Clinical trial NCT03655717: Using Imaging to Assess Effects of THC on Brain Activity
Official title: Using Imaging to Assess Effects of THC on Brain Activity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intoxication Alcohol
Intoxication THC
Intoxication Combined Alcohol THC
Keywords: fNIRS
THC
Intoxication
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2018-08-31
Enrollment: 316
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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.

Primary outcomes:
measure: Change in Concentration of Oxygenated Hemoglobin Between Pre-drug and Post-drug Scans of Patients Completing the N-back Task.
timeFrame: 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.
Secondary outcomes:
Other outcomes:
measure: Change in Concentration of Oxygenated Hemoglobin Between Pre-drug and Post-drug Scans During Resting State.
timeFrame: 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.
Locations:
city: Boston
country: United States
facility: Center for Addiction Medicine, Massachusetts General Hospital, Dept. of Psychiatry
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: A. Eden Evins, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Jodi M Gilman, PhD
role: STUDY_DIRECTOR
References:
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.