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

Cannabis Clinical Trial

Official title:

An Electrophysiological Examination of CB1 and NMDA Receptors in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04199468
• Other study ID #: 2000025927
• Secondary ID: 000
• Status: Completed
• Phase: Phase 1
• Start date: September 24, 2019
• Est. completion date: June 21, 2022

Study information

• Verified date: March 2024
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: June 21, 2022
• Est. primary completion date: June 21, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. 18 to approximately 45 years old

2. 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.

3. Weight of 100 kg (220.46 lbs.) or less (inclusive).

Exclusion Criteria:

1. 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.

2. 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.

3. 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)

4. Positive pregnancy test

Related Conditions & MeSH terms

• Cannabis
• Ketamine

Intervention

Drug:
• Active Delta-9-THC
Active Delta-9-THC (0.015 mg/kg) given intravenously (IV)
• Placebo Delta-9-THC
A placebo dose given intravenously (IV)
• Active Ketamine
Active Ketamine (0.2 mg/kg) given intravenously (IV)
• Placebo Ketamine
A placebo dose given intravenously (IV)

Locations

Country	Name	City	State
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Brain & Behavior Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	EEG Measures 3	The primary EEG outcome 3 will be spectral power (microvolts squared).	0-60 minutes after the onset of drug infusion
Primary	EEG Measures 4	The primary EEG outcome 4 will be Intertrial Coherence (phase locking factor).	0-60 minutes after the onset of drug infusion
Primary	EEG Measures 5	The primary EEG outcome 5 will be neural noise (Lempel Ziv Complexity).	0-60 minutes after the onset of drug infusion
Primary	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)
Primary	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)
Primary	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)
Primary	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	Positive and Negative Symptoms Scale (PANSS)	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.	-60, +70, +120, +240 from baseline (0) (units in minutes).
Secondary	Perceptual Alterations	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.	-60, +70, +120, +240 from baseline (0) (units in minutes).
Secondary	Cannabis Subjective Effects	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).	-60, +70, +120, +240 from baseline (0) (units in minutes).