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]9-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.
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This experimental highly controlled trial in 20 patients with fibromyalgia shows that the cannabinoid THC, but not CBD, is effective in the treatment of fibromyalgia pain.
aDepartment of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands
bBedrocan International BV, Veendam, the Netherlands
Corresponding author. Address: Anesthesia and Pain Research Unit, Department of Anesthesiology, Leiden University Medical Center, H5-022, 2300 RC Leiden, the Netherlands. Tel: +31 71 526 9111. E-mail address: firstname.lastname@example.org (A. Dahan).
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Received August 15, 2018
Received in revised form November 29, 2018
Accepted December 06, 2018