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.
Minimum age of 21 and maximum age of 60;
Minimum of eight years of schooling;
Fluency in Portuguese;
Using any herbal supplements (except with prior approval from the researchers);
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.
Crossover
Psilocybin (Usona Institute)
Drug3x 5mg capsules of Psilocybin (cGMP)
Niacin 100 mg
Drug1x capsule 100mg Niacin (cGMP) + 2x 25mg Capsules of MCC Inert Placebo
Changes in global metacognitive judgment using the Computerized Success-Failure Manipulation Paradigm.
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
Changes in the Multidimensional Assessment of Interoceptive Awareness (MAIA)
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
Changes in the Emotional Regulation Questionnaire (ERQ)
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/
Changes in the Toronto Alexithymia Scale (TAS)
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
Changes in the Ruminative Response Scale-short form
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
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