Medications for substance use disorders (SUD): emerging approaches

Abstract

Introduction: Substance use disorders are a group of chronic relapsing disorders of the brain, which have massive public health and societal impact. In some disorders (e.g., heroin / prescription opioid addictions) approved medications have a major long-term benefit. For other substances (e.g., cocaine, amphetamines and cannabis) there are no approved medications, and for alcohol there are approved treatments, which are not in wide usage. Approved treatments for tobacco use disorders are available, and novel medications are also under study. Areas covered: Medication-based approaches which are in advanced preclinical stages, or which have reached proof-of concept clinical laboratory studies, as well as clinical trials. Expert opinion: Current challenges involve optimizing translation between preclinical and clinical development, and between clinical laboratory studies to therapeutic clinical trials. Comorbidities including depression or anxiety are challenges for study design and analysis. Improved pharmacogenomics, biomarker and phenotyping approaches are areas of interest. Pharmacological mechanisms currently under investigation include modulation of glutamatergic, GABA, vasopressin and κ-receptor function, as well as inhibition of monoamine re-uptake. Other factors that affect potential market size for emerging medications include stigma, availability of treatment settings, adoption by clinicians, and the prevalence of persons with SUD who are not actively treatment-seeking.

Stress Allostasis in Substance Use Disorders: Promise, Progress, and Emerging Priorities in Clinical Research

“…Several available NE medications (e.g., doxazosin, guanfacine) still hold promise, but further research is needed with larger sample sizes to demonstrate these drugs' efficacy regarding stress-relevant outcomes. Among currently available medications that target CNS stress systems, baclofen, mifepristone, and ketamine warrant further immediate investigation (Butelman & Kreek 2017, Greenwald 2018. Of course, there remain many other stress-relevant neurotransmitter systems that have potential for future development (e.g., urocortin, dynorphin, neuropeptide Y, hypocretin/orexin) (Greenwald 2018).…”

GABRA2 rs279858-linked variants are associated with disrupted structural connectome of reward circuits in heroin abusers

“…Heroin misuse makes more attacks on the vulnerable population, such as adolescents and young adults, and can be life-threatening with significantly high morbidity and mortality. Adding new insight into the biological mechanism and identifying precise targets for neuromodulation are vital for the prevention and treatment of this devastating disease 6 .…”

Noncoding RNA therapeutics for substance use disorder

“…Substance use disorder (SUD) continues to be a worldwide public health crisis ( 1 ). Although many of the underlying mechanisms that drive compulsive drug use have been elucidated, the number of pharmacological agents that are approved to treat SUD remains stagnant ( 2 ). Current pharmacotherapies for SUD largely consist of small molecule modulation of neurotransmitter receptor activity ( 2 ).…”