Persisting Effects of Psilocybin

Study Overview
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Brief Summary
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The proposed pilot study will assess whether ingestion of a classic hallucinogen (psilocybin) leads to changes in emotion processing and neural circuitry that may predict repeated self-administration of this drug and underlie an atypical mechanism of abuse liability, which may vitally contribute to the understanding of the potential for abuse and the underlying mechanisms supporting abuse of classic hallucinogens.

Official Title
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Measurement of Persisting Changes in Emotional Brain Functioning Produced by Psilocybin

Conditions
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Healthy

Intervention / Treatment
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* Drug: Psilocybin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have given written informed consent Have at least a high-school level of education or equivalent, and be fluent in English Be healthy and psychologically stable as determined by screening for medical and psychiatric problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the morning of the drug session day. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on the session day. Agree to refrain from using any psychoactive drugs, including alcoholic beverages and nicotine, within 24 hours of each drug administration. The exception is caffeine. Agree not to take any as needed medications on the mornings of drug sessions Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration. Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals. Have limited lifetime use of hallucinogens Exclusion Criteria: Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of birth control. Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrilation), artificial heart valve, or stroke in the past year Epilepsy with history of seizures Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia Currently taking psychoactive prescription medication on a regular (e.g., daily) basis Currently taking on a regular (e.g., daily) basis any medications having a primary centrally-acting serotonergic effect, including mono-amine oxidase inhibitors (MAOIs). For individuals who have intermittent or as needed use of such medications, psilocybin sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose. More than 20% outside the upper or lower range of ideal body weight according to Metropolitan Life height and weight table Current or past history of meeting Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II 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 and nicotine) Have a first or second-degree relative with schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II Disorder Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin 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 -- must complete magnetic resonance imaging (MRI) screening form and be approved by MRI technologist before each scan

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psilocybin<br>Participants will be administered a 25 mg/70 kg dose of psilocybin | Drug: Psilocybin<br>* 25 mg/70 kg Psilocybin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amygdala Response to Stimuli in the Emotion Recognition Test | Blood oxygenation level-dependent (BOLD) percent signal change in response to stimuli in the emotion recognition task was measured in the left and right amygdala. | 1 day pre (baseline), 1 week post, and 1 month post session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Longitudinal Emotion and Mood Questionnaire Scores | Participants were assessed on a variety of questionnaires that probed emotional functioning and mood state. Higher scores on each subscale are indicative of higher levels of each emotion/mood (e.g., low score on Depression (POMS) indicates low level of depressed mood). Depression Anxiety Stress Scale (DASS): Range 0-56 on all subscales Dispositional Positive Emotion Scale (DPES): Range 1-7 on all subscales Positive & Negative Affect Schedule Expanded (PANAS-X): Range 0-50 on all subscales Profile of Mood States (POMS): Ranges vary by subscale. Tension (0-36); Depression (0-60); Anger (0-48); Fatigue (0-28); Confusion (0-28); Vigor (0-36); Mood Disturbance (-36-168) State Trait Anxiety Inventory (STAI): Range 20-80 on all subscales Tellegen Absorption Scale (TAS): Range 0-34 Big Five Inventory (BFI): Range 1-5 on all subscales | 1 day pre (baseline), 1 week post, and 1 month post session | 
| Change in Emotional Functioning Task Accuracy | These tasks measure emotional responding that may be altered by psilocybin. Emotional discrimination task: participants were presented with images of emotional facial expressions or shapes (control), and were instructed to discriminate between the images. Emotion recognition task: participants were presented images of actors and were asked to identify the emotional facial expression (happy, sad, fear, angry, neutral) of each actor. Emotional conflict Stroop task: participants were shown emotional facial expressions (targets) with emotional words overlain (distractors) and were asked to identify the valence of the facial expression, either positive or negative. | 1 day pre (baseline), 1 week post, and 1 month post session | 
| Change in Emotional Functioning Tasks Response Time (Milliseconds) | These tasks measure emotional responding that may be altered by psilocybin. Emotional discrimination task: participants were presented with images of emotional facial expressions or shapes (control), and were instructed to discriminate between the images. Emotion recognition task: participants were presented images of actors and were asked to identify the emotional facial expression (happy, sad, fear, angry, neutral) of each actor. Emotional conflict Stroop task: participants were shown emotional facial expressions (targets) with emotional words overlain (distractors) and were asked to identify the valence of the facial expression, either positive or negative. | 1-day pre (baseline), 1-week post, 1-month post session |