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.