Ketone Supplement for Opioid Use Disorder

Overseen By Kynah Walston, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must not be taking: GLP-1 receptor agonists

Disqualifiers: Severe GI disease, Cirrhosis, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a drink containing ketones can reduce cravings and withdrawal symptoms, such as low mood and pain, in individuals with opioid use disorder (OUD) during their stay at a treatment center. Participants will receive either a ketone drink or a placebo (a drink with no active ingredients) three times daily for a week. This trial suits those admitted to a treatment center for opioid withdrawal and willing to adhere to the study's procedures. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking GLP-1 receptor agonist medications (like semaglutide) at least two weeks before participating, as they can interfere with the ketone supplement. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that ketone supplements might help reduce anxiety and seizures during early withdrawal. Studies observed this effect when combining a ketogenic diet with ketone monoester supplements. While these results are encouraging, clear information about the side effects of ketone supplements in people with opioid use disorder remains unavailable.

Since this trial is in its early stages, researchers are still learning about the treatment's safety in humans. Early trials often focus on participants' ability to handle the treatment, so any possible side effects or problems are still under investigation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for opioid use disorder?

Unlike the standard treatments for opioid use disorder, which often include medications like methadone or buprenorphine to manage cravings and withdrawal, the ketone supplement offers a novel approach. Ketones are unique because they provide an alternative energy source for the brain, potentially reducing opioid cravings by stabilizing brain energy metabolism. Researchers are excited about this treatment because it could offer a non-opioid alternative to existing therapies, which might reduce dependency on traditional medications and offer a new pathway to recovery. This could be particularly beneficial for individuals who are seeking treatments that don't involve further use of opioid-based medications.

What evidence suggests that ketone supplementation could be effective for opioid use disorder?

Research has shown that ketone supplements (KS), which participants in this trial may receive, might help reduce cravings and withdrawal symptoms for opioids. Early studies found that KS can lessen these symptoms similarly to a ketogenic diet, which alters the body's energy use. In animal studies, ketogenic diets enhanced opioid effectiveness, suggesting that ketones might increase sensitivity to opioids and help reduce cravings. Evidence also indicates that ketones can ease withdrawal symptoms in conditions like alcohol use disorder, which resemble opioid use disorder. These findings suggest that ketone supplements could be a useful tool in managing opioid dependency. ^{3 4 6 7 8}

Who Is on the Research Team?

Peter Manza, PhD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for adults with opioid use disorder who are currently undergoing in-patient acute withdrawal management. Participants must not have conditions like ketoacidosis that could be worsened by ketone supplements.

Inclusion Criteria

Meets currents DSM-5 criteria for OUD and admitted for opioid withdrawal management treatment at Caron Treatment Center

Willingness to provide signed, informed consent and commit to completing the procedures in the study

I am between 18 and 75 years old.

Exclusion Criteria

Judged by the principal investigator, study physician, or their designee to be an unsuitable candidate for the study

I have been taking GLP-1 receptor agonist medications like semaglutide in the last two weeks.

Currently pregnant or lactating, for people of childbearing potential

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive ketone supplementation or placebo three times daily for seven days

1 week

Daily in-patient visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketones

Trial Overview The study tests if a ketone supplement can reduce opioid cravings and ease withdrawal symptoms compared to a placebo. Participants will receive either the supplement or placebo three times daily for one week, alongside assessments of mood, pain tolerance, and withdrawal.

How Is the Trial Designed?

Group I: Treatment with Placebo Experimental Treatment 1 Intervention

Participants (n=25) will receive three doses of a placebo drink daily for seven days.

Group II: Treatment with Ketone Supplement Experimental Treatment 1 Intervention

Participants (n=25) will receive three doses of a ketone supplement drink daily for seven days.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Caron Treatment Centers

Collaborator

Citations

1. nature.com nature.com/articles/s41598-023-33458-8

Ketogenic diet enhances the effects of oxycodone in mice KD mice displayed increased oxycodone-induced locomotor activity and enhanced antinociceptive effects of oxycodone, suggesting a dietary effect on opiate ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10414993/

Ketogenic diet: a potential adjunctive treatment for substance ... Recent studies suggest that KD can compensate for the glucose metabolism disorders caused by alcohol use disorder by increasing ketone metabolism.

3. withpower.com withpower.com/trial/phase-2-opioid-related-disorders-8-2025-ff336

Ketone Supplement for Opioid Use Disorder Trial Overview The study tests if a ketone supplement can reduce opioid cravings and ease withdrawal symptoms compared to a placebo. Participants will receive ...

4. news-medical.net news-medical.net/news/20230510/Ketogenic-diets-surprising-impact-on-opioid-sensitivity-and-withdrawal.aspx

Ketogenic diet's surprising impact on opioid sensitivity and ... Researchers at Yale University School of Medicine evaluated the potential effects of a ketogenic diet (KD) on oxycodone responses in a mouse model.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10901540/

Ketone Supplementation Dampens Subjective and ... Preclinical studies have shown KS to reduce alcohol withdrawal symptoms and reinforcement similarly to a ketogenic diet (Bornebusch et al., 2021) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7914216/

Effects of ketogenic diet and ketone monoester supplement on ... The regular diet with ketone monoester was sufficient to reduce handling-induced convulsions and anxiety-like behaviors in early withdrawal.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06815237

Effects Ketone Supplement and Alcohol on Brain Metabolism The research study is being conducted to better understand the effects of ketones and alcohol on brain functioning and brain metabolism.

8. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1191903/full

Ketogenic diet: a potential adjunctive treatment for ... Recent studies suggest that KD can compensate for the glucose metabolism disorders caused by alcohol use disorder by increasing ketone metabolism.