Repeated CBD Administration and Cannabis Outcomes

The Effects of Repeated CBD Administration on Cannabis Abuse Liability and Analgesia: A Human Laboratory Study

This outpatient study examines how cannabidiol (CBD) affects the behavioral and pain-relieving effects of cannabis.

Study Overview

• Status: Recruiting
• Conditions: Cannabis; Experimental Pain in Healthy Human Participants; Abuse Liability
• Intervention / Treatment: Drug: Placebo Cannabidiol; Drug: Placebo Inhaled Cannabis; Drug: Active Inhaled Cannabis; Drug: Cannabidiol, Medium Dose; Drug: Cannabidiol, Higher Dose

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Paul A Nuzzo, M.A.; Phone Number: 859-323-0002; Email: pnuzz2@email.uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • Recruiting
      • University Of Kentucky
      • Contact: Paul A Nuzzo, M.A.; Phone Number: 859-323-0002; Email: pnuzz2@email.uky.edu
      • Contact: Hannah M Harris, Ph.D.; Email: hannah.harris@uky.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• English-speaking, literate adults,
• Male or female,
• Between the ages of 18-55,
• Body Mass Index from 18.5-32.0 kg/m2,
• Not currently seeking treatment for cannabis or drug use,
• Able to provide written informed consent and perform all study procedures,
• If female, a negative pregnancy test and use of an effective form of contraception during study participation (e.g., oral contraceptive, abstinence, barrier method),
• Negative urine drug test for drugs of abuse (other than cannabis) prior to every Laboratory Session, and
• Otherwise healthy as determined by the investigator based on medical history, physical examination, vital signs, and laboratory chemistries.

Exclusion Criteria:

• Physiologic drug dependence on opioids, benzodiazepines, barbiturates, and/or alcohol that would require medical management,
• Clinically significant acute medical problem (e.g., infection) or chronic medical problem requiring daily medication or ongoing medical care (e.g., hypertension, cardiovascular disease, diabetes, respiratory disorders [e.g., asthma, COPD]),
• Current or past history of major psychiatric disorder that would limit ability to participate in the study,
• Use of cannabis exclusively for medical reasons (no recreational use reported),
• Current, unrelenting chronic pain that prevents participation (i.e., unable to sit in chair for 8 hours),
• Currently using daily prescription medications to manage medical conditions or any drug that could interfere with the study, including potent CYP2C9, CYP3A4, or CYP2C19 inducers,
• Clinically significant abnormal ECG (as determined by study physician/cardiologist),
• Clinically significant abnormal laboratory findings,
• History of seizure disorder,
• Clinically significant history of head injuries requiring medical management or long lasting sequalae, and
• Self-report of past 30-day use of synthetic cannabis (i.e., K2, Spice).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo CBD/Placebo Inhaled Cannabis; Participants will receive non-therapeutic, experimental doses of placebo/inactive cannabidiol in combination with non-therapeutic, placebo/inactive vaporized marijuana. Inactive cannabidiol and inactive marijuana will be administered once per session. It is possible to receive both inactive drugs on the same day. Inactive/Placebo Cannabidiol: Placebo/inactive cannabidiol will be administered orally. Inactive/Placebo: Experimental, non-therapeutic administration of an inactive/placebo marijuana dose will be administered through a vaporizer.	Drug: Placebo Cannabidiol; Inactive/Placebo Cannabidiol: Inactive/placebo cannabidiol will be administered orally for 14 days.; Drug: Placebo Inhaled Cannabis; Inactive/Placebo Marijuana: Experimental, non-therapeutic administration of an inactive/placebo marijuana dose will be administered through a vaporizer at each study session day (Days 1, 7, 14) per block (3 blocks total).
Experimental: Placebo CBD/Active Inhaled Cannabis; Participants will receive a non-therapeutic, experimental dose of inactive/placebo cannabidiol in combination with non-therapeutic, active vaporized marijuana. It is possible to receive inactive cannabidiol and active marijuana on the same day. Inactive/Placebo Cannabidiol: Active cannabidiol will be administered orally. Active Marijuana: Experimental, non-therapeutic administration of an active marijuana dose will be administered through a vaporizer.	Drug: Placebo Cannabidiol; Inactive/Placebo Cannabidiol: Inactive/placebo cannabidiol will be administered orally for 14 days.; Drug: Active Inhaled Cannabis; Active Marijuana: Active Marijuana (active inhaled cannabis) will be administered through a vaporizer once per study session day (Day 1, 7, 14) per block (3 blocks total).
Experimental: CBD (Medium Dose)/Placebo Inhaled Cannabis; Participants will receive a non-therapeutic, experimental dose of active cannabidiol in combination with non-therapeutic, inactive vaporized marijuana. It is possible to receive active cannabidiol, and inactive marijuana on the same day. Active Cannabidiol: Active cannabidiol will be administered orally. Inactive/Placebo Marijuana: Experimental, non-therapeutic administration of an inactive/placebo marijuana dose will be administered through a vaporizer.	Drug: Placebo Inhaled Cannabis; Inactive/Placebo Marijuana: Experimental, non-therapeutic administration of an inactive/placebo marijuana dose will be administered through a vaporizer at each study session day (Days 1, 7, 14) per block (3 blocks total).; Drug: Cannabidiol, Medium Dose; Active Cannabidiol: Active cannabidiol (medium dose) will be administered orally for 14 days.
Experimental: CBD (Medium Dose)/Active Inhaled Cannabis; Participants will receive non-therapeutic, experimental doses of active cannabidiol in combination with non-therapeutic, experimental doses of active vaporized marijuana. Cannabidiol and marijuana doses will be administered once during each session. It is possible to receive both active drugs on the same day. Vaporized Marijuana: Active Marijuana administered through a vaporizer Cannabidiol: Active cannabidiol will be administered orally	Drug: Active Inhaled Cannabis; Active Marijuana: Active Marijuana (active inhaled cannabis) will be administered through a vaporizer once per study session day (Day 1, 7, 14) per block (3 blocks total).; Drug: Cannabidiol, Medium Dose; Active Cannabidiol: Active cannabidiol (medium dose) will be administered orally for 14 days.
Experimental: CBD (Higher Dose)/Placebo Inhaled Cannabis; Participants will receive a non-therapeutic, experimental dose of active cannabidiol in combination with non-therapeutic, inactive vaporized marijuana. It is possible to receive active cannabidiol, and inactive marijuana on the same day. Active Cannabidiol: Active cannabidiol will be administered orally. Inactive/Placebo Marijuana: Experimental, non-therapeutic administration of an inactive/placebo marijuana dose will be administered through a vaporizer.	Drug: Placebo Inhaled Cannabis; Inactive/Placebo Marijuana: Experimental, non-therapeutic administration of an inactive/placebo marijuana dose will be administered through a vaporizer at each study session day (Days 1, 7, 14) per block (3 blocks total).; Drug: Cannabidiol, Higher Dose; Description: Active Cannabidiol: Active cannabidiol (higher dose) will be administered orally for 14 days.
Experimental: CBD (Higher Dose)/Active Inhaled Cannabis; Participants will receive non-therapeutic, experimental doses of active cannabidiol in combination with a non-therapeutic, experimental dose of active vaporized marijuana. Active cannabidiol and marijuana doses will be administered once during each session. It is possible to receive both active drugs on the same day. Active Cannabidiol: Active cannabidiol will be administered orally. Active Marijuana: Active Marijuana will be administered through a vaporizer.	Drug: Active Inhaled Cannabis; Active Marijuana: Active Marijuana (active inhaled cannabis) will be administered through a vaporizer once per study session day (Day 1, 7, 14) per block (3 blocks total).; Drug: Cannabidiol, Higher Dose; Description: Active Cannabidiol: Active cannabidiol (higher dose) will be administered orally for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline-Subject-Related Outcome-VAS Drug Liking	Participants rated their subjective drug liking on a standardized VAS scale (0 to 100). These Scores will indicate how participants are feeling at that moment, including questions on mood, physical symptoms, and drug effects. Low scores mean little to no drug liking. Higher scores mean greater drug liking. Raw data transformed to peak scores.	Days 1 (baseline), 7, 14, prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session).
Change from Baseline-Marijuana Purchase Task: Elasticity	Behavioral economic demand for cannabis: how much a participant values cannabis as its "price" (cost, effort, or availability) increases. Participants indicate how much marijuana they would buy and consume at increasing, hypothetical prices. This outcome describes how sensitive marijuana consumption is to price changes and how quickly demand decreases as marijuana becomes more expensive.	Days 1 (baseline), 7, 14, measured ~3 hours post cannabis administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline-Cold Pressor Test (CPT) Threshold	Participants first immerse a dominant hand into the warm-water bath for 2 minutes. The participants are then instructed to immerse the dominanat hand in the cold-water bath and report when pain is first experienced, and to keep the hand submerged as long as possible, and to withdraw the hand from the water when the sensation becomes uncomfortable. Latency (in seconds) to first pain sensations (threshold) will be measured and recorded.	Days 1 (baseline), 7, 14, This outcome will be recorded before and at two additional intervals after active and placebo cannabis administration during the laboratory session (a total of 6 measurements per session).
Change from Baseline-Cold Pressor Test (CPT) Tolerance	Participants first immerse a dominant hand into the warm-water bath for 2 minutes. The participants are then instructed to immerse the dominant hand in the cold-water bath and report when pain is first experienced, and to keep the hand submerged as long as possible, and to withdraw the hand from the water when the sensation becomes uncomfortable. Latency to withdrawal from the water (tolerance) will be measured and recorded.	Days 1 (baseline), 7, 14, This outcome will be recorded before and at two additional intervals after active and placebo cannabis administration during the laboratory session (a total of 6 measurements per session).
Change from Baseline-Cold Pressor Visual Analog Scale (CPT-VAS): Painful	Participants first immerse a dominant hand in the warm-water bath for 2 minutes. The participants are then instructed to immerse the dominant hand in the cold-water bath and report when pain is first experienced, and to keep the hand submerged as long as possible, and to withdraw the hand from the water when the sensation becomes uncomfortable. Participants will report how painful the pain was on a visual analog scale. Low scores mean little to no pain. Higher scores mean greater pain. Raw data transformed to peak scores.	Days 1 (baseline), 7, 14, This outcome will be recorded before and after the CPT for a total of 6 measurements per session.

Collaborators and Investigators

• Sponsor: Hannah Harris
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Hannah M Harris, Ph.D., University Of Kentucky

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: February 19, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: marijuana; cannabidiol (CBD); marijuana users
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Cannabidiol
• Other Study ID Numbers: 107878; K01DA056692 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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