This is a double-blind, randomized controlled trial designed to test the effects of cannabidiol (CBD) on validated biomarkers of Alzheimer's disease (AD) progression, and behavioral, neurocognitive, and clinical measures, with putative mechanisms of action.

To better understand the effects of hemp-derived CBD with and without a small amount of THC, we propose a Phase II randomized clinical trial (RCT) to examine the clinical effects of Full Spectrum CBD (fsCBD, contains less than 0.3% THC) vs. Broad Spectrum CBD (bsCBD, does not contain THC), vs. a matching placebo in a population of individuals diagnosed with mild cognitive impairment (MCI).

This is a double-blind, placebo-controlled, parallel group study designed to assess the efficacy of fsCBD and bsCBD, compared to a placebo control, on biomarkers of Alzheimer's disease progression, cognitive function, pain, sleep quality, anxiety, oxidative stress, and inflammation. If eligible for the study, subjects will be randomized to receive one of the conditions for 24 weeks.

The current study will test the hypothesis that a moderate dose of CBD will improve measures of Alzheimer's disease progression, cognitive function, pain, sleep quality, anxiety, oxidative stress, and inflammation as compared to placebo. The study will also test whether endocannabinoids mediate the effects of CBD on these outcomes.

Inclusion Criteria:

1. Must be between the ages of 55 - 85 and provide valid informed consent.
2. Participant must receive a diagnosis of Mild Cognitive Impairment after a careful cognitive and functional evaluation by a clinician, or have symptoms of Mild Cognitive Impairment as determined by the study physician.
3. Functional Activities Questionnaire (FAQ) score of 8 or less and self-reported ability to function independently.
4. Montreal Cognitive Assessment (MoCa) score is ≤ 25
5. Participant must have a CDR score of .5 or 1 on the Clinical Dementia Rating scale (CDR), which includes an assessment of function and is often used to distinguish MCI from dementia. A score of 0.5 indicates mild cognitive impairment but not dementia and a score of 1 indicates mild-to-moderate cognitive impairment.
6. Must have an informant that will be utilized over the course of the 24 week study (must be the same person for all CDR assessments completed via phone).
7. Participant must pass a test of consent comprehension
8. Must be interested in using CBD to help with cognitive function
9. Must plan on living in the Denver metro area over the next 6 months
10. Able to attend in-person visits at the study site

Exclusion Criteria:

1. Any other central nervous system (CNS) disease that would be expected to affect cognition, Parkinson's disease, multiple sclerosis.
2. History of brain injury resulting in current memory loss symptoms (e.g., concussion with significant loss of consciousness)
3. Any significant systemic illness or unstable medical condition
4. Current use of Parkinson's medications, antipsychotic medications, anti-seizure medications, or anticholinergic medications
5. Current or lifetime diagnosis of a schizophrenia spectrum disorder, psychotic disorder, bipolar disorder type I & II, cluster B personality disorders (antisocial, borderline, narcissistic, histrionic), eating disorders, as defined by the DSM-5-TR
6. Participation in other clinical studies involving neuropsychological measures being collected more than one time per year.
7. Reported use of other drugs (cocaine, opiates, methamphetamine, MDMA) in the past 60 days or test positive on a urine test for those drugs of abuse at baseline.
8. Report using more than 150mg of cannabis edible products per week.
9. Report using more than 7 grams of cannabis flower product (not including CBD) per week.
10. Recent history of, or meets criteria for major depression with suicidal ideation.
11. Reports use of medical CBD.
12. Liver function enzymes (AST, ALT) that are greater than 2x normal.
13. Currently taking medications known to be contraindicated with Epidiolex (buprenorphine, leflunomide, levomethadyl acetate, lomitapide, mipomersen, pexidartinib, propoxyphene, sodium oxybate, teriflunomide, clobazam, lamotrigine, valproate).
14. Pregnant at the time of study enrollment or unwilling to use contraception through the duration of the study (if not yet post-menopausal)
15. Individuals with potentially reversible causes of mild cognitive impairment (i.e., hypothyroidism, Vitamin B12 deficiency).