Objective:
Cocaine addiction continues to be an important public health problem with over 1.7 million users in the US alone. Cocaine addiction is characterized by compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. Cocaine addiction may be mediated by neuroadaptations in reward-related learning and memory processes in the mesocorticolimbic dopamine system and glutamatergic corticolimbic circuitry. Metabotropic glutamate subtype 5 receptors (mGluR5) likely play essential roles in mediating some of the actions of drugs of abuse. Animal studies have shown that mGluR5 knock-out or blockade reduces self-administration of cocaine and cocaine-induced hyper-locomotion. However, to what extent mGluR5 are involved in the pathophysiology of cocaine addiction in humans is currently unknown, partly due to the lack of suitable methods to reliably quantify mGluR5 in the living human brain.
This protocol aims to determine whether the density of mGluR5 in brain is altered in participants with cocaine addiction compared to healthy controls using positron emission tomography (PET) and the recently developed radiotracer for mGluR5, \[18F\]SP203. We also aim to determine whether this density is related to genotype, history of cocaine use, and/or craving for cocaine.
Study Population:
The study populations will consist of healthy adults with no history of substance abuse and a matched group of healthy current primary cocaine dependent male and female participants (20-50 years old.; N=40/group).
Design:
Density of mGluR5 will be measured in cocaine dependent participants and healthy adults volunteers with PET and (18F)SP203, a radioligand with specificity for mGluR5. All participants will undergo genotyping to identify normal or variant mGluR5 gene associated with drug abuse. The intensity of craving for cocaine will be assessed while watching a video about cocaine use.
Outcome measures:
Density of mGluR5 will be compared between cocaine dependent participants and healthy controls. In addition, correlation among the genetic polymorphism, the craving response, and the density of mGluR5 will be determined.
Who can participate
Age range
20 Years – 55 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Exclusion criteria
. Psychiatric disease: DSM-IV criteria will be used (American Psychiatric Association, 1994). No subject with a current axis I diagnosis (except for nicotine dependence) will be allowed. Claustrophobia is also exclusionary.
. History of Drug Abuse: Volunteers reporting current or having a significant history of illicit drug abuse will be excluded from the study. Subjects may use moderate amounts of alcohol and caffeine and smoke an occasional marijuana cigarette, but must not be dependent on alcohol, caffeine or marijuana. No alcohol or marijuana for at least 24 hours prior to scanning. No smoking after midnight on the night before a scan.
. Current or Past Medication Use: Volunteers may not currently use chronic (daily for more than 10 to 14 days in the last month) prescription or over the counter medications, (including, but not limited to, anti-hypertensive, anti-allergy, pain). Over the counter or prescription medications may be used on an occasional basis (for treatment of self-limited conditions, such as occasional headache, musculoskeletal discomfort, allergic symptoms or pain). All medications will be discontinued at least 5 days before the experimental session.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Determine if cocaine dependent participants have a different mGluR5 density than healthy controls
. CNS disease: History of known structural brain abnormalities (e.g., neoplasm, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), history of head trauma (defined as documented loss of consciousness \> 5 min), history of seizures as an adult, sleep apnea, tic disorder.
. Cardiovascular, pulmonary, or systemic disease: Repeated (measured on three separate occasions) diastolic blood pressure \>90 mm Hg, or systolic blood pressure \>135 mm Hg, known arrhythmia, symptomatic or known coronary artery disease; history of endocarditis, cerebral embolism, obstructive pulmonary disease, Factive tuberculosis, known endocrine disease (derangements in adrenal, thyroid, bone or reproductive function), known chronic renal or hepatic dysfunction, HIV seropositive, known current autoimmune disease involving the CNS.
. Miscellaneous exclusionary criteria: Body weight greater than 300 lbs. Hematocrit \< 39.0 for males or \< 36.0 for females. Participants are also excluded if veins are inaccessible.
. Radiation exposure: Any subject who has participated in any research studies in which he/she received a radiation exposure that would result in combination with the present study, in a total effective radiation exposure (from research studies) exceeding 5.0 rem in a year.
. Novocain allergy or lack of bilateral ulner and radial arterial patency in subjects receiving arterial catheter as assessed by an Allen s test or Dopler test artery patency for all subjects to be catheterized.