Cocaine: Sleep and Cytokines
Michael Irwin, Principal Investigator

Sleep disturbance is a prominent complaint of cocaine dependent patients during usage, and also following withdrawal and abstinence. However, the high frequency of disordered sleep stands in sharp contrast with limited effort to fully evaluate sleep or to identify the mechanisms that account for sleep abnormalities associated with chronic cocaine abuse. Given evidence that cocaine addiction also leads to a striking increase in the risk of infectious disease, we hypothesize that the complex cytokine network is one physiological system that mediates both sleep and immune abnormalities in cocaine dependence. Basic observations demonstrate that cytokines play a key role in the regulation of sleep. Translation of cytokine-sleep mechanisms into the clinic show that sleep loss and disturbances of sleep architecture are coincident with alterations in pro-inflammatory and helper T cell type 1/type 2 (Th1/Th2) cytokines, and that cytokine abnormalities predict disordered sleep in cocaine dependent patients. Thus, the over-arching objective of this study is to evaluate sleep and the reciprocal relationships between sleep and cytokine expression in cocaine dependent patients during acute and protracted abstinence as compared to controls. Acute administration of cocaine will serve as a pharmacologic probe of cytokine-sleep regulatory processes. The specific aims of this study are to: 1) evaluate whether cocaine and cocaine dependence are associated with disturbances of sleep including loss of delta sleep and increases of REM sleep; 2) determine the predictive validity of proteomic measures of nocturnal pro-inflammatory-, Th1, and Th2 cytokines on sleep depth in cocaine dependent subjects during acute- and protracted abstinence and following acute cocaine administration; 3) examine the consequences of disordered sleep on the expression of pro-inflammatory, Th1, and Th2 cytokines and daytime sleepiness during acute- and protracted abstinence and following acute cocaine administration. Given the prominence of sleep disturbance in cocaine dependent subjects and evidence of sleep architecture abnormalities into recovery, understanding the bi-directional relationships between cytokines and sleep in cocaine dependence has implications for answering why sleep is disordered in cocaine dependent patients and for the development of novel treatments for sleep disturbance in cocaine dependence.