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NCT Number: NCT07732166

Changes in Self-awareness Induced by Psychoactive Substances: an Experimental Study With Psilocybin.

Self-awareness, the capacity of becoming the object of one's own awareness, is a frontier of scientific knowledge. Over centuries, distinct philosophical and religious traditions have grappled with the subject, but only recently has the importance of self-awareness been established as a central concept for scientific investigation, to which scientific methods can be applied to explore and characterize this phenomenon. Self-awareness has important implications, notably from a clinical perspective. Psychedelics can affect the sense of self, with 'ego dissolution' being an essential feature of the experience of substances such as psilocybin and dimethyltryptamine. Recent evidence indicates that psychedelics can rearrange brain connectivity, with these changes being linked to alterations in self-awareness. Nevertheless, the extent to which specific components of self-awareness are modified by these substances has not been fully explored. It is possible that part of the clinical benefits of psychedelics, for conditions such as depression, OCD, and anxiety, is mediated by changes in self-awareness. Given this clinical potential, the current study aims to examine the effects of psilocybin on various components of self-awareness in healthy participants. 100 participants will be allocated to receive either 15mg of psilocybin (n=50) or an active placebo (100mg niacin; n=50). Participants will be assessed one week before, immediately after, and one week after the administration of the substances, performing tasks and completing questionnaires measuring self-awareness at these time points. The neural correlates of self-awareness, before and after substance effects, will be investigated using near-infrared spectroscopy. Participants allocated to the placebo group will be invited to an open-label extension with psilocybin upon availability of the substance. It is expected that the results of the study will elucidate the brain regions involved in self-awareness, as well as the alterations induced by psilocybin in this process, opening the possibility of new therapeutic interventions for different clinical groups.

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Key information

Conditions

Age range

21 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Minimum age of 21 and maximum age of 60;
  • Minimum of eight years of schooling;
  • Fluency in Portuguese;
  • Agree, one week before the experiment, to abstain from:
  • Using any herbal supplements (except with prior approval from the researchers);
  • Using any non-prescribed medication (except non-steroidal anti-inflammatory drugs or paracetamol, provided they have prior approval from the research team);
  • Using any prescribed medication (except birth control pills, thyroid hormones, or other medications, provided they have prior approval from the research team);
  • Using recreational psychoactive substances;
  • Agree to abstain, 24 hours before the experiment, from:
  • Consuming beverages with high caffeine content (e.g., coffee, mate, cola);
  • Consuming alcoholic beverages;
  • Agreeing not to use caffeine or nicotine for two and six hours, respectively, after the experiment;
  • Agree not to drive a motor vehicle or operate machinery for 24 hours after the experiment;
  • Be available to be contacted by telephone for all planned stages;
  • Agree to use effective contraception throughout the study;
  • Agree to inform researchers of any medical condition or procedure that may arise prior to the experiment;
  • Agree not to participate in any other interventional clinical trial for the duration of this study.

Exclusion criteria

  • History of traumatic brain injury, stroke, epilepsy, neurological disease, or cardiovascular disease;
  • Evidence or history of coronary or cerebral artery disease, peripheral vascular disease, liver disease with altered liver enzymes, or any other medical condition that the researchers, including the responsible physician, deem to significantly increase the risk of administering any substance;
  • Pregnant or breastfeeding women, or women who could potentially become pregnant and are not using any effective contraceptive method;
  • Women who, at the screening stage, do not have a negative pregnancy test.
  • Having a history of or currently having a primary psychotic disorder, schizophrenia spectrum disorder, bipolar affective disorder (type 1 and 2), dissociative identity disorder, major depressive disorder;
  • History of psychotic disorders in a first-degree relative;
  • Have resting blood pressure that does not exceed 140 mmHg (systolic) and 90 mmHg (diastolic) - measured in four assessments on at least two different days;
  • Have resting blood pressure below 90 mmHg (systolic) and 60 mmHg (diastolic) - measured in four assessments on at least two different days;
  • Weigh less than 48 kg;
  • Require therapy with psychiatric medications concurrently with the study;
  • Have a history of or present with gastrointestinal disease;
  • Previous use of psilocybin or similar substances;
  • Frequent use (at least once a month) of any other psychoactive substance in the last year, except for nicotine, caffeine and alcohol;
  • Have a history of disorders or problems related to the use of psychoactive substances;
  • Not be able to provide adequate informed consent;
  • Any other condition that may compromise the results or that represents any risk to the participant, according to the assessment of the research team and the responsible physician.

Treatment and study plan

Psilocybin (Usona Institute)

Drug

3x 5mg capsules of Psilocybin (cGMP)

Niacin 100 mg

Drug

1x capsule 100mg Niacin (cGMP) + 2x 25mg Capsules of MCC Inert Placebo

Primary outcomes

  1. Changes in global metacognitive judgment using the Computerized Success-Failure Manipulation Paradigm.

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session).

    The success-failure manipulation (SFM) task is a computerized paradigm designed to study metacognition. After a practice phase, the task uses a titration procedure to establish each participant's reaction-time threshold. In the experimental phase, the program presents trials above or below this threshold to systematically induce controlled failure or success states. Participants are asked to estimate the percentage of trials they have succeeded in. The paradigm allows precise experimental control over actual performance, enabling direct comparisons of metacognitive abilities under identical conditions. More information can be found at: http://www.redalyc.org/articulo.oa?id=513751529005

Secondary outcomes

  1. Changes in the Multidimensional Assessment of Interoceptive Awareness (MAIA)

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session)

    The Multidimensional Assessment of Interoceptive Awareness (MAIA) is a 32-item self-report questionnaire designed to measure multidimensional interoceptive body awareness across eight distinct subscales: Noticing, Not-Distracting, Not-Worrying, Attention Regulation, Emotional Awareness, Self-Regulation, Body Listening, and Trusting. Respondents rate items on a 6-point Likert scale ranging from 0 ("never") to 5 ("always"). Subscale scores are calculated as the average of their respective items, with higher scores reflecting greater interoceptive awareness and adaptive body focus. The instrument evaluates how individuals perceive, process, and regulate internal bodily sensations. The total cumulative raw score across all items ranges from 0 to 160. Higher average scores reflect a greater and more mindful degree of interoceptive awareness. More information at https://doi.org/10.1371/journal.pone.0048230

  2. Changes in the Emotional Regulation Questionnaire (ERQ)

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session)

    The Emotion Regulation Questionnaire (ERQ) is a 10-item self-report scale designed to assess individual differences in two widely used emotion regulation strategies: Cognitive Reappraisal (6 items) and Expressive Suppression (4 items). Respondents rate statements on a 7-point Likert scale ranging from 1 ("strongly disagree") to 7 ("strongly agree"). Subscale scores are calculated by averaging the items corresponding to each strategy, with higher scores reflecting a greater, more habitual reliance on that specific emotional regulation strategy. More information at: https://pubmed.ncbi.nlm.nih.gov/12916575/

  3. Changes in the Toronto Alexithymia Scale (TAS)

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session)

    The TAS is a 20-item, self-administered questionnaire that measures difficulty in identifying and describing emotions (alexithymia) across three subscales: Difficulty Identifying Feelings (DIF, 7 items), Difficulty Describing Feelings (DDF, 5 items), and Externally-Oriented Thinking (EOT, 8 items). Respondents rate items on a 5-point Likert scale ranging from 1 ("strongly disagree") to 5 ("strongly agree"), with five items negatively keyed. Total scores are calculated by summing item responses, with higher overall and subscale scores indicating greater difficulty with emotional processing, awareness, and expression. The instrument evaluates individual deficits in recognizing, articulating, and reflecting on emotional states. More information at: https://doi.org/10.1016/0022-3999(94)90005-1

  4. Changes in the Ruminative Response Scale-short form

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session)

    The 10-item Ruminative Response Scale (RRS-10) is a brief self-report questionnaire designed to assess repetitive, depressive rumination without confounding items related to depressive symptoms. It evaluates two distinct subscales with 5 items each: Brooding (a passive, maladaptive focus on unachieved standards) and Reflection (a purposeful, adaptive engagement in cognitive problem-solving). Respondents rate statements on a 4-point Likert scale ranging from 1 ("almost never") to 4 ("almost always"). Subscale and total scores are calculated by summing or averaging the respective item responses, with higher scores reflecting a greater frequency of ruminative thought patterns. More information at: doi.org/10.1007/978-3-030-77644-2_84-1

  5. Ego Dissolution Inventory (EDI) Score

    Time frame: Immediately after the dosing session (4 hours after intake)

    Self-report questionnaire designed to measure ego-dissolution-the temporary breakdown or loss of a distinct sense of self and personal identity. Uses an 8-item scale rated on a visual analog scale (VAS) from 0 to 100. 0 means "No, not more than usual" and 100 means "Yes, I experienced this completely/entirely". Total Score is calculated as the mean of all eight items, yielding an overall score from 0 to 100 that represents the strength of the experience. More information at: https://pubmed.ncbi.nlm.nih.gov/27378878/

  6. Altered States of Consciousness Rating Scale (OAV) Score

    Time frame: Immediately after the dosing session (4 hours after intake)

    Self-report questionnaire used to measure subjective experiences during non-ordinary states of consciousness. It evaluates three core dimensions: Oceanic Boundlessness, Dread of Ego Dissolution, and Visionary Restructuralization. It contains 66 items rated on a continuous line or numerical scale (0 to 100), from "No, not more than usual" (0) to "Yes, much more than usual" (100). Higher scores mean a greater intensity of subjective changes during an experience for each dimension. More information at: https://doi.org/10.1371/journal.pone.0012412

  7. Changes in Interoceptive Accuracy and Awareness, measured by a Heartbeat Discrimination Task

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session)

    In this task, participants silently count their felt heartbeats within randomized time windows of 25 to 50 seconds, without manually checking their pulse. Actual heartbeats are measured with an electrocardiogram (ECG). Participants are also asked how confident they feel about their estimates. These responses are then used to quantify metacognitive interoceptive awareness by correlating confidence with actual performance accuracy. More information can be found at: http://dx.doi.org/10.1016/j.biopsycho.2014.11.004

  8. Changes in Sense of Agency, measured by an Intentional Binding paradigm

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session)

    This task measures explicit sense of agency (SoA) through a retrospective judgment of self-authorship, where participants rate their perceived control over a sensory event triggered by their action, and implicit SoA via "intentional binding," which assesses the compression of subjective temporal intervals between a voluntary motor action and its sensory effect. The task derives two primary scores: an explicit Agency Rating Score obtained from a 9-point Likert scale (ranging from 1 for "not at all" to 9 for "extremely strongly"), and an implicit Intentional Binding Score calculated as an estimation ratio of subjective interval durations between baseline (passive) and active tasks. More details can be found at: https://doi.org/10.1016/j.concog.2018.11.005.

  9. Changes in the Spontaneous Sensations Task

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session)

    The Spontaneous Sensations Task is a standard behavioral method for evaluating body awareness by measuring sensations in the absence of external triggers. Participants rest one hand palm-up on a white fabric and focus their direct gaze on it for 10 seconds. Immediately after, they must report any detected sensations on a standardized hand map, specifying their location, extent, intensity (1-10 scale), confidence level, and sensory descriptors. More details can be found at: https://doi.org/10.1080/08990220.2021.1914018

  10. Changes in an Online Paradigm of Self-reference Effect

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session)

    The online self-referential encoding paradigm assesses memory enhancement driven by self-related concepts. The task evaluates how information is systematically processed and retained when encoded in relation to the self versus structural or semantic controls. During the encoding phase, participants answer specific questions about single-trait adjectives (e.g., "Does this word describe yourself?"). The task measures memory performance through an incidental free-recall activity or a recognition format administered after a short filler task. More information can be found at: https://doi.org/10.1371/journal.pone.0176611

  11. Changes in the Eriksen Flanker Task adapted to measure Sense of Agency

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session)

    To assess the prospective contribution of action selection to the sense of agency, participants perform the Eriksen flanker task, in which they respond to a central target letter flanked by supraliminal stimuli that are congruent, neutral, or incongruent. Correct responses trigger the appearance of a colored circle after a variable delay, and participants judge their level of control over the color. The protocol evaluates how conflict in action selection affects agency ratings, more specifically, whether dysfluency reduces the perceived sense of control. More information ca be found at: http://dx.doi.org/10.1016/j.actpsy.2016.03.003

  12. Changes in Proprioceptive Information Processing measured by a Mirror-induced Bias Paradigm

    Time frame: From baseline (one week before the dosing session) to follow up (one week after the dosing session)

    This task measures the integration of visual and proprioceptive information regarding hand location using a mirror along the midsagittal plane. Participants perform reaching movements to a target with their unseen hand behind the mirror under different conditions of exposure to the mirror-reflected hand. The task evaluates how spatial congruence between visual and real hand positions affects reach accuracy, as visual conflicts can significantly bias reaching movements. The goal is to determine how multisensory conflict affects the visual recalibration of proprioception. More information can be found at: doi.org/10.1007/s00221-005-2389-4

Study contacts

Contact information is provided by the study sponsor or research team.

Daniel C Mograbi, PhD

CONTACT

[email protected]

+ 55 21 35272505

Sponsors and collaborators

Lead sponsor

Pontifícia Universidade Católica do Rio de Janeiro

Other

Registry information

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Jul 28, 2026
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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