Neurology Service, MS 127, Veterans Affairs (VA) Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516, USA.
Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Psychopharmacology (Berl). 2020 Oct;237(10):3097-3107. doi: 10.1007/s00213-020-05595-9. Epub 2020 Jul 6.
Animal studies and anecdotal human reports suggest that cannabinoids have antinociceptive effects. Controlled human studies have produced mixed results.
We sought to reduce existing variability by investigating the effects of intravenous delta-9-tetrahydrocannabinol (THC) in several pain paradigms within the same human subjects, addressing some of the limitations to the published literature.
In this exploratory randomized, double-blind, placebo-controlled, cross-over study, healthy human subjects received 0.01 mg/kg or 0.03 mg/kg intravenous THC or placebo (ethanol vehicle) infused over 10 min on three test days, each separated by at least 72 h. Capsaicin (250 μg) was injected intradermally to induce chemical pain and hyperalgesia. Four other forms of acute pain were induced: mechanical (von Frey filament), hot and cold (thermode), and electrical (pulse generator). Pain ratings were obtained before drug administration, at peak drug effects, and 2 h after drug administration and included both objective and subjective measures. THC drug effects and vital signs were also collected during experimental sessions. Nonparametric analysis with repeated measures was performed.
THC induced euphoria, perceptual and cognitive alterations, and tachycardia in a dose-related manner, but failed to have significant effects in experimentally induced acute chemical, mechanical, thermal, or electrical pain and capsaicin-induced hyperalgesia.
In this exploratory controlled study, intravenous THC lacked significant antinociceptive properties in experimental models of acute pain and capsaicin-induced hyperalgesia in healthy human subjects. Continued study of THC and other cannabinoids through high-quality, controlled studies in both healthy volunteers and patients with pain conditions is warranted to inform the growing demand for the clinical application of cannabinoids in pain management.
动物研究和一些人类病例报告表明，大麻素具有抗伤害感受作用。人体对照研究的结果喜忧参半。
我们旨在通过在相同的人体受试者中研究静脉内给予 δ-9-四氢大麻酚（THC）对几种疼痛模型的影响，减少现有差异，从而解决已发表文献中的一些局限性。
在这项探索性随机、双盲、安慰剂对照、交叉研究中，健康的人类受试者在 3 个测试日分别接受 0.01mg/kg 或 0.03mg/kg 静脉内 THC 或安慰剂（乙醇载体）输注 10 分钟，每个测试日至少间隔 72 小时。皮内注射辣椒素（250μg）以诱导化学性疼痛和痛觉过敏。另外还诱发了 4 种急性疼痛模型：机械性（von Frey 纤维）、热和冷（热模型）和电（脉冲发生器）。在药物给药前、药物作用峰值时和药物给药后 2 小时进行疼痛评分，并包括客观和主观测量。在实验过程中还收集了 THC 药物作用和生命体征。进行了重复测量的非参数分析。
THC 以剂量相关的方式诱导欣快、知觉和认知改变以及心动过速，但在实验性诱导的急性化学性、机械性、热和电疼痛以及辣椒素诱导的痛觉过敏中无显著作用。
在这项探索性对照研究中，静脉内给予 THC 对健康人体受试者的急性疼痛模型和辣椒素诱导的痛觉过敏模型均缺乏显著的镇痛作用。有必要通过高质量、对照研究进一步研究 THC 和其他大麻素，以满足在疼痛管理中临床应用大麻素日益增长的需求。
