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Completed

NCT Number: NCT04199468

THC and Ketamine Effects in Humans: Relation to Neural Oscillations and Psychosis

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.

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Key information

Conditions

Cannabis Chemically-Induced Disorders Ketamine Marijuana Abuse Mental Disorders Substance-Related Disorders

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

About this study

The investigators will examine the contributions of the cannabinoid receptor (CB1R) and N-methyl D-aspartate receptor (NMDAR) systems to psychosis in healthy humans beings using THC and ketamine respectively (both alone and in combination). Healthy subjects (n=21) will receive THC (active or placebo) followed by ketamine (active or placebo) in a double blind, randomized, crossover (2x2) design. Psychotomimetic effects will be assessed before and at various time points after the drug infusions. EEG indices of information processing, specifically neural oscillations, will be assessed during peak drug effects.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 18 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).

Exclusion criteria

  • 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

Treatment and study plan

Active Delta-9-THC

Drug

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

Placebo Delta-9-THC

Drug

A placebo dose given intravenously (IV)

Active Ketamine

Drug

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

Placebo Ketamine

Drug

A placebo dose given intravenously (IV)

Primary outcomes

  1. EEG Measures 1

    Time frame: 0-60 minutes after the onset of drug infusion

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

  2. EEG Measures 2

    Time frame: 0-60 minutes after the onset of drug infusion

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

  3. EEG Measures 3

    Time frame: 0-60 minutes after the onset of drug infusion

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

  4. EEG Measures 4

    Time frame: 0-60 minutes after the onset of drug infusion

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

  5. EEG Measures 5

    Time frame: 0-60 minutes after the onset of drug infusion

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

  6. Neurochemical Measures: THC levels

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

    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.

  7. Neurochemical Measures: THC-COOH levels

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

    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.

  8. Neurochemical Measures: ketamine/norketamine levels

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

    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.

  9. Genetics

    Time frame: Collected at the screening visit.

    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.

Secondary outcomes

  1. Positive and Negative Symptoms Scale (PANSS)

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

    Positive, negative, and general psychosis symptoms will be assessed using the Positive and Negative Syndrome Scale (PANSS). The PANSS is divided into three sub-scales: Positive Scale (7 items), Negative Scale (7 items), and General Psychopathology Scale (16 items). Each item is scored from 1 to 7 (1=absent, 2=minimum, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme). Scores range from 30 to 210, where higher scores indicate greater symptom severity.

  2. Perceptual Alterations

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

    Perceptual alterations will be measured using the Clinician Administered Dissociative Symptoms Scale (CADSS), a scale consisting of 19 self-report items and 8 clinician-rated items (0 = not at all, 4 = extremely) that we have shown to be sensitive to THC effects. The scale captures alterations in environmental/time/body perception, feelings of unreality, and memory impairment.

  3. Cannabis Subjective Effects

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

    Feeling states associated with cannabis intoxication will be measured using a self-reported visual analog scale of 3 feeling states ("high", "calm and relaxed", and "tired") associated with cannabis effects. Subjects will be asked to score the perceived intensity of these feeling states at that moment on a 100 mm line (0 = not at all, 100 = extremely).

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

  • Brain & Behavior Research Foundation

Registry information

Official study title

An Electrophysiological Examination of CB1 and NMDA Receptors in Humans

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Dec 16, 2019
Registry last updated
Mar 25, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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