Imaging the Neurochemistry of Drug Addiction With PET

NCT02817698 | Completed Early Phase 1 Results FDA Drug

• 4 other identifiers: 16040175941R01DA038709-01A11R01DA038832-01A11R03DA047588-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

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

Conditions

Smoking; Cannabis

Keywords

smoking; cannabis; cocaine

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  120 minute PET scan acquisition. Drug of dependence will be given at -35 mins

Study Arms (1)

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.

Drug: cannabis

Interventions

cannabis DRUG

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

Also known as: marijuana

Drug of dependence

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• \. Current significant medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology.
• \. History of or current neurological or significant psychiatric disorder such as schizophrenia or bipolar disorder (DSM-IV Axis 1).
• \. 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).
• \. 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).
• \. 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.
• \. Have MRI-incompatible implants and other contraindications for MRI, such as a pacemaker, artificial joints, non-removable body piercings, claustrophobia, etc.
• \. 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.
• \. Subjects with current, past or anticipated exposure to radiation in the work place within one year of proposed research PET scans.
• \. Subjects with history of IV drug use which would prevent venous access for PET tracer injection.

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (3)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Location

Yale Magnetic Resonance Research Center

New Haven, Connecticut, 06519, United States

Location

Yale PET Center

New Haven, Connecticut, 06519, United States

Location

Related Publications (1)

• 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.

  PMID: 34399137 DERIVED

MeSH Terms

Conditions

Smoking; Marijuana Abuse

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Marc Grasso
• Organization: Yale University

marc.grasso@yale.edu

2037377074

Study Officials

• Kelly Cosgrove, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 27, 2016
• First Posted: June 29, 2016
• Study Start: November 29, 2017
• Primary Completion: January 12, 2022
• Study Completion: June 14, 2024
• Last Updated: December 12, 2024
• Results First Posted: December 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)