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

Primary Purpose

Intoxication Alcohol, Intoxication THC, Intoxication Combined Alcohol THC

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Dronabinol

Ethanol

Placebo dronabinol

Placebo ethanol

About this trial

This is an interventional basic science trial for Intoxication Alcohol focused on measuring fNIRS, THC, Intoxication

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria General

Men and women aged 18-55 years, inclusive; (for Phase 2B: men and women aged 21-55 years, inclusive)
Competent and willing to provide written informed consent;
Able to communicate in English language.
Regular, at least monthly, marijuana use, confirmed by positive urine screen for THC
Additional Inclusion Criteria For Phase 2B:
Past consumption of at least two alcoholic beverages in one occasion.
Past co-consumption of alcohol and THC at least once in lifetime with no serious adverse effects.
Weigh more than 100 lbs.

Exclusion Criteria:

General (Phase 2A, 2B 3)

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

Sites / Locations

Center for Addiction Medicine, Massachusetts General Hospital, Dept. of Psychiatry

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Phase 2A

Phase 2B

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change in Concentration of Oxygenated Hemoglobin Between Pre-drug and Post-drug Scans of Patients Completing the N-back Task.

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).

Secondary Outcome Measures

Full Information

NCT ID

NCT03655717

First Posted

July 20, 2018

Last Updated

July 5, 2022

Sponsor

Massachusetts General Hospital

Collaborators

National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT03655717

Brief Title

Using Imaging to Assess Effects of THC on Brain Activity

Acronym

fNIRS

Official Title

Using Imaging to Assess Effects of THC on Brain Activity

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

November 5, 2018 (Actual)

Primary Completion Date

January 21, 2021 (Actual)

Study Completion Date

January 21, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Intoxication Alcohol, Intoxication THC, Intoxication Combined Alcohol THC

Keywords

fNIRS, THC, Intoxication

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

In Phase 2A, 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. In Phase 2B, 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 24 sequences of each of the following treatments: placebo dronabinol and placebo ethanol, placebo dronabinol and ethanol, dronabinol and placebo ethanol, and dronabinol and ethanol.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Subjects will be randomly assigned to one of the possible orders according to a randomization schedule generated by the study staff using a random number generator and computer program. The Massachusetts General Hospital (MGH) research pharmacy will generate a blinded randomization code for order of dosing and will dispense blinded drug in the dose ordered and identical placebo for use on separate study days. Ethanol or placebo drink will be prepared by a member of the research unit staff not otherwise associated with study visits.

Allocation

Randomized

Enrollment

316 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 2A

Arm Type

Experimental

Arm Description

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.

Arm Title

Phase 2B

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Dronabinol

Other Intervention Name(s)

oral THC

Intervention Description

Dronabinol at physician determined doses of 10-80mg designed to produce intoxication.

Intervention Type

Drug

Intervention Name(s)

Ethanol

Other Intervention Name(s)

oral ethanol

Intervention Description

Oral Ethanol, dosed to obtain a breath alcohol concentration (BrAC) of approximately 0.05 BrAC (equal to 1-2 standard drinks).

Intervention Type

Drug

Intervention Name(s)

Placebo dronabinol

Other Intervention Name(s)

placebo oral THC

Intervention Description

Identical in appearance to active dronabinol (overencapsulation of both active and placebo dronabinol)

Intervention Type

Drug

Intervention Name(s)

Placebo ethanol

Other Intervention Name(s)

oral placebo ethanol

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in Concentration of Oxygenated Hemoglobin Between Pre-drug and Post-drug Scans of Patients Completing the N-back Task.

Description

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.

Other Pre-specified Outcome Measures:

Title

Change in Concentration of Oxygenated Hemoglobin Between Pre-drug and Post-drug Scans During Resting State.

Description

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).

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria General Men and women aged 18-55 years, inclusive; (for Phase 2B: men and women aged 21-55 years, inclusive) Competent and willing to provide written informed consent; Able to communicate in English language. Regular, at least monthly, marijuana use, confirmed by positive urine screen for THC Additional Inclusion Criteria For Phase 2B: Past consumption of at least two alcoholic beverages in one occasion. Past co-consumption of alcohol and THC at least once in lifetime with no serious adverse effects. Weigh more than 100 lbs. Exclusion Criteria: General (Phase 2A, 2B 3) Any unstable, serious medical illness, or cardiovascular disease or events. New or unstable psychiatric symptoms, schizophrenia, or bipolar I disorder, Diabetes, cirrhosis, renal failure, Hepatitis C, HIV, History of syncope without an identified situational stressor, migraines >1x/month, head injury with prolonged unconsciousness (> 24 hours); Allergy to sesame oil (contained in Marinol pills) or Marinol capsules Daily use of benzodiazepines or barbiturates, antihistamines, atropine, scopolamine, or other strong anticholinergic agents; Current pregnancy or lactation, or trying to become pregnant (confirmed by urine pregnancy test) In the opinion of the investigator, not able to safely participate in this study. Additional Exclusion Criteria For Phase 2B: Currently seeking treatment, in treatment, or in recovery from an alcohol use disorder.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

A. Eden Evins, MD, MPH

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jodi M Gilman, PhD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Center for Addiction Medicine, Massachusetts General Hospital, Dept. of Psychiatry

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Individual participant data (IPD) will not be available

Citations:

PubMed Identifier

34999737

Citation

Gilman JM, Schmitt WA, Potter K, Kendzior B, Pachas GN, Hickey S, Makary M, Huestis MA, Evins AE. Identification of ∆9-tetrahydrocannabinol (THC) impairment using functional brain imaging. Neuropsychopharmacology. 2022 Mar;47(4):944-952. doi: 10.1038/s41386-021-01259-0. Epub 2022 Jan 8. Erratum In: Neuropsychopharmacology. 2022 Feb 28;:

Results Reference

derived

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Using Imaging to Assess Effects of THC on Brain Activity

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