To deal successfully with the opioid crisis, we need to discover novel analgesics whose mechanisms do not involve the mu opioid receptor but that have high analgesic potency and low risk of adverse effects, particularly no abuse liability.The question is how to achieve this.
Future studies with ICSS could help (a) to clarify mechanisms that increase MOR agonist abuse potential during early opioid exposure or during chronic exposure leading to dependence, (b) to evaluate novel opioids either developed as candidate analgesics with reduced abuse potential or identified as designer opioids being synthesized and distributed for illicit use, and (c) to test candidate pharmacotherapies for treatment of opioid abuse in non-dependent and dependent subjects.
The combination of MOR agonists with non-MOR agonists may increase the analgesic potency of MOR agonists, reduce the development of tolerance and dependence, reduce the diversion and abuse, overdose, and reduce other clinically significant side effects associated with prolonged opioid use such as constipation.
The OPRM1rs1799971" genes_norm="4988">A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the rs1799971" genes_norm="4988">N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
This study assessed the impact of one synthetic cannabinoid, JWH-018, on the effects of two μ opioid receptor agonists using two procedures that address different aspects of abuse.
The δ opioid receptor (δR) is a promising alternate target for pain management because δR agonists show decreased abuse potential compared with current opioid analgesics that target the μ opioid receptor.
These results support the hypothesis that genetic variability in the μ-opioid receptor gene influences the subjective effects of amphetamine and may suggest new strategies for prevention and treatment of psychostimulant abuse.
Evidence points to the endogenous opioid system, and the mu-opioid receptor (MOR) in particular, in mediating the rewarding effects of drugs of abuse, including nicotine.
The recently shown efficacy of these analgesics combined with a possible lower abuse potential and side effect burden than mu opioid receptor agonists makes delta and peripherally restricted kappa opioid receptor agonists promising targets for treating pain.
Opioidergic neurotransmission and, specifically, the mu opioid receptor have been implicated in the reinforcing effects of a variety of drugs of abuse.