Today, I review, link to, and excerpt from The Curbsiders Addiction Medicine‘s “#536 Q&Apalooza: Your Addiction Questions Answered!”.*

*Kryzhanovskaya E, Morford K, Cohen S, Huxley-Reicher Z, Chan CA “#Q&Apalooza: Your Addiction Questions Answered!” The Curbsiders Addiction Medicine Podcast. https://thecurbsiders.com/addiction August 17th, 2026.

All that follows is from the above resource.

The Curbsiders podcast: #536 Q&Apalooza: Your Addiction Questions Answered!

This episode explores complex questions around addiction treatment from our audience, including the off-label use of GLPs for SUDs, the nuances of naloxone, and managing high-dose methadone in hospital settings. Experts Drs. Shawn Cohen and Zina Huxley-Reicher, in addition to the co-hosts Drs. Carolyn Chan and Era Kryzhanovskaya share insights, resources, and practical tips for clinicians navigating these challenging scenarios.

Claim CME for this episode at curbsiders.vcuhealth.org!
By listening to this episode and completing CME, this can be used to count towards the new DEA 8-hr requirement on substance use disorders education.

Show Segments

• Intro, disclaimer
• Picks of the Week
• Off-Label GLP use
• Naloxone review
• Acute pain in patients with opioid use disorder (OUD)
• Care Coordination with opioid treatment programs (OTPs)
• New medications for pain; suzetrigine
• Perioperative pain management for patients with OUD
• Outro

Q&A Pearls

1. GLP-1 receptor agonists are not FDA-approved for alcohol use disorder (AUD), but emerging RCT data (particularly with semaglutide) suggest they may reduce drinks per drinking day, heavy drinking, and cravings—though they do not appear to promote abstinence. Consider them when overlapping indications exist (e.g., obesity or type 2 diabetes), and don’t forget first-line AUD medications (naltrexone, acamprosate, disulfiram) remain underutilized.
2. The naloxone that works is the naloxone that’s available to treat an opioid overdose. Standard IM (0.4 mg) and intranasal (4 mg) formulations remain effective for opioid overdose reversal. Higher-dose formulations (8 mg, 10 mg intranasal) are FDA-approved but may be associated with more severe precipitated withdrawal without demonstrated superiority.
3. Don’t stop medications for opioid use disorder (MOUD) when managing acute pain. Continue methadone and buprenorphine at stable doses during acute pain episodes and perioperatively. Stopping or tapering these medications creates an “opioid deficit” that can increase opioid requirements and risk of opioid withdrawal and return to opioid use. Use multimodal analgesia and add short-acting opioids as needed, recognizing patients with opioid tolerance will need higher doses.
4. Avoid flumazenil for suspected benzodiazepine overdose. It increases the risk of seizures, arrhythmias, and other serious adverse events compared to placebo, particularly in patients with unknown history or benzodiazepine dependence. Supportive care (airway management, monitoring, oxygenation) is the mainstay.
5. Suzetrigine* [Google Search Page] is a first-in-class NaV1.8 inhibitor approved only for moderate to severe acute pain in adults, studied for up to 14 days in abdominoplasty and bunionectomy. There is no data for its use in patients with OUD, no data for chronic pain, and potential CYP3A4-mediated drug interactions with buprenorphine and methadone.

Q&Apalooza: Your Addiction Questions Answered! – Notes

GLP-1 Receptor Agonists for Alcohol Use Disorder

GLP-1 receptor agonists (GLP-1 RAs) act on the GI tract, pancreas, and brain. At higher doses used for obesity, they affect satiety and reward pathways, which may underlie their potential effects on alcohol consumption. Observational data from a Swedish national registry showed that semaglutide and liraglutide use were associated with reduced AUD hospitalizations (aHR 0.64 and 0.72, respectively) (Lähteenvuo 2024). VA data similarly demonstrated greater reductions in AUDIT-C scores among patients taking GLP-1 RAs compared to unexposed individuals and those taking DPP-4 inhibitors (Farokhnia 2025).

The first RCT of semaglutide for AUD (Hendershot 2025) tested low-dose semaglutide (up to 1 mg/week) in 48 non-treatment-seeking adults and found reduced laboratory alcohol self-administration, drinks per drinking day, heavy drinking, and weekly cravings—but did not reduce total drinking days. This suggests GLP-1 RAs may reduce consumption per occasion rather than promote abstinence. A subsequent larger RCT (Klausen 2026) of semaglutide 2.4 mg/week in 108 treatment-seeking patients with AUD and comorbid obesity showed significant reductions in heavy drinking days (the primary endpoint) and multiple secondary alcohol consumption measures.

RCT data for other SUDs (tobacco, opioid, cocaine use disorders) remain limited or unpublished. Multiple ongoing trials on clinicaltrials.gov are investigating semaglutide and tirzepatide across various SUDs.

Naloxone Formulations and Dosing

Standard naloxone dosing for opioid overdose includes IM 0.4 mg or intranasal 4 mg, with repeat dosing every 2–3 minutes as needed. The American Heart Association (AHA) recommends 2–4 mg intranasally or 0.2–2 mg IV/IM. Since 2023, 3 mg and 4 mg nasal naloxone formulations have been available over the counter in the US. Higher-dose formulations (8 mg, 10 mg intranasal) have been FDA-approved but are associated with more frequent and severe withdrawal symptoms without demonstrated survival benefit. An observational study comparing 8 mg vs. 4 mg intranasal naloxone found no difference in survival but significantly more withdrawal symptoms (including vomiting) with the higher dose (Payne 2024).

Nalmefene is a longer-acting opioid antagonist not currently available in the US, with limited data supporting superiority over naloxone (ACMT and AACT statement, 2023). Naltrexone is not indicated for acute opioid overdose reversal due to its slower onset of action.

Key practical points: Naloxone is available over the counter; harm reduction organizations distribute it for free; the intranasal spray is easiest for lay use; and the best naloxone option is the one that is available and can be given.

Flumazenil in Benzodiazepine Overdose

Flumazenil is a competitive benzodiazepine antagonist at the GABA-A receptor. Its clearest indication is reversal of iatrogenic benzodiazepine-induced sedation (e.g., procedural sedation) in patients without benzodiazepine dependence (tolerance and/or withdrawal).

In suspected benzodiazepine overdose, a meta-analysis of RCTs found higher rates of serious adverse events (seizures, SVT, arrhythmias) in the flumazenil group compared to placebo, though no deaths occurred in either group because patients received good supportive care (Penninga 2016). The AHA guidelines note that the risks of flumazenil likely exceed the benefit in patients with undifferentiated coma where medical history and co-intoxications are unknown. Supportive care—airway management, monitoring, supplemental oxygen—remains the mainstay of benzodiazepine overdose management.