Short-Term Cannabidiol with Δ-9-Tetrahydrocannabinol in Parkinson's Disease: A Randomized Trial

Abstract

Background: Cannabis use is frequent in Parkinson's disease (PD), despite inadequate evidence of benefits and risks.

Objective: The aim is to study short-term efficacy and tolerability of relatively high cannabidiol (CBD)/low Δ-9-tetrahydrocannabinol (THC) to provide preliminary data for a longer trial.

Methods: Persons with PD with ≥20 on motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) who had negative cannabis testing took cannabis extract (National Institute of Drug Abuse) oral sesame oil solution for 2 weeks, increasing to final dose of 2.5 mg/kg/day. Primary outcome was change in motor MDS-UPDRS from baseline to final dose.

Results: Participants were randomized to CBD/THC (n = 31) or placebo (n = 30). Mean final dose (CBD/THC group) was 191.8 ± 48.9 mg CBD and 6.4 ± 1.6 mg THC daily. Motor MDS-UPDRS was reduced by 4.57 (95% CI, -8.11 to -1.03; P = 0.013) in CBD/THC group, and 2.77 (-4.92 to -0.61; P = 0.014) in placebo; the difference between groups was non-significant: -1.80 (-5.88 to 2.27; P = 0.379). Several assessments had a strong placebo response. Sleep, cognition, and activities of daily living showed a treatment effect, favoring placebo. Overall adverse events were mild and reported more in CBD/THC than placebo group. On 2.5 mg/kg/day CBD plasma level was 54.0 ± 33.8 ng/mL; THC 1.06 ± 0.91 ng/mL.

Conclusions: The brief duration and strong placebo response limits interpretation of effects, but there was no benefit, perhaps worsened cognition and sleep, and there was many mild adverse events. Longer duration high quality trials that monitor cannabinoid concentrations are essential and would require improved availability of research cannabinoid products in the United States. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; cannabidiol; cannabis.

Figure 1.. Flow of Study Participants

Abbreviations: MDS-UPDRS, International Parkinson and Movement Disorder Society Unified Parkinson’s Disease Rating Scale; CBD, cannabidiol; THC, delta-9-tetrahydrocannabinol; AEs, adverse events ^aIncludes 13 that had a screening visit. ^b7 Were in or preferred another clinical trial, 5 lived outside Colorado, 1 did not have Parkinson disease, and 1 was too young. ^c17 Declined due to long distance travel and 6 due to schedule conflicts. ^d12 Were not responsive after phone screening, 3 had health concerns, and 2 had legal conflicts ^eNo participants were lost to follow-up.

Figure 2.. Plasma cannabinoid levels

Three hours after the CBD/THC study drug administration plasma concentrations of CBD (A) in participants on 1.25mg/kg/day, n=23, was mean (SD) 37.1 (26.7), range 5.7 – 109.4 ng/mL and on 2.5mg/kg/day, n=20, was 54.0 (33.8), range 10.1 – 124.0 ng/mL. Plasma concentrations of THC (B) in participants on 1.25 mg/kg/day, n = 23, was 0.61 (0.53), range 0.20 – 2.20 ng/mL and on 2.5 mg/kg/day was 1.06 (0.91), range 0.20 – 3.86 ng/mL. Abbreviations: CBD = cannabidiol; THC = delta-9-tetrahydrocannabinol