Visual Surround Suppression and Perceptual Expectation Under Psilocybin

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.

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.

Eligibility Criteria:
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.