Effects of Salvinorin A on Brain Function

NCT03418714 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: IRB001315375R01DA003889-31
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the effects of salvinorin A on human brain activity and connectivity using functional magnetic resonance imaging (fMRI) methods. An inhalation route of administration will be used as it is the most common route for contemporary use of Salvia divinorum, a plant containing salvinorin A.

Conditions

Drug Effect

Outcome Measures

Primary Outcomes (2)

• Changes in Brain Activity (fMRI) as Assessed by Variance in BOLD Signal

  Changes in brain activity from before to after salvinorin A administration within canonical brain networks \[medial frontal (MF), frontoparietal (FP), default mode (DM), subcortical-cerebellum (SubC), somatosensory-motor (SM), medial visual (MedV), occipital pole (OccP), and lateral visual or (LatV)\] will be assessed using blood-oxygenation level dependent (BOLD) techniques. Due to salvinorin A's potential confounding influence on blood flow, activity was assessed by looking at the variance in the BOLD signal. Variance in BOLD signal is a dimensionless variable that can vary from 0 to infinity.

  Pre salvinorin A administration and 20 minutes post-salvinorin A administration

• Changes in Brain Connectivity (fMRI) as Assessed by Pearson's Correlation

  Changes in within and between network functional connectivity (FC) from pre to post-salvinorin A (SA) administration in several brain networks \[medial frontal (MF), frontoparietal (FP), default mode (DM), subcortical-cerebellum (SubC), somatosensory-motor (SM), medial visual (MedV), occipital pole (OccP), lateral visual or (LatV)\] is assessed via analysis of blood-oxygenation level dependent (BOLD) data. FC is the association between the BOLD activity of two regions over time. This is measured with a Pearson's correlation that is made parametric via z-transformation. FC within a network is the average of all possible pairwise combinations of z-transformed correlations within a network. FC between two networks is the average of all possible pairwise combinations of z-transformed correlations between two networks. We looked at the change in FC from pre to post-SA averaged across participants (this also gives a measure of dispersion).

  Pre-salvinorin A administration and 20 minutes post-salvinorin A administration

Study Arms (1)

Salvinorin A administration

EXPERIMENTAL

All volunteers will be assigned to the salvinorin A administration arm.

Drug: Salvinorin A

Interventions

Salvinorin A DRUG

Salvinorin A, blinded doses

Also known as: salvia, salvia divinorum

Salvinorin A administration

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Have given written informed consent
• Have a high school level of education
• Have a history of hallucinogen use and experience with an inhaled psychoactive drug.
• Recent experience (within the past year) with an inhaled psychoactive drug.
• 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 mornings of drug session days. If the volunteer does not usually consume caffeinated beverages, he or she must agree not to do so on session days
• Agree to refrain from using any psychoactive drugs, including alcoholic beverages and any tobacco product such as cigarettes or any other nicotine product such as e-cigarettes, within 24 hours of each drug administration. Exceptions include daily use of caffeine.
• Be healthy and psychologically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, and routine medical blood and urinalysis laboratory tests
• Agree that for one week before each session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except if 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
• Agree not to take any Pro-re-nata (PRN) prescription medications on the mornings of the sessions

You may not qualify if:

• 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, or Transient Ischemic Attack (TIA) in the past year
• Seizure disorder or 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
• More than 25% outside the upper or lower range of ideal body weight
• Current or past history of meeting Diagnostic and Statistical Manual (DSM)-V criteria for schizophrenia, psychotic disorder (unless substance-induced or due to a medical condition), dissociative disorder, bipolar I or II disorder, an eating disorder
• Current or past history of substance-induced psychosis.
• Current or past history within the last 2 years of meeting DSM-5 criteria for moderate or severe alcohol or substance use disorder (excluding caffeine)
• Daily or more frequent tobacco or nicotine use
• Current severe obsessive-compulsive disorder, dysthymic disorder, or panic disorder.
• Current, severe, major depression
• Have a first or second degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I or II disorder
• Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to salvinorin A
• Head trauma, traumatic brain injury, or concussion with loss of consciousness for \>2 minutes

Sponsors & Collaborators

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

Study Sites (1)

Behavioral Pharmacology Research Unit, Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Related Links

• Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum

MeSH Terms

Interventions

salvinorin A

Results Point of Contact

• Title: Frederick Barrett
• Organization: Johns Hopkins University

fbarret2@jhmi.edu

4105509777

Study Officials

• Frederick S Barrett, Ph.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Participants will not be aware of exact doses salvinorin A (i.e. they will be told they may receive placebo or up to a moderately high dose of of salvinorin A).
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2018
• First Posted: February 1, 2018
• Study Start: December 14, 2017
• Primary Completion: March 2, 2020
• Study Completion: March 2, 2020
• Last Updated: March 4, 2021
• Results First Posted: March 4, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)