# The Endocannabinoid System and Enhanced Analgesia of a Novel NSAID Derivative > **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637) > **Publisher:** CED Clinic (https://cedclinic.com) > **Canonical URL:** https://cedclinic.com/hydrogen-sulfide-releasing-nsaid-derivative/ > **Published:** 2021-03-02T14:22:10-04:00 | **Last Modified / Clinically Audited:** 2026-09-28T11:17:13-04:00 > **Clinical Summary:** Explore the hydrogen sulfide releasing NSAID derivative ATB-352 and its enhanced analgesic effects with improved gastrointestinal safety. --- ### Enhanced Analgesic Effects and GI Safety of A Novel Hydrogen Sulfide‐Releasing Anti‐Inflammatory Drug (ATB‐352): A Role for Endogenous Cannabinoids ​In Summary Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the preferable alternatives to opioids in management of post-operative pain because they are not addictive; however, their use is limited by the substantial risk of bleeding and ulcer, particularly in the gastrointestinal (GI) tract. In animal models, derivatives of NSAIDs that contain a hydrogen sulfide (H2S)‐releasing group have been shown to cause markedly less GI damage than the parent NSAIDs. Ketoprofen is a very potent but also among the most GI-toxic NSAID. ATB-352 is a newly developed H2S-releasing derivative of ketoprofen. Scientists recently evaluated the pain-relieving efficacy and the toxicity of ATB-352 in comparison with ketoprofen using a mouse model of enhanced sensitivity to pain. They found that ATB-352 elicits less GI damage. Furthermore, the study also showed that ATB-352 is significantly more potent as an analgesic (pain-relieving substance) than ketoprofen. When the [cannabinoid receptor type 1](https://cedclinic.com/mediation-of-the-cannabinoid-receptor-type-1-can-enhance-the-antidepressant-powers-of-conventional-therapy/) (CB1) was blocked prior to administration, the analgesic effect of ATB-352 was compromised, but that of ketoprofen was not. This observation led researchers to believe that a major mechanism of ATB-352’s analgesic effects – but not ketoprofen’s – is mediated by the [cannabinoid receptor type 1](https://cedclinic.com/mediation-of-the-cannabinoid-receptor-type-1-can-enhance-the-antidepressant-powers-of-conventional-therapy/) (CB1). Not only does this study demonstrate the various advantages of ATB‐352, a H2S‐releasing derivative of ketoprofen, for pain control in postoperative setting, it also provides further evidence of the the endogenous cannabinoid system’s important role in biological pathways regulating pain sensation. [More access here](https://cedclinic.com/) [https://cedclinic.com/contact/](https://cedclinic.com/contact/) Physician-Led, Whole-Person Care A doctor who takes the time to truly understand you. Personal care that starts with listening and is guided by experience and ingenuity. 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