Recovering from cocaine: insights from clinical and preclinical investigations

Abstract

Cocaine remains one of the most addictive substances of abuse and one of the most difficult to treat. Although increasingly sophisticated experimental and technologic advancements in the last several decades have yielded a large body of clinical and preclinical knowledge on the direct effects of cocaine on the brain, we still have a relatively incomplete understanding of the neurobiological processes that occur when drug use is discontinued. The goal of this manuscript is to review both clinical and preclinical data related to abstinence from cocaine and discuss the complementary conclusions that emerge from these different levels of inquiry. This commentary will address observed alterations in neural function, neural structure, and neurotransmitter system regulation that are present in both animal models of cocaine abstinence and data from recovering clinical populations. Although these different levels of inquiry are often challenging to integrate, emerging data discussed in this commentary suggest that from a structural and functional perspective, the preservation of cortical function that is perhaps the most important biomarker associated with extended abstinence from cocaine.

Keywords: Abstinence; Addiction; Cocaine; Glutamate; Neuroimaging; White matter.

Figure 1

Preliminary data demonstrating alterations in cerebral glucose metabolism in among a cohort of former cocaine users living in a residential treatment facility (n = 23) relative to age, gender and education matched controls (n = 14). These individuals had been abstinent for either less than 1 month (short-term, n = 6), between 1–5 months (middle-term, n = 10), or 10–20 months (long-term, n = 7). The colors superimposed on the gray-scale template indicate the areas of significant increases (red colormap, t-values) and decreases (blue colormap, t-values) in regional glucose metabolism in these subgroups relative to age, gender, and education matched controls (p<0.05, corrected clusters). The numbers above the images indicate the location of the coronal section in a standardized human template (Montreal Neurologic Institute).

Figure 2

Representative autoradiograms of [³H]SCH 23390 binding to dopamine D1 receptors (top panel) and [³H]WIN 35,428 binding to dopamine transporters (bottom panel) in coronal sections of rhesus monkey striatum. Panels A and D: control animal responding for food-reinforcement. Panels B and E: cocaine self-administration animal with 30 days abstinence. Panels C and F: cocaine self-administration animal with 90 days abstinence (adapted from Beveridge et al, 2009).