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
August 15, 2013
Jeongkyu Shin, George A. Mashour, Seungwoo Ku et al.
16 citations
General anesthesia rapidly alters brain network connectivity, and standard graph-theoretical methods that assume static networks are poorly suited to capture these changes. A new technique was introduced to track the temporal evolution of network modules. Multichannel EEG was recorded from 18 surgical patients anesthetized with propofol or sevoflurane. Networks were reconstructed by treating each EEG channel as a node and correlated activity between channels as a link. The frequency of subgraphs with a defined number of links was analyzed; subgraphs with high occurrence probability were called network "backbones." Constitutive, variable, and state-specific backbones were identified across consciousness, induction, maintenance, and recovery. This approach enables a granular, dynamic description of network evolution.
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
May 13, 2024
Otto Simonsson, Stephen D. Fisher
2 citations
In 2021, 16 percent of adults in Britain had learned to practice mindfulness. Among those who practiced during the COVID-19 pandemic, 60 percent reported positive mental health effects, while 24 percent reported negative effects. Negative effects were more common among respondents with children under 18 (41 percent) compared to those without minors (13 percent). Mindfulness practice was more common among young and middle-aged adults, London residents, and Liberal Democrat voters. The findings indicate that mindfulness use is widespread but concentrated in certain groups, and that negative mental health effects affect a notable minority, warranting further research.
PLoS ONE
August 28, 2019
Simon B. Goldberg, Matthew J. Hirshberg, Lawrence Y. Tello et al.
2 citations
Long-term meditators are perceived by observers as less neurotic and more conscientious, mindful, and comfortable in their own skin than meditation-naïve individuals, based solely on ratings of still photographs. These differences were not explained by age, gender, race/ethnicity, body mass index, or attractiveness. No such differences were observed after an eight-week mindfulness meditation course, an active control program, or a waitlist period, suggesting that observable facial cues linked to meditation may require extensive training to emerge.
PLoS ONE
March 6, 2026
Caden Poh, Cheyanne Head, John-Jose Nunez et al.
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.
PLoS ONE
August 27, 2025
Amy Kartar, Toru Horinouchi, Balázs Örzsik et al.
1 citation
High ventilation breathwork (HVB), which involves rapid or deep breathing often accompanied by music, can produce altered states of consciousness (ASCs) similar to those caused by psychedelic substances, including euphoria, bliss, and perceptual changes. The neurobiological mechanisms behind these effects were largely unknown. In experienced practitioners, the intensity of ASCs from HVB was proportional to cardiovascular sympathetic activation and to changes in cerebral blood flow in the left operculum/posterior insula and right amygdala/anterior hippocampus—brain regions involved in sensing breathing and processing emotional memories. These brain changes may underlie the positive therapeutic outcomes associated with HVB.
PLoS ONE
October 24, 2024
Kyurim Kim, Abban Yusuf, Abhimanyu Sud et al.
1 citation
Psychedelic clinics in Ontario, Canada, advertise psychedelics such as ketamine, MDMA, and psilocybin for 47 medical conditions, most commonly depression. An analysis of 10 clinic websites found that only 2 mentioned potential risks. The clinics cited 29 studies, the majority of which were case-series and case-control studies (level 4 evidence, the second lowest quality). Overall, the evidence quality supporting the clinics' claims was low to moderate. The study underscores the need for transparent, high-quality evidence to ensure safe and effective use of psychedelics in mental health treatment.
PLoS ONE
June 18, 2026
Elisa Liberati, Hv Curran, Peter Fonagy et al.
MDMA-assisted psychotherapy shows promise for treating PTSD, but the psychological mechanisms behind its effects are not well understood. This qualitative study will have approximately 25 experienced psychodynamic psychotherapists receive two doses of MDMA (80-120 mg, oral) in an open-label design. Participants will complete interviews before, during, and after MDMA sessions, plus daily journals. Researchers will use phenomenological and thematic analysis, along with grounded theory, to develop a model of MDMA's psychological mechanisms of action. The study treats therapists as expert observers of their own psychological processes, aiming to generate insights that can inform future treatment models and offer a framework for qualitative mechanistic research on psychedelics.
PLoS ONE
November 10, 2025
Marina D. Luccioni, Jules T. Wyman, Edgard O. Espinoza et al.
The Sonoran Desert toad is the only animal known to secrete the psychedelic compound 5-MeO-DMT as a chemical defense, but its source was unknown. All Sonoran Desert toads secreted high concentrations of 5-MeO-DMT, while other sympatric toads did not. The diet of the Sonoran Desert toad was similar to that of other anurans living in the same area, indicating no dietary specialization. Slight dietary differences existed between toads in native and urban habitats. These findings suggest diet is not directly linked to 5-MeO-DMT production, supporting the hypothesis that the toad synthesizes the compound endogenously or via a microbial symbiont.
PLoS ONE
October 13, 2025
Francisco González-espejito, Laura Esteban Rodríguez, Eduardo J. Pedrero Pérez et al.
Ibogaine, a compound from the iboga plant used in traditional Bwiti rituals, shows promise for treating opioid dependence and neurological conditions, but existing tools fail to capture its dream-like subjective effects. A new 70-item Ibogaine Experience Scale (IES) was developed from a prior qualitative study and tested with 499 participants in neuropsychiatric and substance use treatment settings. The final scale has seven factors—including narrative visions, visual changes, discomfort, cosmic visions, introspection, somatosensory sensitivity, and dissociation—explaining 53.9% of variance, with excellent statistical fit and high internal consistency. The IES offers a reliable way to measure ibogaine's multidimensional effects for research and clinical use.
PLoS ONE
February 6, 2019
Vince Polito, Richard J. Stevenson
People who regularly ingest very small amounts of psychedelic substances (microdosing) report minimal acute effects but claim long-term health and wellbeing benefits. In an observational study, 98 microdosers provided daily ratings of psychological functioning over six weeks; 63 also completed psychometric measures at baseline and study end. Daily ratings showed a general increase in reported psychological functioning on dosing days but limited evidence of residual effects. Pre- and post-study measures revealed reductions in depression and stress, lower distractibility, increased absorption, and increased neuroticism. A second study of 263 naïve and experienced microdosers found that participants believed microdosing would have large, wide-ranging benefits, contrasting with the limited outcomes reported by actual microdosers.