Persisting Effects of Psilocybin

Measurement of Persisting Changes in Emotional Brain Functioning Produced by Psilocybin

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Psilocybin

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Behavioral Pharmacology Research Unit, Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin; Participants will be administered a 25 mg/70 kg dose of psilocybin	Drug: Psilocybin; 25 mg/70 kg Psilocybin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Frederick S Barrett, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): August 21, 2018
• Study Completion (Actual): August 21, 2018

Study Registration Dates

• First Submitted: November 21, 2016
• First Submitted That Met QC Criteria: November 22, 2016
• First Posted (Estimate): November 23, 2016

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: IRB00102081; R03DA042336 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized data will be shared with qualified scientists upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No