Rationale

Opioids are effective medications, but they have several key limitations including the development of tolerance, establishment of dependence, diversion for non-medical use, and the development of addiction. Therefore, any drugs which act in an additive or synergistic fashion with opioids to address medical applications have the potential to reduce opioid-related harms.

Objectives

To determine if heroin and Δ⁹-tetrahydrocannabinol (THC) interact in an additive or independent manner to alter nociception, body temperature, and spontaneous locomotor activity when inhaled or injected.

Methods

Groups of female and male rats, implanted with radiotelemetry transmitters, were exposed to vapor generated from heroin (50 mg/mL in propylene glycol vehicle; PG), THC (50 mg/mL), or the combination for assessment of effects on temperature and activity. Thermal nociception was assessed with a warm water tail-withdrawal assay.

Results

Heroin inhalation increased temperature and activity whereas THC inhalation decreased temperature and activity in both female and male Sprague–Dawley rats. Effects of combined inhalation were in opposition, and additional experiments found the same outcome for the injection of heroin (0.5 mg/kg, s.c.) and THC (10 mg/kg, i.p.) alone and in combination. In contrast, the co-administration of heroin and THC by either inhalation or injection produced additive effects on thermal nociception in both male and female Sprague–Dawley and Wistar rats.

Conclusions

This study shows that additive effects of THC with an opioid on a medical endpoint such as analgesia may not generalize to other behavioral or physiological effects, which may be a positive outcome for unwanted side effects.

中文翻译：

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四氢大麻酚和海洛因蒸气联合吸入对大鼠的影响

基本原理

阿片类药物是有效的药物，但它们有几个关键限制，包括耐受性的发展、依赖性的建立、非医疗用途的转移以及成瘾的发展。因此，任何与阿片类药物以相加或协同方式作用以解决医疗应用的药物都有可能减少与阿片类药物相关的危害。

目标

确定海洛因和 Δ ⁹ -四氢大麻酚 (THC) 是否以相加或独立的方式相互作用，从而在吸入或注射时改变伤害感受、体温和自发运动活动。

方法

植入无线电遥测发射器的雌性和雄性大鼠组暴露于海洛因（丙二醇载体中 50 mg/mL；PG）、THC（50 mg/mL）或组合以评估对温度和活动。用温水缩尾法评估热伤害感受。

结果

海洛因吸入增加了温度和活动，而四氢大麻酚吸入降低了雌性和雄性 Sprague-Dawley 大鼠的温度和活动。联合吸入的效果是相反的，另外的实验发现单独和联合注射海洛因（0.5 mg/kg，sc）和 THC（10 mg/kg，ip）的结果相同。相比之下，海洛因和 THC 通过吸入或注射共同给药对雄性和雌性 Sprague-Dawley 和 Wistar 大鼠的热伤害感受产生了累加效应。

结论

这项研究表明，四氢大麻酚与阿片类药物对镇痛等医疗终点的累加效应可能不会推广到其他行为或生理效应，这可能是不良副作用的积极结果。