SmokingEarly Phase 1NCT02817698

Imaging the Neurochemistry of Drug Addiction With PET

A Early Phase 1 study testing cannabis in people with Smoking and Cannabis, run by Yale University at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The investigators' project has two overarching goals. 1) The investigators will use newly developed positron emission tomography (PET) technology to investigate the dopaminergic neurochemistry of drugs of abuse including marijuana, traditional cigarettes, and cocaine, and 2) The investigators will extend PET… Read more about this study

Who is it for?: Ages 18 to 55 years
Conditions the study is for: Smoking, Cannabis
What is being tested?: cannabis
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 3 sitesUnited States
Study dates: 29 Nov 2017to 14 Jun 2024
Phase: Early Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 55 years
All sexes
No healthy volunteers
Adult

Who may be able to join

General Inclusion Criteria:
Men and women, aged 18-55 years
Able to read and write English and give voluntary written informed consent
Not treatment seeking or using treatment medications
Tobacco Smokers
Have a Fagerström Test for Nicotine Dependence (FTND) rating of at least 3.

Show all 19Show fewer

Have been using at least 7 cigarettes per day for at least 1 year
Carbon monoxide levels > 10 ppm during intake evaluation
Urine cotinine levels of > 150 ng/mL during intake evaluation
Are not current users of marijuana or other illicit drugs
Marijuana Smokers
Meet DSM-V criteria for cannabis use disorder based on the structured clinical interview diagnostic (SCID) or regular cannabis use of >5 times/week
Test positive for THC
Have been smoking cannabis on a regular basis for > 1 year
Cocaine Users
DSM-V criteria for Cocaine Abuse or Dependence
Recent street cocaine use in excess of amounts to be administered in the current study
Intravenous and/or smoked (crack/ freebase) use
Positive urine toxicology screen for cocaine

Who cannot join

1. Current significant medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology.
2. History of or current neurological or significant psychiatric disorder such as schizophrenia or bipolar disorder (DSM-IV Axis 1).
3. History of significant head trauma. 4. Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD).
5. Regular or current significant use of any prescription, herbal or illegal psychotropic medications (e.g., antidepressants, antipsychotics, anxiolytics, ecstasy) in the past 6 mo, with no current illegal drug use confirmed by urine toxicology (except for cocaine and marijuana when relevant).
6. Significant substance misuse (including alcohol, and excluding cannabis and marijuana when relevant) that in the PI's determination interferes with the study results or safety of the subject.
7. Have MRI-incompatible implants and other contraindications for MRI, such as a pacemaker, artificial joints, non-removable body piercings, claustrophobia, etc.

Show all 9Show fewer

8. Subjects with history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure. This guideline is an effective dose of 5 rem received per year.
9. Subjects with current, past or anticipated exposure to radiation in the work place within one year of proposed research PET scans.
10. Subjects with history of IV drug use which would prevent venous access for PET tracer injection.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Connecticut Mental Health Center
New Haven, Connecticut, 06519
Yale Magnetic Resonance Research Center
New Haven, Connecticut, 06519
Yale PET Center
New Haven, Connecticut, 06519

Other trials in United States

About this study

Read the detailed description

Aim 1. To examine the magnitude, location and timing of drug-induced dopamine release.

Tobacco smokers (n=20) will be imaged with [11C]raclopride PET, after overnight abstinence from tobacco. Subjects will smoke their preferred brand of cigarette during the PET scan.
Marijuana smokers (n=20) will be imaged with [11C]raclopride PET, after overnight abstinence from marijuana. Subjects will smoke a marijuana cigarette during the PET scan.
Cocaine users (n=20) will be imaged with [11C]raclopride PET, after overnight abstinence from cocaine. Subjects will be administered cocaine during the PET scan.

Aim 2. To examine the magnitude, location and timing of drug-induced beta-endorphin release. *The Investigators will attempt to use the same subjects from Aim 1 for Aim 2.

Tobacco smokers (n=20) will be imaged with [11C]carfentanil PET, after overnight abstinence from tobacco. Subjects will smoke their preferred brand of cigarette during the PET scan.
Marijuana smokers (n=20) will be imaged with [11C]carfentanil PET, after overnight abstinence from marijuana. Subjects will smoke a marijuana cigarette during the PET scan.
Cocaine users (n=20) will be imaged with [11C]carfentanil PET, after overnight abstinence from cocaine. Subjects will be administered cocaine during the PET scan.

Conditions: Smoking, Cannabis
Being tested: cannabis
Keywords: smoking, cannabis, cocaine
Medical subject headings: Smoking, Marijuana Abuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

cannabisDrug
Also called marijuana
All cannabis dependent subjects will use cannabis cigarettes to induce elevated dopamine and beta endorphin levels in the brain.

Study groups in NCT02817698
Study group	Role	What they receive
Drug of dependence	Experimental	There is only one arm to the study. All subjects will receive their drug of dependence in this study. Nicotine dependent subjects will receive tobacco cigarettes, cannabis dependent subjects will receive cannabis cigarettes, and cocaine dependent subjects will receive IV cocaine. Receives: Drug: cannabis

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images.
PET images will be obtained in dependent subjects at baseline and after drug of dependence administration. Change in DA levels will be determined by change in binding potential of raclopride. Baseline levels will be assessed during the first scan in the morning after overnight abstinence from their drug of dependence using a 90-minute PET acquisition. Then, drug of dependence will be administered 35 minutes before a second 90-minute PET acquisition. The beginning of the second PET scan will be approximately 5 hours after the beginning of the first PET scan, however in some cases this may be longer, or the scans may take place on separate days due to scheduling constraints or scan cancellations.
Measured: 90 minute PET scan acquisition. Drug of dependence will be given at -35 mins
Change in Beta Endorphin Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images.
PET images will be obtained in dependent subjects at baseline and after drug of dependence administration. Change in beta endorphin levels will be determined by change in binding potential of carfentanil. Baseline levels will be assessed during the first scan in the morning after 12 hour abstinence from their drug of dependence using a 90-minute PET acquisition. Then, drug of dependence will be administered 35 minutes before a second 90-minute PET acquisition. The beginning of the second PET scan will be approximately 5 hours after the beginning of the first PET scan, however in some cases this may be longer, or the scans may take place on separate days due to scheduling constraints or scan cancellations.
Measured: 120 minute PET scan acquisition. Drug of dependence will be given at -35 mins

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Nov 201714 Jun 2024

First posted29 Jun 2016 (estimated)
Study start29 Nov 2017
Primary completion12 Jan 2022
Study completion14 Jun 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for SmokingStudies 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: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02817698
Sponsor's protocol ID: 1604017594
Other IDs: 1R01DA038709-01A1, 1R01DA038832-01A1, 1R03DA047588-01
Status last verified: Nov 2024
First submitted: 27 Jun 2016
Last updated: 12 Dec 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Calakos KC, Liu H, Lu Y, Anderson JM, Matuskey D, Nabulsi N, Ye Y, Skosnik PD, D'Souza DC, Morris ED, Cosgrove KP, Hillmer AT. Assessment of transient dopamine responses to smoked cannabis. Drug Alcohol Depend. 2021 Oct 1;227:108920. doi: 10.1016/j.drugalcdep.2021.108920. Epub 2021 Jul 29.
PubMed 34399137

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 12 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Imaging the Neurochemistry of Drug Addiction With PET
ClinicalTrials.gov ID: NCT02817698
Acronym / sponsor ID: 1604017594
Conditions: Smoking, Cannabis
Keywords: smoking, cannabis, cocaine
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: 29 Nov 2017 (actual)
Primary completion: 12 Jan 2022 (actual)
Study completion: 14 Jun 2024 (actual)
First posted: 29 Jun 2016 (estimated)
Results: Posted 12 Dec 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Aim 1. To examine the magnitude, location and timing of drug-induced dopamine release.

Tobacco smokers (n=20) will be imaged with [11C]raclopride PET, after overnight abstinence from tobacco. Subjects will smoke their preferred brand of cigarette during the PET scan.
Marijuana smokers (n=20) will be imaged with [11C]raclopride PET, after overnight abstinence from marijuana. Subjects will smoke a marijuana cigarette during the PET scan.
Cocaine users (n=20) will be imaged with [11C]raclopride PET, after overnight abstinence from cocaine. Subjects will be administered cocaine during the PET scan.

Aim 2. To examine the magnitude, location and timing of drug-induced beta-endorphin release. *The Investigators will attempt to use the same subjects from Aim 1 for Aim 2.

Tobacco smokers (n=20) will be imaged with [11C]carfentanil PET, after overnight abstinence from tobacco. Subjects will smoke their preferred brand of cigarette during the PET scan.
Marijuana smokers (n=20) will be imaged with [11C]carfentanil PET, after overnight abstinence from marijuana. Subjects will smoke a marijuana cigarette during the PET scan.
Cocaine users (n=20) will be imaged with [11C]carfentanil PET, after overnight abstinence from cocaine. Subjects will be administered cocaine during the PET scan.

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Drug of dependence	Experimental	Drug: cannabisThere is only one arm to the study. All subjects will receive their drug of dependence in this study. Nicotine dependent subjects will receive tobacco cigarettes, cannabis dependent subjects will receive cannabis cigarettes, and cocaine dependent subjects will receive IV cocaine.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (19 listed)

General Inclusion Criteria:
Tobacco Smokers
Have a Fagerström Test for Nicotine Dependence (FTND) rating of at least 3.
Have been using at least 7 cigarettes per day for at least 1 year
Carbon monoxide levels > 10 ppm during intake evaluation

Key exclusion criteria (9 listed)

1. Current significant medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology.
2. History of or current neurological or significant psychiatric disorder such as schizophrenia or bipolar disorder (DSM-IV Axis 1).
3. History of significant head trauma. 4. Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD).
5. Regular or current significant use of any prescription, herbal or illegal psychotropic medications (e.g., antidepressants, antipsychotics, anxiolytics, ecstasy) in the past 6 mo, with no current illegal drug use confirmed by urine toxicology (except for cocaine and marijuana when relevant).
6. Significant substance misuse (including alcohol, and excluding cannabis and marijuana when relevant) that in the PI's determination interferes with the study results or safety of the subject.

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
cannabisAlso: marijuanaAll cannabis dependent subjects will use cannabis cigarettes to induce elevated dopamine and beta endorphin levels in the brain.	Drug	Drug of dependence

Primary outcome

Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images.
Time frame: 90 minute PET scan acquisition. Drug of dependence will be given at -35 mins
PET images will be obtained in dependent subjects at baseline and after drug of dependence administration. Change in DA levels will be determined by change in binding potential of raclopride. Baseline levels will be assessed during the first scan in the morning after overnight abstinence from their drug of dependence using a 90-minute PET acquisition. Then, drug of dependence will be administered 35 minutes before a second 90-minute PET acquisition. The beginning of the second PET scan will be approximately 5 hours after the beginning of the first PET scan, however in some cases this may be longer, or the scans may take place on separate days due to scheduling constraints or scan cancellations.
Change in Beta Endorphin Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images.
Time frame: 120 minute PET scan acquisition. Drug of dependence will be given at -35 mins
PET images will be obtained in dependent subjects at baseline and after drug of dependence administration. Change in beta endorphin levels will be determined by change in binding potential of carfentanil. Baseline levels will be assessed during the first scan in the morning after 12 hour abstinence from their drug of dependence using a 90-minute PET acquisition. Then, drug of dependence will be administered 35 minutes before a second 90-minute PET acquisition. The beginning of the second PET scan will be approximately 5 hours after the beginning of the first PET scan, however in some cases this may be longer, or the scans may take place on separate days due to scheduling constraints or scan cancellations.

Results and safety

Results posted to the registry on 12 Dec 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Drug of Dependence	25	25

Primary outcome: Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images.

Time frame: 90 minute PET scan acquisition. Drug of dependence will be given at -35 mins. Mean (Full Range). Unit: mm^3

Measure	Drug of Dependence n = 12
R VS	0.0388 (0.022 to 0.058)
R Putamen	0.033 (0.028 to 0.038)
R Caudate	0.0285 (0.027 to 0.03)
L VS	0.0368 (0.025 to 0.052)
L Caudate	0.038 (0.035 to 0.041)
R VS/Caudate	0.035 (0.035 to 0.035)
L Putamen	0.037 (0.022 to 0.052)

Population analysed: Subjects were analyzed based on cluster size with a threshold of 16 voxels.

Primary outcome: Change in Beta Endorphin Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images.

Time frame: 120 minute PET scan acquisition. Drug of dependence will be given at -35 mins. Mean (Full Range). Unit: mm^3

Measure	Drug of Dependence n = 8
Front	-0.0068 (-0.0501 to 0.0237)
Amygdala	0.0190 (-0.2803 to 0.3490)
Thalamus	0.0146 (-0.0355 to 0.0748)
Caudate	0.0082 (-0.1278 to 0.1310)
Putamen	0.0100 (-0.0342 to 0.0865)
Cingulum	0.0233 (-0.0687 to 0.0909)
Insula	0.0153 (-0.0432 to 0.0910)

Adverse events

Time frame: 5 years. Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Drug of Dependence	0 of 25 (0%)	1 of 25 (4%)	0 of 25

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34399137Calakos KC, Liu H, Lu Y, Anderson JM, Matuskey D, Nabulsi N, Ye Y, Skosnik PD, D'Souza DC, Morris ED, Cosgrove KP, Hillmer AT. Assessment of transient dopamine responses to smoked cannabis. Drug Alcohol Depend. 2021 Oct 1;227:108920. doi: 10.1016/j.drugalcdep.2021.108920. Epub 2021 Jul 29.
Individual participant dataSharing planned: No

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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.

Kelly Cosgrove, PhD principal investigator

Yale University

3 sites 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 cannabis in people with Smoking and Cannabis, run by Yale University at 3 sites 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 19 inclusion and 9 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 12 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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. 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?

Yes. Results are posted in the registry (first posted 12 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. (time frame: 90 minute PET scan acquisition. Drug of dependence will be given at -35 mins). 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?

On the ClinicalTrials.gov record for NCT02817698, which also lists 1 linked publication.

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 12 Dec 2024.