This Phase 3 trial (NAB-IT) investigates whether nabilone, a synthetic cannabinoid, is an effective treatment for agitation in Alzheimer's Disease (AD) patients. Agitation is one of the most distressing and challenging-to-treat neuropsychiatric symptoms in AD, associated with faster progression to institutionalization, increased caregiver burden, and poorer quality of life.
| Parameter |
Value |
| NCT Number |
NCT04516057 |
| Status |
Recruiting |
| Phase |
Phase 3 |
| Sponsor |
Sunnybrook Health Sciences Centre |
| Collaborators |
Alzheimer's Drug Discovery Foundation |
| Intervention |
Nabilone (up to 2 mg/day) |
| Acronym |
NAB-IT |
| Purpose |
Treatment |
| Study Type |
Interventional |
| Enrollment |
112 participants (estimated) |
| Start Date |
February 1, 2021 |
| Primary Completion |
April 2027 |
| Study Duration |
8 weeks treatment + 8 weeks follow-up |
Nabilone (brand name Cesamet) is a synthetic cannabinoid that exerts its effects through:
- CB1 Receptor Agonism — Nabilone acts as a selective agonist at cannabinoid CB1 receptors, which are abundantly expressed in brain regions involved in emotion regulation and memory
- CB2 Receptor Effects — Modulation of CB2 receptors may contribute to anti-inflammatory effects relevant to neurodegeneration
- Anxiolytic Properties — Cannabinoid signaling modulates anxiety responses through amygdala pathways
- Appetite Stimulation — May help address weight loss and nutritional concerns in AD patients
Agitation affects up to 70% of AD patients during the disease course and represents a major unmet medical need:
- Current treatments are inadequate — Antipsychotics show modest efficacy but carry significant risks (stroke, mortality)
- Caregiver burden — Agitation is the strongest predictor of institutionalization
- Quality of life — Agitation severely impacts both patient and caregiver wellbeing
- Preliminary evidence — A prior 6-week pilot trial (n=38) showed nabilone significantly improved agitation, neuropsychiatric symptoms, and caregiver distress
¶ Randomized Controlled Trial
- Design: Quadruple-blind, randomized, placebo-controlled, parallel-group
- Allocation: 1:1 randomization to nabilone or placebo
- Duration: 8 weeks of treatment followed by 8 weeks of observation
- Nabilone Arm: Titration up to maximum dose of 2 mg/day
- Placebo Arm: Identical-appearing placebo capsules
- Blinding: Participant, care provider, investigator, and outcomes assessor all blinded
Inclusion:
- Age ≥55 years
- DSM-5 criteria for Major Neurocognitive Disorder due to AD
- MMSE ≤24 (moderate-to-severe AD)
- Clinically significant agitation per IPA definition
- Stable cognitive-enhancing medication dose for ≥3 months
- Availability of primary caregiver
Exclusion:
- Current uncontrolled cardiovascular disease
- Significant liver disease
- Psychiatric disorders (psychotic disorders, schizophrenia, stroke, epilepsy)
- Current major depressive episode
- Previous or current cannabis use disorder
- Clinically significant delusions/hallucinations (NPI-NH subscore ≥4)
| Measure |
Timeframe |
| Cohen-Mansfield Agitation Inventory (CMAI) |
Baseline to 8 weeks |
| Measure |
Timeframe |
| Neuropsychiatric Inventory - Nursing Home (NPI-NH) |
Baseline to 8 weeks |
| Standardized Mini-Mental State Examination (sMMSE) |
Baseline to 8 weeks |
| Mini Nutritional Assessment - Short Form (MNA-SF) |
Baseline to 8 weeks |
| Pain Assessment Checklist for Seniors (PACSLAC-II) |
Baseline to 8 weeks |
| ADCS-CGIS/C (Clinical Global Impression) |
Baseline to 8 weeks |
| Weight |
Baseline to 8 weeks |
| Measure |
Timeframe |
| UKU Side-Effect Rating Scale (Sedation subscale) |
Baseline to 8 weeks |
This pivotal Phase 3 trial could:
- Establish new treatment paradigm — First large-scale evidence for cannabinoid-based treatment of AD agitation
- Address safety concerns — Systematic evaluation of nabilone safety in AD population
- Reduce caregiver burden — Effective agitation treatment delays institutionalization
- Identify responders — Exploring predictors of treatment response including nutritional status and pain
| Compound |
Developer |
Target |
Indication |
Status |
| Nabilone |
Sunnybrook Health Sciences Centre |
CB1/Agitation |
Agitation in AD |
Phase 3 |
| Masupirdine |
Suilute |
Tyrosine hydroxylase |
Agitation in AD |
Phase 2 |
| Pimavanserin |
Acadia |
5-HT2A |
Parkinson's disease psychosis |
Approved |