Ben Clements on Rescuing Opioids with GPCR Modulators

Dr. GPCR Podcast
May 6
2 min read

Updated: May 27

Watch Episode 166

Pain management is broken. And Benjamin Clements is on a mission to fix it.

In this powerful episode of the Dr. GPCR Podcast, Ben, a postdoctoral fellow at the University of Michigan, walks us through how positive allosteric modulators (PAMs) targeting the mu-opioid receptor could preserve pain relief while reducing the devastating side effects of traditional opioids.

Redefining Opioid Pharmacology

Ben and his colleagues discovered that PAMs can dramatically increase the efficacy of existing opioids. In fact, one of their recent neuroma pain studies showed a tenfold increase in methadone potency. That’s not an incremental advance; that’s a potential paradigm shift.

“We’ve seen these modulators rescue opioid function where it completely fails in neuroma models. That’s huge.” – Ben Clements

By combining chronic pain models with receptor-level pharmacology, Ben is bridging molecule to model, and model to patient. His work highlights how foundational GPCR science can drive therapeutic innovation.

Beyond Acute Pain: Into the Chronic Unknown

Opioids work well for acute pain. Chronic pain? Not so much. Neuropathic conditions like neuromas often resist standard opioid treatments. Ben’s approach injects new life into an area most clinicians have given up on.

Using PAMs, his team aims to re-sensitize these conditions to opioids without increasing toxicity.

The GPCR Angle

Ben sees GPCRs as untapped goldmines for drug discovery. Allosteric modulation is already proven in ion channels (think benzodiazepines and barbiturates) but still novel for GPCRs.

And that’s where the excitement lies: "There’s so much space left to explore in GPCR-targeted modulation," he says. With collaborations across medicinal chemistry and neuropathic pain research, Ben is bridging molecule to model and molecule to patient.