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Heroin Addiction and Related Clinical Problems: 2026, 28: 29-36

Opioid Agonist Therapy with Levomethadone in Primary Dependence on Nitazenes – A Case Study

Uli Mühlan Muehlan, Fabian Pitter Steinmetz, Clemens Muehlan, Timur Liwinski, and Christoph Stoll

Digital Object Identifier:
https://doi.org/10.62401/2531-4122-2026-5

Summary: Background: 2-benzylbenzimidazole opioid agonists, also known as nitazenes, are highly potent synthetic opioids developed in the 1950s but never approved for clinical use. Their recent appearance on the illicit drug market has raised significant concern due to their strong μ-opioid receptor agonism and the high risk of intoxication and rapid dependence. Methods: We report a case of a 29-year-old opioid-naïve patient who used multiple nitazenes (including fluetonitazepyne at nominal doses up to 90 mg/day, etonitazene, and N-desethylisonitazene) obtained via an online clearnet vendor, with clinical evaluation and subsequent management through outpatient opioid agonist therapy and adjunctive pharmacological support. Results: The patient developed a severe opioid dependence syndrome within a few days, characterised by pronounced physical and psychological withdrawal symptoms and repeated unsuccessful self-directed cessation attempts. Ultimately, the patient declined inpatient detoxification but achieved stabilisation with levomethadone titrated to 60 mg/day, initially combined with pregabalin (up to 150 mg three times daily), followed by gradual dose reduction and complete discontinuation over 10 months without relapse or hospitalisation, while maintaining full occupational functioning. Conclusion: This case underscores the exceptionally high dependence liability of nitazenes even after brief exposure in opioid-naïve individuals and supports the effectiveness of a flexible, patient-centred opioid substitution strategy, with short-term adjunctive pregabalin potentially aiding withdrawal management, highlighting the urgent need for increased clinical awareness and public health response to emerging synthetic opioids.

Keywords: Synthetic opioids; withdrawal; levomethadone; nitazenes; pregabalin; case report