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This study aims to measure synaptic density in the brains (including in ventral striatum [VS] and medial prefrontal cortex [mPFC]) of abstinent subjects with Cocaine Use Disorder (CUD) or Opiate Use Disorder (OUD) as compared to healthy control (HC) subjects using 11C-UCB-J PET. Subjects will undergo a single 11C-UCB-J (also known as 11C-APP311) PET scan. This would be the very first to image synaptic density in human cocaine and opiate users, thereby testing whether altered synaptic density in the rodent brain is recapitulated in CUD and OUD humans. If confirmed, the current study would provide compelling clinical-translational support for an important pathophysiological mechanism of addiction - aberrant structural synaptic plasticity. As such, the current study has considerable potential for advancing the neurobiological understanding of human cocaine and opiate addiction.
Cocaine abuse is associated with serious physical, psychiatric and social problems. Addiction results in the compulsive use of a substance with loss of control and persistence despite the negative consequences.The act of re-engaging in the search for drugs is called relapse and a particularly insidious aspect of addiction is that vulnerability to relapse lasts for many years after stopping drug use. The main reason why people continue to use cocaine is because of its influence on the reward system.Indeed, this substance makes it possible to increase the level of dopamine, particularly in the nucleus accumbens.This increase in dopamine is not related to the hedonic pleasure that consumption provides. Instead, it imprints a positive value to enhancers and facilitates the learning of reward associations through the modulation of the cortical and subcortical regions of the brain.In other words, it suggests that users become sensitive to a series of stimuli that combine with a rewarding feeling, which drives them to consume when they encounter them. N-acetylcysteine (NAC) has been used for a long time, mainly as mucolytic. It has also been used as a glutathione antioxidant precursor in the treatment of paracetamol overdose for more than 30 years. NAC has shown beneficial effects in animal models of cocaine addiction by reversing neuroplasticity and reducing the risk of restoring consumer behavior in rodents. Human studies show that NAC is potentially effective in preventing relapse in abstinent patients and ineffective in reducing current consumption. In this study the investigators will test a sample of newly detoxified (and therefore abstinent) patients who have taken a 3-4 week course of treatment, in order determine if NAC can be a useful medication candidate to avoid relapse in patients with cocaine dependence.
In the United States, 1.5 million people abuse cocaine leading to a host of negative health and economic consequences, yet no FDA approved treatment exists. To develop effective treatments, the following must be considered: 1) do potential medications ameliorate brain disruptions associated with cocaine use? 2) are multiple, targeted treatments necessary? To meet these goals, innovative multi-modal neuroimaging will be used to determine whether rebalancing the serotonergic (5-HT) system reduces cocaine cue reactivity, impulsivity, and normalizes related neurochemistry and brain connectivity.
Repetitive bilateral (left cathodal/ right anodal) transcranial Direct Current Stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) seems to reduce craving and relapse risk. However, little is known about the relapse rates in cocaine addiction after tDCS, despite the need for new treatment interventions to reduce the high relapse rates in cocaine addiction. The investigators aim to explore the effects of repetitive tDCS in a larger sample (N=80) of cocaine addicted patients on number of relapse days after three months. In addition, the underlying working mechanism will be explored (e.g. cognitive control functioning). Ecological momentary assessment (EMA) will be used to measure relapse, craving and mood since retrospective self-reports seem to be less reliable in this respect.
The primary objective is to investigate the potential ability of Inderal (propranolol hydrochloride) to diminish the reconsolidation of motivationally potent drug-related cues in cocaine dependent participants. If effective in this laboratory model, Inderal may have clinical efficacy.