Acute Effects of Cannabis on Cognition and Affect

NCT07296874 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 25-0421
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine how a moderate dose of THC affects mood, stress responses, and cognitive functioning in regular cannabis users. The study uses a double-blind, placebo-controlled, crossover design, meaning each participant will complete two sessions. Specifically, each participant will be given active cannabis (20 mg THC) in one session, and placebo in the other session. The order will be randomized across participants, so half will receive cannabis first, and the other half will receive placebo first. Ninety adults who use cannabis at least weekly will be recruited from the local community. After an online screening survey, eligible participants will attend a laboratory visit where the participants will provide informed consent and complete saliva and urine drug tests to confirm recent abstinence from cannabis and absence of other drugs. Participants who pass screening will complete baseline questionnaires of cannabis use patterns, depression, anxiety, ADHD symptoms, emotion regulation, affect, and demographic information. Cannabis and placebo materials (obtained from NIDA) will be vaporized using a Volcano vaporizer device. Participants will inhale the vapor under supervision, and neither the participant nor the researcher assessing outcomes will know which product is administered. After vaping, participants will complete repeated mood ratings, saliva samples, and a battery of cognitive tests assessing executive functions like planning, inhibition, working memory, and cognitive flexibility. Participants will also complete a standardized stress challenge (the Maastricht Acute Stress Test), which involves repeated trials of placing their hand in cold water and doing challenging mental math, followed by additional mood ratings and saliva samples. The participants will then watch a nature video and report their feelings of awe and affect. At the end of each session, participants will remain in a supervised room with entertainment and snacks until at least four hours have passed since vaping and the participants report feeling sober. The participants will then return for a second session with the opposite study condition (THC or placebo) one week later. Both sessions follow the same procedures. Participants are fully debriefed after completing the study.

Conditions

Cannabis Use

Keywords

Cannabis; THC; Executive functioning; Stress reactivity; Affect

Outcome Measures

Primary Outcomes (29)

• Event-Based Prospective Memory - Number of Difficulty Ratings Provided

  Event-based prospective memory will be assessed using a difficulty ratings task. At the beginning of the session, participants will be asked to try to remember to rate how difficult they found each test immediately after it is completed, using a 0 (not at all difficult) to 10 (extremely difficult) scale. The primary outcome of interest is the number of difficulty ratings they remember to provide.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Time-Based Prospective Memory - Token Task

  Time-based prospective memory will be assessed using a token task. Participants will be instructed to try to remember to request a token every 10 minutes. A clock will be positioned face down on the table for them to refer to the time, and we will record their clock-checking behavior. The primary outcome is the number of times they remember to request the token, out of the total time of the cognitive assessment session.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Flexibility - N-back Test Accuracy

  Cognitive flexibility and working memory updating will be assessed using the N-back test. Participants are shown strings of letters one at a time and are instructed to indicate whenever a letter appears that matches the letter shown two trials earlier. Outcomes include the percentage of correct responses made (i.e., the number of times they correctly recognize that the current letter matches the one from two trials before, etc.).

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Flexibility - N-back Reaction Time

  Cognitive flexibility and working memory updating will be assessed using the N-back test. Participants are shown strings of letters one at a time and are instructed to indicate whenever a letter appears that matches the letter shown two trials earlier. Outcomes include the mean reaction time (milliseconds) for correct responses on the task.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Flexibility - N-back ERP

  Cognitive flexibility and working memory updating will be assessed using the N-back test. Participants are shown strings of letters one at a time and are instructed to indicate whenever a letter appears that matches the letter shown two trials earlier. The Muse S Athena wearable EEG device will capture time-locked event-related potential data during this task.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Verbal Working Memory - Digit Span Backwards

  Verbal working memory will be assessed using the Backwards portion of the Digit Span Test. For this test, participants are read lists of digits (of increasing lengths) and are asked to recall them in reverse order. The primary outcome of interest is the total number of correct trials.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Planning - Tower Test Total Achievement Score

  Planning and problem-solving abilities will be assessed using the Tower Test. Participants are asked to move disks to reach a specified end configuration in as few moves as possible. They can move only one disk at a time and cannot place a larger disk on top of a smaller disk. Outcomes on this task include the Total Achievement Score across the tower problems, which reflects planning effectiveness.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Planning - Tower Test Rule Violations

  Planning and problem-solving abilities will be assessed using the Tower Test. Participants are asked to move disks to reach a specified end configuration in as few moves as possible. They can move only one disk at a time and cannot place a larger disk on top of a smaller disk. Outcomes on this task include the number of rule violations (e.g., moving stacking a larger disk on top of a smaller one).

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Planning - Zoo Maps Test Total Achieved Score

  Planning and strategic thinking will be assessed using the Zoo Maps Test. Participants must plan a route through a provided zoo map while adhering to specified rules and efficiency constraints. For example, they may be instructed to start at the entrance, end at the picnic area, and use the designated paths only once. Outcomes on this task include the total achieved score, representing accuracy when generating a self-directed route under the provided constraints.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Planning - Zoo Maps Test Rule Violations

  Planning and strategic thinking will be assessed using the Zoo Maps Test. Participants must plan a route through a provided zoo map while adhering to specified rules and efficiency constraints. For example, they may be instructed to start at the entrance, end at the picnic area, and use the designated paths only once. Outcomes on this task include the number of rule violations on the task.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Inhibitory Control - Stroop Test Interference Score

  Inhibitory control will be assessed using the Stroop test. Participants will be shown words whose letters are in a specific color (e.g., the word "blue" in red letters. They will be tasked with naming the color of the word, which may be incongruent with the word itself. Outcomes on this task include the interference score, which reflects the difference in reaction times between the incongruent and congruent trials.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Inhibitory Control - Stroop Test Accuracy

  Inhibitory control will be assessed using the Stroop test. Participants will be shown words whose letters are in a specific color (e.g., the word "blue" in red letters. They will be tasked with naming the color of the word, which may be incongruent with the word itself. Outcomes on this task include the percentage of correct responses on incongruent trials.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Inhibitory Control - Stroop Test ERP

  Inhibitory control will be assessed using the Stroop test. Participants will be shown words whose letters are in a specific color (e.g., the word "blue" in red letters. They will be tasked with naming the color of the word, which may be incongruent with the word itself. The Muse S Athena wearable EEG device will capture time-locked event-related potential data during this task.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Inhibitory Control - Flanker Test Interference Score

  Inhibitory control and attention will be assessed using the Flanker Test. Participants will respond to a central target stimulus (e.g., an arrow pointing in one direction) while ignoring surrounding distractor stimuli, that may be either congruent (e.g., an arrow pointing the same way) or incongruent (e.g., an arrow pointing the opposite way). Outcomes on this task include the interference score, which is the difference in reaction time between incongruent and congruent trials.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Inhibitory Control - Flanker Test Accuracy

  Inhibitory control and attention will be assessed using the Flanker Test. Participants will respond to a central target stimulus (e.g., an arrow pointing in one direction) while ignoring surrounding distractor stimuli, that may be either congruent (e.g., an arrow pointing the same way) or incongruent (e.g., an arrow pointing the opposite way). Outcomes on this task include the percentage of correct responses across trial types.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Inhibitory Control - Flanker Test ERP

  Inhibitory control and attention will be assessed using the Flanker Test. Participants will respond to a central target stimulus (e.g., an arrow pointing in one direction) while ignoring surrounding distractor stimuli, that may be either congruent (e.g., an arrow pointing the same way) or incongruent (e.g., an arrow pointing the opposite way). The Muse S Athena wearable EEG device will capture time-locked event-related potential data during this task.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Control - Oddball Task Target Detection Accuracy

  Cognitive control and sustained attention will be assessed using the Oddball Task. Participants will be asked to tap the screen when they see an infrequent red ball stimulus, and refrain from tapping when they see a green ball stimulus. Outcomes include the percentage of correctly identified target stimuli.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Control - Oddball Task Target Reaction Time

  Cognitive control and sustained attention will be assessed using the Oddball Task. Participants will be asked to tap the screen when they see an infrequent red ball stimulus, and refrain from tapping when they see a green ball stimulus. Outcomes include the mean reaction time (milliseconds) for responses to target stimuli.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Control - Oddball Task ERP

  Cognitive control and sustained attention will be assessed using the Oddball Task. Participants will be asked to tap the screen when they see an infrequent red ball stimulus, and refrain from tapping when they see a green ball stimulus. The Muse S Athena wearable EEG device will capture time-locked event-related potential data during this task.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Flexibility - Wisconsin Card Sorting Test Perseverative Errors

  Cognitive flexibility (attentional set-shifting) will be assessed using the Wisconsin Card Sorting Task (WCST). Participants will sort cards of various shapes, colors, and numbers to match an undisclosed rule. After each card placement, participants will receive either "correct" or "incorrect" feedback to help them deduce the sorting rule. The sorting rule will periodically and unpredictably change (typically after a series of correct responses), and the participant must then infer the new rule. Outcomes on this task include the number of perseverative errors (i.e., failure to switch sorting strategies when the old sorting rule becomes incorrect).

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Flexibility - Wisconsin Card Sorting Test Categories Completed

  Cognitive flexibility (attentional set-shifting) will be assessed using the Wisconsin Card Sorting Task (WCST). Participants will sort cards of various shapes, colors, and numbers to match an undisclosed rule. After each card placement, participants will receive either "correct" or "incorrect" feedback to help them deduce the sorting rule. The sorting rule will periodically and unpredictably change (typically after a series of correct responses), and the participant must then infer the new rule. Outcomes on this task include the total number of sorting categories correctly completed.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Flexibility - Wisconsin Card Sorting Test Failure-to-Maintain-Set Errors

  Cognitive flexibility (attentional set-shifting) will be assessed using the Wisconsin Card Sorting Task (WCST). Participants will sort cards of various shapes, colors, and numbers to match an undisclosed rule. After each card placement, participants will receive either "correct" or "incorrect" feedback to help them deduce the sorting rule. The sorting rule will periodically and unpredictably change (typically after a series of correct responses), and the participant must then infer the new rule. Outcomes on this task include the number of errors reflecting a breakdown in sustained performance (e.g., not following the correct sorting rule after having learned it and without feedback indicating the rule has changed).

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Flexibility - Verbal Fluency, Category Switching Fluency

  Cognitive flexibility (category switching) will be assessed using the verbal fluency category switching task. Participants will be given two categories (e.g., fruits and furniture) and be asked to generate words that belong to those categories, in alternating order, within a time limit of 60 seconds. Outcomes on this task include the category fluency score, which is the number of correct words generated.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cognitive Flexibility - Verbal Fluency, Category Switching Accuracy

  Cognitive flexibility (category switching) will be assessed using the verbal fluency category switching task. Participants will be given two categories (e.g., fruits and furniture) and be asked to generate words that belong to those categories, in alternating order, within a time limit of 60 seconds. Outcomes on this task include category switching accuracy, which is the number of correct switches between the categories.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Stressor Challenge - Maastricht Acute Stress Test Subjective Pain Ratings

  Participants will complete an acute stress challenge, involving alternating trials of a physical stressor (placing their hand in a cooler of cold water) and a cognitive stressor (mental arithmetic). Outcomes on this test include subjective pain ratings, which are collected after each cold water trial on a 0 (not at all painful) to 10 (extremely painful) scale.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Stressor Challenge - Maastricht Acute Stress Test Subjective Stress Ratings

  Participants will complete an acute stress challenge, involving alternating trials of a physical stressor (placing their hand in a cooler of cold water) and a cognitive stressor (mental arithmetic). Outcomes on this test include subjective stress ratings, which are collected after each mental math trial on a 0 (not at all stressed) to 10 (extremely stressed) scale.

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• EEG Power

  The Muse S Athena wearable EEG device will be worn by participants for the duration of the session, up until they are left to relax and sober up at the end of the session. The EEG device will be continuously recording, to allow for later quantification of power (e.g., theta, gamma, etc.) using spectral density analysis.

  This outcome will be continuously assessed during both sessions, from baseline (i.e., during the testing session but before treatment) through two hours post-treatment.

• Awe Ratings

  Participants will complete ratings of awe after watching a brief (\~20 minute) nature video.

  This outcome will be assessed during both sessions, within two hours post-treatment.

• Connectedness to Nature Ratings

  Participants will complete ratings of their feelings of connectedness to nature after watching a brief (\~20 minute) nature video.

  This outcome will be assessed during both sessions, within two hours post-treatment.

Secondary Outcomes (24)

• Event-Based Prospective Memory - Difficulty Ratings

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Time-Based Prospective Memory - Token Task Clock-Checking

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Planning - Tower Test Time to Completion

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Cogntiive Flexibility - Verbal Fluency, Category Switching Errors

  This outcome will be assessed during both sessions, within 90 minutes post-treatment.

• Baseline (T0) Intoxication Rating

  This outcome will be assessed during both sessions at baseline (i.e., during the testing session but before treatment).

Other Outcomes (14)

• Cannabis Consumption Patterns

  This outcome will be assessed at baseline (i.e., during the testing session but before treatment).

• Drug Screen

  This outcome will be assessed during both sessions at baseline (i.e., during the testing session but before treatment).

• Electrodermal Activity

  This outcome will be continuously assessed during both sessions from before drug/placebo administration to immediately before they leave the lab (approximately 5 hours).

Study Arms (2)

THC -> Placebo

EXPERIMENTAL

Participants will inhale vapor from .17 grams of cannabis containing 11.86% THC (20mg THC total) during the first session. They will inhale vapor from a placebo product during the second session.

Drug: THC 20mg; Drug: Placebo

Placebo -> THC

EXPERIMENTAL

Participants will inhale vapor from a placebo product during the first session. They will inhale vapor from .17 grams of cannabis containing 11.86% THC (20mg THC total) during the second session.

Drug: THC 20mg; Drug: Placebo

Interventions

THC 20mg DRUG

20 mg THC delivered by vaporizing 0.17 g of 11.86% THC cannabis flower obtained from NIDA, using a Volcano vaporizer.

Placebo -> THC; THC -> Placebo

Placebo DRUG

Placebo obtained from NIDA and vaporized using a Volcano vaporizer.

Placebo -> THC; THC -> Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• be 21 years of age or older
• be fluent in English
• use of cannabis at least once a week for at least one year
• inhalation as their typical method of administration
• be willing to abstain from cannabis on the day of their scheduled testing session

You may not qualify if:

• neurological conditions (e.g., neurodegenerative disorders, severe head injury, multiple concussions)
• serious psychiatric conditions (e.g., psychosis, bipolar disorder)
• family history of psychosis
• intellectual disabilities or learning disorders (e.g., dyslexia)
• chronic medical conditions that affect cognition or increase risk of cannabis use or exposure to cold water (e.g., heart disease, diabetes, Reynaud's disease, history of frostbite, peripheral neuropathy, history of fainting or seizures, fractures or wounds on both hands or wrists),
• heart disease
• BMI \> 34
• pregnant or lactating
• use of illicit drugs in past 6 months
• heavy use of alcohol (drinking \>4 drinks \>4 times per week)
• nicotine/tobacco use
• have experienced a severe adverse reaction to cannabis (e.g., panic attack, psychosis)

Sponsors & Collaborators

• Washington State University: lead

Study Sites (1)

Washington State University

Pullman, Washington, 99163, United States

Location

MeSH Terms

Conditions

Marijuana Abuse

Interventions

Dronabinol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Ryan J McLaughlin, PhD

  Washington State University

  PRINCIPAL INVESTIGATOR

• Carrie Cuttler, PhD

  Washington State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ryan J McLaughlin, PhD

CONTACT

5093356448; ryan.mclaughlin@wsu.edu

Carrie Cuttler, PhD

CONTACT

5093350681; carrie.cuttler@wsu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The participants and the research assistants who administer the cognitive assessments (and other outcomes) will be blinded to the drug condition. The PI (Dr. McLaughlin) will be unblinded and will handle the drug, including weighing and pre-loading it into the Volcano vaporizer prior to each testing session. Additionally, the PI (Dr. McLaughlin or Dr. Cuttler) who supervises the vaping session will not be blinded.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Double-blind, placebo-controlled, crossover clinical trial

Study Record Dates

• First Submitted: December 3, 2025
• First Posted: December 22, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After the publication of primary findings.
• Access Criteria: The IPD will be available upon email request to one of the PIs on this study. De-identified data and the study protocol, statistical analysis plan, and informed consent form can/will be shared upon request.

Locations

US (1)