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阿片类疫苗作为治疗阿片类药物使用障碍和预防过量用药的一种新策略的发展。

The development of opioid vaccines as a novel strategy for the treatment of opioid use disorder and overdose prevention.

作者信息

Tuncturk Mustafa, Kushwaha Shikha, Heider Robin M, Oesterle Tyler, Weinshilboum Richard, Ho Ming-Fen

机构信息

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States.

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States.

出版信息

Int J Neuropsychopharmacol. 2025 Feb 4;28(2). doi: 10.1093/ijnp/pyaf005.

Abstract

Opioid use disorder (OUD) affects over 40 million people worldwide, creating significant social and economic burdens. Medication for opioid use disorder (MOUD) is often considered the primary treatment approach for OUD. MOUD, including methadone, buprenorphine, and naltrexone, is effective for some, but its benefits may be limited by poor adherence to treatment recommendations. Immunopharmacotherapy offers an innovative approach by using vaccines to generate antibodies that neutralize opioids, blocking them from crossing the blood-brain barrier and reducing their psychoactive effects. To date, only 3 clinical trials for opioid vaccines have been published. While these studies demonstrated the potential of opioid vaccines for relapse prevention, there is currently no standardized protocol for evaluating their effectiveness. We have reviewed recent preclinical studies that demonstrated the efficacy of vaccines targeting opioids, including heroin, morphine, oxycodone, hydrocodone, and fentanyl. These studies showed that vaccines against opioids reduced drug reinforcement, decreased opioid-induced antinociception, and increased survival rates against lethal opioid doses. These studies also demonstrated the importance of vaccine formulation and the use of adjuvants in enhancing antibody production and specificity. Finally, we highlighted the strengths and concerns associated with the opioid vaccine treatment, including ethical considerations.

摘要

阿片类药物使用障碍(OUD)在全球影响着超过4000万人,造成了巨大的社会和经济负担。阿片类药物使用障碍药物治疗(MOUD)通常被视为治疗OUD的主要方法。MOUD包括美沙酮、丁丙诺啡和纳曲酮,对一些人有效,但其益处可能会因对治疗建议的依从性差而受到限制。免疫药物疗法提供了一种创新方法,即使用疫苗产生中和阿片类药物的抗体,阻止它们穿过血脑屏障并降低其精神活性作用。迄今为止,仅发表了3项关于阿片类疫苗的临床试验。虽然这些研究证明了阿片类疫苗在预防复发方面的潜力,但目前尚无评估其有效性的标准化方案。我们回顾了最近的临床前研究,这些研究证明了针对阿片类药物(包括海洛因、吗啡、羟考酮、氢可酮和芬太尼)的疫苗的疗效。这些研究表明,抗阿片类药物疫苗降低了药物强化作用,减少了阿片类药物引起的镇痛作用,并提高了对致死性阿片类药物剂量的存活率。这些研究还证明了疫苗配方以及佐剂在增强抗体产生和特异性方面的重要性。最后,我们强调了与阿片类疫苗治疗相关的优势和问题,包括伦理考量。

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