Wallace Mark, Schulteis Gery, Atkinson J Hampton, Wolfson Tanya, Lazzaretto Deborah, Bentley Heather, Gouaux Ben, Abramson Ian
Department of Anesthesiology, University of California, San Diego, USA.
Anesthesiology. 2007 Nov;107(5):785-96. doi: 10.1097/01.anes.0000286986.92475.b7.
Although the preclinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin.
In a randomized, double-blinded, placebo-controlled, crossover trial in 15 healthy volunteers, the authors evaluated concentration-response effects of low-, medium-, and high-dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannabinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 min after drug exposure, and pain, hyperalgesia, tetrahydrocannabinol plasma levels, and side effects were assessed.
Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 min after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose, nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma delta-9-tetrahydrocannabinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests.
This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain.
尽管临床前文献表明大麻素具有抗伤害感受和抗痛觉过敏作用，但在人类疼痛状态下的疗效仍不明确。作者使用人类实验性疼痛模型，推测吸入大麻会减轻皮内注射辣椒素引起的疼痛和痛觉过敏。
在一项针对15名健康志愿者的随机、双盲、安慰剂对照、交叉试验中，作者评估了低、中、高剂量吸食大麻（分别含重量比为2%、4%和8%的9-δ-四氢大麻酚）对皮内注射辣椒素引起的疼痛和皮肤痛觉过敏的浓度-反应效应。在药物暴露后5分钟和45分钟，将辣椒素注射到双侧前臂，评估疼痛、痛觉过敏、四氢大麻酚血浆水平和副作用。
大麻暴露后5分钟，任何剂量对辣椒素引起的疼痛均无影响。然而，在大麻暴露后45分钟，中剂量使辣椒素引起的疼痛显著减轻，高剂量使辣椒素引起的疼痛显著增加。低剂量无影响，任何剂量对痛觉过敏区域也无影响。在调整总体剂量效应后发现，疼痛感知与血浆δ-9-四氢大麻酚水平之间存在显著负相关。神经心理学测试的表现无显著差异。
本研究表明，吸食大麻存在适度镇痛的窗口期，较低剂量减轻疼痛，较高剂量增加疼痛。
