Dysregulation of Diurnal Cortisol Secretion Affects Abstinence Induction during a Lead‐in Period of a Clinical Trial for Depressed Cocaine‐Dependent Patients

Abstract

Background and Objective Hypothesizing that stress dysregulation may worsen cocaine dependence, we investigated the effect of diurnal cortisol secretion profile, suppression of cortisol secretion, and total cortisol secretion on retention, abstinence-based voucher earnings, days of cravings, and mood status of participants at the end of a 2-week medication-free lead-in prior to randomization in a clinical trial of mirtazapine (60 mg vs. placebo) for depressed cocaine-dependent patients. Methods We measured saliva cortisol levels at 9am, 2pm, and 5pm on the first two consecutive days of a 2-week medication-free lead-in period. Results from saliva samples were used to estimate the total daily level of cortisol, the diurnal profile of secretion (typical vs. atypical), and response to dexamethasone suppression (0.1 mg). Seventy-seven patients collected saliva samples at baseline, and 65 (85%) were suitable for profile analysis. Results Patients with typical profiles (52%) collected significantly more abstinence-based voucher earnings during the lead-in (U = 299.50, p = .025). Diurnal secretion profile did not significantly affect mood status, days of craving, or retention. There were no significant effects of suppression of cortisol secretion or of total cortisol levels on any outcome measures. Conclusion In a subgroup of cocaine-dependent patients, deviation of cortisol secretion away from the homeostatic diurnal pattern was associated with reduced success at achieving early abstinence, an important determinant of treatment success.

Salivary Cortisol Levels Are Associated with Craving and Cognitive Performance in Cocaine-Abstinent Subjects: A Pilot Study

“…We observed these cortisol measurements were positively associated with craving levels and negatively with the age of onset of drug consumption. Some studies about this topic have revealed that a deviation of cortisol secretion away from the homeostatic diurnal pattern in cocaine-dependent subjects was associated with reduced success at achieving early abstinence [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. This finding suggests a feed-forward cascade of effects of drugs on stress biology [ 58 ].…”

“…Concerning this, some studies have demonstrated the influence of parental history of substance abuse on the risk of early drug abuse in their offspring [ 63 , 64 ], and for instance, higher morning cortisol levels have been found among crack cocaine users with positive family history and lower treatment retention [ 44 ]. Indeed, activation of the HPA response may be an early dysregulation associated with excessive and early drug taking that ultimately sensitizes the extrahypothalamic CRH systems [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , ...…”

“…For instance, acute administration of cortisol increased cocaine craving in individuals with cocaine use disorder compared to a placebo injection [ 20 ]. Moreover, increased cortisol levels have been also associated with withdrawal symptoms and early relapse [ 21 , 22 , 23 ]. On the other hand, we also consider that some persons can take drugs to cope with stress-related symptoms and situations.…”

Social Self-Control Is a Statistically Nonredundant Correlate of Adolescent Substance Use

“…The Restlessness and Agitation Questionnaire ( RAQ ; Wong & Leventhal, 2014) used in this study consisted of 19 items (e.g. “Feeling wound up” and “Having difficulty keeping still”).…”