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The goal of this clinical trial is to learn whether certain methods of detecting awareness in vegetative or minimally conscious patients (using neuroimaging) are sensitive to the effects of psilocybin (a psychedelic drug). One of these methods includes scanning peoples' brains while they watch a film. When different individuals watch a film, their brains become synchronized with each other as they watch the plot unfold. Most importantly, if a seemingly unconscious patient also shows the same brain-synchronization, it means they might actually be conscious and aware.
To approach this goal, the investigators will be carrying out this trial in healthy volunteers. This will help better understand whether psilocybin may be a potential treatment for restoring awareness in these patients. The main questions it aims to answer are:
Participants will be asked to:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Psilocybin First | Experimental | Individuals in this arm will be given psilocybin for their first scanning session. For their second scanning session (at least two weeks later), they will receive the placebo. |
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| Placebo First | Experimental | Individuals in this arm will be given the placebo for their first scanning session. For their second scanning session (at least two weeks later), they will receive psilocybin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Psilocybin | Drug | Individuals will be given 15 milligrams (mg) of psilocybin orally, and will be asked to lay flat in a functional magnetic resonance imaging (fMRI) brain scanner. The following scans will be collected: anatomical and resting state; while they watch a scrambled film clip; while they watch an intact film clip; while they perform a mental imagery task; while they listen to two pieces of music. Participants will then be given two questionnaires: one assessing their overall plot comprehension, and the other asking about their experience in the scanner. They will then be asked to perform a series of visual illusions tasks, and following, play a variety of web-based games assessing their cognitive function. After this, they will be interviewed by one of the study researchers about their overall experience before/during/after the scan. |
| Measure | Description | Time Frame |
|---|---|---|
| Intersubject Correlation (ISC) | The degree to which different participants' brain activity is correlated with one another (or synchronized) across the time-course of an in-scanner task (e.g. during a resting state, while watching film clips, while listening to music, etc.). Higher ISC scores indicate greater brain synchronization between individuals (minimum value=0, indicating no ISC/synchronization). | Through study completion, an average of 2 weeks. ISC for each drug/task condition is computed and analyzed following second scan (from neuroimaging data). |
| Interpretive Phenomenological Analysis | An analysis of the different themes that emerge (e.g. "feeling joy") when interviewing participants about their experience under the placebo or psilocybin. These themes will be correlated against ISC scores for each drug condition. Not scored on any scale; each theme's prevalence will be reported as a ratio and/or percentage. | Through study completion, an average of 2 weeks. Analyzed following second scan (from interview data). |
| Measure | Description | Time Frame |
|---|---|---|
| Short-Term Memory | An assessment of the short-term memory abilities of each participant. These scores are computed by the Creyos online cognitive testing platform, from each participants' performance on the suite of web-based games (which assess memory, spatial/verbal reasoning, planning, and concentration). Data will likely be reported as a normalized score with no min/max value (higher scores will indicate a better outcome). |
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Inclusion Criteria:
Participants must:
Exclusion Criteria:
The following people will be excluded from the study. Those who:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Adrian M. Owen | Contact | 519-661-2111 | 84672 | uwocerc@uwo.ca |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31024740 | Background | Scott G, Carhart-Harris RL. Psychedelics as a treatment for disorders of consciousness. Neurosci Conscious. 2019 Apr 21;2019(1):niz003. doi: 10.1093/nc/niz003. eCollection 2019. | |
| 28422113 | Background | Schartner MM, Carhart-Harris RL, Barrett AB, Seth AK, Muthukumaraswamy SD. Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin. Sci Rep. 2017 Apr 19;7:46421. doi: 10.1038/srep46421. |
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| ID | Term |
|---|---|
| D003244 | Consciousness Disorders |
| ID | Term |
|---|---|
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D011562 | Psilocybin |
| ID | Term |
|---|---|
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
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| Placebo | Other | Individuals will be given a placebo orally, and will be asked to lay flat in a functional magnetic resonance imaging (fMRI) scanner. The following scans will be collected: anatomical and resting state; while they watch a scrambled film clip; while they watch an intact film clip; while they perform a mental imagery task; while they listen to two pieces of music. Participants will then be given two questionnaires: one assessing their overall plot comprehension, and the other asking about their experience in the scanner. They will then be asked to perform a series of visual illusions tasks, and following, play a variety of web-based games assessing their cognitive function. After this, they will be interviewed by one of the study researchers about their overall experience before/during/after the scan. |
|
| Through study completion, an average of 2 weeks. Analyzed following second scan (from Creyos cognitive scores). |
| Verbal Reasoning | An assessment of the verbal reasoning abilities of each participant. These scores are computed by the Creyos online cognitive testing platform, from each participants' performance on the suite of web-based games (which assess memory, spatial/verbal reasoning, planning, and concentration). Data will likely be reported as a normalized score with no min/max value (higher scores will indicate a better outcome). | Through study completion, an average of 2 weeks. Analyzed following second scan (from Creyos cognitive scores). |
| Reasoning Skills | An assessment of the logical reasoning skills of each participant. These scores are computed by the Creyos online cognitive testing platform, from each participants' performance on the suite of web-based games (which assess memory, spatial/verbal reasoning, planning, and concentration). Data will likely be reported as a normalized score with no min/max value (higher scores will indicate a better outcome). | Through study completion, an average of 2 weeks. Analyzed following second scan (from Creyos cognitive scores). |
| Background | Hasson U, Landesman O, Knappmeyer B, Vallines I, Rubin N, Heeger DJ. Neurocinematics: The neuroscience of film. Projections. 2008;2(1):1-26. |
| 25225384 | Background | Naci L, Cusack R, Anello M, Owen AM. A common neural code for similar conscious experiences in different individuals. Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):14277-82. doi: 10.1073/pnas.1407007111. Epub 2014 Sep 15. |
| 26679327 | Background | Naci L, Sinai L, Owen AM. Detecting and interpreting conscious experiences in behaviorally non-responsive patients. Neuroimage. 2017 Jan 15;145(Pt B):304-313. doi: 10.1016/j.neuroimage.2015.11.059. Epub 2015 Dec 8. |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D014363 | Tryptamines |
| D054836 | Indolizidines |
| D007212 | Indolizines |