Using Imaging to Assess Effects of THC on Brain Activity (fNIRS)

July 5, 2022 updated by: A. Eden Evins, Massachusetts General Hospital
This study will assess effects of tetrahydrocannabinol (THC) and THC + alcohol in marijuana users on prefrontal brain activity, using functional near-infrared spectroscopy (fNIRS) during resting state and during memory task performance. Participants will complete fNIRS testing 120 minutes following THC or identical placebo (Phase 2A), or THC/ethanol, THC/placebo ethanol, placebo THC/ethanol, and placebo THC/placebo ethanol (Phase 2B), and oxygenated hemoglobin (HbO) concentration will be measured.

Study Overview

Detailed Description

This study will assess the effects of THC intoxication using dronabinol (synthetic THC) on the oxyhemoglobin (HbO) signal during resting state and task-based activation in the prefrontal cortex (PFC) and resting state connectivity, as well as on neurocognitive task performance and correlations between these measurements and clinical signs of intoxication. Participants will be 150 adults who use marijuana at least monthly (aged 18-55) will be recruited to participate in this study. Participants will be given up to 80 mg of dronabinol, an FDA-approved synthetic form of THC that is used to treat loss of appetite that causes weight loss in people with AIDS. THC is the principle psychoactive drug in marijuana. The study will be conducted in regular cannabis users who present at their first study visit with a positive urine screen for THC metabolites.

Phase 2A. Investigate the effect of THC on fNIRS brain signature and its association with self-reported intoxication, laboratory measures of impairment, and the gold-standard behavioral field test of driving impairment used by law enforcement, the primary classifier.

Phase 2B. Examine potential interaction following co-administration of THC with oral ethanol exposure in healthy volunteers. Phase II is a randomized, double-blind, placebo-controlled, 2 by 2 crossover study of effect of dronabinol, ethanol, and combined dronabinol and ethanol on brain activation and connectivity as measured by fNIRS.

Study Type

Interventional

Enrollment (Actual)

316

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Center for Addiction Medicine, Massachusetts General Hospital, Dept. of Psychiatry

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria General

  1. Men and women aged 18-55 years, inclusive; (for Phase 2B: men and women aged 21-55 years, inclusive)
  2. Competent and willing to provide written informed consent;
  3. Able to communicate in English language.
  4. Regular, at least monthly, marijuana use, confirmed by positive urine screen for THC

    Additional Inclusion Criteria For Phase 2B:

  5. Past consumption of at least two alcoholic beverages in one occasion.
  6. Past co-consumption of alcohol and THC at least once in lifetime with no serious adverse effects.
  7. Weigh more than 100 lbs.

Exclusion Criteria:

General (Phase 2A, 2B 3)

  1. Any unstable, serious medical illness, or cardiovascular disease or events.
  2. New or unstable psychiatric symptoms, schizophrenia, or bipolar I disorder,
  3. Diabetes, cirrhosis, renal failure, Hepatitis C, HIV,
  4. History of syncope without an identified situational stressor, migraines >1x/month, head injury with prolonged unconsciousness (> 24 hours);
  5. Allergy to sesame oil (contained in Marinol pills) or Marinol capsules
  6. Daily use of benzodiazepines or barbiturates, antihistamines, atropine, scopolamine, or other strong anticholinergic agents;
  7. Current pregnancy or lactation, or trying to become pregnant (confirmed by urine pregnancy test)
  8. In the opinion of the investigator, not able to safely participate in this study.

    Additional Exclusion Criteria For Phase 2B:

  9. Currently seeking treatment, in treatment, or in recovery from an alcohol use disorder.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 2A
In a double-blind placebo-controlled, random order cross-over study of single dose dronabinol, participants received dronabinol or identical placebo on two separate study visits in randomized order.
Dronabinol at physician determined doses of 10-80mg designed to produce intoxication.
Other Names:
  • oral THC
Identical in appearance to active dronabinol (overencapsulation of both active and placebo dronabinol)
Other Names:
  • placebo oral THC
Experimental: Phase 2B
In a randomized, double-blind, 4-treatment, 4-period, crossover study with THC or placebo administration and ethanol or placebo administration, participants were randomly assigned to 1 of 4 sequences and received each of the following treatments: placebo dronabinol + placebo ethanol, placebo dronabinol + ethanol, dronabinol + placebo ethanol, & dronabinol + ethanol.
Dronabinol at physician determined doses of 10-80mg designed to produce intoxication.
Other Names:
  • oral THC
Identical in appearance to active dronabinol (overencapsulation of both active and placebo dronabinol)
Other Names:
  • placebo oral THC
Oral Ethanol, dosed to obtain a breath alcohol concentration (BrAC) of approximately 0.05 BrAC (equal to 1-2 standard drinks).
Other Names:
  • oral ethanol
Placebo ethanol will consist of diet soda used in the active ethanol condition with 0.25ml ethanol floated on top to provide the odor of ethanol and blind the study drug.
Other Names:
  • oral placebo ethanol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Concentration of Oxygenated Hemoglobin Between Pre-drug and Post-drug Scans of Patients Completing the N-back Task.
Time Frame: The first Nback scan session was run before dosing (t ≈ -35min). Drug was administered (t = 0min). The second Nback scan session was run at the time of expected peak pharmacokinetic effect (t ≈ 100min). Each scan session was six minutes in duration.

Subjects completed the N-back task before and after receiving a combination of active dronabinol or placebo dronabinol and active ethanol or placebo ethanol. During the task, the fNIRS device was used to capture change in concentration of oxygenated hemoglobin to assess prefrontal brain activity.

Outcomes reflect average change from baseline in HbO concentration over pre-dose scan and average change from baseline in HbO concentration over post-dose scan (expected peak intoxication).

The first Nback scan session was run before dosing (t ≈ -35min). Drug was administered (t = 0min). The second Nback scan session was run at the time of expected peak pharmacokinetic effect (t ≈ 100min). Each scan session was six minutes in duration.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Concentration of Oxygenated Hemoglobin Between Pre-drug and Post-drug Scans During Resting State.
Time Frame: The first resting-state scan session was run before dosing (t ≈ -45min). Drug was administered (t = 0min). The second resting-state scan session was run at the time of expected peak high (t ≈ 90min). Each scan session was six minutes in duration.

Subjects completed resting-state fNIRS scans before and after receiving a combination of active dronabinol or placebo dronabinol and active ethanol or placebo ethanol. During the task, the fNIRS device was used to capture concentration of oxygenated hemoglobin to assess prefrontal brain activity.

Outcomes reflect average change from baseline in HbO concentration over pre-dose scan and average change from baseline in HbO concentration over post-dose scan (expected peak intoxication).

The first resting-state scan session was run before dosing (t ≈ -45min). Drug was administered (t = 0min). The second resting-state scan session was run at the time of expected peak high (t ≈ 90min). Each scan session was six minutes in duration.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Jodi M Gilman, PhD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 5, 2018

Primary Completion (Actual)

January 21, 2021

Study Completion (Actual)

January 21, 2021

Study Registration Dates

First Submitted

July 20, 2018

First Submitted That Met QC Criteria

August 29, 2018

First Posted (Actual)

August 31, 2018

Study Record Updates

Last Update Posted (Actual)

July 28, 2022

Last Update Submitted That Met QC Criteria

July 5, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Individual participant data (IPD) will not be available

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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