Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2013 May 28;110(22):9036-41. doi: 10.1073/pnas.1219159110. Epub 2013 May 6.
Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin's rapid metabolism to 6-acetylmorphine and morphine. We recently developed a "dynamic" vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin's metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin's psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance.
海洛因成瘾是一种慢性复发性疾病，其特征是过度吸毒和觅药，需要持续的心理治疗和药物治疗干预，以最大限度地减少进一步滥用的可能性。目前正在开发针对许多滥用药物的疫苗策略，这些策略产生的抗体可以与血液中的药物结合，防止其进入大脑并消除其精神活性。然而，这种策略受到海洛因迅速代谢为 6-乙酰吗啡和吗啡的影响而变得复杂。我们最近开发了一种“动态”疫苗，通过向免疫系统呈现与海洛因代谢相匹配的多半抗原结构，产生针对海洛因及其精神活性代谢物的抗体。目前的研究提供了证据，表明接种疫苗后，血液中可穿透大脑的海洛因成分能够被有效地隔离。其结果是，在接受治疗的大鼠中，海洛因的活性被有效地阻断，防止了滥用药物的各种特征：海洛因奖赏、药物引起的觅药行为恢复以及依赖大鼠戒断后强迫性海洛因自我给药的反弹。这种动态疫苗显示出了显著降低海洛因强化和激励特性的能力，即使在有依赖史的受试者中也是如此。此外，针对较少穿透大脑的下游代谢物吗啡，不足以防止这些模型中海洛因引起的活性，这表明海洛因和 6-乙酰吗啡是海洛因精神活性的关键因素。由于海洛因疫苗不针对阿片受体或常见的阿片类药物治疗，因此它可以与现有的治疗选择结合使用。因此，我们的疫苗代表了一种有前途的海洛因成瘾辅助治疗方法，提供持续的海洛因拮抗作用，需要最小的医疗监测和患者依从性。
