Short-Term Cannabidiol with Δ-9-Tetrahydrocannabinol in Parkinson’s Disease: A Randomized Trial
Ying Liu MD, Jacquelyn Bainbridge PharmD, Stefan Sillau PhD, Sarah Rajkovic PharmD, Michelle Adkins PharmD, Christopher H. Domen PhD, John A. Thompson PhD, Tristan Seawalt MS, Jost Klawitter PhD, Cristina Sempio PhD, Grace Chin PharmD, Lisa Forman MD, Michelle Fullard MD, Trevor Hawkins MD, Lauren Seeberger MD, Heike Newman MS, David Vu BS, Maureen Anne Leehey MD
Department of Neurology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA
Affiliationer
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.
