A randomized clinical trial of low-dose cannabis extract in Alzheimer’s disease

Background: Preclinical and clinical evidence suggest that low-dose cannabinoids could ameliorate Alzheimer’s disease (AD) signs and symptoms. We designed this trial to evaluate the safety and efficacy of low-dose THC-CBD balanced cannabinoid extract in the treatment of patients with AD-associated dementia. Objective: The objective of this phase 2 trial was to evaluate the safety and efficacy of a balanced THC-CBD cannabinoid extract for symptomatic patients with AD. Methods: A Phase 2, randomized, double-blind, placebo-controlled, clinical trial including patients between 60 and 80 years-old diagnosed with AD-associated dementia. For 26 weeks, participants orally received either placebo or THC-CBD extract (0.350 mg/THC and 0.245 mg/CBD), daily. Results: At week 26, Mini-Mental State Exam total score was significantly higher in cannabis- when compared to placebo-treated patients, which was assessed using the mixed model analysis. No significant difference was detected between placebo and cannabis groups in terms of secondary outcomes and adverse events incidence. Conclusions: To this date, this is the longest clinical trial evaluating cannabinoids effects on AD patients. We initially demonstrate that low-dose THC-CBD potentially can be an effective and safe therapeutic option for AD-related dementia. Nonetheless, larger and longer trials are necessary to confirm this finding and establish cannabinoid administration as therapy for AD dementia. Trial Registration: The Brazilian Registry of Clinical Trials (ReBEC) registration #U1111-1258-2058 - REBEC (ensaiosclinicos.gov.br).