Background

Recent data suggest that glial cells may be involved in the analgesic effects and abuse liability of opioids. Preclinical studies have demonstrated that mu-opioid-receptor-selective agonists, such as oxycodone, activate glia and increase the release of cytokines, causing a suppression of opioid-induced analgesic effects. Preclinical studies also show that certain medications, such as the broad-spectrum tetracycline antibiotic minocycline, inhibit opioid-induced glial activation and thereby enhance the analgesic effects of opioids. Importantly, minocycline reduces the rewarding effects of opioids at the same doses that it enhances opioid-induced analgesia.

Aims

The purpose of the present study was to assess the effects of acute administration of minocycline on the subjective, physiological, and analgesic effects of oxycodone in human research volunteers.

Design

This study was a within-subject, randomized, double-blind outpatient study. Participants completed five separate sessions in which they received 0, 100, or 200 mg minocycline (MINO) simultaneously with either 0 or 40 mg oxycodone (OXY). The subjective, physiological, and analgesic effects of OXY were measured before and repeatedly after drug administration.

Settings and participants

Participants were between 21 and 45 years of age, non-treatment seeking, non-dependent recreational opioid users (N = 12). This study was conducted between 2013 and 2014 at the New York State Psychiatric Institute in New York, NY.

Findings

MINO 100 and 200 mg were safe and well-tolerated in combination with OXY 40 mg. MINO 200 mg administered with OXY 40 mg attenuated OXY-induced positive subjective effects such as “Good Effect” and “Liking” compared to OXY alone. MINO did not alter the physiological or analgesic effects of OXY.

Conclusions

MINO may attenuate the abuse liability of mu-opioid-receptor-selective agonists.

中文翻译：

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米诺环素减弱羟考酮诱导的非依赖性休闲阿片类药物使用者的积极主观反应

背景

最近的数据表明，神经胶质细胞可能与阿片类药物的镇痛作用和滥用倾向有关。临床前研究表明，mu-阿片受体选择性激动剂，如羟考酮，可激活神经胶质细胞并增加细胞因子的释放，从而抑制阿片类药物诱导的镇痛作用。临床前研究还表明，某些药物，如广谱四环素抗生素米诺环素，可抑制阿片类药物诱导的神经胶质激活，从而增强阿片类药物的镇痛作用。重要的是，米诺环素降低阿片类药物的奖励作用的剂量与它增强阿片类药物诱导的镇痛作用相同。

目标

本研究的目的是评估急性给药米诺环素对人类研究志愿者中羟考酮的主观、生理和镇痛作用的影响。

设计

本研究是一项受试者内、随机、双盲门诊研究。参与者完成了五个单独的疗程，其中他们同时接受了 0、100 或 200 mg 米诺环素 (MINO) 和 0 或 40 mg 羟考酮 (OXY)。在给药前和给药后重复测量 OXY 的主观、生理和镇痛作用。

设置和参与者

参与者年龄在 21 至 45 岁之间，不寻求治疗，不依赖娱乐性阿片类药物使用者（N = 12）。这项研究于 2013 年至 2014 年间在纽约州纽约市的纽约州精神病学研究所进行。

发现

MINO 100 和 200 mg 与 OXY 40 mg 联合使用是安全且耐受性良好的。与单独使用 OXY 相比，MINO 200 mg 与 OXY 40 mg 一起使用减弱了 OXY 引起的积极主观影响，例如“良好效果”和“喜欢”。MINO 没有改变 OXY 的生理或镇痛作用。

结论

MINO 可能会减轻 mu-阿片受体选择性激动剂的滥用倾向。