Persisting Effects of Psilocybin

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02971605
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 13
• Location: 1
• Arm: 1
• Actual Duration (Months): 13.7
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Psilocybin	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Measurement of Persisting Changes in Emotional Brain Functioning Produced by Psilocybin
• Actual Study Start Date: Jul 1, 2017
• Actual Primary Completion Date: Aug 21, 2018
• Actual Study Completion Date: Aug 21, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Amygdala Response to Stimuli in the Emotion Recognition Test [1 day pre (baseline), 1 week post, and 1 month post session]

   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.

Secondary Outcome Measures

1. Change in Longitudinal Emotion and Mood Questionnaire Scores [1 day pre (baseline), 1 week post, and 1 month post session]

   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

2. Change in Emotional Functioning Task Accuracy [1 day pre (baseline), 1 week post, and 1 month post session]

   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.

3. Change in Emotional Functioning Tasks Response Time (Milliseconds) [1-day pre (baseline), 1-week post, 1-month post session]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Behavioral Pharmacology Research Unit, Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224

Sponsors and Collaborators

• Johns Hopkins University
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Frederick S Barrett, PhD, Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 24, 2017

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02971605
• Other Study ID Numbers: IRB00102081; R03DA042336
• First Posted: Nov 23, 2016
• Last Update Posted: Sep 10, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Psilocybin

Study Results

Participant Flow

Arm/Group Title	Psilocybin
Arm/Group Description	Participants will be administered a 25 mg/70 kg dose of psilocybin Psilocybin: 25 mg/70 kg Psilocybin
Period Title: Overall Study
STARTED	13
COMPLETED	12
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Psilocybin
Arm/Group Description	Participants will be administered a 25 mg/70 kg dose of psilocybin Psilocybin: 25 mg/70 kg Psilocybin
Overall Participants	13
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.2 (7.2)
Sex: Female, Male (Count of Participants)
Female	8 61.5%
Male	5 38.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	13 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Education Level (Count of Participants)
High School/GED	1 7.7%
College	4 30.8%
Post-Graduate	8 61.5%

Outcome Measures

1. Primary Outcome

Title	Amygdala Response to Stimuli in the Emotion Recognition Test
Description	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.
Time Frame	1 day pre (baseline), 1 week post, and 1 month post session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	1-week Post Session	1-month Post Session
Arm/Group Description	One day prior to psilocybin administration.	One week post psilocybin (25 mg/70 kg) administration.	One month post psilocybin (25 mg/70 kg) administration.
Measure Participants	12	12	12
L Amygdala contrast: Happy	0.835 (0.342)	-0.759 (0.63)	0.619 (0.449)
L Amygdala contrast: Sad	0.503 (0.403)	-0.514 (0.635)	0.999 (0.563)
L Amygdala contrast: Fearful	0.525 (0.421)	-0.928 (0.696)	0.664 (0.584)
L Amygdala contrast: Angry	0.514 (0.357)	-0.881 (0.703)	1.131 (0.569)
L Amygdala contrast: Neutral	0.794 (0.437)	-0.825 (0.572)	1.098 (0.582)
R Amygdala contrast: Happy	0.938 (0.388)	-0.052 (0.431)	0.749 (0.478)
R Amygdala contrast: Sad	0.927 (0.423)	0.004 (0.37)	0.816 (0.444)
R Amygdala contrast: Fearful	0.979 (0.424)	-0.254 (0.481)	0.617 (0.563)
R Amygdala contrast: Angry	0.834 (0.449)	-0.028 (0.39)	0.689 (0.454)
R Amygdala contrast: Neutral	1.081 (0.428)	-0.256 (0.358)	0.719 (0.476)

2. Secondary Outcome

Title	Change in Longitudinal Emotion and Mood Questionnaire Scores
Description	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
Time Frame	1 day pre (baseline), 1 week post, and 1 month post session

Outcome Measure Data

Analysis Population Description

The Big Five Inventory (BFI) and the Tellegen Absorption Scale (TAS) were not administered at 1-week post, and were only administered at Baseline and 1-month post.

Arm/Group Title	Baseline	1-week Post Session	1-month Post Session
Arm/Group Description	One day prior to psilocybin administration.	One week post psilocybin (25 mg/70 kg) administration.	One month post psilocybin (25 mg/70 kg) administration.
Measure Participants	12	12	12
Depression (DASS)	1.82 (0.57)	1.09 (0.73)	1.64 (0.59)
Anxiety (DASS)	1.64 (1.07)	1.64 (0.75)	1.45 (0.90)
Stress (DASS)	4.91 (1.06)	2.00 (0.60)	3.27 (1.12)
Joy (DPES)	5.45 (0.21)	6.02 (0.17)	5.92 (0.21)
Content (DPES)	5.62 (0.24)	6.27 (0.16)	6.13 (0.23)
Pride (DPES)	5.42 (0.22)	5.96 (0.14)	5.95 (0.18)
Love (DPES)	5.61 (0.17)	5.92 (0.25)	5.98 (0.17)
Compassion (DPES)	5.75 (0.31)	6.25 (0.26)	6.00 (0.30)
Amusement (DPES)	5.02 (0.31)	5.60 (0.32)	5.71 (0.31)
Awe (DPES)	5.52 (0.26)	6.06 (0.22)	5.88 (0.24)
Positive Affect (PANAS-X)	38.18 (1.41)	40.64 (1.28)	40.18 (1.92)
Negative Affect (PANAS-X)	16.09 (1.00)	12.36 (0.93)	16.09 (0.80)
Tension (POMS)	4.82 (1.22)	1.73 (0.49)	3.82 (1.19)
Depression (POMS)	3.36 (0.81)	0.55 (0.25)	2.64 (1.03)
Anger (POMS)	4.91 (1.34)	2.18 (0.58)	4.64 (0.98)
Fatigue (POMS)	4.09 (1.37)	2.27 (1.21)	2.72 (1.06)
Confusion (POMS)	5.55 (1.19)	4.27 (0.79)	4.72 (1.21)
Vigor (POMS)	19.09 (1.35)	21.45 (1.77)	22.09 (2.15)
Mood Disturbance (POMS)	3.64 (5.67)	-10.5 (3.23)	-3.55 (6.19)
State Anxiety (STAI)	28.0 (2.41)	22.82 (1.37)	25.64 (2.56)
Trait Anxiety (STAI)	31.36 (1.91)	28.55 (1.32)	25.64 (27.55)
Extraversion (BFI)	3.46 (0.190)	3.69 (0.183)
Agreeableness (BFI)	4.43 (0.099)	4.33 (0.117)
Conscientiousness (BFI)	3.82 (0.172)	3.98 (0.159)
Neuroticism (BFI)	1.82 (0.213)	1.67 (0.175)
Openness (BFI)	4.17 (0.129)	4.22 (0.151)
Absorption (TAS)	0.98 (0.176)	1.31 (0.233)

3. Secondary Outcome

Title	Change in Emotional Functioning Task Accuracy
Description	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.
Time Frame	1 day pre (baseline), 1 week post, and 1 month post session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	1-week Post Session	1-month Post Session
Arm/Group Description	One day prior to psilocybin administration.	One week post psilocybin (25 mg/70 kg) administration.	One month post psilocybin (25 mg/70 kg) administration.
Measure Participants	12	12	12
Emotion recognition task: Happy	92.6 (2.7)	95.8 (2.1)	97.9 (1.5)
Emotion recognition task: Sad	95.7 (2.1)	93.8 (2.5)	94.8 (2.3)
Emotion recognition task: Fearful	100.0 (0.0)	99.0 (1.0)	97.9 (1.5)
Emotion recognition task: Angry	97.9 (1.5)	95.8 (2.1)	99.0 (1.0)
Emotion recognition task: Neutral	93.8 (2.5)	96.9 (1.8)	100.0 (0.0)
Emotion discrimination: Shapes (Control)	97.0 (1.0)	97.0 (1.0)	95.0 (1.3)
Emotion discrimination: Faces	87.1 (2.4)	92.3 (1.8)	93.2 (1.7)
Emotional conflict Stroop: Congruent	99.5 (0.3)	99.8 (0.2)	99.5 (0.3)
Emotional conflict Stroop: Incongruent	98.1 (0.7)	97.9 (0.7)	98.4 (0.6)

4. Secondary Outcome

Title	Change in Emotional Functioning Tasks Response Time (Milliseconds)
Description	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.
Time Frame	1-day pre (baseline), 1-week post, 1-month post session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	1-week Post Session	1-month Post Session
Arm/Group Description	One day prior to psilocybin administration.	One week post psilocybin (25 mg/70 kg) administration.	One month post psilocybin (25 mg/70 kg) administration.
Measure Participants	12	12	12
Emotion recognition task: Happy	1670 (59.5)	1383 (41.2)	1454 (45.6)
Emotion recognition task: Sad	1539 (53.0)	1458 (45.6)	1596 (56.8)
Emotion recognition task: Fearful	1061 (27.2)	1045 (31.8)	1130 (40.8)
Emotion recognition task: Angry	1380 (45.9)	1193 (36.4)	1310 (40.9)
Emotion recognition task: Neutral	1305 (49.1)	1594 (49.2)	1017 (33.4)
Emotion discrimination task: Shapes	977.0 (212.9)	1697 (414.1)	1735 (434.9)
Emotion discrimination task: Faces	1803 (51.1)	1572 (41.1)	1522 (35.3)
Emotional conflict Stroop: Congruent	613.5 (6.32)	606.3 (5.88)	603.2 (7.18)
Emotional conflict Stroop: Incongruent	641.3 (7.14)	631.4 (7.03)	614.1 (6.71)

Adverse Events

Time Frame	Adverse events were assessed from Screening to 1-month post psilocybin session (32-70 days).
Arm/Group Title	Psilocybin
Arm/Group Description	Participants will be administered a 25 mg/70 kg dose of psilocybin Psilocybin: 25 mg/70 kg Psilocybin
All Cause Mortality
	Psilocybin
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Serious Adverse Events
	Psilocybin
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Other (Not Including Serious) Adverse Events
	Psilocybin
	Affected / at Risk (%)	# Events
Total	3/13 (23.1%)
Cardiac disorders
Cardiac event	2/13 (15.4%)	2
Endocrine disorders
Thyroid hormone changes	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.