Synthetic opioids: a review and clinical update

Abstract

The term ‘opioids’ refers to both the natural compounds (‘opiates’) which are extracted from the opium poppy plant ( Papaver somniferum) and their semi-synthetic and synthetic derivatives. They all possess relatively similar biochemical profiles and interact with the opioid receptors within the human body to produce a wide range of physiological effects. They have historically been used for medicinal purposes, their analgesic and sedative effects, and in the management of chronic and severe pain. They have also been used for non-medicinal and recreational purposes to produce feelings of relaxation, euphoria and well-being. Over the last decade, the emergence of an illegal market in new synthetic opioids has become a major global public health issue, associated with a substantial increase in unintentional overdoses and drug-related deaths. Synthetic opioids include fentanyl, its analogues and emerging non-fentanyl opioids. Their popularity relates to changes in criminal markets, pricing, potency, availability compared to classic opioids, ease of transport and use, rapid effect and lack of detection by conventional testing technologies. This article expands on our previous review on new psychoactive substances. We now provide a more in-depth review on synthetic opioids and explore the current challenges faced by people who use drugs, healthcare professionals, and global public health systems.

Tonantzitlolone B Modulates the Endogenous Opioid System to Promote Antinociception in Mice

“…The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jnatprod.3c00731. Additional experimental results as follows: figures of the effect of TZL-B on the rota-rod test; overlay of TZL-B with endogenous opioid peptide agonists; UV chromatogram of TZL-B; 1 H NMR spectrum of TZL-B; 13 ■ AUTHOR INFORMATION…”

“…TZL-B was purified from the hexane extract of the roots of S. loranthacea, as previously described. 27 The purity level of TZL-B (95%) was evaluated based on an HPLC chromatogram (Figure S3) and 1 H and 13 C NMR spectra (Figures S4 and S5).…”

“…12 On the other hand, opioid analgesics such as morphine inhibit both phases of the test, as they block nociceptive input at the spinal cord level. 13 Hence, the next steps of this study aimed to investigate both mechanistic hypotheses: control of inflammation and centrally mediated antinociception.…”

Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D3 (D3R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics

“…Moreover, prevention of dependence on opioids prescribed for pain management, such as oxycodone, has not been addressed pharmacologically. Indeed, dependence on prescription opioids remains a major contributor to the current opioid crisis in the United States, − although recently, the easy and cheap access to synthetic opioids such as fentanyl has become the major driver in opioid overdose . Alongside social and public health programs, the National Institutes of Health (NIH) has supported improvement in access to treatment and recovery, campaigns to promote safe opioid prescription practices and overdose prevention, and movements to combat the stigma associated with OUD.…”

“…Indeed, dependence on prescription opioids remains a major contributor to the current opioid crisis in the United States, 1−6 although recently, the easy and cheap access to synthetic opioids such as fentanyl has become the major driver in opioid overdose. 7 Alongside social and public health programs, the National Institutes of Health (NIH) has supported improvement in access to treatment and recovery, campaigns to promote safe opioid prescription practices and overdose prevention, and movements to combat the stigma associated with OUD. The development of innovative medications for OUD and safe, effective, non-addictive strategies to manage pain, while minimizing risk of relapse, is the focus of a highly translational NIH scientific effort, culminating with the launch of the HEAL initiative (helping to end addiction long-term).…”