Learn more about cebranopadol

Cebranopadol is an investigational first-in-class analgesic in clinical development for the treatment of moderate-to-severe pain. Its novel mechanism has the potential to transform pain treatment so that patients can obtain relief with minimized risk of significant side effects. To date, cebranopadol has been studied in over 2,200 adults across 33 clinical trials with data demonstrating a promising efficacy and safety profile.

Cebranopadol’s novel mechanism of action targets two key receptors, the nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptors. These receptors play complementary and distinct roles to modulate pain biology, synergizing the analgesic and safety characteristics of the NOP receptor with the analgesic advantages of the MOP receptor.

The human body utilizes sophisticated pain modulation pathways with key receptors that receive and transmit pain signals. Two of these key receptors are the NOP and the MOP receptors, which co-localize in the brain to work together to regulate pain.1 Current treatments for moderate-to-severe pain involving conventional opioids have well-described adverse effects that may largely derive from preferentially targeting the MOP receptor.2 Activation of the NOP receptor has demonstrated distinct and complementary effects to MOP, resulting in less respiratory depression, less stimulation of the brain reward pathway and less euphoria.1 This coactivation of NOP and MOP receptors (“dual-NMR”) is the key to cebranopadol’s unique mechanism of action.

References:
1. Toll L, Bruchas MR, Caló G, Cox BM, Zaveri NT. Nociceptin/orphanin FQ receptor structure, signaling, ligands, functions, and interactions with opioid systems. Pharmacol Rev. 2016 Apr;68(2):419-57.
2. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC clinical practice guideline for prescribing opioids for pain – United States, 2022. MMWR Recomm Rep. 2022;71(3):1-95.

In clinical trials to date, cebranopadol has exhibited significant efficacy and has the potential to address an unmet medical need for patients suffering from pain. With its novel, dual-NMR mechanism of action, cebranopadol offers the potential to effectively treat moderate-to-severe pain with reduced risk of side effects such as:

  • Reduced abuse potential1,2
  • Lowered risk of developing tolerance and withdrawal symptoms
  • Less incidence of respiratory depression3

References:
1. Shram M, Apseloff G, Grieco J, Fam D, Lesnick M, Hackworth J. Abuse potential assessment of cebranopadol, a novel eual nociceptin (NOP) and Mu opioid (MOP) receptor (NMR) agonist: Implications for scheduling. Presented at: The College on Problems of Drug Dependence; June 2025. 
2. Apseloff G, Pardo A, Shram M, Grieco JC, Lesnick ML, Hackworth JC. Limited oral abuse potential of cebranopadol, a novel potent analgesic, compared to tramadol and oxycodone in recreational opioid users. Presented at: PainWeek; September 2023. 
3. Jansen S, Olofsen E, Moss L, et al. Respiratory and antinociceptive effects of a dual NOP-MOP receptor agonist cebranopadol versus full opioid receptor agonist oxycodone: a comparison in healthy volunteers. Anesthesiology. Published online December 11, 2025. doi:10.1097/ALN.0000000000005894

Two cebranopadol human abuse potential studies conducted head-to head against Class-II and Class-IV opioids have demonstrated that cebranopadol-treated subjects, even at supratherapeutic doses, showed less abuse potential as measured by drug-liking.1-2 Moreover, data to date suggest that cebranopadol does not produce meaningful physical dependence.3 In studies of subjects treated with cebranopadol for up to 14 weeks, abrupt discontinuation of cebranopadol did not require tapering or cause patients to exhibit clinically relevant withdrawal symptoms.3

Cebranopadol’s novel mechanism of action also lends promise in treating patients with substance use disorders. The National Institutes of Health (NIH) has awarded Adneuris Therapeutics a grant up to $16.6 million to study cebranopadol as a potential treatment for opioid use disorder.

References:
1. Apseloff G, Pardo A, Shram M, Grieco JC, Lesnick ML, Hackworth JC. Limited oral abuse potential of cebranopadol, a novel potent analgesic, compared to tramadol and oxycodone in recreational opioid users. Presented at: PainWeek; September 2023. 
2. Shram M, Apseloff G, Grieco J, Fam D, Lesnick M, Hackworth J. Abuse potential assessment of cebranopadol, a novel eual nociceptin (NOP) and Mu opioid (MOP) receptor (NMR) agonist: Implications for scheduling. Presented at: The College on Problems of Drug Dependence; June 2025. 
3. Fam D, Pardo A, Hackworth J. Cebranopadol, a novel potent analgesic: Pooled analysis of clinical opiate withdrawal scales. Presented at: PainWeek; September 2022.

Adneuris Therapeutics anticipates submitting an NDA for the treatment of moderate-to-severe acute pain in 2026.

In Q1 2025, Adneuris conducted two registrational acute pain trials in patients following abdominoplasty and bunionectomy surgeries. These data are foundational to discussions with regulators in anticipation of NDA submission. For data and more information about these trials, see the press releases in the News section of this website.

Adneuris anticipates conducting clinical trials in chronic pain conditions, including neuropathic pain. Cebranopadol has been granted Fast Track Designation for chronic low back pain. In addition, the National Institutes of Health (NIH) has awarded Adneuris Therapeutics grant up to $16.6 million to study cebranopadol as a potential treatment for opioid use disorder.