The long-term treatment of Parkinson’s disease (PD) may be complicated by the development of levodopa-induced dyskinesia. Clinical and animal model data support the view that modulation of cannabinoid function may exert an antidyskinetic effect. A randomised, double-blind, placebo-controlled crossover trial was conducted to examine the hypothesis that C. sativa may have a beneficial effect on dyskinesia in PD. A 4-week dose escalation study was performed to assess the safety and tolerability of C. sativa in six PD patients with levodopa-induced dyskinesia. Subsequently a randomised, placebo-controlled, crossover study was performed, in which 19 PD patients were randomised to receive oral C. sativa extract followed by placebo or vice versa. Each treatment phase lasted for 4 weeks with an intervening 2-week washout phase. The primary outcome measure was a change in Unified Parkinson’s Disease Rating Scale (UPDRS) (items 32 to 34) dyskinesia score. Secondary outcome measures included the Rush scale, Bain scale, tablet arm drawing task and total UPDRS score following a levodopa challenge, as well as patient-completed measures of a dyskinesia activities of daily living scale, the PDQ-39, on-off diaries and a range of category rating scales. Seventeen patients completed the RCT. Cannabis sativa was well tolerated and had no pro- or antiparkinsonian action. There was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed by the UPDRS or any of the secondary outcome measures.