PainPhase 1NCT04226690
Safety and Effects on Responses to Stress and Pain of Natural Medical Marijuana Products
A Phase 1 study testing Active CBD/THC Dose 1 and Active CBD/THC Dose 2 in people with Pain, run by Yale University at 1 site in United States.
Trial summary
This proposal aims to systematically examine the safety and pharmacokinetic/pharmacodynamic profile and the physiologic, neuroendocrine and behavioral stress and pain responses to acute single doses and repeated dosing of oral tablet formulation of natural Cannabidiol (CBD) alone and in combination with… Read more about this study
- Who is it for?
- Ages 21 to 68 years
- Conditions the study is for
- Pain
- What is being tested?
- Active CBD/THC Dose 1 and Active CBD/THC Dose 2
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2022to 15 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 21 to 68 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to read and write English;
- Recreational cannabis use with a minimum history recent use of at least one joint of smoked marijuana or marijuana edible or other equivalent form;
- Current chronic pain, as defined by the International Classification of Diseases (ICD)-10, and stabilized for a minimum of 2 weeks on pain medication, (minimum pain ratings of 4 on a 10-point scale) and agree to not change pain medication during course of the study;
- Body Mass Index (BMI) in the 18-36 range;
Who cannot join
- Any psychotic disorder or current psychiatric symptoms requiring specific attention, including active symptoms of psychosis or suicidal/homicidal ideation.
- Any Current moderate/severe Substance Use Disorder, including alcohol and cannabis.
- Women who are nursing or have premenstrual dysphoric disorder;
- Women who are pregnant as determined by the urine pregnancy test at each assessment period;
- Inability to give informed consent;
- Traumatic brain injury or loss of consciousness;
- Individuals with current or past history of seizure disorders;
Trial locations and contacts
1 site in 1 country.
United States1 site
The Yale Stress Center: Yale University
New Haven, Connecticut, 06519
About this study
Official title: Safety of Acute and Repeated Doses of Natural Medical Marijuana Products and Effects on Subjective and Physiological Responses to Stress and Pain
This proposal aims to systematically examine the safety and pharmacokinetic/pharmacodynamic profile and the physiologic, neuroendocrine and behavioral stress and pain responses to acute single doses and repeated dosing of oral tablet formulation of natural Cannabidiol (CBD) alone and in combination with Tetrahydrocannabinol and matched Placebo (PLA).
Read the detailed description
This proposal aims to systematically examine the safety and pharmacokinetic/pharmacodynamic (PK/PD) profile and the physiologic, neuroendocrine and behavioral stress and pain responses to acute single doses and repeated dosing of oral tablet formulation of natural Cannabidiol (CBD) at 40 mg and 100 mg alone and in combination with Tetrahydrocannabinol (THC) at 10, 20 and 30 mg, and matched Placebo (PLA) under the following specific aims:
Aim 1: To assess the safety and PK/PD profile of acute single doses of natural oral tablet of CBD (40 mg, 100 mg), and the CBD/THC combination (40/10, 40/20 and 100/30 mg) and matching placebo (PLA) over six separate sessions one week apart in healthy adult men and women who are current recreational cannabis users (STUDY 1).
Aim 2: To examine the effects of separate CBD, THC, CBD/THC combination vs. PLA on subjective, physiological, neuroendocrine, cognitive and behavioral measures of stress, pain and anxiety at baseline and under acute pain provocation using an adapted Cold Pressor Test (CPT) in STUDY 1.
Aim 3: To examine the safety and tolerability of the two specific doses of CBD/THC, selected on the basis of best PK/PD and tolerability profile from Study 1 vs. PLA on baseline and CPT provoked pain in individuals with chronic pain over a 7-day repeated dosing (STUDY 2).
Study 1:
Eight 21-45-year-old men and women , who are recreational marijuana users but do not meet criteria for moderate-severe cannabis use disorder will be recruited to complete six separate inpatient laboratory sessions one week apart during which they will be assigned to receive an acute dose of either 40 mg CBD or 100 mg CBD alone, a CBD/THC combination of 40/10, 40/20 or 100/30 or PLA, in a random, counter-balanced, double-blind, cross-over design over a 6-week period. Sessions will be completed one -week apart to allow for an adequate washout period between sessions.
Study 2:
Adult men and women ages 21-60 (N=24) with chronic pain (not fully controlled by opioid pain medication), will be recruited and randomly assigned to receive the two most tolerable CBD/THC doses (two active doses of n=8 in each) or PLA (n=8) repeated dosing for 7 days. On day 1 and day 6/7 of the 7-day dosing, subjects will complete laboratory sessions. For 14 days after the 7-day dosing, subjects will complete daily ratings of pain and other patient-related outcomes. Subjects cannot meet criteria for moderate to severe levels of cannabis use disorder or other substance use disorders.
This registration will focus on Study 2.
- Conditions
- Pain
- Being tested
- Active CBD/THC Dose 1, Active CBD/THC Dose 2, matched placebo comparator
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active CBD/THC Dose 1Drug
Also called Medical marijuana medicine
Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.
Active CBD/THC Dose 2Drug
Also called Medical marijuana medicine
Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.
matched placebo comparatorDrug
Also called Placebo
Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.
| Study group | Role | What they receive |
|---|---|---|
| Active Dose 1 | Experimental | Participants will receive the most tolerable CBD/THC dose with repeated dosing for 7 days. On day 1 and 6/7 of the 7-day dosing, subjects will complete laboratory sessions. Receives: Drug: Active CBD/THC Dose 1 |
| Matching Placebo | Placebo comparator | Participants will receive a placebo with repeated dosing for 7 days. On day 1 and 6/7 of the 7-day dosing, subjects will complete laboratory sessions. Receives: Drug: matched placebo comparator |
| Active Dose 2 | Experimental | Participants will receive the second most tolerable CBD/THC dose with repeated dosing for 7 days. On day 1 and 6/7 of the 7-day dosing, subjects will complete laboratory sessions Receives: Drug: Active CBD/THC Dose 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain Ratings
Change in provoked pain ratings on day 1 and day 7 on visual analog scale of pain (range 0-10)
Measured: Day 1 and 7 provocation during 7-day treatment period
Secondary outcomes (1)
Anxiety Ratings
Change in provoked anxiety ratings on day 1 and day 7 on visual analog scale of anxiety (range 0-10)
Measured: Day 1 and 7 provocation during 7-day treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start15 Nov 2022
- Primary completion15 Dec 2023
- Study completion15 Dec 2023
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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Connecticut Pharmaceutical Solutions
- Responsible party
- Principal investigator, RAJITA SINHA, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04226690
- Sponsor's protocol ID
- 2000020896
- Other IDs
- No NIH funding
- Status last verified
- Jul 2024
- First submitted
- 9 Jan 2020
- Last updated
- 19 Jul 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Acute and Repeated Doses of Natural Medical Marijuana Products and Effects on Subjective and Physiological Responses to Stress and Pain
- ClinicalTrials.gov ID
- NCT04226690
- Acronym / sponsor ID
- 2000020896
- Conditions
- Pain
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Connecticut Pharmaceutical Solutions
- Study start
- 15 Nov 2022 (actual)
- Primary completion
- 15 Dec 2023 (actual)
- Study completion
- 15 Dec 2023 (actual)
- First posted
- 13 Jan 2020 (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.
This proposal aims to systematically examine the safety and pharmacokinetic/pharmacodynamic profile and the physiologic, neuroendocrine and behavioral stress and pain responses to acute single doses and repeated dosing of oral tablet formulation of natural Cannabidiol (CBD) alone and in combination with Tetrahydrocannabinol and matched Placebo (PLA).
Detailed description
This proposal aims to systematically examine the safety and pharmacokinetic/pharmacodynamic (PK/PD) profile and the physiologic, neuroendocrine and behavioral stress and pain responses to acute single doses and repeated dosing of oral tablet formulation of natural Cannabidiol (CBD) at 40 mg and 100 mg alone and in combination with Tetrahydrocannabinol (THC) at 10, 20 and 30 mg, and matched Placebo (PLA) under the following specific aims:
Aim 1: To assess the safety and PK/PD profile of acute single doses of natural oral tablet of CBD (40 mg, 100 mg), and the CBD/THC combination (40/10, 40/20 and 100/30 mg) and matching placebo (PLA) over six separate sessions one week apart in healthy adult men and women who are current recreational cannabis users (STUDY 1).
Aim 2: To examine the effects of separate CBD, THC, CBD/THC combination vs. PLA on subjective, physiological, neuroendocrine, cognitive and behavioral measures of stress, pain and anxiety at baseline and under acute pain provocation using an adapted Cold Pressor Test (CPT) in STUDY 1.
Aim 3: To examine the safety and tolerability of the two specific doses of CBD/THC, selected on the basis of best PK/PD and tolerability profile from Study 1 vs. PLA on baseline and CPT provoked pain in individuals with chronic pain over a 7-day repeated dosing (STUDY 2).
Study 1:
Eight 21-45-year-old men and women , who are recreational marijuana users but do not meet criteria for moderate-severe cannabis use disorder will be recruited to complete six separate inpatient laboratory sessions one week apart during which they will be assigned to receive an acute dose of either 40 mg CBD or 100 mg CBD alone, a CBD/THC combination of 40/10, 40/20 or 100/30 or PLA, in a random, counter-balanced, double-blind, cross-over design over a 6-week period. Sessions will be completed one -week apart to allow for an adequate washout period between sessions.
Study 2:
Adult men and women ages 21-60 (N=24) with chronic pain (not fully controlled by opioid pain medication), will be recruited and randomly assigned to receive the two most tolerable CBD/THC doses (two active doses of n=8 in each) or PLA (n=8) repeated dosing for 7 days. On day 1 and day 6/7 of the 7-day dosing, subjects will complete laboratory sessions. For 14 days after the 7-day dosing, subjects will complete daily ratings of pain and other patient-related outcomes. Subjects cannot meet criteria for moderate to severe levels of cannabis use disorder or other substance use disorders.
This registration will focus on Study 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Active Dose 1 | Experimental | Drug: Active CBD/THC Dose 1Participants will receive the most tolerable CBD/THC dose with repeated dosing for 7 days. On day 1 and 6/7 of the 7-day dosing, subjects will complete laboratory sessions. |
| Matching Placebo | Placebo comparator | Drug: matched placebo comparatorParticipants will receive a placebo with repeated dosing for 7 days. On day 1 and 6/7 of the 7-day dosing, subjects will complete laboratory sessions. |
| Active Dose 2 | Experimental | Drug: Active CBD/THC Dose 2Participants will receive the second most tolerable CBD/THC dose with repeated dosing for 7 days. On day 1 and 6/7 of the 7-day dosing, subjects will complete laboratory sessions |
Who may qualify
- Ages
- 21 to 68 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Able to read and write English;
- Recreational cannabis use with a minimum history recent use of at least one joint of smoked marijuana or marijuana edible or other equivalent form;
- Current chronic pain, as defined by the International Classification of Diseases (ICD)-10, and stabilized for a minimum of 2 weeks on pain medication, (minimum pain ratings of 4 on a 10-point scale) and agree to not change pain medication during course of the study;
- Body Mass Index (BMI) in the 18-36 range;
Key exclusion criteria (7 listed)
- Any psychotic disorder or current psychiatric symptoms requiring specific attention, including active symptoms of psychosis or suicidal/homicidal ideation.
- Any Current moderate/severe Substance Use Disorder, including alcohol and cannabis.
- Women who are nursing or have premenstrual dysphoric disorder;
- Women who are pregnant as determined by the urine pregnancy test at each assessment period;
- Inability to give informed consent;
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 |
|---|---|---|
| Active CBD/THC Dose 1Also: Medical marijuana medicineSubjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance. | Drug | Active Dose 1 |
| Active CBD/THC Dose 2Also: Medical marijuana medicineSubjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance. | Drug | Active Dose 2 |
| matched placebo comparatorAlso: PlaceboSubjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance. | Drug | Matching Placebo |
Primary outcome
Pain Ratings
Time frame: Day 1 and 7 provocation during 7-day treatment period
Change in provoked pain ratings on day 1 and day 7 on visual analog scale of pain (range 0-10)
1 secondary outcome
Anxiety Ratings
Time frame: Day 1 and 7 provocation during 7-day treatment period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2024.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Active CBD/THC Dose 1 and Active CBD/THC Dose 2 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 4 inclusion and 7 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: finished, as of the sponsor's last update on 19 Jul 2024. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain Ratings (time frame: Day 1 and 7 provocation during 7-day treatment period). 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 19 Jul 2024.