吸入Δ-四氢大麻酚不会增强羟考酮引起的呼吸抑制：健康志愿者的随机对照试验

Inhaled Δ-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers.

作者信息

van Dam Cornelis Jan, van der Schrier Rutger, van Velzen Monique, van Lemmen Maarten, Simons Pieter, Kuijpers Kiki W K, Jansen Simone, Kowal Mikael A, Olofsen Erik, Kramers Cornelis, Dahan Albert, Niesters Marieke

机构信息

Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.

Bedrocan International B.V., Veendam, the Netherlands.

出版信息

Br J Anaesth. 2023 Apr;130(4):485-493. doi: 10.1016/j.bja.2022.12.018. Epub 2023 Jan 31.

DOI:10.1016/j.bja.2022.12.018

PMID:36725378

Abstract

BACKGROUND

In humans, the effect of cannabis on ventilatory control is poorly studied, and consequently, the effect of Δ-tetrahydrocannabinol (THC) remains unknown, particularly when THC is combined with an opioid. We studied the effect of THC on breathing without and with oxycodone pretreatment. We hypothesised that THC causes respiratory depression, which is amplified when THC and oxycodone are combined.

METHODS

In this randomised controlled crossover trial, healthy volunteers were administered inhaled Bedrocan® 100 mg (Bedrocan International B.V., Veendam, The Netherlands), a pharmaceutical-grade high-THC cannabis variant (21.8% THC; 0.1% cannabidiol), after placebo or oral oxycodone 20 mg pretreatment; THC was inhaled 1.5 and 4.5 h after placebo or oxycodone intake. The primary endpoint was isohypercapnic ventilation at an end-tidal Pco of 55 mm Hg or 7.3 kPa (V55), measured at 1-h intervals for 7 h after placebo/oxycodone intake.

RESULTS

In 18 volunteers (age 22 yr [3]; 9 [50%] female), oxycodone produced a 30% decrease in V55, whereas placebo was without effect on V55. The first cannabis inhalation resulted in V55 changing from 20.3 (3.1) to 23.8 (2.4) L min (P=0.06) after placebo, and from 11.8 (2.8) to 13.0 (3.9) L min (P=0.83) after oxycodone. The second cannabis inhalation also had no effect on V55, but slightly increased sedation.

CONCLUSIONS

In humans, THC has no effect on ventilatory control after placebo or oxycodone pretreatment.

CLINICAL TRIAL REGISTRATION

2021-000083-29 (EU Clinical Trials Register.).

摘要

背景

在人类中，大麻对通气控制的影响研究较少，因此，Δ-四氢大麻酚（THC）的作用仍不明确，尤其是当THC与阿片类药物合用时。我们研究了THC在无羟考酮预处理和有羟考酮预处理情况下对呼吸的影响。我们假设THC会导致呼吸抑制，当THC与羟考酮合用时，这种抑制会增强。

方法

在这项随机对照交叉试验中，健康志愿者在接受安慰剂或口服20 mg羟考酮预处理后，吸入100 mg的Bedrocan®（荷兰芬丹的Bedrocan国际有限公司），这是一种药用级高THC大麻变体（21.8% THC；0.1% 大麻二酚）；在服用安慰剂或羟考酮后1.5小时和4.5小时吸入THC。主要终点是在呼气末二氧化碳分压为55 mmHg或7.3 kPa（V55）时的等碳酸通气，在服用安慰剂/羟考酮后7小时内每隔1小时测量一次。

结果

在18名志愿者（年龄22岁[3]；9名[50%]女性）中，羟考酮使V55降低了30%，而安慰剂对V55无影响。第一次吸入大麻后，服用安慰剂后V55从20.3（3.1）升/分钟变为23.8（2.4）升/分钟（P = 0.06），服用羟考酮后从11.8（2.8）升/分钟变为13.0（3.9）升/分钟（P = 0.83）。第二次吸入大麻对V55也无影响，但镇静作用略有增加。