Imaging the Neurochemistry of Drug Addiction With PET

NCT ID: NCT02817698

Last Updated: 2024-12-12

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-29

Study Completion Date

2024-06-14

Brief Summary

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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 technology to an additional neurotransmitter system - namely, the opioid-ergic system, using the same drugs of abuse.

Detailed Description

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

1. 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.
2. 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.
3. 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.

1. 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.
2. 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.
3. 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

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Smoking Cannabis

Keywords

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smoking cannabis cocaine

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Drug of dependence

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.

Group Type EXPERIMENTAL

cannabis

Intervention Type DRUG

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

Interventions

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cannabis

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

Intervention Type DRUG

Other Intervention Names

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marijuana

Eligibility Criteria

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Inclusion Criteria

1. Men and women, aged 18-55 years
2. Able to read and write English and give voluntary written informed consent
3. Not treatment seeking or using treatment medications

Tobacco Smokers

1. Have a Fagerström Test for Nicotine Dependence (FTND) rating of at least 3.
2. Have been using at least 7 cigarettes per day for at least 1 year
3. Carbon monoxide levels \> 10 ppm during intake evaluation
4. Urine cotinine levels of \> 150 ng/mL during intake evaluation
5. Are not current users of marijuana or other illicit drugs

Marijuana Smokers

1. Meet DSM-V criteria for cannabis use disorder based on the structured clinical interview diagnostic (SCID) or regular cannabis use of \>5 times/week
2. Test positive for THC
3. Have been smoking cannabis on a regular basis for \> 1 year

Cocaine Users

1. DSM-V criteria for Cocaine Abuse or Dependence
2. Recent street cocaine use in excess of amounts to be administered in the current study
3. Intravenous and/or smoked (crack/ freebase) use
4. Positive urine toxicology screen for cocaine

Exclusion Criteria

* 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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Kelly Cosgrove

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kelly Cosgrove, PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

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Connecticut Mental Health Center

New Haven, Connecticut, United States

Site Status

Yale Magnetic Resonance Research Center

New Haven, Connecticut, United States

Site Status

Yale PET Center

New Haven, Connecticut, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 34399137 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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1R01DA038709-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01DA038832-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R03DA047588-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1604017594

Identifier Type: -

Identifier Source: org_study_id