Using Imaging to Assess Effects of THC on Brain Activity

Not Applicable

Completed

Conditions: Intoxication Alcohol
Intoxication THC
Intoxication Combined Alcohol THC

Interventions: Drug: Dronabinol
Drug: Ethanol
Drug: Placebo dronabinol
Drug: Placebo ethanol

Registration Number: NCT03655717

Lead Sponsor: Massachusetts General Hospital

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 316

Inclusion Criteria

Not provided

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Phase 2A	Dronabinol	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.
Phase 2B	Placebo dronabinol	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.
Phase 2B	Placebo ethanol	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.
Phase 2A	Placebo dronabinol	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.
Phase 2B	Ethanol	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.
Phase 2B	Dronabinol	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.

Primary Outcome Measures

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

Secondary Outcome Measures