CannabisPhase 2NCT04596644
Impact of Repeatedly-Administered THC-cannabis on Experimental Pain and Abuse Liability in Humans
A Phase 2 study testing Active Cannabis in people with Cannabis and Pain, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically been the standard treatment. This has resulted in striking rates of opioid use disorders and fatal overdoses. Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- What is being tested?
- Active Cannabis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2021to 31 Oct 2026
- Phase
- Phase 2
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males/non-pregnant females, 21-60 years old
- Current cannabis user
- Able to perform all study procedures
Who cannot join
- Use of other illicit drugs
- If medical history, physical and psychiatric examination, or laboratory tests performed during the screening process reveal any significant illness that the study physician deems contraindicated for study participation
- Insensitivity to the cold-water stimulus of the Cold Pressor Test or the heat stimulus of Quantitative Sensory Testing
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically been the standard treatment. This has resulted in striking rates of opioid use disorders and fatal overdoses. Identifying non-opioid medications for the management of chronic pain with minimal abuse liability is a public health necessity, and cannabinoids are a promising drug class for this purpose. More than 80% of medicinal cannabis users report pain as their primary medical indication, and they report experiencing minimal psychoactive effects. However, there are few well-controlled human laboratory studies assessing cannabis' efficacy for pain in the context of abuse, and even less is known regarding the effects of daily repeated use of cannabis on pain and its relationship to abuse liability. Carefully controlled research is needed.
The proposed within-subjects, placebo-controlled 16-day crossover inpatient human laboratory study (N = 20 healthy cannabis users; 10 men, 10 women) will address three important gaps in our understanding of the potential therapeutic utility of cannabis for pain: 1) Does tolerance develop to repeated, daily smoked cannabis administration on measures of experimental pain and abuse liability; 2) If so, is tolerance reversed during the 7 days of abstinence from active-THC cannabis; 3) Does abrupt abstinence from active cannabis increase experimental pain sensitivity, i.e. hyperalgesia, relative to baseline, and do these effects parallel measures of cannabis withdrawal such as disrupted mood and sleep?
Two distinct modalities of experimental pain will be assessed: The Cold Pressor Test (CPT) and Quantitative Sensory Testing Thermal Temporal Summation (QST-TTS). Throughout the study, experimental pain and abuse-related effects will be assessed, as will sleep and subjective mood assessments.
- Conditions
- Cannabis, Pain, Tolerance, Hyperalgesia
- Being tested
- Active Cannabis, Placebo Cannabis
- Medical subject headings
- Marijuana Abuse, Pain, Hyperalgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active CannabisDrug
6.58% THC + <0.01% CBD cannabis (in one cigarette)
Placebo CannabisDrug
<0.01% THC:CBD cannabis.
| Study group | Role | What they receive |
|---|---|---|
| Dose A: Standardization Phase | Experimental | On the first full inpatient day (Day 1), participants smoke one specified strength (Dose A; 75% of two 6.58% cannabis cigarettes) of cannabis at three timepoints. Receives: Drug: Active Cannabis |
| Dose B: Placebo Phase | Placebo comparator | On Days 2-8, participants smoke a second strength (Dose B; 75% of two < 0.01%THC:CBD cannabis cigarettes) of cannabis will be administered 3x/day. Receives: Drug: Placebo Cannabis |
| Dose A: Active Phase | Experimental | On Days 9-15, cannabis Dose A will be administered again (75% of two 6.58% cannabis cigarettes) at three timepoints each day. Receives: Drug: Active Cannabis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cold Pressor Test (CPT) latency
The CPT apparatus consists of two refrigerated circulators, filled with warm (36.5-37.5°C). participants will complete the CPT 30 minutes before the 1000h cannabis administration (baseline), and 0, 15, 30, 45, 60, and 90 minutes post-cannabis administration. and cold (3.5 - 4.5°C) water. Participants will insert their non-dominant hand into the warm water and remove it after 3 minutes; skin temperature of the thumb pad will be measured. Participants will then insert their hand in the cold water and will be instructed to report when they first experience pain (pain threshold) and remove their hand when the cold water can no longer be tolerated (pain tolerance). Maximum immersion time will be 3 minutes. Repeats on days 1, 2, 5, 8, 9, 12, and 15.
Measured: Up to 15 days
Secondary outcomes (2)
Change in Quantitative Sensory Testing-Thermal Temporal Summation (QST-TTS) ratings
The QST-TTS apparatus is a thermal testing analyzer with a 30 x 30 mm Peltier thermode, which will use repetitive nociceptive heat stimulation of a fixed frequency and intensity. At the beginning of the procedure, a research assistant (same gender as the participant) will read a script describing the procedure to the participant. Tonic noxious heat stimulation will be applied to the palm using a ramp-and-hold method, in which the baseline temperature will be set at 32.0°C, and will increase at a rate of 1°C/s up to 46.5°C, remaining constant for 120 sec. During the total duration of stimulation (135 seconds), participants will continuously rate the magnitude of perceived pain using a visual analog scale. participants will complete the CPT 30 minutes before the 1000h cannabis administration (baseline), and 0, 15, 30, 45, 60, and 90 minutes post-cannabis administration. Repeats on days 1, 2, 5, 8, 9, 12, and 15.
Measured: Up to 15 days
Change in Cannabis Rating Form (CRF) ratings
Participants rate the strength, liking, desire to take again, good drug effect and bad. 7x on each of drug effect of cannabis on a 100mm visual analog scale. Repeats on days 1, 2, 5, 8, 9, 12, and 15.
Measured: Up to 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2020
- Study start1 Aug 2021
- Primary completion31 Aug 2024
- Study completion31 Oct 2026 (estimated)
Why it stopped: In response to quality assurance and compliance concerns, OHRP issued an FWA restriction on NYSPI research that included a pause of human research as of June 23, 2023.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CannabisStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- This study comprises a 16-day inpatient stay. After Move-in Day (Day 0), on the first full inpatient day (Day 1), participants will smoke one specified strength (Dose A) of cannabis. Days 2-8 will comprise Phase 1, in which a second strength (Dose B) of cannabis will be administered 3x/day. The next 7 days (Day 9-15) will be Phase 2, in which cannabis Dose A will be administered once again, at the same 3 daily time points.
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Caroline A. Arout, Ph.D., New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04596644
- Sponsor's protocol ID
- 8058
- Other IDs
- R21DA050752
- Status last verified
- Sep 2026
- First submitted
- 16 Oct 2020
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Repeatedly-Administered THC-cannabis on Experimental Pain and Abuse Liability in Humans
- ClinicalTrials.gov ID
- NCT04596644
- Acronym / sponsor ID
- 8058
- Conditions
- Cannabis, Pain, Tolerance, Hyperalgesia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: In response to quality assurance and compliance concerns, OHRP issued an FWA restriction on NYSPI research that included a pause of human research as of June 23, 2023.
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 1 Aug 2021 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 22 Oct 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.
Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically been the standard treatment. This has resulted in striking rates of opioid use disorders and fatal overdoses. Identifying non-opioid medications for the management of chronic pain with minimal abuse liability is a public health necessity, and cannabinoids are a promising drug class for this purpose. More than 80% of medicinal cannabis users report pain as their primary medical indication, and they report experiencing minimal psychoactive effects. However, there are few well-controlled human laboratory studies assessing cannabis' efficacy for pain in the context of abuse, and even less is known regarding the effects of daily repeated use of cannabis on pain and its relationship to abuse liability. Carefully controlled research is needed.
The proposed within-subjects, placebo-controlled 16-day crossover inpatient human laboratory study (N = 20 healthy cannabis users; 10 men, 10 women) will address three important gaps in our understanding of the potential therapeutic utility of cannabis for pain: 1) Does tolerance develop to repeated, daily smoked cannabis administration on measures of experimental pain and abuse liability; 2) If so, is tolerance reversed during the 7 days of abstinence from active-THC cannabis; 3) Does abrupt abstinence from active cannabis increase experimental pain sensitivity, i.e. hyperalgesia, relative to baseline, and do these effects parallel measures of cannabis withdrawal such as disrupted mood and sleep?
Two distinct modalities of experimental pain will be assessed: The Cold Pressor Test (CPT) and Quantitative Sensory Testing Thermal Temporal Summation (QST-TTS). Throughout the study, experimental pain and abuse-related effects will be assessed, as will sleep and subjective mood assessments.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This study comprises a 16-day inpatient stay. After Move-in Day (Day 0), on the first full inpatient day (Day 1), participants will smoke one specified strength (Dose A) of cannabis. Days 2-8 will comprise Phase 1, in which a second strength (Dose B) of cannabis will be administered 3x/day. The next 7 days (Day 9-15) will be Phase 2, in which cannabis Dose A will be administered once again, at the same 3 daily time points.
| Arm | Type | Receives |
|---|---|---|
| Dose A: Standardization Phase | Experimental | Drug: Active CannabisOn the first full inpatient day (Day 1), participants smoke one specified strength (Dose A; 75% of two 6.58% cannabis cigarettes) of cannabis at three timepoints. |
| Dose B: Placebo Phase | Placebo comparator | Drug: Placebo CannabisOn Days 2-8, participants smoke a second strength (Dose B; 75% of two < 0.01%THC:CBD cannabis cigarettes) of cannabis will be administered 3x/day. |
| Dose A: Active Phase | Experimental | Drug: Active CannabisOn Days 9-15, cannabis Dose A will be administered again (75% of two 6.58% cannabis cigarettes) at three timepoints each day. |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Males/non-pregnant females, 21-60 years old
- Current cannabis user
- Able to perform all study procedures
Key exclusion criteria (3 listed)
- Use of other illicit drugs
- If medical history, physical and psychiatric examination, or laboratory tests performed during the screening process reveal any significant illness that the study physician deems contraindicated for study participation
- Insensitivity to the cold-water stimulus of the Cold Pressor Test or the heat stimulus of Quantitative Sensory Testing
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 Cannabis6.58% THC + <0.01% CBD cannabis (in one cigarette) | Drug | Dose A: Active Phase, Dose A: Standardization Phase |
| Placebo Cannabis<0.01% THC:CBD cannabis. | Drug | Dose B: Placebo Phase |
Primary outcome
Change in Cold Pressor Test (CPT) latency
Time frame: Up to 15 days
The CPT apparatus consists of two refrigerated circulators, filled with warm (36.5-37.5°C). participants will complete the CPT 30 minutes before the 1000h cannabis administration (baseline), and 0, 15, 30, 45, 60, and 90 minutes post-cannabis administration. and cold (3.5 - 4.5°C) water. Participants will insert their non-dominant hand into the warm water and remove it after 3 minutes; skin temperature of the thumb pad will be measured. Participants will then insert their hand in the cold water and will be instructed to report when they first experience pain (pain threshold) and remove their hand when the cold water can no longer be tolerated (pain tolerance). Maximum immersion time will be 3 minutes. Repeats on days 1, 2, 5, 8, 9, 12, and 15.
2 secondary outcomes
Change in Quantitative Sensory Testing-Thermal Temporal Summation (QST-TTS) ratings
Time frame: Up to 15 days
Change in Cannabis Rating Form (CRF) ratings
Time frame: Up to 15 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 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. 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 2 study testing Active Cannabis in people with Cannabis and Pain, run by New York State Psychiatric Institute 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 3 inclusion and 3 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: paused, as of the sponsor's last update on 24 Sep 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Change in Cold Pressor Test (CPT) latency (time frame: Up to 15 days). 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 24 Sep 2026.