Nabilone for Agitation in Alzheimer's Disease (NCT04516057)

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Overview

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This Phase 3 trial (NAB-IT) investigates whether nabilone, a synthetic cannabinoid, is an effective treatment for agitation in [Alzheimer's Disease](/diseases/alzheimers-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.

Trial Details

...

Overview

Mermaid diagram (expand to render)

Trial Details

| 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 |

Mechanism of Action

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

Rationale for Agitation in AD

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

Study Design

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

Treatment Protocol

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

Key Eligibility Criteria

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)

Outcome Measures

Primary Outcomes

| Measure | Timeframe |
|--------|-----------|
| Cohen-Mansfield Agitation Inventory (CMAI) | Baseline to 8 weeks |

Secondary Outcomes

| 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 |

Safety Outcomes

| Measure | Timeframe |
|--------|-----------|
| UKU Side-Effect Rating Scale (Sedation subscale) | Baseline to 8 weeks |

Clinical Significance

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](/diseases/parkinsons-disease) psychosis | Approved |

[Alzheimer's Disease](/diseases/alzheimers-disease)
[Agitation in Dementia](/mechanisms/dementia-agitation)
[Cannabinoid Signaling](/mechanisms/cannabinoid-signaling)
[Neuropsychiatric Symptoms in AD](/mechanisms/neuropsychiatric-symptoms-ad)
[Sunnybrook Health Sciences Centre](/institutions/sunnybrook-health-sciences-centre)
[Alzheimer's Drug Discovery Foundation](/institutions/alzheimers-drug-discovery-foundation)

External Links

[ClinicalTrials.gov](https://clinicaltrials.gov/study/NCT04516057)
[Sunnybrook Research - NAB-IT Trial](https://sunnybrook.ca/research/)

References

Unknown, NCT04516057 - Nabilone for Agitation in AD (n.d.)

Unknown, NAB-IT Study - Sunnybrook Health Sciences Centre (n.d.)

[Herrmann et al., Cannabinoids for Agitation in AD (2019) (2019)](https://doi.org/10.1016/j.jagp.2019.01.014)

[Unknown, Cohen-Mansfield Agitation Inventory (CMAI) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/26552476/)

[Unknown, Neuropsychiatric Inventory - Nursing Home (NPI-NH) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/11882156/)

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Nabilone for Agitation in Alzheimer's Disease (NCT04516057)

Overview

Trial Details

Overview

Trial Details

Mechanism of Action

Rationale for Agitation in AD

Study Design

Randomized Controlled Trial

Treatment Protocol

Key Eligibility Criteria

Outcome Measures

Primary Outcomes

Secondary Outcomes

Safety Outcomes

Clinical Significance

Related Compounds

Related Pages

External Links

References