A comprehensive clinical and neuroimaging approach of sex differences in crack cocaine use disorder

Abstract

In Brazil, 1.4% of the population reports lifetime use of smoked cocaine (crack). The use of the drug relates to social and economic issues for society and poses serious health problems, including early death. Crack cocaine use disorder (CUD) is the medical condition which refers the pathological use of the drug. CUD relates to several negative outcomes such as higher rates of HIV and HCV infections, familiar problems and crime involvement, in addition to a higher prevalence of concurrent mental disorders. Scientific agendas promote evidence-based studies as a need for better therapeutics. In this regard, some gaps in the field require attention. In this line, distinct factors confer vulnerability for crack cocaine use in males and females: more males use the drug (a 3:1 proportion), but females show a faster transition from initial drug use to CUD. The course of the disease also show differences; females report a higher craving for the drug, while males have more frequent involvement with violent crimes. Thus, scientific commitments highlight a calling for the integration of those biopsychosocial models that consider individual characteristics in addition to those who consider addictive disorders as “brain diseases.” A more consistent interdisciplinary integration of knowledge from classical theories in combination with advances provided for technologic methods is a promising route. Hence, the aim of this doctoral thesis was to investigate sex differences in crack cocaine users. To address the main objective, the thesis has two studies with groups of participants diagnosed with CUD and hospitalized for drug detoxification. These two groups were one of males (CK-M) and a second of females (CK-F). Study 1 had as its objective to get a picture of sex differences in the psychosocial profile. Study 2 had as its objective the identification of sex differences in brain functioning level. Study 1 had 798 CK-M and 546 CK-F. Results consistently revealed CK-M as having a more severe alcohol use history and higher rates of concurrent alcohol use disorder than CK-F. On the other hand, CK-F showed an earlier crack cocaine use onset, higher drug use severity, and more familiar and work problems along with a higher prevalence for lifetime mental disorders. Particularly, CK-F showed higher rates for trauma and stress. Study 2 had a sample of 80 participants: CK-M (n = 20), CK-F (n = 20), a group of males (HC-M, n = 20), and another of healthy female controls (HC-F, n = 20). Participants did a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The method makes it possible to investigate temporal associations between nonspatially related brain areas by using as a measure fluctuations in the blood oxygen-level dependent (BOLD) level. It is an indirect measure of energy consumption, and by testing those correlations, functional connectivity (FC) can be investigated. Results supported CK-M as having an overall higher intra- and internetwork FC, while CK-F showed an overall lower FC in this regard. Taking both studies, the conclusions of this thesis point toward the existence of sex differences in all biopsychosocial domains. Thus, the interpretation of studies in crack cocaine use, particularly those testing interventions, need to resemble the possible existence of sex differences. Therefore, a hope from studies like this is that sex-specific models for crack cocaine use and CUD emerge and become tested. Similarly, possible interventions, also need to be aware of such backgrounds and consider possible sex differences when developing interventions, researches and public health policies as well.