Conolidine: A Novel Plant Extract for Chronic Pain.

Pain, the most common symptom reported among patients in the primary care setting, is complex to manage. Opioids are among the most potent analgesics agents for managing pain. Since the mid-1990s, the number of opioid prescriptions for the management of chronic non-cancer pain (CNCP) has increased by more than 400%, and this increased availability has significantly contributed to opioid diversion, overdose, tolerance, dependence, and addiction. Despite the questionable effectiveness of opioids in managing CNCP and their high rates of side effects, the absence of available alternative medications and their clinical limitations and slower onset of action has led to an overreliance on opioids. Conolidine is an indole alkaloid derived from the bark of the tropical flowering shrub Tabernaemontana divaricate used in traditional Chinese, Ayurvedic, and Thai medicine. Conolidine could represent the beginning of a new era of chronic pain management. It is now being investigated for its effects on the atypical chemokine receptor (ACK3). In a rat model, it was found that a competitor molecule binding to ACKR3 resulted in inhibition of ACKR3's inhibitory activity, causing an overall increase in opiate receptor activity. Although the identification of conolidine as a potential novel analgesic agent provides an additional avenue to address the opioid crisis and manage CNCP, further studies are necessary to understand its mechanism of action and utility and efficacy in managing CNCP.