Visual Surround Suppression and Perceptual Expectation Under Psilocybin

Psychedelic Experiences Clinical Trial

Official title:

Visual Surround Suppression and Perceptual Expectation Under Psilocybin

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04424225
• Other study ID #: PSYCH-2019-28235
• Status: Terminated
• Phase: Phase 1
• Start date: August 30, 2021
• Est. completion date: September 1, 2023

Study information

• Verified date: May 2024
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The prospective pilot study will address the critical need for more precise characterizations of the acute visual effects of the drug psilocybin by measuring the impact of acute psilocybin intoxication on a perceptual task known as visual surround suppression, compared to an active placebo control.

Description:

The proposed pilot study will address the critical need for more precise characterizations of the acute visual effects of the drug psilocybin by measuring the impact of acute psilocybin intoxication on a perceptual task known as visual surround suppression, compared to an active placebo control. The data collected in the proposed experiment will make important contributions to knowledge of how psilocybin impacts contextual processing in the brain. Moreover, this will in turn inform the neurobiology of visual surround suppression in general, providing the first investigation of links between surround suppression and serotonergic pathways in humans. Furthermore, the impact of psilocybin on surround suppression will complement recent discoveries of differences in surround suppression present in certain clinical populations. Taken together, these points suggest that this relatively simple and straightforward study could have significant payoff in its contribution to knowledge, not only of the effects of psilocybin but also of key brain processes underpinning human vision and context processing more broadly.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: September 1, 2023
• Est. primary completion date: September 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

Inclusion Criteria:

• Have given written informed consent

• Have at least a high-school level of education or equivalent (e.g. GED), and be able to read and write in English

• General health status: Participants should be in good physical (BMI between 20.0 and 28.0 kg/m2) and psychiatric health.

• Experience taking psilocybin (at the PI's discretion).

• Participants must also have a person that can reliably transport them to and from the CRU for dosing session days.

• Geographic location: Minnesota counties that are approximately within 1 hour driving distance to Twin Cities, including not limited to Hennepin, Ramsey, Washington, Anoka, Wright, Carver, Scott, Dakota, Sherburn

• Participants must be willing to wear a face mask at all times during in-person study visits, except for dosing sessions, to ensure COVID-19 protection.

• Participants must be willing to get a COVID-19 test and share results with the study team prior to all in-person visits.

• Participants must be up-to-date on COVID-19 vaccines, per CDC guidelines, and share a copy of their proof of vaccination status with the study team prior to the consenting visit.

• Agrees to refrain from using recreational drugs while enrolled in the study, including, but not limited to, hallucinogens, ketamine, and marijuana.

Exclusion Criteria:

• Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except due to another medical condition), or Bipolar I or II Disorder, personality disorder, major depressive disorder, posttraumatic stress disorder, panic disorder, obsessive compulsive disorder, dysthymic disorder.

• Current or past history within the last 5 years of meeting DSM-5 criteria for a moderate or severe alcohol or drug use disorder (excluding caffeine, nicotine, and hallucinogens)

• Those with a first or second-degree relative with a current or past history of meeting DSM-5 criteria for schizophrenia or other psychotic disorders or bipolar I or II disorder, because they might have an underlying genetic susceptibility for psychosis.

• Presence of symptoms of the following DSM-5 disorders within the past 6 months (as assessed by the MINI-7):

• Major depressive Episode

• Suicidality

• Manic and Hypomanic Episodes

• Panic disorder

• Agoraphobia

• Social Anxiety Disorder

• Obsessive-Compulsive Disorder

• Posttraumatic Stress Disorder

• Alcohol Use Disorder

• Substance Use Disorder (Non-Alcoholic)

• Psychotic Disorders and Mood Disorders with Psychotic Features

• Anorexia Nervosa

• Bulimia Nervosa

• Binge Eating Disorder

• Generalized Anxiety Disorder

• Antisocial Personality Disorder

• Mood Disorders:

• Major Depressive Disorder (MDD)

• MDD with Psychotic Features

• Bipolar I

• Bipolar II

• Other Specified Bipolar and Related Disorder

• Presence of abuse or dependence of drugs measured by the MINI-7 in the past 12 months:

• Lithium, Sodium Valproate (Depakote), Lamotrigine (Lamictal) - Manic/Bipolar disorders

• Stimulants: amphetamines, "speed", crystal meth, "crank", Dexedrine, Ritalin, diet pills.

• Cocaine: snorting, IV, freebase, crack, "speedball".

• Opiates: heroin, morphine, Dilaudid, opium, Demerol, methadone, Darvon, codeine, Percodan, Vicodin, OxyContin.

• Dissociative Drugs: PCP (Phencyclidine ,"Angel Dust", "Peace Pill", "Hog"), or ketamine ("Special K").

• Inhalants: "glue", ethyl chloride, "rush", nitrous oxide ("laughing gas"), amyl or butyl nitrate ("poppers").

• Cannabis: marijuana, hashish ("hash"), THC, "pot", "grass", "weed", "reefer".

• Sedatives, Hypnotics or Anxiolytics: Quaalude, Seconal ("reds"), Valium, Xanax, Librium, Ativan, Dalmane, Halcion, barbiturates, Miltown, GHB, Roofinol, "Roofies".

• Miscellaneous: steroids, nonprescription sleep or diet pills. Cough Medicine?

• History of medication or substance induced psychosis.

• Medically significant condition considered unsuitable for the current study (e.g. diabetes, epilepsy, severe cardiovascular disease, etc)

• History of suicide attempts or mania

• Positive pregnancy test or currently breast-feeding

• Currently taking on a regular (e.g., daily) basis any prescription medications, with the exception of birth control or other hormone therapy

• A strong bias either for or against psychedelic substances, or if their responses about psychedelic use indicate that they abuse them from frequent use (more than once per month, with the exception of microdosing).

• MRI EXCLUSION: we will also exclude anyone with head trauma, claustrophobia incompatible with scanning, cardiac pacemaker, implanted cardiac defibrillator, aneurysm brain clip, inner ear implant, prior history as a metal worker and/or certain metallic objects in the body that cannot be approved for MR scanning by the CMRR safety committee, history of clinically significant vertigo, seizure disorder, middle ear disorder, or double vision, or tattoos that were done less than 4 weeks from the first scheduled MRI.

• Significant movement disorders including tardive dyskinesia that could disrupt EEG recordings will also be excluded.

• Uncontrolled hypertension, with an average blood pressure reading across 4 measurements over 2 separate days greater than 140/90mmHg.

• Unwilling to wear a face mask during in-person study visits that require them.

• Unwilling to get tested for COVID-19 and share results with study personnel prior to all in-person visits.

• Are unvaccinated against COVID-19, are not current with their COVID-19 vaccine booster, or are unwilling to share their proof of COVID-19 vaccination with the study team.

Related Conditions & MeSH terms

• Perception Disturbance
• Psychedelic Experiences
• Vision Disorders
• Visual Suppression

Intervention

Drug:
• Psilocybin
25 mg capsules (white opaque, Capsugel Vcaps Plus HPMC size 2)
• Niacin
100 mg capsules (white opaque, Capsugel Vcaps Plus HPMC size 2)

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
University of Minnesota	Heffter Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (1)

Swanson, L., Jungers, S., Varghese, R., Cullen, K. R., Evans, M. D., Nielson, J., & Schallmo, M. (2024, January 11). Enhanced visual contrast suppression during peak psilocybin effects: A psychophysical study. https://doi.org/10.31234/osf.io/5rm62

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Psychophysical Discrimination Threshold	Visual psychophysics tasks will consist of perceptual judgments (e.g., subject will report which of two visual stimuli presented appears to have higher contrast). Based on these responses, psychophysical discrimination thresholds are calculated using an adaptive staircase technique and reported in units of percent contrast.	3-5 hours
Secondary	Difference in Event Related Potential Amplitude	Electroencephalography (EEG) will be collected during a visual surround suppression task and event related potential (ERP) amplitudes (in units of microvolts/millisecond) will be compared for visual target stimuli in different stimulus conditions (e.g., with vs. without surrounding stimuli).	3-5 hours
Secondary	Change in resting state brain activity	Changes in brain connectivity, which will be measured with functional Magnetic Resonance Imaging (fMRI) while participants are at rest. Measurements will be taken at baseline, and 1 day, 3 days, and 7 days after each dosing session.	Approximately 4 weeks
Secondary	Change of white matter structural connectivity	Structural networks were weighted by measures of white matter microstructure of Neurite orientation dispersion and density imaging (NODDI) (fractional anisotropy, neurite density and orientation dispersion index). Measurements will be taken at baseline, and 1 day, 3 days, and 7 days after each dosing session.	Approximately 4 weeks
Secondary	Positive and Negative Affect Schedule (PANAS) Positive Scale	The positive and negative affect schedule is a self-report questionnaire that consists of two 10-item scales - positive and negative affect. Each item is rated on a 5-point scale of 1 (not at all) to 5 (very much). Positive scale score is calculated as the sum of items 1, 3, 5, 9, 10, 12, 14, 16, 17, and 19. Scores range from 10-50, with higher scores representing higher levels of positive affect.	approximately 4 weeks
Secondary	Positive and Negative Affect Schedule (PANAS) Negative Scale	The positive and negative affect schedule is a self-report questionnaire that consists of two 10-item scales - positive and negative affect. Each item is rated on a 5-point scale of 1 (not at all) to 5 (very much). Negative scale score is calculated as the sum of items 2, 4, 6, 7, 8, 11, 13, 15, 18, and 20. Scores range from 10-50, with higher scores representing higher negative affect.	approximately 4 weeks
Secondary	Revised Mystical Experience Questionnaire (RMEQ-30)	The Revised Mystical Experience Questionnaire, a self-report of experiences associated with psilocybin use, contains 30 items rated on a scale from 0 (none; not at all) to 5 (extreme). From the report, 4 scores are produced - Mystical Experience, Positive Mood, Transcendence of Time and Space, and Ineffability.; The mystical experience score is calculated by summing 15 items scores and ranges from 0 to 75, with higher scores indicating a stronger mystical experience.; The positive mood score is calculated by summing 6 items scores and ranges from 0 to 30, with higher scores indicating greater positive mood.; The transcendence of time and space score is calculated by summing 6 items scores and ranges from 0 to 30, with higher scores indicating greater transcendence of space and time.; The ineffability score is calculated by summing 3 items scores and ranges from 0 to 15, with higher scores indicating greater feelings of ineffability.	approximately 4 weeks
Secondary	Ego-Dissolution Inventory (EDI)	The ego-dissolution inventory (EDI) contains 16 items relating to altered ego-consciousness - 8 items relating to the experience of ego-dissolution and 8 items relating to the antithetical experience of ego-inflation. Items are rated using a visual analog scale that is converted to a numeric range from 0-100.; The ego-dissolution score is calculated as an unweighted average of the 8 items relating to the experience of ego dissolution. Scores for this subscale range from 0-100, with higher scores indicating greater ego dissolution.; The ego-inflation score if calculated as an unweighted average of the 8 items relating to the experience of ego inflation. Scores for this subscale range from 0-100, with higher scores indicating greater ego inflation.	approximately 4 weeks
Secondary	5 Dimensions of Altered States of Consciousness (5D-ASC)	The 5 Dimensions of Altered States of Consciousness contains 94 items and 5 sub-scales: Oceanic Boundlessness (OB, 27 items), Anxious Ego Dissolution (AED, 21 items), Auditory Alterations (AA, 15 items), Vigilance Reduction (VIR, 12 items), Visionary Restructuralization (VR, 18 items). Each item is rated using a visual analogue scale from 0-10. Scores are presented as % of scale maximum (either total for total score, or subtotal for each sub-score).	approximately 4 weeks
Secondary	Change in Serum Brain-Derived Neurotrophic Factor (BDNF)	Serum will be collected at baseline and post each treatment for the measurement of BDNF using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of BDNF will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum C-Reactive Protein (CRP)	Serum will be collected at baseline and post each treatment for the measurement of CRP using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of CRP will be reported in units of ng/ml.	approximately 4 weeks
Secondary	Change in Serum Transforming Growth Factor Beta-1 (TGFb-1)	Serum will be collected at baseline and post each treatment for the measurement of TGFb-1 using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of TGFb-1 will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum Glial Fibrillary Acidic Protein (GFAP)	Serum will be collected at baseline and post each treatment for the measurement of GFAP using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of GFAP will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum Tumor Necrosis Factor Alpha (TNFa)	Serum will be collected at baseline and post each treatment for the measurement of TNFa using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of TNFa will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum Interleukin-1beta (IL-1b)	Serum will be collected at baseline and post each treatment for the measurement of IL-1b using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of IL-1b will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum Interleukin-6 (IL-6)	Serum will be collected at baseline and post each treatment for the measurement of IL-6 using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of IL-6 will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum Interleukin-10 (IL-10)	Serum will be collected at baseline and post each treatment for the measurement of IL-10 using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of IL-10 will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum Interferon Gamma (IFNy)	Serum will be collected at baseline and post each treatment for the measurement of IFNy using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of IFNy will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum Tumor Necrosis Factor Receptor 1 (TNF-R1)	Serum will be collected at baseline and post each treatment for the measurement of TNF-R1 using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of TNF-R1 will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum Tumor Necrosis Factor Receptor 2 (TNF-R2)	Serum will be collected at baseline and post each treatment for the measurement of TNF-R2 using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of TNF-R2 will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum S100 Calcium-Binding Protein B (S100B)	Serum will be collected at baseline and post each treatment for the measurement of S100B using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of S100B will be reported in units of pg/ml.	approximately 4 weeks
Secondary	Change in Serum Ubiquitin C-Terminal Hydrolase L1 (UCHL-1)	Serum will be collected at baseline and post each treatment for the measurement of UCHL-1 using enzyme-linked immunosorbent assay (ELISA). Change in serum concentrations of UCHL-1 will be reported in units of pg/ml.	approximately 4 weeks