Open AccessPlacebo Effects in a Multiple Sclerosis Spasticity Enriched Clinical Trial with the Oromucosal Cannabinoid Spray ( THC / CBD ): Dimension and Possible Causes
Author(s) -
Di Marzo Vincenzo,
Centonze Diego
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12358
Subject(s) - placebo , cannabidiol , medicine , clinical trial , multiple sclerosis , cannabinoid , spasticity , randomization , clinical endpoint , cannabis , randomized controlled trial , tetrahydrocannabinol , pharmacology , physical therapy , psychiatry , alternative medicine , pathology , receptor
Summary Regulatory authorities admit clinical studies with an initial enrichment phase to select patients that respond to treatment before randomization (Enriched Design Studies; EDS s). The trial period aims to prevent long‐term drug exposure risks in patients with limited chances of improvement while optimizing costs. In EDS s for symptom control therapies providing early improvements and without a wash‐out period, it is difficult to show further improvements and thus large therapeutic gains versus placebo. Moreover, in trials with cannabinoids, the therapeutic gains can be further biased in the postenrichment randomized phase because of carryover and other effects. The aims of the present review article are to examine the placebo effects in the enrichment and postenrichment phases of an EDS with Δ 9 ‐tetrahydrocannabinol and cannabidiol ( THC / CBD ) oromucosal spray in patients with multiple sclerosis ( MS ) spasticity and to discuss the possible causes of maintained efficacy after randomization in the placebo‐allocated patients. The overall mean therapeutic gain of THC / CBD spray over placebo in resistant MS spasticity after 16 weeks can be estimated as a ~1.27‐point improvement on the spasticity 0–10 Numerical Rating Scale ( NRS ; ~−20.1% of the baseline NRS score). We conclude that careful interpretation of the results of EDS s is required, especially when cannabinoid‐based medications are being investigated.