Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
Bedrocan International BV, Veendam, the Netherlands.
Pain. 2019 Apr;160(4):860-869. doi: 10.1097/j.pain.0000000000001464.
In this experimental randomized placebo-controlled 4-way crossover trial, we explored the analgesic effects of inhaled pharmaceutical-grade cannabis in 20 chronic pain patients with fibromyalgia. We tested 4 different cannabis varieties with exact knowledge on their [INCREMENT]-tetrahydrocannabinol (THC) and cannabidiol (CBD) content: Bedrocan (22.4-mg THC, <1-mg CBD; Bedrocan International BV, Veendam, the Netherlands), Bediol (13.4-mg THC, 17.8-mg CBD; Bedrocan International BV, Veendam, the Netherlands), Bedrolite (18.4-mg CBD, <1-mg THC; Bedrocan International BV, Veendam, the Netherlands), and a placebo variety without any THC or CBD. After a single vapor inhalation, THC and CBD plasma concentrations, pressure and electrical pain thresholds, spontaneous pain scores, and drug high were measured for 3 hours. None of the treatments had an effect greater than placebo on spontaneous or electrical pain responses, although more subjects receiving Bediol displayed a 30% decrease in pain scores compared to placebo (90% vs 55% of patients, P = 0.01), with spontaneous pain scores correlating with the magnitude of drug high (ρ = -0.5, P < 0.001). Cannabis varieties containing THC caused a significant increase in pressure pain threshold relative to placebo (P < 0.01). Cannabidiol inhalation increased THC plasma concentrations but diminished THC-induced analgesic effects, indicative of synergistic pharmacokinetic but antagonistic pharmacodynamic interactions of THC and CBD. This experimental trial shows the complex behavior of inhaled cannabinoids in chronic pain patients with just small analgesic responses after a single inhalation. Further studies are needed to determine long-term treatment effects on spontaneous pain scores, THC-CBD interactions, and the role of psychotropic symptoms on pain relief.
在这项随机、安慰剂对照的四交叉实验中，我们对 20 名患有纤维肌痛的慢性疼痛患者吸入药用级大麻的镇痛效果进行了研究。我们测试了 4 种不同的大麻品种，这些品种确切地知道它们的 [INCREMENT]-四氢大麻酚（THC）和大麻二酚（CBD）含量：Bedrocan（22.4mg THC，<1mg CBD；Bedrocan International BV，Veendam，荷兰），Bediol（13.4mg THC，17.8mg CBD；Bedrocan International BV，Veendam，荷兰），Bedrolite（18.4mg CBD，<1mg THC；Bedrocan International BV，Veendam，荷兰）和一种不含 THC 或 CBD 的安慰剂品种。单次吸入后，测量了 THC 和 CBD 血浆浓度、压力和电痛阈值、自发疼痛评分和药物高反应 3 小时。与安慰剂相比，没有一种治疗方法对自发或电痛反应有更大的影响，尽管接受 Bediol 治疗的受试者中，疼痛评分降低 30%的比例高于安慰剂（90%与 55%的患者，P=0.01），自发疼痛评分与药物高反应的程度相关（ρ=-0.5，P<0.001）。含有 THC 的大麻品种与安慰剂相比，显著增加了压力痛阈值（P<0.01）。CBD 吸入增加了 THC 血浆浓度，但减弱了 THC 诱导的镇痛作用，表明 THC 和 CBD 的药代动力学协同作用和药效学拮抗作用。这项实验研究显示了吸入大麻素在慢性疼痛患者中的复杂行为，单次吸入后仅有很小的镇痛反应。需要进一步的研究来确定长期治疗对自发疼痛评分、THC-CBD 相互作用以及精神症状对疼痛缓解的作用。
