Bladder pain study points to cannabinoid receptors as treatment target
Flinders University researchers say activating CB1 and CB2 receptors outside the brain reduced cystitis-related pain signals in a preclinical model.
By Priya Raghavan · Science Reporter
3 min read
Researchers led by Flinders University say a pair of cannabinoid receptors in bladder sensory pathways may offer a way to reduce pain from cystitis without the psychoactive effects linked to cannabis. The findings matter because cystitis and related chronic bladder pain conditions can leave patients with burning pain, urinary urgency and limited treatment options, according to the university.
The study, published in Autonomic Neuroscience, examined peripheral cannabinoid CB1 and CB2 receptors in a preclinical model of cystitis-induced bladder hyperalgesia. Flinders said the team found that activating both receptors together shut down the heightened pain response seen in the model.
Cystitis is bladder inflammation, most often tied to a bacterial urinary tract infection, Flinders said. In some patients, pain and urgency persist as interstitial cystitis/bladder pain syndrome, or IC/BPS, a chronic condition that the researchers said affects up to 13% of people and occurs mainly in women.
Flinders said existing treatments for IC/BPS can be invasive or have limited success. The university also noted that medicinal cannabis products containing THC can relieve pain, but their use may be constrained by unwanted psychoactive effects.
How the approach differs from cannabis
First author Stewart Ramsay, a neuroscience research fellow at Flinders University, said the study identified cannabinoid receptors in peripheral bladder sensory pathways as possible drug targets. According to Ramsay, activating those receptors together in the preclinical model blocked the exaggerated pain response associated with cystitis.
The researchers focused on compounds designed to act outside the central nervous system. Flinders said these “peripherally restricted” cannabinoid compounds cannot cross the blood-brain barrier, which the team said could avoid the mind-altering effects associated with cannabis use.
Senior author Vladimir Zagorodnyuk, an associate professor in the Flinders Health and Medical Research Institute’s neuroscience group, said the results support further development of combination therapies that act on both cannabinoid receptor types while limiting central nervous system side effects. Flinders said the approach is aimed at bladder pain and related symptoms in IC/BPS.
Why CB1 and CB2 matter
The study builds on prior evidence about the two receptor types, according to the researchers. Flinders said peripheral CB1 receptors have been linked with visceral and somatic pain, while CB2 receptors are increasingly associated with dampening inflammation.
By targeting both receptors in the bladder’s sensory pathways, the researchers said a future therapy might address pain signaling while avoiding direct brain effects. The current findings remain preclinical, and Flinders did not report results from human trials.
The next step, according to the university, is to test the safety and effectiveness of the strategy further. The researchers said their goal is to move the work toward clinical studies in people.
The paper is titled “Combined peripheral cannabinoid CB1 and CB2 receptor activation abolishes cystitis-induced bladder hyperalgesia,” by Stewart Ramsay and colleagues. It was published in 2026 in Autonomic Neuroscience, according to Flinders University.
This story draws on original reporting from Medical Xpress.