Cannabidiol for Alzheimer's Disease Prevention (NCT05822362)

Overview

This Phase 2 clinical trial investigates whether cannabidiol (CBD) can prevent or delay the onset of [Alzheimer's Disease](/diseases/alzheimers-disease) in individuals at elevated genetic risk for AD. The trial is conducted by researchers at the University of Colorado and represents a novel preventive therapeutic approach targeting the endocannabinoid system in at-risk populations.

Trial Details

| Parameter | Value |
|-----------|-------|
| NCT Number | NCT05822362 |
| Phase | Phase 2 |
| Enrollment | 236 participants |
| Sponsor | University of Colorado |
| Intervention | Cannabidiol (CBD) |
| Purpose | Prevention |
| Study Type | Interventional |
| Allocation | Randomized, controlled |

Study Population

Target Population

• Individuals at genetic risk for Alzheimer's Disease
• May include carriers of Apolipoprotein E (APOE) ε4 allele or other known AD risk genetic variants
• Cognitively normal at baseline

Rationale for Prevention in At-Risk Individuals

The rationale for CBD-based prevention in at-risk populations includes:

Overview

This Phase 2 clinical trial investigates whether cannabidiol (CBD) can prevent or delay the onset of [Alzheimer's Disease](/diseases/alzheimers-disease) in individuals at elevated genetic risk for AD. The trial is conducted by researchers at the University of Colorado and represents a novel preventive therapeutic approach targeting the endocannabinoid system in at-risk populations.

Trial Details

| Parameter | Value |
|-----------|-------|
| NCT Number | NCT05822362 |
| Phase | Phase 2 |
| Enrollment | 236 participants |
| Sponsor | University of Colorado |
| Intervention | Cannabidiol (CBD) |
| Purpose | Prevention |
| Study Type | Interventional |
| Allocation | Randomized, controlled |

Study Population

Target Population

• Individuals at genetic risk for Alzheimer's Disease
• May include carriers of Apolipoprotein E (APOE) ε4 allele or other known AD risk genetic variants
• Cognitively normal at baseline

Rationale for Prevention in At-Risk Individuals

The rationale for CBD-based prevention in at-risk populations includes:

Mechanism of Action

Cannabidiol (CBD) Neuroprotective Mechanisms

[CBD](/mechanisms/endocannabinoid-system) is a non-psychoactive phytocannabinoid that exerts neuroprotective effects through multiple pathways:

• CB2 receptor activation on [microglia](/cell-types/microglia) shifts polarization from pro-inflammatory (M1) to anti-inflammatory (M2) phenotype
• Suppression of [NLRP3 inflammasome](/mechanisms/nlrp3-inflammasome) assembly
• Reduction in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6)

• Direct scavenging of reactive oxygen species (ROS) through phenolic ring structure
• Activation of Nrf2-dependent antioxidant gene expression
• Protection against lipid peroxidation

• Modulation of glutamate release
• Protection against NMDA receptor-mediated excitotoxicity
• Calcium homeostasis maintenance

• Enhancement of [BDNF](/mechanisms/neurotrophic-factors) expression
• Support of synaptic plasticity
• Promotion of neurogenesis

• Reduction of Aβ production through APP processing modulation
• Inhibition of tau hyperphosphorylation
• Enhancement of Aβ clearance

Study Design

Trial Structure

• Randomized, double-blind, placebo-controlled design
• Parallel-group comparison
• Dose-finding components may be included

Endpoints

Primary Endpoints:

• Cognitive performance measures
• Biomarker changes indicative of AD progression

• Brain imaging biomarkers
• Fluid biomarker panels
• Clinical conversion rates

Assessment Timeline

Participants will undergo comprehensive assessments at baseline and follow-up visits:

• Cognitive testing batteries
• Neuroimaging (MRI/PET)
• Fluid biomarker collection (blood, CSF)

Endocannabinoid System in AD Prevention

The [endocannabinoid system](/mechanisms/endocannabinoid-system) represents a promising therapeutic target for AD prevention:

Key Findings Supporting ECS Modulation

• CB1R downregulation in AD cortex correlates with cognitive decline
• CB2R upregulation on microglia surrounding plaques represents an endogenous anti-inflammatory response
• Endocannabinoid deficiency in AD brain may contribute to disease progression
• MAGL and FAAH enzymes represent additional therapeutic targets

CBD Advantages Over Other ECS Modulators

| Target | Advantage of CBD |
|--------|---------------|
| CB1R agonists | CBD acts as negative allosteric modulator — avoids psychoactivity |
| CB2R-selective | CBD provides anti-inflammatory effects without immunosuppression |
| FAAH inhibitors | CBD has mild FAAH inhibitory activity |
| Direct antioxidants | CBD provides direct ROS scavenging |

Safety Considerations

CBD Safety Profile

• Generally well-tolerated at doses up to 1500-3000 mg/day
• Most common adverse events: diarrhea, fatigue, weight changes
• Drug interactions via CYP450 enzymes
• Minimal psychoactivity compared to THC

Monitoring Requirements

• Liver function tests
• Drug interaction screening
• Adverse event tracking
• Concomitant medication review

Related Clinical Trials

• [Nabilone for Agitation in AD (NCT04516057)](/clinical-trials/nabilone-ad-agitation-nct04516057) — CBD analog for behavioral symptoms
• [Endocannabinoid System in Neurodegeneration](/mechanisms/endocannabinoid-system) — mechanistic background

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Cannabidiol](/mechanisms/endocannabinoid-system)
• [Endocannabinoid System in Neurodegeneration](/mechanisms/endocannabinoid-system)
• [Neuroinflammation](/mechanisms/neuroinflammation)
• [APOE Gene](/genes/apoe)
• [Alzheimer's Prevention](/ideas/novel-therapy-index)

References