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Short-Term Therapy With a High Cannabidiol/Low Δ-9-Tetrahydrocannabinol Formulation in Patients With Parkinson's Disease
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
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.
Additional Info
Disclosure statements are available on the authors' profiles:
Short-Term Cannabidiol with Δ-9-Tetrahydrocannabinol in Parkinson's Disease: A Randomized Trial
Mov. Disord. 2024 May 01;39(5)863-875, Y Liu, J Bainbridge, S Sillau, S Rajkovic, M Adkins, CH Domen, JA Thompson, T Seawalt, J Klawitter, C Sempio, G Chin, L Forman, M Fullard, T Hawkins, L Seeberger, H Newman, D Vu, MA LeeheyFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The lack of effective and well-tolerated symptomatic treatments for Parkinson’s disease (PD) motivates patients to pursue alternative options like Cannabis. Although the medical use of Cannabis has expanded for multiple neurological conditions, evidence for its efficacy in patients with PD is limited. Small randomized controlled trials (RCTs) involving patients with PD tested multiple cannabinoid formulations, doses, and administration routes and found conflicting effects on motor and non-motor symptoms.1-7
In this recent trial, Liu et al performed a well-designed phase II RCT assessing a combination of CBD and THC or placebo for 2 weeks in 61 patients with PD. Similar to prior studies,1,8,9 this study found no significant between-group differences in the mean MDS-UPDRS part III (motor) scores and subscores. However, when within-group changes were analyzed, there was a trend of improved motor function in both arms, supporting a placebo effect. Of note, cognitive function worsened in the treated group compared with the placebo group. Previous studies have shown a detrimental effect of Cannabis on cognition,7,10 whereas one study assessing nabilone (synthetic THC) revealed no cognitive deterioration.11 There was a higher incidence of adverse events during CBD/THC treatment compared with placebo, which in line with the findings of other studies.7,9 There was a trend toward improvement in dyskinesia in the placebo group and worsening in the CBD/THC group. These findings contrast with those of previous studies, which showed either no effect8,12 or a benefit2 for dyskinesia.
The strengths of this study include the blinded RCT design with a comprehensive set of clinical and pharmacokinetic measures. Prior cannabinoid studies involving patients with PD include RCTs with smaller sample sizes and designs with a lower level of evidence such as surveys and single-armed open-label trials.13-16 CBD/THC was administered orally in this study, which is the most feasible route in patients with PD.
To date, controlled trials using cannabinoid formulations have failed to demonstrate a clinically meaningful treatment effect on PD motor and nonmotor symptoms. A significant short-term placebo effect on motor and nonmotor scores was uncovered by Liu et al. RCTs with longer follow-up observations are warranted to ascertain the duration of the placebo effect as PD progresses and the long-term safety and efficacy of cannabinoids. Larger sample sizes are also warranted to assess the treatment effects of smaller magnitudes.
References
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