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Introduction Multiple sclerosis (MS) is a progressive neurological disorder with debilitating symptoms. Some people with MS use cannabis for symptom management although its impact on motor function remains unclear.Aim Does self-reported cannabis usage affect time to clinically meaningful 10-point increase in the MSIS29-motor domain.Methods Propensity matching UKMS Register data (1:1) produced two groups of 884. Cannabis users for MS (CUfMS) and non-cannabis users. Matching was based on smoking status, baseline normalised MSIS29-motor and MSIS29-psych: age, gender, and MS subtype. Kaplan-Meier (KM) survival analysis compared cumulative incidence of MSIS29-motor deterioration. Cox proportional hazards models examined confounders between cannabis use, smoking status, and motor decline time.Results KM analysis showed shorter time to 10-point MSIS29-motor increase for CUfMS (p=0.0022). In a Cox model controlling for age, smoking history, MSIS-psych, gender, and MS phenotype, cannabis use was independently associated with increased hazard MSIS29-motor deterioration (HR = 1.43, p=0.002). Higher baseline MSIS9-psych scores were slightly protective (HR = 0.99, p << 0.0001), and having SPMS conferred additional risk (HR = 1.50, p=0.004).Discussion These findings suggest cannabis use is linked to elevated risk of motor worsening in MS, this effect is moderated by individual characteristics such as psychological status and disease phenotype.r.m.middleton@swansea.ac.uk