Cocaine Use Disorder

Studies proposed in this application will image mitochondrial Complex-I in cocaine use disorder (CUD) and matched healthy controls

The goal of the study is to investigate the feasibility, safety, and effect of rTMS on mPFC/dACC activity using a combination of fMRI and clinical outcome measures, when used as an augmentation to CBT. Our hypothesis is that we will meet the following milestones prior to moving forward to the UH3 phase (a clinical trial for CUD). * Feasibility: At least 75% of participants will receive at least 15 out of 20 rTMS sessions with no participants experiencing a study-related serious adverse event * Mechanism: Compared to baseline, after 1 week of rTMS, participants who received active rTMS will demonstrate a 15% decrease in RSFC (resting state functional connectivity) between the DLPFC (dorsolateral prefrontal cortex) and anterior cingulate * Efficacy: During the final 12 weeks of the trial (weeks 2-13), at least 15% of participants who received active rTMS will demonstrate 3 consecutive weeks of abstinence Participants will: * Have two brain MRI scans; * Undergo 1 week of daily rTMS (or sham) treatments (up to 20 sessions), and; * Have 12 weeks of once-weekly cognitive-behavioral therapy for the treatment of cocaine use disorder. Researchers will compare active (real) rTMS to sham (placebo) rTMS. All participants will receive cognitive-behavioral therapy. The former principle investigator, Dr. Derek Blevins, has vacated his position (February 2025), and has transferred the principle investigator role to Dr. John Mariani, the STARS Clinic Director.

This study uses \[11C\]NPA positron emission tomography (PET) and a d-amphetamine challenge to image amphetamine induced dopamine release in the striatum in subjects with cocaine use disorders (CUD). Amphetamine-induced dopamine release data from this study will be correlated with \[11C\]NOP-1A VT measured at baseline in the midbrain. \[11C\]NOP-1A PET data will be used from aim 1 (see, Study Record: Imaging CRF X NOP interactions in Cocaine Use Disorders)

This study uses \[11C\]NOP-1A positron emission tomography (PET) and a hydrocortisone challenge to image the interaction between nociceptive opioid peptide (NOP) receptors and cortisol/corticotrophin releasing factor (CRF) in subjects with cocaine use disorders (CUD) and matched healthy controls (HC). It will also examine whether alterations in CRF x NOP interactions predict relapse in subjects with CUD.

This study investigates how cocaine use and withdrawal affect sleep and circadian rhythms in individuals undergoing inpatient detoxification. Using wearable sleep monitors, actigraphy, questionnaires, and hormonal biomarkers, it aims to capture both objective and subjective changes in sleep across three key stages: active use, early withdrawal, and late withdrawal. The study is unique in its ability to explore sleep microstructure, the circadian system's role via melatonin and cortisol measurements, and the dynamic relationship between subjective sleep perception and objective sleep data. It also examines whether sleep quality may serve as a predictive marker of long-term withdrawal success.

This will be a human laboratory study evaluating the influence of pentoxifylline treatment on the effects of cocaine. Supported by and included in the Helping to End Addiction Long-term® (HEAL) Initiative.

In The Netherlands, each year, about 15 thousand people come into treatment because of problems with cocaine use. There is no approved medication for treatment of cocaine addiction and the psychosocial treatment patients receive is not successful for everyone; many return to treatment several times. There is evidence that agonist ("replacement") medications are effective in treating addiction: methadone for heroin addiction; nicotine replacement for smokers. Dexamphetamine is a stimulant medication registered for treatment of ADHD. It may also be effective as agonist treatment for people with cocaine addiction. It will be investigated whether sustained-release dexamphetamine in people with cocaine addiction, participating in routine methadone maintenance treatment for their comorbid opioid use disorder, (1) reduces cocaine use and (2) improves their health and quality of life.

The purpose of this study is to evaluate semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in combination with cognitive behavioral therapy (CBT) for the treatment of cocaine use disorder (CUD). This project is part of the NIH Helping to End Addiction Long-term (HEAL) initiative (https://heal.nih.gov/).

The researchers will test whether cognitively enhanced transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex can reduce craving in inpatients with cocaine use disorder. Neuroimaging before and after stimulation will establish the neural correlates of recovery and allow predictions of outcomes, which will be assessed throughout the study and one month after its completion. Results could pave the way towards development of a new self-administered intervention to reduce craving when it is needed the most, enhancing recovery real-time and in the natural environment in people with cocaine addiction as generalizable to other drugs of abuse and other disorders of self-control.

This is a single-center, randomized intervention study in a volunteer population of patients with cocaine/crack use disorder to evaluate the pharmacological treatment of cocaine/crack craving, comparing the drug clonidine with the active placebo clonazepam.

Combatting the rise of the opioid epidemic is a central challenge of U.S. health care policy. A promising approach for improving welfare and decreasing medical costs of people with substance abuse disorders is offering incentive payments for healthy behaviors. This approach, broadly known as "contingency management" in the medical literature, has repeatedly shown to be effective in treating substance abuse. However, the use of incentives by treatment facilities remains extremely low. Furthermore, it is not well understood how to design optimal incentives to treat opioid abuse. This project will conduct a randomized evaluation of two types of dynamically adjusting incentive schedules for people with opioid use disorders or cocaine use disorders: "escalating" schedules where incentive amounts increase with success to increase incentive power, and "de-escalating" schedules where incentive amounts decrease with success to improve incentive targeting. Both schemes are implemented with a novel "turnkey" mobile application, making them uniquely low-cost, low-hassle, and scalable. Effects will be measured on abstinence outcomes, including longest duration of abstinence and the percentage of negative drug tests. In combination with survey data, variation from the experiment will shed light on the barriers to abstinence more broadly and inform the understanding of optimal incentive design.

This research focuses on behavioral sensitization (BS) a specific behavioural disturbance in crack-cocaine addiction. The primary objective is to observe whether BS can be demonstrated in an ecological setting in crack dependent users by continuous actimetry for 3 weeks. It is planned to include 20 persons with a current crack-cocaine addiction with a preferential use of rapid administration route (intravenous or smoke), in a care institution: Fernand Widal Hospital. In the proposed research, the investigators will assess the movements of crack-cocaine dependent users in relation to consumption. They will have to wear continuously for 3 weeks an actimeter. They will also have 3 blood tests trying to identify biomarkers of BS.

The purpose of this research study is to measure synaptic density in the brain comparing individuals with cocaine use disorder to healthy controls.

The purpose of this research study is to find out if semaglutide is safe and well tolerated in adults with cocaine use disorder who do and do not have human immunodeficiency virus (HIV). Participants will complete a screening process and if you are able to participate, you will be assigned to one of two treatment groups: semaglutide or placebo. Participants will: * Visit the clinic once a week for semaglutide or placebo injections * Visit the clinic once every two weeks for labwork, assessments and/or surveys * If consented to optional MRI's, complete two MRI's

In this study, the research team proposes to longitudinally assess incubation of cue-reactivity, its reduction with cognitive reappraisal (CR; a self-regulation technique) and examine the impact of CR on clinical outcomes in individuals with cocaine use disorder (CUD). The primary objective is to use psychophysiological markers for tracking brain activity and behavior and changes therein with the use of CR during abstinence in CUD. The secondary objective is to examine whether brain and behavioral changes are associated with clinical outcomes in individuals with CUD. The primary endpoint is the time-related change in brain and behavioral indices with CR during abstinence in individuals with CUD. The secondary endpoint is the impact of CR-mediated changes on clinical outcomes of individuals with CUD. In this 5-yearlong study the research team will recruit 252 individuals seeking-treatment for CUD, 126 of whom will be randomly assigned to complete the Cognitive Reappraisal task repeatedly at 2 weeks, 1-2 months, 3 months, and 5 months after abstinence initiation (CR+ group), and the other 126 will be assigned to complete a Control task at the same time points (CR- group). All individuals between the ages of 18 and 65 years, irrespective of sex and sexual orientation will be recruited. Participation in the research study will be 5 sessions taking place (one at 2 weeks from screening, one at a month from screening, one at 3 months from screening, one at 5 months from screening, and one the month after the 5 month session) over the course of 6 months. The study will include EEG testing and will be administered multiple times over the course of 6 months. Participants will be randomized to one of the two groups; one group will get the Cognitive Reappraisal (CR+) intervention and the other group will get a Control intervention (CR-).

The purpose of this study is to assess effects of intermittent theta burst stimulation (iTBS) to left dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) compared to sham on electrophysiological indices of reward sensitivity and motivated attention in adults with cocaine use disorder.

The goal of this clinical trial is to learn about the effects of the combination of ketamine and realtime functional magnetic resonance imaging (fMRI) neurofeedback training in individuals with cocaine use disorder. The main questions the investigators aim to answer are: * Can the investigators observe a positive, significant effect on percentage of cocaine use days of both interventions combined as well as stand alone interventions? * Is there a significant transfer effect of the neurofeedback training? * Is there a significant, ketamine-dependent change in glutamate levels in the nucleus accumbens? Participants will be given ketamine and a realtime fMRI neurofeedback training. Both interventions are placebo-controlled. The investigators will compare the four intervention groups to investigate the effects of the stand-alone effects of the intervention and the combination of it.

During the first funding period (1st FP), the investigators developed a novel full Pavlovian-to-instrumental transfer (PIT) task that allows assessing both, general and specific PIT to investigate whether specific PIT differs between alcohol use disorder (AUD) and control subjects. Preliminary analyses of the full transfer task indicate that AUD participants exhibit a stronger specific PIT effect compared to controls. Based on these findings, the investigators want to compare specific and general PIT effects in patients with moderate to severe substance use disorders (alcohol, cannabis, methamphetamine, amphetamine and cocaine) to healthy controls on the behavioral and neural level (fMRI).

Cocaine is the 2nd most used illicit substance in Europe and its use implies numerous health complications as well as an annual social cost of 8.7 G d'€. Classical (picture, video, audio, imagery based or in vivo) cue exposure therapy for substance craving (CET), i.e. the irrepressible and non-voluntary desire to use the substance, failed to prove efficacious in treating substance use disorder. Virtual reality cue exposure therapy for substance craving (VRCET), is more immersive, realistic and controllable, and is suggested as being a more efficacious intervention in reducing craving as compared to classical CET. So far it's still not known, thus the secondary aim of the present randomized and clinical trial is to investigate, whether virtual reality cue exposure is more efficacious, as compared to classical cue exposure, in both eliciting and reducing cocaine craving in a clinical context of CET for cocaine craving. The main study aim to is to investigate whether a VRCET for cocaine craving based cognitivo-behavioral therapy (i.e. VRCET followed by memory focused cognitive therapy) is more efficacious than a behavioural therapy (i.e. classical exposure therapy to craving) in reducing cocaine craving. To do so, 54 voluntary residential patients in treatment for cocaine use disorder will be recruited from the Universitary Hospital Center of Martinique (CHUM, Martinique, France) and Saint-Esprit Hospital Center (CHSE, Martinique, France) and randomly allocated in either a 3 weeks individual experimental treatment (10 meetings of VRET for cocaine craving followed by 5 meetings of memory focused cognitive therapy) or a 3 weeks individual control treatment (15 meetings of pictures based exposure therapy for cocaine craving). Self-reported measures of retrospective (last 14 days) and in virtuo exposure cocaine craving will be collected at the beginning, after 10 days, after 15 days of treatment and 1 month post. Others secondary subjective, urinary and physiological cocaine use related measures will also be collected.