NCT04199468

Brief Summary

The aim of the research protocol is to evaluate cannabinoid-glutamate interactions in humans. As part of this aim the investigators will assess the safety and tolerability of the combination of NMDA antagonist, ketamine, and the cannabinoid, delta-9-tetrahydrocannabinol (THC), in healthy adult subjects, and characterize the interactive effects of ketamine and THC on various electrophysiological (EEG), cognitive, and behavioral outcomes.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Sep 2019

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 24, 2019

Completed
27 days until next milestone

First Submitted

Initial submission to the registry

October 21, 2019

Completed
2 months until next milestone

First Posted

Study publicly available on registry

December 16, 2019

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 21, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 21, 2022

Completed
Last Updated

March 25, 2024

Status Verified

March 1, 2024

Enrollment Period

2.7 years

First QC Date

October 21, 2019

Last Update Submit

March 21, 2024

Conditions

CannabisKetamine

Outcome Measures

Primary Outcomes (9)

  • EEG Measures 1

    The primary EEG outcome 1 will be EEG event related potential voltage amplitude (microvolts).

    0-60 minutes after the onset of drug infusion

  • EEG Measures 2

    The primary EEG outcome 2 will be EEG event related potential latency (milliseconds).

    0-60 minutes after the onset of drug infusion

  • EEG Measures 3

    The primary EEG outcome 3 will be spectral power (microvolts squared).

    0-60 minutes after the onset of drug infusion

  • EEG Measures 4

    The primary EEG outcome 4 will be Intertrial Coherence (phase locking factor).

    0-60 minutes after the onset of drug infusion

  • EEG Measures 5

    The primary EEG outcome 5 will be neural noise (Lempel Ziv Complexity).

    0-60 minutes after the onset of drug infusion

  • Neurochemical Measures: THC levels

    THC blood levels (ng/mL) will be assayed to determine the relationships between blood levels and EEG measures (outcomes 1-5) and behavioral measures (outcomes 10-12). Blood sampled at 4 time-points will be centrifuged and the resultant plasma will be aliquoted into appropriate vials and stored at -80 degrees C until the time of the assay.

    -30, +25, +60, +120 minutes after start of drug infusion (0)

  • Neurochemical Measures: THC-COOH levels

    THC-COOH blood levels (ng/mL) will be assayed to determine the relationships between blood levels and EEG measures (outcomes 1-5) and behavioral measures (outcomes 10-12). Blood sampled at 4 time-points will be centrifuged and the resultant plasma will be aliquoted into appropriate vials and stored at -80 degrees C until the time of the assay.

    -30, +25, +60, +120 minutes after start of drug infusion (0)

  • Neurochemical Measures: ketamine/norketamine levels

    Ketamine/norketamine blood levels (ng/mL) will be assayed to determine the relationships between blood levels and EEG measures (outcomes 1-5) and behavioral measures (outcomes 10-12). Blood sampled at 4 time-points will be centrifuged and the resultant plasma will be aliquoted into appropriate vials and stored at -80 degrees C until the time of the assay.

    -30, +25, +60, +120 minutes after start of drug infusion (0)

  • Genetics

    Blood samples for DNA extraction will be collected to examine whether any of the genes e.g., calcyon, BDNF, neuregulin-1, dysbindin, NOTCH4, COMT and the 22q11 PRODH2/DGCR6 locus that have been associated with schizophrenia, modify the effects of delta-9-THC, ketamine or the combination.

    Collected at the screening visit.

Secondary Outcomes (3)

  • Positive and Negative Symptoms Scale (PANSS)

    -60, +70, +120, +240 from baseline (0) (units in minutes).

  • Perceptual Alterations

    -60, +70, +120, +240 from baseline (0) (units in minutes).

  • Cannabis Subjective Effects

    -60, +70, +120, +240 from baseline (0) (units in minutes).

Study Arms (4)

Active Delta-9-THC and Placebo Ketamine

EXPERIMENTAL

Active IV Delta-9-THC and Placebo Ketamine

Drug: Active Delta-9-THCDrug: Placebo Ketamine

Active Delta-9-THC and Active Ketamine

EXPERIMENTAL

Active IV Delta-9-THC and Active Ketamine

Drug: Active Delta-9-THCDrug: Active Ketamine

Placebo Delta-9-THC and Placebo Ketamine

EXPERIMENTAL

IV Placebo Delta-9-THC and Placebo Ketamine

Drug: Placebo Delta-9-THCDrug: Placebo Ketamine

Placebo Delta-9-THC and Active Ketamine

EXPERIMENTAL

IV Placebo Delta-9-THC and Active Ketamine

Drug: Placebo Delta-9-THCDrug: Active Ketamine

Interventions

Active Delta-9-THCDRUG

Active Delta-9-THC (0.015 mg/kg) given intravenously (IV)

Active Delta-9-THC and Active KetamineActive Delta-9-THC and Placebo Ketamine
Placebo Delta-9-THCDRUG

A placebo dose given intravenously (IV)

Placebo Delta-9-THC and Active KetaminePlacebo Delta-9-THC and Placebo Ketamine
Active KetamineDRUG

Active Ketamine (0.2 mg/kg) given intravenously (IV)

Active Delta-9-THC and Active KetaminePlacebo Delta-9-THC and Active Ketamine
Placebo KetamineDRUG

A placebo dose given intravenously (IV)

Active Delta-9-THC and Placebo KetaminePlacebo Delta-9-THC and Placebo Ketamine

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • to approximately 45 years old
  • Good physical and mental health as determined by history, the Structured Clinical Interview for DSM-5 TR (SCID-NP) and collateral information, physical and laboratory examinations, ECG and vital signs.
  • Weight of 100 kg (220.46 lbs.) or less (inclusive).

You may not qualify if:

  • Unstable serious medical conditions. At the discretion of the investigator, subjects with unstable medical conditions that may necessitate changes in medical treatment and hence influence study outcomes will be excluded.
  • Uncontrolled hypertension, long QT syndrome, and seriously abnormal EKG results. EKG abnormalities will be reviewed by the PI and eligibility decisions will be made at the discretion of the PI.
  • A hearing deficit in greater than one band in an ear detected using a Welch-Allyn audioscope (500, 1000, 2000 and 4000 Hz threshold will be evaluated)
  • Positive pregnancy test

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Marijuana Abuse

Condition Hierarchy (Ancestors)

Substance-Related DisordersChemically-Induced DisordersMental Disorders

Study Officials

  • Rajiv Radhakrishnan, M.D.

    Yale University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

October 21, 2019

First Posted

December 16, 2019

Study Start

September 24, 2019

Primary Completion

June 21, 2022

Study Completion

June 21, 2022

Last Updated

March 25, 2024

Record last verified: 2024-03

Locations

US(1)