There is increasing interest in the therapeutic potential of cannabis-based medicinal extracts in multiple sclerosis. Cognitive deficits that have been attributed to long-term heavy recreational use of cannabis are not necessarily extended to controlled pharmaceutical use of cannabis-based medicinal extracts. Available data indicate that after relatively short-term administration of cannabis-based medicinal extracts no significant cognitive decline occurs. Due to the absence of large scale long-term systematic clinical trials of cannabis-based medicinal extracts in multiple sclerosis therapeutics, however, many issues remain unresolved, including the possible adverse effects of cannabis-based medicinal extracts on cognition. This article critically reviews the current literature and considers the potential for cognitive adverse effects of long-term cannabinoid use in multiple sclerosis therapeutics.