Study register · detailOpen-Label Dosiseskalationsstudie · Parkinson Disease · 2020
Safety and Tolerability of Cannabidiol in Parkinson Disease: An Open Label, Dose-Escalation Study.
Leehey et al.·Cannabis and Cannabinoid ResearchImpact 2.5
MixedGRADELow68 citations
Samplen = 13 Pat.
Duration10–15 days maintenance phase
EndpointMDS-UPDRS
Blindingoffen
DesignOpen-Label Dosiseskalationsstudie
Cannabinoidcbd
Routeoral
”Key finding
CBD significantly improved motor and non-motor Parkinson's symptoms, but caused frequent side effects and relevant liver enzyme elevations at high dose.
Summary
Open-label study (n=13 PD patients); CBD (Epidiolex, 5–25 mg/kg/day, 10–15 days); MDS-UPDRS total improved by 17,8% (p=0,012) and motor score by 24,7% (p=0,004); liver transaminases elevated in 38,5% of participants (20–25 mg/kg/day); discontinuation rate 23% due to intolerability.
P
PopulationAdults with Parkinson's disease and pronounced resting tremor, no prior cannabis use, n=13 (after exclusion of 2 screen failures out of 15 enrolled)
I
InterventionPlant-derived highly purified CBD (Epidiolex, 100 mg/mL oral), titration from 5 to 20–25 mg/kg/day, maintenance phase 10–15 days
O
OutcomeAll 13 participants reported adverse events (mainly diarrhea 85%, somnolence 69%, fatigue 62%); liver enzyme elevations in 5/13 (38,5%) at maximum dose; MDS-UPDRS total score improved by 17,8% (p=0,012), motor score by 24,7% (p=0,004)
Confidence in the evidence
Very lowLowModerateHigh
Low
The second of four GRADE levels, the effect estimate is of limited reliability.
Downgraded for
Risk of biasImprecision
Quality profile
Sample size★★★★★
BlindingOpen-label
Effect sizeMixed
Citations / year★★★★★
Authors
Leehey MA, Liu Y, Hart F, Epstein C, Cook M, Sillau S, Klawitter J, Newman H, Sempio C, Forman L, Seeberger L, Klepitskaya O, Baud Z, Bainbridge J.
<b>Background:</b> Cannabis is increasingly used in Parkinson disease (PD), despite little information regarding benefits and risks. <b>Objectives:</b> To investigate the safety and tolerability of a range of doses of cannabidiol (CBD), a nonintoxicating component of cannabis, and it's effect on common parkinsonian symptoms. <b>Methods:</b> In this open-label study Coloradans with PD, substantial rest tremor, not using cannabis received plant-derived highly purified CBD (Epidiolex<sup>®</sup>; 100 mg/mL). CBD was titrated from 5 to 20-25 mg/kg/day and maintained for 10-15 days. <b>Results:</b> Fifteen participants enrolled, two were screen failures. All 13 participants (10 male), mean (SD) age 68.15 (6.05), with 6.1 (4.0) years of PD, reported adverse events, including diarrhea (85%), somnolence (69%), fatigue (62%), weight gain (31%), dizziness (23%), abdominal pain (23%), and headache, weight loss, nausea, anorexia, and increased appetite (each 5%). Adverse events were mostly mild; none serious. Elevated liver enzymes, mostly a cholestatic pattern, occurred in five (38.5%) participants on 20-25 mg/kg/day, only one symptomatic. Three (23%) dropped out due to intolerance. Ten (eight male) that completed the study had improvement in total and motor Movement Disorder Society Unified Parkinson Disease Rating Scale scores of 7.70 (9.39, mean decrease 17.8%, <i>p</i>=0.012) and 6.10 (6.64, mean decrease 24.7%, <i>p</i>=0.004), respectively. Nighttime sleep and emotional/behavioral dyscontrol scores also improved significantly. <b>Conclusions:</b> CBD, in the form of Epidiolex, may be efficacious in PD, but the relatively high dose used in this study was associated with liver enzyme elevations. Randomized controlled trials are needed to investigate various forms of cannabis in PD.