Table 5.

Reported clinical trials of cannabis for patients with Parkinson disease

Study	Size	Design	Duration	Intervention	Controls	Outcomes	AEs
Frankel et al. (1990) [87]
UK	5	Case series	1 session	Smoking 1 g marijuana	–	Motor: no improvement in tremor after the intervention	Drowsiness
Chagas et al. (2014b) [88]
Brazil	4	Case series	Variable	CBD capsules up to 300 mg/day	–	Motor: prompt and substantial reduction in RBD-related events	Did not report
Zuardi et al. (2009) [89]
Brazil	6	Open-label	4 weeks	CBD capsules up to 400 mg/day	–	Motor: improvement in total UPDRS score from baseline Non-motor: The BPRS, PPQ, and CGI all improved from baseline	No adverse effects and no change in cognition on MMSE or FAB
Lotan et al. 2014 [90]
Brazil	22	Open-label	1 session	Smoking cannabis (variable dosing)	–	Motor: The mUPDRS improved 30 min after smoking cannabis, including tremor, rigidity, and bradykinesia. Non-motor: Visual Analog Scale, present pain intensity scale both improved from baseline Qualitative: 12 reported greatly improved sleep quality, and 8 had mild relief	Dizziness in 1 patient; long-term effects include somnolence, drowsiness, palpitations, and bad taste from smoking
Shohet et al. (2017) [91]
Israel	20	Open-label	1 session	Smoking or vaporizing cannabis	–	Motor: The mUPDRS significantly improved 30 min after smoking. Non-motor: There was a significant improvement in the VAS from baseline, and a trend toward improvement in PRI. After long-term exposure, the mean heat pain threshold in the affected limb decreased significantly	Did not report
Leehey et al. (2020) [92]
USA	13	Open-label	10–15 days	CBD (Epidiolex) up to 25 mg/kg/day	–	Motor: Total and mUPDRS scores improved from baseline (17.8% (p = 0.012) and 24.7% (p = 0.004), respectively)	Mild adverse events in all patients, including diarrhea (85%), somnolence (69%), fatigue (62%), weight gain (31%), dizziness (23%), abdominal pain (23%), and headache, weight loss, nausea, anorexia, and increased appetite (all 5%). 5 had increased LFTs
Sieradzan et al. (2001) [93]
USA	7	Randomized, double-blind, placebo-controlled	2 sessions, 2 weeks apart	Cannabinoid receptor agonist, nabilone	Placebo	Motor: significant improvement in levodopa-induced dyskinesias, with no change in “off” or “on” time	Vertigo, postural hypotension, mild sedation, dizziness, hyperacusis, “floating sensation,” partial disorientation, formed visual hallucinations
Carroll et al. (2004) [94]
UK	19	Randomized, double-blind, placebo-controlled, cross-over study	4 weeks	Cannador capsules—2.5 mg THC, 1.25 cannabidiol per capsule with dose titration	Placebo	Motor: no improvement in dyskinesia, the primary endpoint Non-motor: no improvement in PDQ-39, sleep, and pain	No serious adverse events Physical and psychological adverse events were similar in both groups, but more than double in the cannabis group
Chagas et al. (2014a) [95]
Brazil	21	Randomized, double-blind, placebo-controlled	6 weeks	CBD capsules 75 mg/day (n = 7), CBD capsules 300 mg/day (n = 7)	Placebo	Motor: no improvement in any part of UPDRS compared to placebo (p > 0.05) Non-motor: Total PDQ-39 improved at 300 mg/day compared to placebo (p = 0.05)	No adverse events

AEs = adverse events; BPRS = Brief Psychiatric Rating Scale; CBD = cannabidiol; CGI = Clinical Global Impression; LFTs = liver function tests; mUPDRS = Unified Parkinson’s Disease Rating Scale, motor subscale; PDQ-39 = 39-item Parkinson’s Disease Questionnaire; PPQ = Parkinson Psychosis Questionnaire; PRI = Pain Rating Index; RBD = Rapid Eye Movement Sleep Behavior Disorder; THC = tetrahydrocannabinol; UPDRS = Unified Parkinson’s Disease Rating Scale; VAS = Visual Analog Scale