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

Mass General Brigham

Status: Completed

Conditions: Intoxication Combined Alcohol THC; Intoxication THC; Intoxication Alcohol

Treatments: Drug: Dronabinol; Drug: Placebo dronabinol; Drug: Ethanol; Drug: Placebo ethanol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03655717

R42DA043977 (U.S. NIH Grant/Contract)

2015P001516

Details and patient eligibility

About

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.

Full 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.

Enrollment: 316 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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316 participants in 2 patient groups

Phase 2A

Experimental group

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.

Treatment:

Drug: Placebo dronabinol

Drug: Dronabinol

Phase 2B

Experimental group

Description:

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.

Treatment:

Drug: Placebo ethanol

Drug: Ethanol

Drug: Placebo dronabinol

Drug: Dronabinol