Introduction: Major neurocognitive disorder (MNCD) affects millions of people worldwide. However, the pharmacological options for its management are limited, ineffective and frequently associated with severe adverse reactions. Case report: An 85-year-old man with history of multiple chronic brain injuries (alcohol-use disorder, haemorrhagic stroke, brain trauma, chronic use of benzodiazepines) developed an MNCD, reaching 7 points on the Reisberg Global Deterioration Scale. He had minimal response to antidepressants, antipsychotics and anticholinergic medications. After the use of mother tincture of Indian hemp (cannabis), a significant improvement was found in his cognitive function, ability to carry out activities of daily living and independence. Discussion: The endocannabinoid system seems to be implicated in age-related cognitive decline. In addition, the evidence derived from in-vitro and animal models suggest that this system could play an important role in the management of MNCD of different causes. Conclusions: Cannabinoid treatment for MNCD emerges as a promising therapeutic approach that may benefit a growing number of patients who do not have other treatment options. It is therefore necessary to encourage more research efforts that will help to remove political and scientific barriers to its clinical use. © 2019 Asociación Colombiana de Psiquiatría