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
June 23, 2014
Christopher Allen, Benjamin T. Dunkley, Suresh Muthukumaraswamy et al.
45 citations
Continuous theta burst stimulation (cTBS) over the occipital cortex, expected to impair conscious vision, instead enhanced it relative to a sham control. The stimulation decreased cortical excitability and increased regional GABA concentration, suggesting that suppression of neural noise can improve the signal-to-noise ratio for conscious vision. No significant effects on magnetoencephalography measures were observed, though weak evidence for potentiation of beta-band event-related desynchronisation appeared. The authors propose that gating-by-inhibition in the visual cortex may be a foundation of consciousness.
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
February 22, 2016
Daniela Dentico, Fabio Ferrarelli, Brady A. Riedner et al.
43 citations
After two intensive days of mindfulness or compassion meditation, long-term meditators showed increased low-frequency brain activity (1-12 Hz, peaking around 7-8 Hz) over prefrontal and left parietal areas during non-rapid eye movement sleep. This increase was strongest early in the night and extended to higher frequencies (25-40 Hz) during the third sleep cycle. The changes depended on meditation experience and did not differ between the two meditation styles. No such changes occurred in meditation-naive individuals. The findings suggest that intensive meditation practice acutely alters brain activity in regions linked to top-down regulation, complementing chronic changes seen in posterior areas.
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
Ellen M. Lee, Kathryn R. Klement, James K. Ambler et al.
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
July 23, 2020
Joshua M. Martin, Danyal Wainstein Andriano, Natália Bezerra Mota et al.
41 citations
Dream reports collected after rapid eye movement (REM) sleep are typically longer, more vivid, and more story-like than those from non-REM sleep, but traditional measures may be confounded by report length. By analyzing 133 dream reports from 20 participants as non-semantic directed word graphs, researchers found that REM dream reports have greater connectedness—words recur with longer range—compared to N2 sleep reports. Graph measures predicted dream complexity, with higher connectedness and lower randomness linked to more complex reports. The largest connected component improved models using report length alone for predicting sleep stage and complexity. Graph analysis offers an automated method to complement traditional dream report analysis.
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.
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
February 23, 2016
Kim P. C. Kuypers, Eef L. Theunissen, Janelle H. P. van Wel et al.
23 citations
Verbal memory performance in people who use Ecstasy (MDMA) does not differ from that of healthy non-users when they are not under the drug's influence, and there is substantial evidence supporting no long-term memory deficit. Clinically significant memory impairment—defined as performance more than 1.5 standard deviations below the average of healthy controls—was absent during abstinence. However, during acute MDMA intoxication, verbal memory was impaired. Pooled data from four experimental studies compared 65 Ecstasy users tested on placebo with 65 matched drug-naïve controls. History of use did not predict memory impairment. The findings suggest that Ecstasy/MDMA use does not cause clinically deficient long-term verbal memory.
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.