How CASPR is helping advance next generation addiction medicine

Trials and programs that CASPR is running or making possible.

I haven’t had as much time to write recently because CASPR’s programs have been scaling up quickly. Here’s an update.

Why we do it

Our core thesis, if you haven’t heard me say it a dozen times before, is that breakthrough therapies for addiction are failing to reach doctors and patients due to market failures. A combination of pharmaceutical companies’ avoidance of addiction medication development and spiral of neglect and low expectations has led to virtually zero novel medications in the past 20 years. The medications we do have are lifesaving but lack either sufficient efficacy or sufficient patient appeal to make population-level impacts. Treatments that combine appeal and efficacy are urgently needed.

At the peak of the AIDS crisis, in 1994, 43,000 Americans died. Meanwhile a movement of patients and advocates fought tremendous bias to drive additional research funding and rapidly bring new treatments to market. When breakthrough anti-retroviral medicines arrived to patients, deaths dropped in half in just a few years and are now 90% lower.

In the past few years, opioid deaths in the US have been over 100,000 per year, more than double than the peak of HIV/AIDS. And that’s just a small portion of the over 700,000 annual American deaths from addictions including smoking, alcohol, opioids, and stimulants. But addiction has never had a patient self-advocacy movement like there was for HIV/AIDS. Most people with substance use disorders and their families have internalized our cultural message that personal responsibility is the core problem, so demanding more effective medicine doesn’t quite compute. This is where we hope to be effective.

All this is simply to say: CASPR is doing everything we can to try to bring a new generation of addiction therapies to doctors and patients. We are particularly interested in GLP-1RA therapies, like Ozempic, which can reduce addictive drive across substances, can be used with all existing addiction medications, and have very high patient appeal (in no small part due to their weight loss effects). Here’s the science and stories from doctors and patients.

What we do

CASPR always looks for high impact opportunities— here’s what we’re doing now:

Ozempic and Opioid Overdoses: Study at the VA

CASPR has funded a study of opioid overdose rates among veterans with OUD history who received Ozempic for diabetes— are veterans who take Ozempic less likely to overdose? We hope to have results in the next few months. For now, I will just say that we are extremely optimistic about the impact in this population. We’re working with our friend Dr. Dave Oslin, MD at the VA.

Semaglutide Treatment for Women in Transitional Housing

OpenDoors is a fantastic organization in Providence, RI that serves some of the most vulnerable populations affected by poverty and addiction. Their research director Nick Horton is running a trial that will add semaglutide to OpenDoors’ transitional housing program for women who are coming out of jail and prison. Often the most vulnerable and highest-need populations are the last to be studied, due to instability and difficulty with trial adherence. Our goal with this project is to bring these medicines directly to the populations that might benefit the most. The trial may begin as early as April– we’ll have more updates soon and here’s a great video about the project.

Support for semaglutide for OUD trial

CASPR is making a modest contribution to Dr. Sue Grigson’s wonderful trial of semaglutide for OUD, in combination with methadone or buprenorphine. This is a trial that could change opioid addiction treatment forever. The study is currently recruiting and treating patients, but still hopes to add an additional site.

Policy to Increase Addiction Medication Development

The lack of pharmaceutical activity in addiction medicine must be addressed structurally. The pipeline of new therapies is far too small and promising programs often get cut before they reach phase 3 trials. A few months ago, we published the Innovation Agenda for Addiction, along with the Institute for Progress and the Federation of American Scientists. We are now working to advance two of the recommendations in DC: expanding the FDA’s Priority Review Voucher (PRV) program to include addiction medicine indications and pushing the FDA to clarify and update the validated endpoints for addiction therapies. Both of these interventions are zero cost to the government and would substantially increase biotech activity and the rate of addiction medicine approvals. We are meeting with members of Congress and agency leadership. We are always eager to collaborate with others on this effort, so please be in touch if you are interested.

Expanding GLP-1 Addiction Therapy at Caron Treatment Centers

As more and more doctors have begun prescribing GLP-1s for substance use disorders, Caron Treatment Centers has been at the forefront of research and adoption. Caron is one of the most established addiction treatment centers in the world and was the location of Sue Grigsons’s initial RCT of liraglutide for opioid cravings. Now CASPR is funding a new Caron program that will provide GLP-1 access to even more patients, including those who cannot afford Ozempic or Mounjaro at list prices of $1000+ per month. Led by Dr. Steven Klein, PhD, this innovative program is part of a broader movement that has made GLP-1s one of the most common off-label addiction therapies, joining treatments like clonidine for opioid withdrawal and wellbutrin for stimulant use disorder.

Phase 3 Trial of a GLP-1 for AUD

CASPR’s most ambitious goal is to launch a phase 3 trial of a GLP-1 for alcohol use disorder. While the progress in off-label adoption of GLP-1s is promising, these treatments will never reach a large percentage of substance use disorder patients without large-scale phase 3 trials and FDA approval. High quality RCT evidence and coverage from public and private health insurance programs depends on this. We are making significant progress on this project and hope to have more to announce soon. As always, if you have expertise or resources to contribute towards this effort, please be in touch.

Strategies that can scale

CASPR is a high leverage organization– we are doing a lot with a lean and ambitious team and that includes this publication, Recursive Adaptation, which we believe is the most-read newsletter in the field of addiction. All of CASPR’s efforts above are funded by the foundations and individuals that support our work. We receive no money from pharmaceutical companies. If you are interested in helping us do more, please be in touch– your contributions will be spent wisely on high-impact projects.