Fibromyalgia
Study register · detail RCT (4-way crossover) · Fibromyalgia · 2019

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

Mixed GRADE Moderate 278 citations
Samplen = 20 Pat.
Duration3 hours follow-up after single…
ControlPlacebo cannabis
EndpointSpontaneous pain score / pain…
Blindingdoppelblind
DesignRCT (4-way crossover)
Cannabinoidvollspektrum
Routeinhalativ
Key finding

Cannabis varieties with THC showed an effect on pressure pain threshold, but no consistent effects on spontaneous or electrical pain responses; Bediol showed a 30% pain decrease in 90% vs. 55% of patients vs. placebo.

Summary

n=20 fibromyalgia patients, randomised 4-way crossover design with inhaled cannabis (Bedrocan 22,4mg THC/<1mg CBD, Bediol 13,4mg THC/17,8mg CBD, Bedrolite 18,4mg CBD/<1mg THC, placebo). No significant superiority over placebo for spontaneous or electrical pain responses after single inhalation. Bediol: 90% of patients showed ≥30% pain reduction vs. 55% with placebo (p=0,01). THC-containing varieties significantly increased pressure pain threshold vs. placebo (p<0,01). CBD increased THC plasma levels but reduced THC's analgesic effects (pharmacokinetically synergistic, pharmacodynamically antagonistic).

P
PopulationAdults with chronic pain and fibromyalgia, n=20
I
InterventionInhaled pharmaceutical cannabis: 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), single-dose vaporisation
C
ControlPlacebo cannabis (no THC, no CBD)
O
OutcomeNo treatment effect greater than placebo on spontaneous pain or electrical pain threshold; Bediol: 30% pain reduction in 90% vs. 55% (placebo, p=0,01); THC-containing varieties increased pressure pain threshold vs. placebo (p<0,01)
Confidence in the evidence
Moderate

The third of four GRADE levels, the effect estimate is probably reliable.

Downgraded for
Imprecision
Quality profile
Sample size
Blinding Double-blind
Effect size Mixed
Citations / year
Authors
van de Donk T, Niesters M, Kowal M A et al.
DOI 10.1097/j.pain.0000000000001464
Design: RCT (4-way crossover)
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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 (rho = -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.

The impediment to action advances action. — Marcus Aurelius