Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
Neurogastroenterol Motil. 2011 Jan;23(1):30-5, e2. doi: 10.1111/j.1365-2982.2010.01587.x. Epub 2010 Aug 16.
Visceral hypersensitivity to distension is thought to play an important role in the pathophysiology of the irritable bowel syndrome (IBS). Cannabinoids are known to decrease somatic pain perception, but their effect on visceral sensitivity in IBS remains unclear. Therefore, we evaluated the effect of the mixed CB(1) /CB(2) receptor agonist delta-9-tetrahydrocannabinol (Δ(9) -THC, dronabinol) on rectal sensitivity.
Ten IBS patients and 12 healthy volunteers (HV) underwent a barostat study to assess rectal sensitivity using an intermittent pressure-controlled distension protocol before and after sigmoid stimulation. Repetitive sigmoid stimulation is a validated method to increase visceral perception in IBS patients, consisting of a 10-min period of 30 s stimuli (60 mmHg), separated by 30 s of rest (5 mmHg). The effect of placebo and Δ(9) -THC (5 and 10 mg in healthy volunteers and 10 mg in IBS patients) on rectal sensitivity was evaluated on respectively three and two separate days in a double blind, randomized, crossover fashion.
All participants (HV and IBS) reported central side effects during the highest dose of Δ(9) -THC, most frequently increased awareness of the surrounding, light-headedness and sleepiness, whereas no side effects where reported during placebo. Although blood pressure was not affected, heart rate increased in both HV and IBS, but was most pronounced in IBS patients. The cannabinoid agonist Δ(9) -THC did not alter baseline rectal perception to distension compared to placebo in HV or IBS patients. Similarly, after sigmoid stimulation there were no significant differences between placebo and Δ(9) -THC in sensory thresholds of discomfort.
CONCLUSIONS & INFERENCES: These findings imply that Δ(9) -THC does not modify visceral perception to rectal distension and argue against (centrally acting) CB agonists as tool to decrease visceral hypersensitivity in IBS patients.
内脏对扩张的敏感性增加被认为在肠易激综合征（IBS）的病理生理学中起重要作用。大麻素已知可降低躯体疼痛感知，但它们对 IBS 内脏敏感性的影响尚不清楚。因此，我们评估了混合 CB1/CB2 受体激动剂 delta-9-四氢大麻酚（Δ（9）-THC，dronabinol）对直肠敏感性的影响。
10 名 IBS 患者和 12 名健康志愿者（HV）接受了直肠测压研究，使用间歇压力控制扩张方案评估直肠敏感性，该方案在直肠刺激前后进行。重复直肠刺激是一种经过验证的增加 IBS 患者内脏感知的方法，包括 10 分钟的 30 秒刺激（60mmHg），由 30 秒休息（5mmHg）隔开。在双盲、随机、交叉方式下，分别在三天和两天内评估安慰剂和 Δ（9）-THC（HV 中 5 和 10mg，IBS 患者中 10mg）对直肠敏感性的影响。
所有参与者（HV 和 IBS）在最高剂量的 Δ（9）-THC 时报告了中枢副作用，最常见的是增加对周围环境的感知、头晕和嗜睡，而在安慰剂时则没有报告副作用。尽管血压没有受到影响，但 HV 和 IBS 患者的心率都增加了，但 IBS 患者更为明显。与安慰剂相比，大麻素激动剂 Δ（9）-THC 并未改变 HV 或 IBS 患者基础直肠扩张感知。同样，在直肠刺激后，安慰剂和 Δ（9）-THC 之间在不适感觉阈值方面也没有显著差异。
这些发现表明 Δ（9）-THC 不会改变直肠扩张对内脏感知的影响，并反对（中枢作用）CB 激动剂作为降低 IBS 患者内脏敏感性的工具。
