Safety and Tolerability of Cannabidiol in Parkinson Disease: An Open Label, Dose-Escalation Study.

<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^®; 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.