In this experimental randomized placebo-controlled 4-way crossover trial, we explored the analgesic effects of inhaled pharmaceutical-grade cannabis in twenty chronic pain patients with fibromyalgia. We tested four different cannabis varieties with exact knowledge on their [INCREMENT]9-tetrahydrocannabinol (THC), and cannabidiol (CBD) content: Bedrocan® (22.4 mg THC, < 1 mg CBD), Bediol® (13.4 mg THC, 17.8 mg CBD), Bedrolite® (18.4 mg CBD, < 1 mg THC) and a placebo variety without any THC or CBD. Following 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). CBD inhalation increased THC plasma concentrations but diminished THC-induced analgesic effects, indicative of a 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.
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1Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands;
2Bedrocan International BV, Veendam, The Netherlands
Address for correspondence: prof. dr. Albert Dahan, Department of Anesthesiology, Anesthesia & Pain Research Unit, Leiden University Medical Center, H5-022, 2300 RC Leiden, The Netherlands
Support/conflicts: This investigator-initiated trial was performed in collaboration with Bedrocan International BV (Veendam, The Netherlands). Bedrocan International BV was responsible for the production and delivery of the cannabis products and the Volcano device for cannabis inhalation. MAK is employee of Bedrocan International BV, The Netherlands. He commented on the protocol and final version of the paper. The other authors report no conflict of interest.