Opioid use disorder (OUD) is a chronic and severe psychiatric condition, defined by problematic opioid use, that significantly impairs interpersonal and social functioning. Over the last 10 years, a dramatic increase in the prevalence of OUD and deaths by overdose has occurred in several developed countries, in particular the USA. In France, similarly, the burden associated with OUD is worsening, and now represents a major public health crisis. During last decades, it has been demonstrated that OUD results from combined effects of numerous factors, which have been robustly identified across a variety of research fields, including psychiatry, sociology, and neurobiology. This plurality is embodied in a comprehensive theoretical framework, the biopsychosocial model of addiction, composed of elements whose effects have been well defined individually, but remain poorly characterized and understood in combination. More recently, behavioral epigenetics has emerged as a promising discipline to identify molecular mechanisms that may help explain how life experiences, in particular psychiatric and sociological factors, modulate the regulation of genes, brain function, and emotional regulation. In this context, here we propose a multidisciplinary project that builds on the collaboration of psychiatrists, sociologists and neuro-epigeneticists. The investigators will simultaneously characterize major psychiatric and social factors in a large cohort of individuals with OUD, with the goal of covering the full spectrum of disease severity. By combining deep psychosocial evaluation with the investigation of blood-derived epigenetic biomarkers, they will seek to provide a new and deeper understanding of determinants of OUD severity.

The project builds on 3 main hypotheses:

1. Social and psychiatric factors together contribute to OUD severity;
2. Epigenetic mechanisms, measured in peripheral accessible tissues such as blood, represent biomarkers that may reflect pathophysiological processes resulting, at least in part, from the effects of psychosocial factors;
3. Measures of OUD severity combining both psychosocial factors and epigenetic biomarkers have the potential to improve our ability to describe OUD severity, and better predict its clinical course.

First aim of the study is to systematically characterize OUD severity (DSM-5 criteria) and psychosocial factors in N=350 individuals with OUD, recruited at Safe Injection Sites (SIS), and other addiction-related facilities: French low-risk consumption room (CSAPA), Center for Reception and Accompaniment in Harm Reduction for Drug Users (CAARUD), and pain treatment centers.

Recruitment at SIS will allow to target OUD patients at highest psychosocial risk, who remained mostly out-of-reach of previous studies, and to compare them to stabilized OUD patients, overall covering a wide spectrum of disease course and severity.

Second aim of the study is to examine genome-wide epigenetic regulation (DNA methylation) and gene expression in peripheral blood samples collected from all subjects, at inclusion; then, to leverage systems biology to characterize relationships among these molecular measures and OUD and psychosocial severity;

Third aim of the study is to assess the evolution of OUD and psychosocial severity in the whole cohort, over 2 years, in order to determine how such evolution can be predicted using molecular epigenetic biomarkers defined at inclusion.

Inclusion Criteria:

• Male, female, or transgender person, age > 18 years
• French speaking subject, able to understand the objectives and risks of the research
• Informed signed consent form by the curator (subject under curatorship) / guardian (subject under guardianship), if applicable
• Subject who has written "I consent" on the consent form
• Subject using psychoactive substances and who attends a low-risk consumption room (SCMR), or a Center for Care, Accompaniment and Prevention in Addictology (CSAPA)
• Subject who used one or more illegal opioid drugs or one or more medications (with or without a prescription) at least once in the last 3 months (heroin, buprenorphine, morphine sulfate, methadone, morphine derivatives, oxycontin, oxycodone, oxynorm, Subutex® (Sub), Temgesic®, Suboxone®, Orobupre®, Skenan®, Moscontin®, opium, pethidine, codeine, dinacode, neocodion, codeine efferalgan, Lamaline®, tramadol, durogesic patches, fentanyl...)

Exclusion Criteria:

• Inability to give the subject informed information (subject with difficulties in understanding)
• Subject in an emergency or life-threatening situation
• Subject under court protection (upon subject's declaration)
• Subject participating in an investigational drug study (upon subject's declaration)

Participants will be recruited:

• in the 2 SIS in Paris (Gaia) and Strasbourg (Ithaque),
• in French addiction care centers: CSAPA (primary care outpatient settings for patients with addiction) in Strasbourg, Paris and Lyon