Acute Effects of THC in Older Adult (THC-Aging)

The primary objective of this study is to determine if increasing age confers greater vulnerability to the acute A) cognitive (e.g., memory, attention, psychomotor function), B) subjective (e.g., anxiogenic and rewarding effects), and C) cardiovascular (heart rate and blood pressure), effects of THC in adults > 21 years old. The secondary aims of the study are to explore age-related acute effects of THC on electrophysiological indices of information processing (e.g., auditory steady-state response (ASSR), oddball paradigm [P300], and resting state cortical noise) and to determine age-related differences in the metabolism of THC.

Study Overview

• Status: Recruiting
• Conditions: Age-related Cognitive Decline
• Intervention / Treatment: Drug: Placebo; Drug: Delta-9-THC Low Dose; Drug: Delta-9-THC Medium Dose

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Deepak C D'Souza; Phone Number: 12594 203-932-5711; Email: deepak.douza@yale.edu
• Study Contact Backup: Name: Ashley Schnakenberg Martin, PhD; Email: ashley.martin@yale.edu

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Recruiting
      • VA Connecticut Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

• Ability to provide informed consent
• No history (current or past) of unstable or serious medical, neurological or psychiatric conditions.
• High school education or greater
• No positive pregnancy test and/or lactation/ planning to nurse while in this study
• English speaking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Control: Small amount of alcohol administered intravenously (quarter teaspoon), with no delta-9-THC, over 20 minutes.	Drug: Placebo; Small amount of sterile ethanol (1-2 mLs), with no THC, administered intravenously over 20 minutes.
Active Comparator: Delta-9-THC Very Low Dose; Active delta-9-THC administered intravenously over 20 minutes.	Drug: Delta-9-THC Low Dose; Active Delta-9-THC administered intravenously over 20 minutes.
Active Comparator: Delta-9-THC Medium Dose; Active delta-9-THC administered intravenously over 20 minutes.	Drug: Delta-9-THC Medium Dose; Active Delta-9-THC administered intravenously over 20 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rey Auditory Verbal Learning Task (RAVLT) total immediate recall	The task consists of 5 trials, an interference list, free delayed recall, and recognition.	Each test day will be split into two drug administration sessions. The RAVLT will be administered approximately 25 minutes after each drug administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Scale (VAS)	Various feeling states will be measured using a self-reported visual analog scale of feeling states (ex: "calm and relaxed", and "tired") associated with drug administration. Subjects will be asked to score the perceived intensity of these feeling states at that moment on a 100 mm line (0 = not at all, 100 = extremely). A higher score reflects a positive response.	-60 minutes, 20 minutes, 60 minutes, 120 minutes, 170 minutes, 210 minutes, 270 minutes, 300 minutes, 360 minutes, 420 minutes after the start of the initial THC/placebo drug infusion.

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Deepak C D'Souza, MD, Yale University School of Medicine; VA Connecticut Healthcare System; Principal Investigator: Ashley Schnakenberg Martin, PhD, Yale University School of Medicine; VA Connecticut Healthcare System

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: January 21, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): April 29, 2025

Study Record Updates

• Last Update Posted (Actual): August 18, 2025
• Last Update Submitted That Met QC Criteria: August 14, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: 2000038388; 1R21DA058138-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No