Research Square
December 13, 2023
David K. 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
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
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.
Research Square
April 20, 2022
Aviv Aharon-Almagor, Frederick S. Barrett
People who have used hallucinogens show greater openness to new experiences and higher cognitive ability scores compared to non-users, along with denser structural connectivity in white matter tracts linked to cognition, emotion, and creativity. The study compared 53 hallucinogen users with 53 matched non-users from a public database, using diffusion tensor imaging and psychological assessments. Hallucinogen users also reported more lifetime use of other illicit drugs. These findings suggest hallucinogen use may be associated with lasting changes in brain structure and personality, offering clues to possible neural mechanisms behind therapeutic effects.
Research Square
Majid Eslami, Laleh Khorshidi, Maryam Ghasemi et al.
In rats, the recreational drug MDMA (Ecstasy) impairs spatial memory and increases oxidative stress and cell death in the hippocampus. Atorvastatin (5, 10, 20 mg/kg) and rosuvastatin (20 mg/kg), given orally for 21 days, prevented these memory deficits and reduced the MDMA-induced rise in reactive oxygen species, lipid peroxidation, and caspase-3 and -9 activities. The results suggest that these statins protect against MDMA neurotoxicity by suppressing oxidative stress and apoptosis.
Research Square
Sean Viña
People who use psychedelics are less likely to seek formal mental health care, including medication and outpatient treatment, even when experiencing high psychological distress. Analyzing data from over 458,000 participants in a national US survey between 2010 and 2018, the study found that as distress levels increase, psychedelic users become even less inclined to use formal care compared to non-users. This suggests a heightened risk of self-medication as psychedelics become more culturally and legally accepted.
Research Square
Taqwa B. Thanoon, Zeina A. Althanoon
Depression during pregnancy can harm offspring brain development and behavior. Common antidepressants like SSRIs carry risks because they cross the placenta. Ketamine is being explored as an alternative. This study in mice examined the effects of ketamine on offspring of mothers that experienced stress. Female mice were divided into groups: control, maternal stress, stress plus fluoxetine, and stress plus ketamine. Behavioral tests measured anxiety, anhedonia, and despair in the offspring. Maternal stress increased anxiety-like behaviors, and both ketamine and fluoxetine reversed some effects. However, fluoxetine was more effective at reducing despair. Ketamine moderately reduced anhedonia compared to controls. More research on dose and timing is needed to optimize ketamine treatment.
Research Square
Alice Le Berre
In adults with treatment-resistant depression, esketamine was associated with early microstructural changes in the dentate gyrus of the hippocampus: reduced fractional anisotropy and increased orientation dispersion index, consistent with greater dendritic complexity. Lower baseline left-dentate gyrus fractional anisotropy correlated with greater improvement at two weeks, and a decrease in fractional anisotropy over that period also correlated with improvement. These changes suggest esketamine may promote hippocampal plasticity, and baseline diffusion MRI metrics could serve as candidate biomarkers for treatment response. The study included 12 adults with treatment-resistant depression and 24 matched controls, but larger studies are needed.
Research Square
Amit Kumar
A 24-year-old woman experienced possession trance attacks, a condition involving altered consciousness where a person's identity is replaced by a spirit or deity, with amnesia for the event. Her entire family developed shared delusional beliefs, and multiple members also had possession attacks over time. Such attacks can be misdiagnosed as psychotic illnesses like schizophrenia. The case highlights the cultural and familial context of possession trance, which must cause distress or impairment and not be due to psychosis or substance use.
Research Square
Norihiro Okada, Kenshiro Oshima, Akiko Maruko et al.
Non-responders to ketamine treatment for depression show elevated viral infection markers based on intron retention (IR) gene analysis of RNA-seq data. Several IR genes associated with viral infection returned to healthy levels after ketamine regardless of responder status, suggesting non-responders are not resistant to ketamine but rather have an extremely high inflammatory state that the drug's effects cannot overcome. Excluding one transcriptomic outlier with extreme viral infection did not change IR gene conclusions but did alter differentially expressed gene (DEG) results, supporting the authors' claim that IR genes may be more useful markers of depression than DEGs.
Research Square
Minna Chang
Ketamine can cause ulcerative cystitis, a bladder condition with lower urinary tract symptoms and kidney damage, in over 25% of regular recreational users. This complication had not been reported in therapeutic use for depression until now. A 28-year-old woman started on ketamine for depression developed cystitis, confirmed by urine tests. This is the first reported case of ketamine-induced cystitis from treatment-dose ketamine for antidepressant therapy.
Research Square
Katelyn Halpape, Raelle Pashovitz, Annabelle Wanson et al.
A small pilot program evaluated a hospital-to-outpatient intranasal racemic ketamine maintenance therapy for treatment-resistant depression. Five adult inpatients who had responded to intranasal ketamine in hospital continued treatment at a community centre, completing up to 14 sessions over 192 days. Depressive symptoms decreased or stabilized, and quality of life increased or stabilized. No serious adverse events occurred; mild side effects included anxiety and nausea, and slight blood pressure increases did not require intervention. The authors conclude the therapy appears feasible and well tolerated, but limited effectiveness conclusions can be drawn from this small study.
Research Square
Jack Swain, Davis Carter, Leonardo Vando et al.
Among 13,963 adults with moderate-to-severe sleep disturbances who received at-home ketamine-assisted therapy for depression, 67.4% showed at least a 1-point improvement on a single sleep-related item from a depression screening tool after two sessions. By session six, 76.8% of completers met that threshold, and the average score dropped 48.8% from baseline. However, the study could not separate sleep changes from mood improvement because all participants were treated for depression and no control group was included. Side effects were reported by 3.7% to 5.0% of participants across sessions.
Research Square
July 10, 2026
A multidimensional framework is introduced for comparing theories of consciousness, representing conscious states as vectors with physical (P), cognitive/computational (C), and noetic (N) components. The noetic dimension captures structured aspects of data or phenomenology not explained by current physical and cognitive models, treated as a testable latent variable. Using a linear-algebraic analogy, the framework clarifies how theories differ in explanatory assumptions and how these can be evaluated through perturbation, identifiability, and invariance criteria. It outlines mappings between neuroelectromagnetic dynamics and phenomenology, and describes empirical predictions and protocols for comparing theories based on empirical findings.
Research Square
December 12, 2025
Language used in online discussions about eating disorders and psychedelics shows heightened emotional awareness, suggesting deeper self-insight. Comments from a psychedelic subreddit were analyzed with Linguistic Inquiry and Word Count software to detect clues and patterns in personal experiences. The findings parallel ongoing discourse about psychedelics' potential to support well-being and mental health, particularly by changing perceptions of struggles such as eating-related ones. This intersection of language, eating disorders, and psychedelic integration raises therapeutic possibilities.
Research Square
November 18, 2025
A single session of high ventilation breathwork, compared to body scan meditation, produced substantially greater altered states of consciousness in 24 healthy adults, including mystical experiences, emotional breakthrough, and feelings of oneness. One week later, breathwork led to greater psychological insight and behavioral change. Both groups showed improvements in stress, anxiety, depression, and well-being over time. The results indicate that breathwork induces acute psychedelic-like effects and may have therapeutic potential.
Research Square
September 23, 2025
The visual awareness negativity (VAN) is a brain signal thought to reflect conscious perception. This event-related potential study tested whether the VAN appears during visual illusions, where people report seeing something that is not physically present. Using the sound-induced flash illusion—a single flash accompanied by two beeps often creates the illusion of a second flash—the researchers compared brain responses from 47 participants on trials where the illusion was perceived versus not perceived. An enhanced negativity over posterior electrodes between 250 and 300 milliseconds appeared during illusory trials. Lower pre-stimulus alpha power also accompanied illusion trials, consistent with prior work linking alpha brain waves to perceptual variability. These results suggest the VAN reflects conscious perception even for illusory experiences, supporting its role as a neural correlate of consciousness.
Research Square
August 19, 2025
A national survey of 742 Canadian stakeholders—cancer patients, healthcare providers, and policymakers—found that patients held the most favorable attitudes toward psychedelic-assisted therapy (PAT), though they reported the least knowledge about it. Policymakers reported the highest knowledge but also the greatest safety concerns. Psilocybin was viewed as the most effective agent across all groups. Patients and providers supported PAT for use across the cancer continuum, while most policymakers favored restricting it to advanced-stage cases. The findings indicate that integrating PAT into oncology will require stakeholder-informed education, regulatory guidance, and attention to implementation barriers.
Research Square
July 8, 2025
A generative adversarial AI framework, pitting deep neural networks against interpretable neural field models, produces biologically realistic simulations of conscious and comatose brains that recapitulate features across humans, monkeys, rats, and bats. Without explicit programming, the AI retrodicts known responses to brain stimulation and generates testable predictions about unconsciousness mechanisms. Two predictions are validated: selective disruption of the basal ganglia indirect pathway, supported by diffusion MRI in 51 DOC patients; and increased cortical inhibitory-to-inhibitory synaptic coupling, supported by RNA sequencing from resected brain tissue in six human coma patients and a rat stroke model. The model also identifies high-frequency subthalamic nucleus stimulation as a promising intervention, supported by electrophysiology data from human patients.