PainEarly Phase 1THCNCT04025359
Effects of Dronabinol in Opioid Maintained Patients
A Early Phase 1 study testing Dronabinol in people with Pain, run by Yale University at 1 site in United States.
Trial summary
Twenty male and female (ages 18-70) participants with OUD currently receiving methadone or buprenorphine will be enrolled. Prior to their daily methadone or buprenorphine dose and thus at trough plasma levels of opioid, participants will receive dronabinol (2.5 mg, 5mg) or placebo. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pain
- What is being tested?
- Dronabinol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 31 May 2019to 31 Jan 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Prior exposure to THC or cannabis at least once in the last 10 years; 1-10 times in the last 20 years; or more than 20 times in their lifetime.
- Males and females, Veterans and non-Veterans, aged between 18 and 70.
- Diagnosed with OUD and currently enrolled in methadone or buprenorphine maintenance treatment.
- Capable of providing informed consent in English.
- Compliant in opioid maintenance treatment and on a stable dose for two weeks or longer.
- Not meeting DSM-5 criteria for substance use disorders other than OUD or tobacco use disorder within the last 12 months.
- No current medical problems deemed contraindicated for participation by principal investigator.
- For women, not pregnant as determined by pregnancy screening; not breast-feeding; using acceptable birth control methods.
Who cannot join
- Currently meeting DSM-5 criteria for cannabis use disorder (CUD).
- History of primary psychotic disorders or other current major psychiatric disorders deemed clinically unstable by the principal investigator.
- Serious medical or neurological illness or treatment for a medical disorder that could interfere with study participation as determined by principal investigator.
- Inability to complete neuropsychological tests.
- A physician will carefully evaluate participants for use of over-the-counter or prescription psychoactive drugs known to affect pain threshold or pain tolerance (including NSAIDS, serotonin-norepinephrine reuptake inhibitors (SNRIs), (e.g. venlafaxine, duloxetine), tricyclic antidepressants (e.g., nortriptyline, amitriptyline), anticonvulsant medications (e.g., topiramate, tegretol), benzodiazepines (e.g., alprazolam, diazepam), and other opioid drugs). Only subjects who are on stable doses of these medications, and whose dosing schedules allow participation in the study visits, will be enrolled. If possible, the morning dose will be administered after the study visit.
- Liver function tests (ALT or AST) greater than 3x normal.
- Contraindications for exposure to cold temperatures, such as Raynaud's phenomenon and hypertension.
- Allergy or serious adverse reaction to cannabis, dronabinol or other cannabinoids.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Julia Meyerovich contact
United States1 site, 1 recruiting
- Recruiting
VA Connecticut Healthcare System
West Haven, Connecticut, 06516
Julia Meyerovich, 203-932-5711 ext. 14805, julia.meyerovich@yale.edu
Joao P. De Aquino, M.D.
About this study
Official title: The Effects of Dronabinol in Opioid-Related Outcomes
Twenty male and female (ages 18-70) participants with OUD currently receiving methadone or buprenorphine will be enrolled. Prior to their daily methadone or buprenorphine dose and thus at trough plasma levels of opioid, participants will receive dronabinol (2.5 mg, 5mg) or placebo. Subsequently, all participants will undergo laboratory testing of opioid-related outcomes. Pain sensitivity will be measured using a technique called the (QST) quantitative sensory testing, which involves the administering heat or cold stimulation. A Short-Form McGill Pain Questionnaire (SF-MPQ) and a pain Visual Analog Scale (VAS). Attentional bias will be measured using a visual probe task. Negative affect will be measured using the Positive and Negative Affect Schedule (PANAS). Cognitive performance will be measured by a comprehensive cognitive battery. The order of study medication administration will be counterbalanced order to minimize carryover effects. On the initial screening day and at the end of medication treatment, blood will be drawn to determine serum cytokine levels. One week after the last study medication dose, a follow-up session will be conducted during which participants will undergo urine toxicology testing and a safety evaluation before final discharge from the study.
Read the detailed description
This is a double-blind, randomized, placebo-controlled cross-over human laboratory study. Participants will be asked to come to the testing site for a total of four times: one initial screening session (~ 3 hours) and three test days (~ 6 hours each) where study medication will be administered, separated by at least 72 hours to limit carryover effects for dronabinol administration. Twenty male and female participants with OUD on MAT will be asked to arrive at approximately the same time each morning, coordinating with attendance at their opioid maintenance clinic. Subjects will be asked to refrain from using alcoholic beverages and drugs during study participation. Urine screens and breathalyzer measurements will be done before the test sessions to check abstinence from drugs (e.g., cocaine, illicit opioids, benzodiazepines, barbiturates, and amphetamines) and alcohol respectively. Those who are non-compliant will be discharged from the study. To minimize nicotine and withdrawal effects on cognitive performance, subjects who smoke will be advised to continue smoking as usual. Since we will provide a standard breakfast, participants will be asked not to eat for two hour before they arrive for the test sessions. A study nurse will confirm with their respective program that participants did not receive either methadone or buprenorphine that morning, and will call the program when testing is complete to permit dispersal of that day's methadone or buprenorphine dose. On the initial screening day and at the end of medication treatment, blood will be drawn to determine serum cytokine levels. Participants will undergo a variety of cognitive and self-report measures, as well as assessments to confirm restraint from illicit drug use and lack of adverse effects of medication. Prior to their daily methadone or buprenorphine dose and thus at trough plasma levels of opioid, participants will receive dronabinol (10 mg, 20 mg) or placebo. Subsequently, all participants will undergo laboratory testing of measures relevant to vulnerability to relapse, including physiological, subjective and cognitive outcomes. The order of study medication administration will be counterbalanced order to minimize the impact of potential carryover effects between the sessions. To date: 27 subjects completed the approve protocol.
This study was amended to reduce the study drug (dronabinol) to 2.5mg, 5mg, or placebo. This study is active with recruitment continuing under the new doses.
- Conditions
- Pain
- Being tested
- Dronabinol, Placebo
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DronabinolDrug
Also called Marinol
Dronabinol 2.5 mg
DronabinolDrug
Also called Marinol
Dronabinol 5 mg
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Dronabinol 2.5mg | Active comparator | Dronabinol 2.5mg Receives: Drug: Dronabinol |
| Dronabinol 5mg | Active comparator | Dronabinol 5mg Receives: Drug: Dronabinol |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain sensitivity, measured by the Cold Pressor Test (CPT).
Pain threshold and pain tolerance, in seconds.
Measured: up to 6 hours
Pain sensitivity, measured by the Short form of the McGill Pain Questionnaire (SF-MPQ).
Subjective pain measured by the SF-MPQ. The SF-MPQ values range from 0 to 45, with higher values indicating greater pain sensitivity.
Measured: up to 6 hours
Secondary outcomes (4)
Abuse potential, measured by the Drug Effects Questionnaire (DEQ).
The DEQ values range from 0-100, with higher values indicating more prominent subjective drug effects.
Measured: up to 6 hours
Cognitive Performance, measured by the Continuous Performance Test (CPT)
Sustained attention and verbal learning measured by the CPT. The outcome for the CPT is the percent of correct responses, with a higher percentage indicating greater attention and working memory performance.
Measured: up to 6 hours
Cognitive Performance, measured by the Hopkins Verbal Learning Test (HVLT).
Sustained attention and verbal learning measured by the HVLT. The outcome for the HVLT is the immediate total recall, ranging from 0-36, with higher values indicating greater verbal learning.
Measured: up to 6 hours
Opioid craving measured by the Subjective Opiate Withdrawal Scale (SOWS)
The SOWS is a 16-item, participant-administered questionnaire designed to rate the intensity of opioid withdrawal symptoms. It assesses symptoms on a 0-4 scale ("not at all" to "extremely"), with total scores of 1-10 indicating mild, 11-20 moderate, and 21-30 severe withdrawal.
Measured: Baseline (30 minutes before the administration of dronabinol), and every 30 minutes after the administration of dronabinol (up to +210 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2019
- Study start31 May 2019
- Primary completion1 Dec 2026 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind, randomized, placebo-controlled cross-over human laboratory study. Participants will be asked to come to the testing site for a total of four times: one initial screening session (\~ 3 hours) and three test days (\~ 6 hours each) where study medication will be administered, separated by at least 72 hours to limit carryover effects for dronabinol administration.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- VA Connecticut Healthcare System
- Responsible party
- Sponsor
- Investigators
- Joao De Aquino, M.D., Principal investigator, VA Healthcare System West Haven CT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04025359
- Sponsor's protocol ID
- 2000027065
- Acronym
- THC
- Status last verified
- Jul 2026
- First submitted
- 10 Jul 2019
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Dronabinol in Opioid-Related Outcomes
- ClinicalTrials.gov ID
- NCT04025359
- Acronym / sponsor ID
- THC / 2000027065
- Conditions
- Pain
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- VA Connecticut Healthcare System
- Study start
- 31 May 2019 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 31 Jan 2027 (estimated)
- First posted
- 18 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Twenty male and female (ages 18-70) participants with OUD currently receiving methadone or buprenorphine will be enrolled. Prior to their daily methadone or buprenorphine dose and thus at trough plasma levels of opioid, participants will receive dronabinol (2.5 mg, 5mg) or placebo. Subsequently, all participants will undergo laboratory testing of opioid-related outcomes. Pain sensitivity will be measured using a technique called the (QST) quantitative sensory testing, which involves the administering heat or cold stimulation. A Short-Form McGill Pain Questionnaire (SF-MPQ) and a pain Visual Analog Scale (VAS). Attentional bias will be measured using a visual probe task. Negative affect will be measured using the Positive and Negative Affect Schedule (PANAS). Cognitive performance will be measured by a comprehensive cognitive battery. The order of study medication administration will be counterbalanced order to minimize carryover effects. On the initial screening day and at the end of medication treatment, blood will be drawn to determine serum cytokine levels. One week after the last study medication dose, a follow-up session will be conducted during which participants will undergo urine toxicology testing and a safety evaluation before final discharge from the study.
Detailed description
This is a double-blind, randomized, placebo-controlled cross-over human laboratory study. Participants will be asked to come to the testing site for a total of four times: one initial screening session (~ 3 hours) and three test days (~ 6 hours each) where study medication will be administered, separated by at least 72 hours to limit carryover effects for dronabinol administration. Twenty male and female participants with OUD on MAT will be asked to arrive at approximately the same time each morning, coordinating with attendance at their opioid maintenance clinic. Subjects will be asked to refrain from using alcoholic beverages and drugs during study participation. Urine screens and breathalyzer measurements will be done before the test sessions to check abstinence from drugs (e.g., cocaine, illicit opioids, benzodiazepines, barbiturates, and amphetamines) and alcohol respectively. Those who are non-compliant will be discharged from the study. To minimize nicotine and withdrawal effects on cognitive performance, subjects who smoke will be advised to continue smoking as usual. Since we will provide a standard breakfast, participants will be asked not to eat for two hour before they arrive for the test sessions. A study nurse will confirm with their respective program that participants did not receive either methadone or buprenorphine that morning, and will call the program when testing is complete to permit dispersal of that day's methadone or buprenorphine dose. On the initial screening day and at the end of medication treatment, blood will be drawn to determine serum cytokine levels. Participants will undergo a variety of cognitive and self-report measures, as well as assessments to confirm restraint from illicit drug use and lack of adverse effects of medication. Prior to their daily methadone or buprenorphine dose and thus at trough plasma levels of opioid, participants will receive dronabinol (10 mg, 20 mg) or placebo. Subsequently, all participants will undergo laboratory testing of measures relevant to vulnerability to relapse, including physiological, subjective and cognitive outcomes. The order of study medication administration will be counterbalanced order to minimize the impact of potential carryover effects between the sessions. To date: 27 subjects completed the approve protocol.
This study was amended to reduce the study drug (dronabinol) to 2.5mg, 5mg, or placebo. This study is active with recruitment continuing under the new doses.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Double-blind, randomized, placebo-controlled cross-over human laboratory study. Participants will be asked to come to the testing site for a total of four times: one initial screening session (~ 3 hours) and three test days (~ 6 hours each) where study medication will be administered, separated by at least 72 hours to limit carryover effects for dronabinol administration.
| Arm | Type | Receives |
|---|---|---|
| Dronabinol 2.5mg | Active comparator | Drug: DronabinolDronabinol 2.5mg |
| Dronabinol 5mg | Active comparator | Drug: DronabinolDronabinol 5mg |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Prior exposure to THC or cannabis at least once in the last 10 years; 1-10 times in the last 20 years; or more than 20 times in their lifetime.
- Males and females, Veterans and non-Veterans, aged between 18 and 70.
- Diagnosed with OUD and currently enrolled in methadone or buprenorphine maintenance treatment.
- Capable of providing informed consent in English.
- Compliant in opioid maintenance treatment and on a stable dose for two weeks or longer.
Key exclusion criteria (8 listed)
- Currently meeting DSM-5 criteria for cannabis use disorder (CUD).
- History of primary psychotic disorders or other current major psychiatric disorders deemed clinically unstable by the principal investigator.
- Serious medical or neurological illness or treatment for a medical disorder that could interfere with study participation as determined by principal investigator.
- Inability to complete neuropsychological tests.
- A physician will carefully evaluate participants for use of over-the-counter or prescription psychoactive drugs known to affect pain threshold or pain tolerance (including NSAIDS, serotonin-norepinephrine reuptake inhibitors (SNRIs), (e.g. venlafaxine, duloxetine), tricyclic antidepressants (e.g., nortriptyline, amitriptyline), anticonvulsant medications (e.g., topiramate, tegretol), benzodiazepines (e.g., alprazolam, diazepam), and other opioid drugs). Only subjects who are on stable doses of these medications, and whose dosing schedules allow participation in the study visits, will be enrolled. If possible, the morning dose will be administered after the study visit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DronabinolAlso: MarinolDronabinol 2.5 mg | Drug | Dronabinol 2.5mg |
| DronabinolAlso: MarinolDronabinol 5 mg | Drug | Dronabinol 5mg |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Pain sensitivity, measured by the Cold Pressor Test (CPT).
Time frame: up to 6 hours
Pain threshold and pain tolerance, in seconds.
Pain sensitivity, measured by the Short form of the McGill Pain Questionnaire (SF-MPQ).
Time frame: up to 6 hours
Subjective pain measured by the SF-MPQ. The SF-MPQ values range from 0 to 45, with higher values indicating greater pain sensitivity.
4 secondary outcomes
Abuse potential, measured by the Drug Effects Questionnaire (DEQ).
Time frame: up to 6 hours
Cognitive Performance, measured by the Continuous Performance Test (CPT)
Time frame: up to 6 hours
Cognitive Performance, measured by the Hopkins Verbal Learning Test (HVLT).
Time frame: up to 6 hours
Opioid craving measured by the Subjective Opiate Withdrawal Scale (SOWS)
Time frame: Baseline (30 minutes before the administration of dronabinol), and every 30 minutes after the administration of dronabinol (up to +210 minutes)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Julia Meyerovich contact
Joao De Aquino, M.D. principal investigator
VA Healthcare System West Haven CT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Dronabinol in people with Pain, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joao P. De Aquino, M.D. (203-932-5711 ext. 12916, joao.deaquino@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain sensitivity, measured by the Cold Pressor Test (CPT). (time frame: up to 6 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026; AzTrials last refreshed its copy on 6 Nov 2026.