Conolidine: A Novel Plant Extract for Chronic Pain

Abstract

: 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.

Conolidine: A Magic Morphine or Just Another Scam?

“…The researchers felt that the identification of conolidine as a potential novel analgesic agent provided an additional avenue to address the opioid crisis and manage CNCP. 25 Szpakowska et al 26 studied conolidine and its action on the ACKR3 receptor, explaining a mechanism of action in both acute and chronic pain control. Receptor levels of ACKR3 were as high or even higher as those of the endogenous opiate system and correlated to similar areas of the central nervous system.…”

“…Earlier research studies in a rat model demonstrated that a competitor molecule binding to ACKR3 resulted in inhibition of ACKR3's inhibitory activity, causing an overall increase in opiate receptor activity. The researchers felt that the identification of conolidine as a potential novel analgesic agent provided an additional avenue to address the opioid crisis and manage CNCP 25. Szpakowska et al26 studied conolidine and its action on the ACKR3 receptor, explaining a mechanism of action in both acute and chronic pain control.…”

Immunomodulatory, anti-infammatory and antioxidant activities of aqueous and ethanolic extracts of Cissus quadrangularis Linn. (Vitaceae) in chronic pain

“…Generally, the treatment of neuropathic pain is based on a combination of analgesics and many classes of other drugs, which unfortunately cause kidney failure, gastric ulceration, coronary heart disease, gastrointestinal bleeding and thrombotic cardiovascular events (Vonkeman and van de Laar 2010; Rezabakhsh et al 2021). Scienti c progress has allowed the understanding of the characteristics of chronic neuropathic pain, as well as the knowledge and understanding of their molecular and cellular mechanisms; which has allowed the development of new therapies for the management of this type of pain (Edinoff et al 2021). Thus, the use of plants has become an essential alternative medicine for diseases resistant to modern drugs.…”