CannabisPhase 1NCT04199468

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

A Phase 1 study testing Active Delta-9-THC and Active Ketamine in people with Cannabis and Ketamine, run by Yale University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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… Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Cannabis, Ketamine
What is being tested?: Active Delta-9-THC and Active Ketamine
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 22 participants
Where: 1 siteUnited States
Study dates: 24 Sep 2019to 21 Jun 2022
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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).

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

VA Connecticut Healthcare System
West Haven, Connecticut, 06516

Other trials in United States

About this study

Official title: An Electrophysiological Examination of CB1 and NMDA Receptors in Humans

Read the detailed 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.

Conditions: Cannabis, Ketamine
Being tested: Active Delta-9-THC, Placebo Delta-9-THC, Active Ketamine, Placebo Ketamine
Medical subject headings: Marijuana Abuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT04199468
Study group	Role	What they receive
Active Delta-9-THC and Placebo Ketamine	Experimental	Active IV Delta-9-THC and Placebo Ketamine Receives: Drug: Active Delta-9-THC; Drug: Placebo Ketamine
Active Delta-9-THC and Active Ketamine	Experimental	Active IV Delta-9-THC and Active Ketamine Receives: Drug: Active Delta-9-THC; Drug: Active Ketamine
Placebo Delta-9-THC and Placebo Ketamine	Experimental	IV Placebo Delta-9-THC and Placebo Ketamine Receives: Drug: Placebo Delta-9-THC; Drug: Placebo Ketamine
Placebo Delta-9-THC and Active Ketamine	Experimental	IV Placebo Delta-9-THC and Active Ketamine Receives: Drug: Placebo Delta-9-THC; Drug: Active Ketamine

What is being measured

The primary outcome is the main question the study is designed to answer.

EEG Measures 1
The primary EEG outcome 1 will be EEG event related potential voltage amplitude (microvolts).
Measured: 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).
Measured: 0-60 minutes after the onset of drug infusion
EEG Measures 3
The primary EEG outcome 3 will be spectral power (microvolts squared).
Measured: 0-60 minutes after the onset of drug infusion
EEG Measures 4
The primary EEG outcome 4 will be Intertrial Coherence (phase locking factor).
Measured: 0-60 minutes after the onset of drug infusion
EEG Measures 5
The primary EEG outcome 5 will be neural noise (Lempel Ziv Complexity).
Measured: 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.
Measured: -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.
Measured: -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.
Measured: -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.
Measured: Collected at the screening visit.

Secondary outcomes (3)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Sep 201921 Jun 2022

First posted16 Dec 2019
Study start24 Sep 2019
Primary completion21 Jun 2022
Study completion21 Jun 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for CannabisStudies of the same condition, open and under way.
More trials run by Yale UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04199468
Sponsor's protocol ID: 2000025927
Other IDs: 000
Status last verified: Mar 2024
First submitted: 21 Oct 2019
Last updated: 25 Mar 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Substance Use and Media Preferences
Substance Use Behavior, Cannabis Intoxication
RecruitingObservational study
Study of an Oral Fluid Testing Approach
Cannabis Use, Cannabis Intoxication
RecruitingPhase 3
Nabilone for Agitation Blinded Intervention Trial
Alzheimer Disease, Agitation
Not yet recruitingPhase 1
PK/PD of Vaping THC-containing Liquids vs. Smoked Cannabis
Cigarette Smoking-Related Carcinoma
Active, not recruitingPhase 1
Psilocybin-assisted Treatment for Cannabis Use Disorder
Cannabis Use Disorder

All Cannabis trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Electrophysiological Examination of CB1 and NMDA Receptors in Humans
ClinicalTrials.gov ID: NCT04199468
Acronym / sponsor ID: 2000025927
Conditions: Cannabis, Ketamine
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: Brain & Behavior Research Foundation
Study start: 24 Sep 2019 (actual)
Primary completion: 21 Jun 2022 (actual)
Study completion: 21 Jun 2022 (actual)
First posted: 16 Dec 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Active Delta-9-THC and Placebo Ketamine	Experimental	Drug: Active Delta-9-THC, Drug: Placebo KetamineActive IV Delta-9-THC and Placebo Ketamine
Active Delta-9-THC and Active Ketamine	Experimental	Drug: Active Delta-9-THC, Drug: Active KetamineActive IV Delta-9-THC and Active Ketamine
Placebo Delta-9-THC and Placebo Ketamine	Experimental	Drug: Placebo Delta-9-THC, Drug: Placebo KetamineIV Placebo Delta-9-THC and Placebo Ketamine
Placebo Delta-9-THC and Active Ketamine	Experimental	Drug: Placebo Delta-9-THC, Drug: Active KetamineIV Placebo Delta-9-THC and Active Ketamine

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

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).

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Active Delta-9-THCActive Delta-9-THC (0.015 mg/kg) given intravenously (IV)	Drug	Active Delta-9-THC and Active Ketamine, Active Delta-9-THC and Placebo Ketamine
Placebo Delta-9-THCA placebo dose given intravenously (IV)	Drug	Placebo Delta-9-THC and Active Ketamine, Placebo Delta-9-THC and Placebo Ketamine
Active KetamineActive Ketamine (0.2 mg/kg) given intravenously (IV)	Drug	Active Delta-9-THC and Active Ketamine, Placebo Delta-9-THC and Active Ketamine
Placebo KetamineA placebo dose given intravenously (IV)	Drug	Active Delta-9-THC and Placebo Ketamine, Placebo Delta-9-THC and Placebo Ketamine

Primary outcome

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).
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).
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).
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).
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).
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.
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.
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.
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.

3 secondary outcomes

Positive and Negative Symptoms Scale (PANSS)
Time frame: -60, +70, +120, +240 from baseline (0) (units in minutes).
Perceptual Alterations
Time frame: -60, +70, +120, +240 from baseline (0) (units in minutes).
Cannabis Subjective Effects
Time frame: -60, +70, +120, +240 from baseline (0) (units in minutes).

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2024.

Related trials for Cannabis

Not yet recruiting
Substance Use and Media Preferences
Substance Use Behavior, Cannabis Intoxication
RecruitingObservational study
Study of an Oral Fluid Testing Approach
Cannabis Use, Cannabis Intoxication
RecruitingPhase 3
Nabilone for Agitation Blinded Intervention Trial
Alzheimer Disease, Agitation
Not yet recruitingPhase 1
PK/PD of Vaping THC-containing Liquids vs. Smoked Cannabis
Cigarette Smoking-Related Carcinoma
Active, not recruitingPhase 1
Psilocybin-assisted Treatment for Cannabis Use Disorder
Cannabis Use Disorder

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Rajiv Radhakrishnan, M.D. principal investigator

Yale University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Active Delta-9-THC and Active Ketamine in people with Cannabis and Ketamine, run by Yale University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

EEG Measures 1 (time frame: 0-60 minutes after the onset of drug infusion). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04199468.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2024.