findings suggest that delusions may arise from common mechanisms with social imagination, and that alterations in social cognition contribute to delusional thinking.
Research Square
September 8, 2022
Maria Helha Fernandes-Nascimento, André Brooking Negrão, Karine Viana-Ferreira et al.
A bibliometric analysis of publications on ibogaine for treating substance-related disorders from 1991 to 2020 found that research output grew steadily, with an increase of 5.1 publications per year between 1991 and 2000. The subsequent two decades showed continued but fluctuating publication volumes, with the United States being the most prominent contributor. The analysis suggests that despite variations over time, research on ibogaine persists and points toward future directions for public health interventions.
Research Square
August 3, 2022
Lin Ban, Xiaohong Lv, Dawei Cai et al.
Death ends all biological functions and is inevitable. To cope with the fear of death, early humans developed concepts of the soul and religion, which led to burial and sacrificial customs. Shamanism, practiced by nomadic groups in northern Eurasia, is one such tradition. At the Nairentoligai Cemetery M17 in Inner Mongolia, China, archaeologists found a corpse whose face was covered with all the right ribs of a sheep. Zooarchaeological analysis identified the sheep's characteristics and, through bone-surface traces, reconstructed how the animal was dismembered. The practice may have been intended to declare the body dead and protect the soul from intrusion, reflecting shamanistic beliefs. This finding aids research into the religious views of northern Mongolian Plateau nomads.