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

NCT07732166 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 54547221.1.0000.5263
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Adults

Keywords

Psilocybin; Self-awareness

Outcome Measures

Primary Outcomes (1)

• 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

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

Secondary Outcomes (12)

• Changes in the Multidimensional Assessment of Interoceptive Awareness (MAIA)

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

• Changes in the Emotional Regulation Questionnaire (ERQ)

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

• Changes in the Toronto Alexithymia Scale (TAS)

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

• Changes in the Ruminative Response Scale-short form

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

• Ego Dissolution Inventory (EDI) Score

  Immediately after the dosing session (4 hours after intake)

Study Arms (2)

Psilocybin (15 mg)

EXPERIMENTAL

Drug: Psilocybin (Usona Institute)

Niacin (100mg)

SHAM COMPARATOR

Drug: Niacin 100 mg

Interventions

Psilocybin (Usona Institute) DRUG

3x 5mg capsules of Psilocybin (cGMP)

Psilocybin (15 mg)

Niacin 100 mg DRUG

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

Niacin (100mg)

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Pontifícia Universidade Católica do Rio de Janeiro: lead

Study Sites (1)

Centro de Pesquisas Matteo Ricci

Rio de Janeiro, Rio de Janeiro, 22451-263, Brazil

RECRUITING

Related Publications (6)

• Lage CA, Wolmarans W, Mograbi DC. An evolutionary view of self-awareness. Behav Processes. 2022 Jan;194:104543. doi: 10.1016/j.beproc.2021.104543. Epub 2021 Nov 17.

  PMID: 34800608 BACKGROUND

• Bienemann B, Barbosa AR, Cruz LVMD, Multedo M, Mograbi D. Health Benefits and Positive Acute Effects of Psilocybin Consumption: A Quantitative Textual Analysis of User Self-Reported Data. J Psychoactive Drugs. 2024 Jul-Aug;56(3):324-332. doi: 10.1080/02791072.2023.2226414. Epub 2023 Jun 22.

  PMID: 37348116 BACKGROUND

• Mograbi DC, Hall S, Arantes B, Huntley J. The cognitive neuroscience of self-awareness: Current framework, clinical implications, and future research directions. Wiley Interdiscip Rev Cogn Sci. 2024 Mar-Apr;15(2):e1670. doi: 10.1002/wcs.1670. Epub 2023 Dec 3.

  PMID: 38043919 BACKGROUND

• Bienemann B, Longo MSC, Ridolfi M, Multedo M, Cruz LVM, Schenberg E, Tofoli LF, Mograbi DC. Adaptation and latent structure of the Brazilian version of the Ego Dissolution Inventory (EDI-BR): an exploratory study. Trends Psychiatry Psychother. 2024;46:e20220491. doi: 10.47626/2237-6089-2022-0491. Epub 2022 Oct 18.

  PMID: 36283045 BACKGROUND

• Mograbi DC, Rodrigues R, Bienemann B, Huntley J. Brain Networks, Neurotransmitters and Psychedelics: Towards a Neurochemistry of Self-Awareness. Curr Neurol Neurosci Rep. 2024 Aug;24(8):323-340. doi: 10.1007/s11910-024-01353-y. Epub 2024 Jul 9.

  PMID: 38980658 BACKGROUND

• Rodrigues RS, Wiessner I, Daldegan-Bueno D, Bienemann B, Pontual A, Tofoli LF, Mograbi DC. OAV and 5D-ASC for Brazilian Portuguese: A validation and adaptation study. J Psychopharmacol. 2025 Sep;39(9):990-1006. doi: 10.1177/02698811251344685. Epub 2025 Jun 28.

  PMID: 40579992 BACKGROUND

Related Links

• Related Info

MeSH Terms

Interventions

Psilocybin; Niacin

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Daniel C Mograbi, PhD

CONTACT

+ 55 21 35272505; mograbilab@gmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Participants allocated to the placebo group are invited to an open-label extension phase, upon availability of the substances.

Study Record Dates

• First Submitted: July 21, 2026
• First Posted: July 28, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 28, 2026

Record last verified: 2026-07

Locations

BR (1)