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Randomized Controlled Trial
. 2019 Apr;160(4):860-869.
doi: 10.1097/j.pain.0000000000001464.

An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia

Tine van de Donk  1 , Marieke Niesters  1 , Mikael A Kowal  2 , Erik Olofsen  1 , Albert Dahan  1 , Monique van Velzen  1
Affiliations
Randomized Controlled Trial

An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia

Tine van de Donk et al. Pain. 2019 Apr.

Abstract

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.

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Conflict of interest statement

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1.
Figure 1.
Consort flow diagram. FM, fibromyalgia.
Figure 2.
Figure 2.
Plasma concentrations of ∆9-tetrahydrocannabinol (THC), its metabolite 11-hydroxy-THC (11-OH-THC), and cannabidiol (CBD) after inhalation of 3 cannabis varieties, Bedrocan (A), Bediol (B), and Bedrolite (C). Data are mean ± 95% confidence interval.
Figure 3.
Figure 3.
Effect of cannabis varieties Bedrocan, Bediol, Bedrolite, and placebo cannabis on spontaneous pain scores (A), pressure pain threshold (B), and drug high (C). Data are mean ± SEM and are relative to baseline. NRS, numerical rating score; VAS, visual analogue scale.
Figure 4.
Figure 4.
Cannabis responder rates: (A) Percentage responders with a decrease of at least 30% in spontaneous pain scores on at least one measurement. (B) Percentage responders with a decrease of at least 50% in spontaneous pain scores on at least one measurement.
Figure 5.
Figure 5.
(A) Plasma THC concentration (CP) vs the change in pressure pain threshold after treatment with Bedrocan (blue dots), Bediol (red dots), and Bedrolite (green dots). The arrows indicate the direction of effect, starting at the large yellow circle. (B) Estimated steady-state or effect-site (CE) concentration vs the change in pressure pain threshold for the 3 active cannabis varieties. THC, tetrahydrocannabinol.
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