Cannabis, Smoking
Conditions
Keywords
smoking, cannabis, cocaine
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.
Detailed description
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.
Interventions
DRUGcannabis
All cannabis dependent subjects will use cannabis cigarettes to induce elevated dopamine and beta endorphin levels in the brain.
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* General 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | 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. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
cannabis: All cannabis dependent subjects will use cannabis cigarettes to induce elevated dopamine and beta endorphin levels in the brain. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Drug of Dependence |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Age, Continuous | 29.52 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 1 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
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.
Time frame: 120 minute PET scan acquisition. Drug of dependence will be given at -35 mins
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Drug of Dependence | Change in Beta Endorphin Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | Front | -0.0068 mm^3 |
| Drug of Dependence | Change in Beta Endorphin Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | Amygdala | 0.0190 mm^3 |
| Drug of Dependence | Change in Beta Endorphin Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | Thalamus | 0.0146 mm^3 |
| Drug of Dependence | Change in Beta Endorphin Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | Caudate | 0.0082 mm^3 |
| Drug of Dependence | Change in Beta Endorphin Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | Putamen | 0.0100 mm^3 |
| Drug of Dependence | Change in Beta Endorphin Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | Cingulum | 0.0233 mm^3 |
| Drug of Dependence | Change in Beta Endorphin Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | Insula | 0.0153 mm^3 |
Primary
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.
Time frame: 90 minute PET scan acquisition. Drug of dependence will be given at -35 mins
Population: Subjects were analyzed based on cluster size with a threshold of 16 voxels.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Drug of Dependence | Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | R VS | 0.0388 mm^3 |
| Drug of Dependence | Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | R Putamen | 0.033 mm^3 |
| Drug of Dependence | Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | R Caudate | 0.0285 mm^3 |
| Drug of Dependence | Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | L VS | 0.0368 mm^3 |
| Drug of Dependence | Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | L Caudate | 0.038 mm^3 |
| Drug of Dependence | Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | R VS/Caudate | 0.035 mm^3 |
| Drug of Dependence | Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images. | L Putamen | 0.037 mm^3 |