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Unveiling the link between chronic pain and misuse of opioids and cannabis

  • Psychiatry and Preclinical Psychiatric Studies - Review Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Over 50 million Americans endure chronic pain where many do not receive adequate treatment and self-medicate to manage their pain by taking substances like opioids and cannabis. Research has shown high comorbidity between chronic pain and substance use disorders (SUD) and these disorders share many common neurobiological underpinnings, including hypodopaminergic transmission. Drugs commonly used for self-medication such as opioids and cannabis relieve emotional, bothersome components of pain as well as negative emotional affect that perpetuates misuse and increases the risk of progressing towards drug abuse. However, the causal effect between chronic pain and the development of SUDs has not been clearly established. In this review, we discuss evidence that affirms the proposition that chronic pain is a risk factor for the development of opioid and cannabis use disorders by outlining the clinical evidence and detailing neurobiological mechanisms that link pain and drug misuse. Central to the link between chronic pain and opioid and cannabis misuse is hypodopaminergic transmission and the modulation of dopamine signaling in the mesolimbic pathway by opioids and cannabis. Moreover, we discuss the role of kappa opioid receptor activation and neuroinflammation in the context of dopamine transmission, their contribution to opioid and cannabis withdrawal, along with potential new treatments.

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Acknowledgements

We would like to acknowledge the following organizations for funding support: National Institute on Drug Abuse (Grant No: 5R01DA053752 to C.M.C), National Institute of General Medical Sciences (Grant No: 2K12GM106996 to M.D.), and the Center for Medical Cannabis Research (C.M.C). We would like to acknowledge BioRender for the generation of figures.

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  1. MacDonald Research Laboratory Building, Department of Psychiatry and Biobehavioral Sciences, Shirley and Stefan Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 675 Charles E Young Drive South, Office 2774, Los Angeles, CA, 90095, USA

    Merel Dagher, Myra Alayoubi & Catherine M. Cahill

  2. Neuroscience Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, 90095, USA

    Myra Alayoubi & Catherine M. Cahill

  3. Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, 90095, USA

    Gabriella H. Sigal

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Dagher, M., Alayoubi, M., Sigal, G.H. et al. Unveiling the link between chronic pain and misuse of opioids and cannabis. J Neural Transm 131, 563–580 (2024). https://doi.org/10.1007/s00702-024-02765-3

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