PLoS ONE
December 30, 2015
Vanessa Manchim Favaro, Maurı́cio Yonamine, Juliana Carlota Kramer Soares et al.
33 citations
Long-term daily administration of ayahuasca to rats for 30 days did not affect their performance in the Morris water maze or elevated plus maze tasks. However, a dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning, while the tone-conditioned response remained unaffected. This heightened contextual fear response persisted across repeated sessions several weeks after training. These results indicate that long-term ayahuasca exposure can selectively enhance the contextual association of emotional events, consistent with the beverage's known activation of brain regions involved in emotional processing and memory.
PLoS ONE
September 10, 2013
Niklaus Denier, Hana Gerber, Marc Vogel et al.
32 citations
In 15 heroin-dependent patients receiving stable heroin-assisted treatment, heroin reduced blood flow in the left anterior cingulate cortex, left medial prefrontal cortex, and insula compared to placebo. These brain areas are involved in self-regulation and emotional processing. The findings suggest that heroin's effects on these regions may contribute to its ability to reduce craving and produce relaxation in maintenance therapy.
PLoS ONE
December 18, 2012
Stanley C. Flavel, Jenna D. Koch, Jason M. White et al.
30 citations
Abstinent ecstasy users show abnormally large tremor during movement compared to non-drug users, while resting tremor remains unaffected. The study measured tremor with an accelerometer in abstinent ecstasy users (n=9), users of amphetamine-like drugs (n=7), cannabis users (n=12), and non-drug users (n=23). During finger movement, tremor amplitude was significantly greater in ecstasy users (frequency range 3.9-13.3 Hz) but not in cannabis or amphetamine users. Peak tremor frequency did not differ between groups. The finding suggests chronic ecstasy use may produce lasting motor effects, though further research is needed to determine if this increases risk of movement disorders.
PLoS ONE
December 14, 2022
Meghan DellaCrosse, Mollie Pleet, Emma Morton et al.
28 citations
Adults with bipolar disorder who used psilocybin-containing mushrooms reported both benefits and risks. Benefits included reduced depression severity, improved emotion processing, new perspectives, and better relaxation and sleep. Risks included changes in sleep, increased mania severity, hospitalization, and distressing sensory experiences. Contextual factors such as poly-substance use, psilocybin dose, solo versus social use, and pre-use sleep deprivation influenced outcomes. The findings highlight the need for carefully designed clinical trials to assess safety and preliminary efficacy of psilocybin therapy in this population.
PLoS ONE
January 2, 2024
Caroline Peacock, Erin Brauer, Ali John Zarrabi et al.
27 citations
Spiritual health practitioners bring unique expertise to psychedelic-assisted therapy based on their training and professional experience. Interviews with 15 such practitioners revealed seven themes in two domains: unique contributions (competency with spiritual material, awareness of power dynamics, familiarity with non-ordinary states, holding space, counterbalancing biomedical perspectives) and general contributions (using general therapeutic skills and supporting interdisciplinary collaboration). Their skills complement other clinical team members, and psychedelic-assisted therapy teams may benefit from including them. Further work is needed to define roles, qualifications, and training for these clinicians.
PLoS ONE
December 2, 2010
Gantt P. Galloway, Jennifer D. Siegrist, Lynn C. Robertson et al.
22 citations
A double-blind placebo-controlled study found that the hallucinogen MDA increases closed-eye visions and mystical-type experiences. People who had more intense visions tended to perform worse on tests of contour integration and object recognition, suggesting that drug-induced hallucinations may be stronger in individuals with poorer perceptual processing. This points to possible shared mechanisms with hallucinations in psychiatric and neurological conditions.
PLoS ONE
January 30, 2020
V. Charland-Verville, D. Ribeiro de Paula, C. Martial et al.
20 citations
Near-Death Experiences (NDEs) are commonly portrayed as passing to an afterlife, but empirical research is recent and their definition remains debated. Questionnaires used to identify NDEs may be restrictive and subjective. To address this, researchers analyzed freely expressed narratives from 158 participants who reported a firsthand NDE, using automated text-mining. The analysis identified the most common words and, through hierarchical clustering, revealed three main clusters of features: visual perceptions, emotions, and spatial components. The authors suggest that this user-independent, data-driven approach can help build a more rigorous description and definition of NDEs.
PLoS ONE
March 16, 2022
Katharina Dworatzyk, Tallulah Jansen, Timo Torsten Schmidt
19 citations
Two self-report questionnaires for assessing psychedelic experiences, the Challenging Experience Questionnaire and the Ego-Dissolution Inventory, were translated into German and evaluated in an online survey. The German version of the Challenging Experience Questionnaire showed acceptable fit to the original 7-factor structure, good internal consistency, and convergent validity with measures of anxiety and altered states of consciousness. The German Ego-Dissolution Inventory did not support the original single-factor structure; exploratory analysis suggested a 5-item version that measured ego-dissolution with high internal consistency and convergent validity. These validated translations help standardize assessment in psychological and neuroscientific research on altered states of consciousness.
PLoS ONE
October 25, 2021
Annie Regan, Seth Margolis, Harriet de Wit et al.
18 citations
MDMA produces a moderate-to-large increase in self-reported feelings of sociability—such as feeling loving, talkative, and friendly—according to a meta-analysis of 27 placebo-controlled studies involving 592 participants. The overall effect size was d = 0.86, indicating a substantial boost in sociability-related outcomes. This finding suggests MDMA could have powerful implications for social interactions and clinical settings, such as in psychotherapy. The analysis highlights the need for larger experimental studies and further investigation into the mechanisms linking MDMA to enhanced social connection.
PLoS ONE
June 15, 2016
Andrea E Steuer, Corina Schmidhauser, Eva H Tingelhoff et al.
18 citations
Bupropion pretreatment increased the maximum plasma concentration and overall exposure of both MDMA stereoisomers, while reducing the levels of its major metabolites by about 40%, in healthy volunteers. These changes in MDMA pharmacokinetics due to reduced CYP2D6 activity were similar to those seen in people with naturally lower CYP2D6 function (intermediate metabolizers). The alterations in stereoselectivity based on CYP2D6 activity likely have low clinical relevance. Bupropion and its metabolite levels were not affected by MDMA co-administration.
PLoS ONE
March 7, 2024
Sean M. Viña
14 citations
Lifetime classic psychedelic use is independently linked to lower psychological distress, but household size alters that relationship. Larger households are associated with higher distress, and this negative effect is amplified among psychedelic users. Three-way interactions show that the harmful association between household size and distress is strongest for psychedelic users who are married, divorced, or widowed. The findings suggest that social context—particularly household composition—moderates the potential health benefits of psychedelic use, with married and formerly married individuals in larger households experiencing the worst outcomes.
PLoS ONE
December 16, 2022
Caroline L. Alves, Rubens Gisbert Cury, Kirstin Roster et al.
13 citations
Ayahuasca, an Amazonian plant blend used in traditional medicine for centuries, is a promising therapy for neurological and mental diseases. Using an EEG dataset, machine learning and complex network analysis automatically detected changes in brain activity at three data abstraction levels. Connectivity changes between brain regions (correlation of EEG time series) yielded the highest accuracy (92%), followed by raw EEG (88%) and complex network measures (83%). The frontal and temporal lobes were most activated, consistent with prior work. A novel finding identified F3 and PO4 as the most important brain connections, possibly linked to face-recognition-like cognitive processes during visual hallucinations.
PLoS ONE
December 2, 2021
Imke Hanssen, Vera Scheepbouwer, Marloes Huijbers et al.
12 citations
Adverse effects during Mindfulness-Based Cognitive Therapy for bipolar disorder are not rare but are generally not serious or long-lasting. In a randomized trial with 144 patients, 29 reported adverse effects, most frequently in the first three weeks. Seven types of adverse effects were observed: cognitive, perceptual, affective, somatic, conative, sense of self, and social. Higher baseline anxiety increased risk. More than half of patients later viewed the adverse effects as part of a therapeutic process rather than harmful. Influencing factors included predisposing, precipitating, perpetuating, and mitigating elements.
PLoS ONE
January 7, 2021
Karsten Fatur
11 citations
Among 68 users of hallucinogenic plants and mushrooms in Slovenia, curiosity was the main reason for starting, typically in their 20s. Psilocybe spp. were the most used, mentioned by about 91% of participants, and half used no other natural hallucinogens. Many plants or mushrooms were used only a few times. The internet often introduced users to these substances. Dosing, methods of use, and settings varied widely, as did knowledge of dangers and natural occurrence. Contrary to public opinion linking use to partying or problematic drug use, most users sought interesting effects, personal growth, and overcoming personal difficulties.
PLoS ONE
September 13, 2018
Terje Sparby, Ulrich Ott
11 citations
Interviews with 30 Anthroposophic meditators revealed 14 themes of motivation, organized into three overarching forms: external, internal, and service. The findings suggest a developmental trajectory from external and internal motivations toward service-oriented motivations. This framework expands on a prior scheme by Shapiro, adding new motivation types and distinguishing between self-related (heteronomous and autonomous) and other-related motivations.
PLoS ONE
May 2, 2025
Nikita Singh, Srijith Kambala, Logan Neitzke‐spruill et al.
10 citations
Public interest in psychedelics and adult use has grown alongside research into their clinical potential. A landscape analysis of online, publicly available information identified 298 organizations offering psychedelic retreats to English-speaking consumers between July and December 2023. Most organizations focused on general wellness rather than religious identity. Ayahuasca was the most commonly offered substance, followed by psilocybin and San Pedro. Retreats were held at 440 distinct physical locations worldwide, with 130 inside the United States and 310 outside. Prices varied widely. Further research into retreat practices is recommended to reduce harm and support consumer education.
PLoS ONE
January 17, 2025
Shakila Meshkat, Wendy Lou, Rakesh Jetly et al.
10 citations
A new pilot study will test whether a single 25 mg dose of psilocybin combined with one week of massed cognitive processing therapy (CPT) is feasible, tolerable, and effective for chronic posttraumatic stress disorder (PTSD), which affects 3.9% of the general population. Fifteen participants with chronic PTSD will receive 12 CPT sessions, two psilocybin-related psychotherapy sessions, and one dosing session over 7 days. Feasibility and tolerability will be measured by recruitment, withdrawal, data completion, adherence, and adverse events. Preliminary efficacy will assess reductions in PTSD severity and explore mechanisms of change, with 12 weeks of follow-up and wearable device data. Results will guide a future large-scale randomized trial.
PLoS ONE
June 14, 2016
João Martins, Miguel Castelo-Branco, Ana Batista et al.
10 citations
A single dose of MDMA (ecstasy) given to rats temporarily alters retinal function, as measured by electroretinograms. Three hours after administration, both MDMA-treated and high-temperature control rats showed larger and faster retinal responses, suggesting that the acute effects are partly due to MDMA-induced hyperthermia. After 24 hours, MDMA-treated animals still had increased responses in the outer retinal layers (photoreceptors and bipolar cells), even after temperature effects subsided, indicating a direct subacute effect of the drug. These changes returned to normal within seven days. The findings provide direct evidence that MDMA can enhance outer retinal activity, which may help explain visual disturbances reported by human users.
PLoS ONE
June 10, 2016
Chuang-Hsin Chiu, Tiing-Yee Siow, Shao-Ju Weng et al.
9 citations
MDMA (Ecstasy) damages the fine serotonergic axons that connect the raphe nucleus to the striatum, a disruption previously inferred but not directly observed in living animals. Using manganese-enhanced magnetic resonance imaging (MEMRI) in rats, the study tracked manganese ions injected into the raphe nucleus as they traveled along neural pathways. Eight days after repeated MDMA injections (5 mg/kg daily for six days), MEMRI showed reduced signal enhancement in the medial forebrain bundle and striatum, indicating disrupted axonal transport. Immunohistological staining confirmed a loss of serotonin transporters. The findings provide direct in vivo evidence that MDMA causes axonal damage in these serotonergic projections.
PLoS ONE
April 21, 2017
Emilia M. Lefevre, Gregory Medley, Timothy Reeks et al.
8 citations
Co-administration of the glucocorticoid receptor antagonist RU486 with the NMDA receptor antagonist MK-801 in male Sprague Dawley rats unexpectedly enhanced rather than blocked the development of locomotor sensitisation. Both RU486 and MK-801 individually raised plasma corticosterone levels, and the combination further increased them. RU486 also elevated dopamine, DOPAC, and HVA in nucleus accumbens tissue. The findings indicate that glucocorticoids play a divergent role in sensitisation to MK-801 compared to other psychostimulants.
PLoS ONE
June 11, 2016
Sébastien Ballesta, Gilles Reymond, Matthieu Pozzobon et al.
7 citations
MDMA, known to increase prosocial behaviors in humans and rodents, was tested on three young male long-tailed macaques. Subcutaneous injections of 1.0, 1.5, or 2.0 mg/kg were given, and over 200 hours of behavioral data were recorded using an automatic 3D tracking system. At 1.5 mg/kg only, MDMA significantly increased social grooming, confirming a prosocial effect in macaques. At 1.5 and 2.0 mg/kg, foraging decreased, consistent with an anorexigenic effect. At 2.0 mg/kg, locomotion increased, matching its stimulant property. At 1.0 mg/kg, object play increased, possibly reflecting reduced inhibition or increased motivation. These results support MDMA's effectiveness for studying primate social behavior neurobiology.
PLoS ONE
March 4, 2021
Brandon L Peters, Jinxia Deng, Andrew L Ferguson
4 citations
G protein-coupled receptors (GPCRs) change shape when a ligand binds, which determines whether they activate or block signaling inside cells. Using computer simulations, the free energy landscapes of the serotonin receptor 5-HT2B were calculated for its unbound form, bound to the agonist LSD, and bound to the antagonist lisuride. LSD binding provided a strong driving force of about 110 kJ/mol toward the active conformation, while lisuride binding stabilized the receptor only about 24 kJ/mol more than the unbound form and kept it structurally similar. The work quantifies how different ligands induce distinct conformational changes and functional selectivity, offering a platform for virtual drug screening and rational design of ligand effects.
PLoS ONE
May 7, 2025
Grant Jones
2 citations
Race and ethnicity moderate the link between psilocybin use and lower odds of opioid use disorder. Analyzing data from over 700,000 U.S. respondents, only White and Hispanic participants showed a significant association between psilocybin use and reduced odds of OUD (White adjusted odds ratio: 0.84; Hispanic adjusted odds ratio: 0.68). For Black, Asian, Indigenous, and Multiracial participants, no significant association was found. The findings suggest that the potential protective effect of psilocybin against OUD may not apply equally across racial and ethnic groups.
PLoS ONE
March 6, 2026
1 citation
People with bipolar disorder and their supporters most frequently ask about misdiagnosis and differential diagnoses, according to an analysis of over 2,000 questions submitted during five years of online Reddit AMA events. Other common topics include coping with daily struggles, understanding hypomania and suicidality, medication and use of substances like psilocybin and ketamine, and supporting loved ones with the condition. The findings suggest that future research and clinical conversations should address these prioritized areas to better meet the needs of individuals with bipolar disorder.
PLoS ONE
December 4, 2025
Jonathan Robinson, Andrew W. Corcoran, Christopher J. Whyte et al.
1 citation
Active inference, a framework for modeling how sentient agents behave, is being tested as necessary for changes in conscious content. In an adversarial collaboration, active inference will be contrasted with two other theories that do not require it for consciousness. This study protocol describes an adaptation of the motion-induced blindness paradigm: an active condition where participants direct their gaze toward a target after it disappears from consciousness and report its reappearance, versus a passive condition where participants fixate centrally while the stimulus array moves in a replay of active eye-tracking data. Two experiments will compare target reappearance across conditions to evaluate active inference's contribution to conscious awareness.