Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA.
Department of Psychiatry, New York State Psychiatric Institute, Columbia University Irving Medical Center, 1051 Riverside Drive, Unit 120, New York, NY, 10032, USA.
Psychopharmacology (Berl). 2019 Oct;236(10):2857-2866. doi: 10.1007/s00213-018-5146-7. Epub 2018 Dec 18.
Minocycline, a tetracycline antibiotic, inhibits activation of microglia. In preclinical studies, minocycline prevented development of opioid tolerance and opioid-induced hyperalgesia (OIH). The goal of this study was to determine if minocycline changes pain threshold and tolerance in individuals with opioid use disorder who are maintained on agonist treatment.
In this double-blind, randomized human laboratory study, 20 participants were randomized to either minocycline (200 mg/day) or placebo treatment for 15 days. The study had three test sessions (days 1, 8, and 15 of treatment) and one follow-up visit 1 week after the end of treatment. In each test session, participants were assessed on several subjective and cognitive measures, followed by assessment of pain sensitivity using the Cold Pressor Test (CPT). Daily surveys and cognitive measures using Ecological Momentary Assessment (EMA) were also collected four times a day on days 8 through 14 of treatment, and proinflammatory serum cytokines were assessed before and on the last day of treatment.
Minocycline treatment did not change pain threshold or tolerance on the CPT. Similarly, minocycline did not change severity of pain, opioid craving, withdrawal, or serum cytokines. Minocycline treatment increased accuracy on a Go/No-Go task.
While these findings do not support minocycline's effects on OIH, minocycline may have a potential use as a cognitive enhancer for individuals with opioid use disorder, a finding that warrants further systematic studies.
米诺环素是一种四环素类抗生素,可抑制小胶质细胞的激活。在临床前研究中,米诺环素可预防阿片类药物耐受和阿片类药物引起的痛觉过敏(OIH)的发展。本研究的目的是确定米诺环素是否会改变接受阿片类药物维持治疗的阿片类药物使用障碍患者的疼痛阈值和耐受。
在这项双盲、随机的人体实验室研究中,将 20 名参与者随机分为米诺环素(200mg/天)或安慰剂治疗组,治疗 15 天。该研究有三个测试阶段(治疗的第 1、8 和 15 天)和一个治疗结束后 1 周的随访。在每个测试阶段,参与者都接受了几项主观和认知测试,然后使用冷压测试(CPT)评估疼痛敏感性。在治疗的第 8 天至第 14 天期间,还每天进行四次使用生态瞬时评估(EMA)的日常调查和认知测试,并在治疗的最后一天评估促炎血清细胞因子。
米诺环素治疗并未改变 CPT 的疼痛阈值或耐受。同样,米诺环素也未改变疼痛严重程度、阿片类药物渴求、戒断或血清细胞因子。米诺环素治疗可提高 Go/No-Go 任务的准确性。
尽管这些发现不支持米诺环素对 OIH 的影响,但米诺环素可能有作为阿片类药物使用障碍患者认知增强剂的潜在用途,这一发现值得进一步的系统研究。