PLoS ONE
July 10, 2012
Janelle H. P. van Wel, Kim P. C. Kuypers, Eef L. Theunissen et al.
121 citations
MDMA increases both positive moods (vigor, arousal, friendliness, elation) and negative moods (anxiety, confusion) while also slowing reaction times on impulsivity tasks, indicating greater impulse control. Blocking 5-HT(2) receptors with ketanserin prevented the positive mood effects but not the negative mood or impulsivity changes. Blocking 5-HT(1) receptors with pindolol had no effect on any MDMA-related mood or impulse measures. Thus, 5-HT(2) receptors are specifically involved in MDMA's positive mood enhancement, while 5-HT(1) receptors do not appear to play a role in these effects.
PLoS ONE
January 9, 2017
Pierre Bourdin, Itxaso Barberia, Ramon Oliva et al.
120 citations
An out-of-body illusion induced by virtual reality reduced fear of death compared to a control condition where the illusion was weaker. Sixteen women per group experienced a virtual body from a first-person perspective with synchronized touch and movement, then viewed it from above. In the experimental group, the connection to the virtual body was cut, producing a stronger feeling of disownership; in the control group, synchrony continued. The experimental group reported lower fear of death, consistent with reports that naturally occurring out-of-body experiences are often linked to greater belief in life after death.
PLoS ONE
September 30, 2015
Eduardo Ekman Schenberg, João Felipe Morel Alexandre, Renato Filev et al.
115 citations
Ayahuasca, an Amazonian plant-based brew used ritually in Brazil and increasingly worldwide, produces a two-phase brain effect. Electroencephalogram recordings and blood measurements of the brew's compounds (DMT, harmine, harmaline, tetrahydroharmine, and their metabolites) showed that 50 minutes after ingestion, alpha brainwave power (8–13 Hz) decreased, mostly in the left parieto-occipital cortex. Between 75 and 125 minutes, slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) increased across multiple cortical regions, including left centro-parieto-occipital, left fronto-temporal, and right frontal areas. These brain changes were significantly linked to circulating levels of ayahuasca's active chemicals. The authors interpret these effects within cognitive and emotional frameworks relevant to ritual use and potential therapeutic applications.
PLoS ONE
June 27, 2014
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
88 citations
A single 75 mg dose of MDMA selectively enhances emotional empathy—the ability to share and understand others' feelings—without affecting cognitive empathy (understanding others' mental states), trust, or reciprocity in social interactions. This effect was not altered by adding pindolol, a drug that blocks the 5-HT1A serotonin receptor. Oxytocin nasal spray, a hormone often linked to social bonding, had no effect on any empathy or social interaction measure. Changes in emotional empathy were unrelated to oxytocin levels in the blood. The findings suggest that MDMA's empathy-enhancing effects do not depend on peripheral oxytocin and may instead involve other receptors such as serotonin 2A or vasopressin 1A.
PLoS ONE
February 21, 2020
Bheatrix Bienemann, Nina Stamato Ruschel, Maria Luiza Pesse Campos et al.
81 citations
Psilocybin, found in psilocybe mushrooms, has low toxicity and addiction risk, but negative outcomes from its use are not well understood. Analyzing 346 self-reports from an online platform using textual analysis software, the study identified four main clusters: thinking distortions, emergencies, perceptual alterations, and substance administration. Bad trips were more frequent among female users and linked to thinking distortions. Using multiple doses in one session or combining psilocybin with other substances was associated with long-term negative outcomes, while single high doses of mushrooms were linked to medical emergencies. These findings can inform harm-reduction efforts.
PLoS ONE
November 20, 2009
Stéphane Doly, Jesus Bertran‐gonzalez, Jacques Callebert et al.
80 citations
The drug MDMA (ecstasy) produces its rewarding effects by causing the release of serotonin and dopamine in brain regions linked to reward. This study shows that the 5-HT(2B) receptor, a type of serotonin receptor, is essential for MDMA's reinforcing properties. Mice lacking the 5-HT(2B) receptor did not develop a preference for the location where they received MDMA (10 mg/kg) nor did they show behavioral sensitization. Blocking this receptor with an antagonist also prevented these effects in normal mice. However, at a higher dose (30 mg/kg), MDMA's effects were independent of serotonin and the 5-HT(2B) receptor, relying instead on dopamine. These findings highlight the dose-dependent role of serotonin-dopamine interactions in MDMA's addictive potential.
PLoS ONE
May 23, 2013
Pawel Z. Kosentka, Sarah L. Sprague, Martin Ryberg et al.
79 citations
Mushroom-forming fungi produce many toxic alkaloids, but the evolution of muscarine (a toxin that stimulates the parasympathetic nervous system) and psilocybin (a hallucinogen) had not been studied. This review and new chemical assays of 30 Inocybaceae samples, including tropical and southern-hemisphere species, tested whether muscarine is ancestral in the family. The results show muscarine evolved independently multiple times, with several losses, and is not ancestral for the whole family. It is a shared derived trait for a clade containing three major lineages (Inocybe, Nothocybe, Pseudosperma) whose common ancestor lived about 60 million years ago. Transitions from muscarine-producing ancestors to psilocybin occurred more recently, 10–20 million years ago, after muscarine loss in two separate lineages. Statistical analyses reject a single origin of muscarine-producing taxa.
PLoS ONE
June 29, 2012
Laura Moreno-López, Emmanuel A. Stamatakis, María José Fernández-serrano et al.
73 citations
In a sample of 49 polysubstance users in residential treatment who had been abstinent for a prolonged period, the severity of use of heroin, alcohol, MDMA, and cannabis each showed negative correlations with brain metabolism in the dorsolateral prefrontal cortex and temporal cortex. Alcohol use was additionally linked to lower metabolism in the frontal premotor cortex and putamen, while stimulant use was associated with lower metabolism in the parietal cortex. These findings suggest that different drugs of abuse may produce overlapping and distinct patterns of brain dysfunction even after extended abstinence, which could inform targeted rehabilitation strategies.
PLoS ONE
November 5, 2018
Itxaso Barberia, Ramon Oliva, Pierre Bourdin et al.
71 citations
Immersive virtual reality can simulate death and near-death experiences, offering a new way to study their psychological impact. Participants embodied in virtual bodies on an island witnessed companions' deaths and their own death, including out-of-body experience, life review, and tunnel leading to white light. Fifteen female participants experienced six sessions from childhood to death; sixteen controls formed a waiting group. Those who underwent the simulation reported life attitude changes, becoming more concerned with others and more interested in global rather than material issues compared to the control group. The small sample size means results are indicative rather than conclusive.
PLoS ONE
March 8, 2019
Bernard J. Crespi, Natalie L. Dinsdale, Silven Read et al.
68 citations
Spirituality relates differently to autism spectrum and schizotypal spectrum traits in a large sample of undergraduates. Total spirituality was negatively correlated with autism traits and positively correlated with positive schizotypal traits, supporting the diametrical model of autism and psychosis. These opposing associations were driven mainly by the Search for Meaning subscale, which was the only spirituality dimension significantly negatively linked to autism and positively linked to positive schizotypal traits. Belief in God was positively correlated with positive schizotypal traits but showed no correlation with autism traits. The opposite patterns for Search for Meaning align with cognitive models: weak central coherence in autism and enhanced salience in positive schizotypy.
PLoS ONE
October 24, 2012
Ricardo Pardo-Lozano, M. Farré, Samanta Yubero-Lahoz et al.
67 citations
A single oral weight-adjusted dose of MDMA (1.4 mg/kg) produced similar plasma concentrations and positive subjective effects in healthy recreational users regardless of gender or CYP2D6 and COMT genotypes. Female subjects experienced more intense physiological effects (increased heart rate and oral temperature) and negative effects (dizziness, sedation, depression, psychotic symptoms). Genotypes of COMT val158met or 5-HTTLPR with high functionality led to greater cardiovascular effects, while low-functionality genotypes were linked to negative subjective effects. The contribution of MDMA pharmacokinetics to gender differences in drug effects appears negligible; instead, 5-HTTLPR and COMT val158met genotypes play a major role.
PLoS ONE
March 14, 2024
Adam W Levin, Rafaelle Lancelotta, Nathan D Sepeda et al.
65 citations
In a small randomized trial of psilocybin-assisted therapy for adults with major depressive disorder, the therapeutic alliance between participants and facilitators strengthened from the final preparation session to one week after the intervention. A stronger alliance before the psilocybin sessions predicted lower depression scores at 4 weeks, 6 months, and 12 months afterward. Stronger alliance also correlated with more intense mystical experiences and psychological insight during the drug sessions, which in turn predicted better depression outcomes. The findings suggest the therapeutic relationship is important for treatment success.
PLoS ONE
August 24, 2022
Mary M. Sweeney, Sandeep M. Nayak, Ethan Hurwitz et al.
60 citations
Psychedelic drug experiences and near-death or other non-ordinary experiences both change people's beliefs about death, but direct comparisons are rare. In a survey of 3,192 individuals who reported such experiences, those from non-drug causes (e.g., near-death) were more likely to involve unconsciousness, clinical death, or imminent danger. Both groups reported similar reductions in fear of death, high personal meaning, spiritual significance, and psychological insight. However, psychedelic participants scored higher on standardized measures of mystical and near-death features, while non-drug participants more often rated their experience as the single most meaningful of their lives. Among psychedelics, ayahuasca and DMT produced stronger positive enduring effects than psilocybin and LSD.
PLoS ONE
August 8, 2018
Stephen LaBerge, Kristen Lamarca, Benjamin Baird
59 citations
Taking galantamine, a drug that boosts the brain chemical acetylcholine, significantly increases the chance of having a lucid dream—a dream where the dreamer knows they are dreaming. In a study of 121 people interested in lucid dreaming, 14% reported a lucid dream after a placebo, compared to 27% after a 4 mg dose and 42% after an 8 mg dose. The drug also improved dream recall, sensory vividness, and complexity. Lucid dreams themselves were more vivid, clear, controlled, and emotionally positive than non-lucid dreams. Combining galantamine taken in the last third of the night with a brief awakening and a focused mental technique is one of the most effective ways to induce lucid dreams.
PLoS ONE
March 4, 2010
Thomas S. Ray
57 citations
correction
Psychedelic drugs, particularly phenylalkylamines, interact with many more receptor types than previously thought. New affinity data for 25 psychedelic drugs at 51 receptors, transporters, and ion channels, plus literature data for 10 additional drugs, show these compounds bind to 42 of 49 broadly assayed sites, not just the 5-HT2A and 5-HT2C receptors. A new normalization method allows direct comparison of multi-receptor profiles across drugs. The 35 drugs display diverse interaction patterns with 18 different receptor classes, which may explain their qualitatively different mental effects. This diversity suggests psychedelics could be used as probes to study how various receptor systems contribute to human consciousness.
PLoS ONE
October 14, 2020
E. Marseille, J. Kahn, B. Yazar-Klosinski et al.
55 citations
For people with severe, chronic PTSD that does not respond to standard treatments, MDMA-assisted psychotherapy (MAP) appears to be cost-saving for health care payers while delivering substantial clinical benefit. A decision-analytic model based on pooled results from six phase 2 trials with 105 subjects and a four-year follow-up of 19 subjects estimated that, over 30 years, MAP for 1,000 individuals generates net discounted savings of $103.2 million and 5,553 additional quality-adjusted life-years (QALYs) compared to continued standard care. MAP breaks even on cost at 3.1 years. Even under the conservative assumption that benefits last only one year, MAP costs $26,427 per QALY gained.
PLoS ONE
February 10, 2010
Clara Touriño, Andreas Zimmer, Olga Valverde
55 citations
The main psychoactive compound in cannabis, THC, can protect against brain damage caused by MDMA (ecstasy) in mice, primarily by preventing the dangerous rise in body temperature that MDMA induces. MDMA caused hyperthermia, glial activation, and loss of dopamine terminals in the striatum, especially at a warm ambient temperature of 26 degrees Celsius. THC prevented MDMA-induced hyperthermia and glial activation at both room and warm temperatures, and reversed dopamine terminal loss at the warm temperature. These protective effects were blocked by the CB1 receptor antagonist AM251 and in CB1 knockout mice, but only partially blocked by CB2 receptor antagonism or knockout, indicating that THC's neuroprotection is primarily mediated by CB1 receptor activation reducing hyperthermia, with CB2 receptors contributing to reduced neuroinflammation.
PLoS ONE
January 10, 2024
Rachel Yehuda, Leah Bedrosian, Charlotte Harrison et al.
52 citations
In a randomized, double-blind, placebo-controlled Phase 3 trial of 90 participants with severe PTSD, MDMA-assisted therapy produced significantly greater improvements than therapy with placebo on measures of emotional coping and self-experience. Participants receiving MDMA showed larger gains on the Toronto Alexithymia Scale, the Self-Compassion Scale, and most factors of the Inventory of Altered Self-Capacities, including affect regulation and interpersonal functioning, with identity diffusion being the only exception. Most participants had histories of developmental trauma and multiple traumas. These findings suggest that MDMA-assisted therapy enhances psychological capacities that are often linked to poor treatment outcomes, offering insight into how psychedelic agents may reduce PTSD symptoms.
PLoS ONE
February 25, 2022
Elliot Marseille, Jennifer Mitchell, James G. Kahn
49 citations
For patients with severe or extreme chronic PTSD, MDMA-assisted therapy (MDMA-AT) costs $11,537 per patient and generates net health care savings of $132.9 million over 30 years per 1,000 patients, while accruing 4,856 quality-adjusted life-years (QALYs) and averting 61.4 premature deaths compared with standard care. The therapy breaks even on cost at 3.8 years. A three-session MDMA regimen yields greater medical savings and health benefits than a two-session regimen. Even if no health care cost savings are assumed, the incremental cost-effectiveness ratio is $2,384 per QALY gained. MDMA-AT is cost-saving from a payer's perspective and delivers substantial clinical benefit.
PLoS ONE
July 1, 2021
Marie Therese Bartossek, Johanna Kemmerer, Timo Torsten Schmidt
43 citations
Flickering light with closed eyes temporarily alters consciousness, producing simple visual hallucinations like colors and geometric patterns. In 24 participants, 10 Hz stimulation caused stronger effects than 3 Hz, including vivid visual hallucinations. Participants' Absorption personality trait strongly correlated with the intensity of altered consciousness. The effects were rated similar in strength to those from psychedelic substances, supporting the study of shared brain mechanisms.
PLoS ONE
November 4, 2013
Alvaro Llorente‐berzal, Emma Puighermanal, Aurelijus Burokas et al.
43 citations
Adolescent rats given THC (the main psychoactive component of cannabis) and/or MDMA (ecstasy) showed lasting, sex-dependent changes in behavior and brain chemistry. MDMA reduced exploration and increased anxiety-like behavior shortly after treatment. Long-term, THC disrupted object recognition memory in females but not males. MDMA alone weakened prepulse inhibition (a measure of sensorimotor gating) at the loudest sound tested, while combining it with THC caused a similar deficit at a softer sound. In the brain, THC reduced Arc protein in the hippocampus of both sexes but in the frontal cortex only in females.
PLoS ONE
May 13, 2016
42 citations
An extreme ritual involving temporary body piercings and dancing induced altered states of consciousness in both pierced dancers and non-pierced participants, as measured by tests of transient hypofrontality and flow. Both groups reported decreases in negative affect and psychological stress and increases in intimacy from before to after the ritual. However, physiological responses differed: pierced dancers showed increases in the stress hormone cortisol, while non-pierced participants showed decreases during the ritual. The ritual produced similar psychological effects but different physiological effects across participant roles.
PLoS ONE
April 13, 2019
Patrick Vizeli, Matthias E Liechti
37 citations
MDMA increases oxytocin, empathy, and prosociality. In a pooled analysis of eight double-blind, placebo-controlled studies involving up to 132 healthy subjects, a specific genetic variant of the oxytocin receptor (rs1042778 TT genotype) was linked to greater feelings of trust after MDMA compared to G allele carriers, but only in a subset of 53 subjects. Other variants (rs53576 and rs2254298) did not moderate MDMA's subjective effects. MDMA increased plasma oxytocin concentrations, but oxytocin levels did not differ by gene variant. The results suggest oxytocin receptor variations may influence some prosocial effects of MDMA, but interpretation is cautious due to small sample sizes.
PLoS ONE
April 9, 2013
Oliver G. Bosch, Michael Wagner, Frank Jessen et al.
34 citations
Recreational users of MDMA show verbal learning and recall deficits that are linked to reduced glucose metabolism in the prefrontal and parietal cortex, and word recognition difficulties are additionally associated with reduced metabolism in the mediotemporal region. These findings indicate that memory problems in MDMA users result from combined dysfunction across frontal, parietal, and mediotemporal brain areas.
PLoS ONE
December 12, 2018
M. Hirshberg, Simon B. Goldberg, S. Schaefer et al.
33 citations
Different styles of brief contemplative practices produce distinct effects on affect and behavior, especially under stress. In a randomized experiment with 156 undergraduates, gratitude training improved positive affect more than breath awareness, while loving-kindness reduced implicit negative affect more than a control condition. However, gratitude training also increased reactivity to a cold pressor stressor: participants reported it as more aversive and showed greater increases in negative affect. Those with greater gains in implicit positive affect after gratitude training later rated neutral faces as less likable and were less likely to donate time to help others. These findings suggest that even brief introductory practices can have divergent outcomes, which may be amplified by stress.