Using Imaging to Assess Effects of THC on Brain Activity

Intoxication Alcohol Clinical Trial

— fNIRS  

Official title:

Using Imaging to Assess Effects of THC on Brain Activity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03655717
• Other study ID #: 2015P001516
• Secondary ID: R42DA043977
• Status: Completed
• Phase: N/A
• Start date: November 5, 2018
• Est. completion date: January 21, 2021

Study information

• Verified date: July 2022
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 316
• Est. completion date: January 21, 2021
• Est. primary completion date: January 21, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alcoholic Intoxication
• Intoxication Alcohol
• Intoxication Combined Alcohol THC
• Intoxication THC

Intervention

Drug:
• Dronabinol
Dronabinol at physician determined doses of 10-80mg designed to produce intoxication.
• Ethanol
Oral Ethanol, dosed to obtain a breath alcohol concentration (BrAC) of approximately 0.05 BrAC (equal to 1-2 standard drinks).
• Placebo dronabinol
Identical in appearance to active dronabinol (overencapsulation of both active and placebo dronabinol)
• Placebo 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.

Locations

Country	Name	City	State
United States	Center for Addiction Medicine, Massachusetts General Hospital, Dept. of Psychiatry	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Concentration of Oxygenated Hemoglobin Between Pre-drug and Post-drug Scans During Resting State.	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.
Primary	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).	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.