Using Imaging to Assess Effects of THC on Brain Activity

NCT03655717 | Completed Results

• 2 other identifiers: 2015P001516R42DA043977
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 1

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.

Conditions

Intoxication Alcohol; Intoxication THC; Intoxication Combined Alcohol THC

Keywords

fNIRS; THC; Intoxication

Outcome Measures

Primary Outcomes (1)

• 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.

Other Outcomes (1)

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

  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.

Study Arms (2)

Phase 2A

EXPERIMENTAL

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.

Drug: Dronabinol; Drug: Placebo dronabinol

Phase 2B

EXPERIMENTAL

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.

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

Interventions

Dronabinol DRUG

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

Also known as: oral THC

Phase 2A; Phase 2B

Ethanol DRUG

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

Also known as: oral ethanol

Phase 2B

Placebo dronabinol DRUG

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

Also known as: placebo oral THC

Phase 2A; Phase 2B

Placebo ethanol DRUG

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.

Also known as: oral placebo ethanol

Phase 2B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• Currently seeking treatment, in treatment, or in recovery from an alcohol use disorder.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

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

Boston, Massachusetts, 02114, United States

Location

Related Publications (3)

• Berchansky M, Evins AE, Evohr B, Himmelsbach Z, Pachas GN, Karunakaran KD, Laufer Goldshtein B, Ozana N, Gilman JM. Detection of Delta9-Tetrahydrocannabinol Impairment Using Resting-State Functional Near-Infrared Spectroscopy: A Randomized Clinical Trial. JAMA Netw Open. 2026 Jan 2;9(1):e2556647. doi: 10.1001/jamanetworkopen.2025.56647.

  PMID: 41615687 DERIVED

• Karunakaran KD, Pascale M, Ozana N, Potter K, Pachas GN, Evins AE, Gilman JM. Intoxication due to Delta9-tetrahydrocannabinol is characterized by disrupted prefrontal cortex activity. Neuropsychopharmacology. 2024 Aug;49(9):1481-1490. doi: 10.1038/s41386-024-01876-5. Epub 2024 May 7.

  PMID: 38714786 DERIVED

• 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.

  PMID: 34999737 DERIVED

MeSH Terms

Conditions

Alcoholic Intoxication

Interventions

Dronabinol; Ethanol

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Alcohols

Limitations and Caveats

After reviewing and updating the study record to appropriately reflect the approved protocol, it was determined that the entry for Study Phase is best represented as N/A, rather than Phase 4, as the purpose of the study is NOT to investigate the safety or efficacy of the drug. This study seeks to use dronabinol only to probe and describe brain physiology. The change from Phase 4 to N/A more accurately and reflects the IRB approved protocol, and the aims of the grant that funds the research.

Results Point of Contact

• Title: Dr. Jodi Gilman
• Organization: Massachusetts General Hospital

jgilman1@mgh.harvard.edu

617-643-7293

Study Officials

• A. Eden Evins, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Jodi M Gilman, PhD

  Massachusetts General Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Addiction Medicine

Model Details: 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.

Study Record Dates

• First Submitted: July 20, 2018
• First Posted: August 31, 2018
• Study Start: November 5, 2018
• Primary Completion: January 21, 2021
• Study Completion: January 21, 2021
• Last Updated: July 28, 2022
• Results First Posted: July 28, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)