Cannabinoids and Psychedelics for Neuropsychiatric Symptoms of Alzheimer's: Addressing Disparities Through Clinical Trials

Abstract

AD and other forms of dementia are commonly associated with neuropsychiatric symptoms, including anxiety, agitation, and depression, all of which can lead to more rapid cognitive decline and a poor quality of life for both caregivers and patients.There are currently no FDA approved medications to treat neuropsychiatric symptoms associated with dementia. Instead, current treatment options include off-label use of psychotropic medications that are associated with well-established risks. Alternative therapeutic options include cannabinoids and psychedelics. This session will focus on discussing the safety and efficacy of cannabinoids in treating anxiety and agitation associated with Alzheimer's dementia, as well as the safety and efficacy of psychedelics in treating depression in older adults with dementia.The history of medicinal cannabis use dates back as far as 4000BC. Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis, activates cannabinoid receptors (mainly CB1 and CB2 receptors), producing anxiolytic and antidepressant effects while also reducing reduce brain inflammation. Cannabidiol (CBD), the major non-intoxicating component of cannabis, possesses low affinity to CB1 and CB2 receptors. CBD modulates systems outside of the endocannabinoid system, producing antioxidant and antipsychotic effects. Both THC and CBD have shown evidence of therapeutic effects on anxiety and pain. We will discuss three studies evaluating the use of cannabinoids as potential forms of treatment for agitation and anxiety in dementia.Psychedelics are also being introduced as potential mental health treatments. Past research has shown psychedelics can produce long-term anxiolytic and antidepressant effects after a single administration. A pilot trial at Johns Hopkins is examining the safety and efficacy of psilocybin treatment for participants with mild cognitive impairment (MCI) and depressive symptoms. The study hypothesizes that the psilocybin treatment will be associated with a significant reduction in depressive symptoms.Overall, these trials collectively guide research towards furthering our understanding of the pathology of Alzheimer's dementia and other forms of dementia and improving the quality of life for older adults and their caregivers.