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

Ying Liu; Jacquelyn Bainbridge; Stefan Sillau; Sarah Rajkovic; Michelle Adkins; Christopher H Domen; John A Thompson; Tristan Seawalt; Jost Klawitter; Cristina Sempio; Grace Chin; Lisa Forman; Michelle Fullard; Trevor Hawkins; Lauren Seeberger; Heike Newman; David Vu; Maureen Anne Leehey

doi:10.1002/mds.29768

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

Mov Disord. 2024 Mar 15. doi: 10.1002/mds.29768. Online ahead of print.

Authors

Ying Liu¹, Jacquelyn Bainbridge², Stefan Sillau¹, Sarah Rajkovic³, Michelle Adkins², Christopher H Domen⁴, John A Thompson^{1

4}, Tristan Seawalt¹, Jost Klawitter⁵, Cristina Sempio⁵, Grace Chin², Lisa Forman⁶, Michelle Fullard¹, Trevor Hawkins¹, Lauren Seeberger¹, Heike Newman⁷, David Vu¹, Maureen Anne Leehey¹

Affiliations

¹ Department of Neurology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA.
² Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Anschutz Medical Campus, Aurora, Colorado, USA.
³ Neurosciences, University of Colorado Hospital, Anschutz Medical Campus, Aurora, Colorado, USA.
⁴ Department of Neurosurgery, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA.
⁵ Department of Anesthesiology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA.
⁶ Department of Medicine, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA.
⁷ Department of Regulatory Compliance, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA.

PMID: 38487964
DOI: 10.1002/mds.29768

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.

Abstract

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