Nabilone for Aggression in Intellectual Disabilities

(N-AND Trial)

Overseen By Research Analyst

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hsiang-Yuan Lin

Must not be taking: Benzodiazepines, Opioids, Barbiturates, others

Disqualifiers: Seizure disorder, Psychotic disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Innovative treatments are urgently needed for severe behavioural problems (SBPs) in adults with intellectual and developmental disabilities (IDD). Although a synthetic cannabinoid, nabilone may be a plausible and safe alternative to treat SBP, safety and efficacy of nabilone in people with IDD has never been evaluated. The investigators propose to conduct this first-ever Phase I pre-pilot open-label clinical trial to collect data on the tolerability and safety profile of nabilone in adults with IDD, and explore changes in SBP pre- and post-treatment. The results will inform a next-stage pilot randomized controlled trial, followed by a fully powered trial eventually.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you must stop all current medications, but you cannot take certain drugs like benzodiazepines, psychostimulants, nonbenzodiazepine hypnotics, opioids, barbiturates, or other cannabinoids. If you are taking other cannabinoids, you must stop them for at least 4 weeks before joining the study.

What evidence supports the effectiveness of the drug Nabilone for aggression in individuals with intellectual disabilities?

Nabilone, a synthetic cannabinoid, has shown promise in treating PTSD-related symptoms and chronic pain, suggesting it may help with aggression due to its calming effects. Preliminary studies indicate it could be a safe option for severe behavioral problems in adults with intellectual disabilities, but more research is needed to confirm its effectiveness. ^{1 2 3 4 5}

Is nabilone safe for use in humans?

Nabilone has been studied for various conditions, including PTSD-related symptoms, chronic pain, and chemotherapy-induced nausea, showing promise as a safe treatment option. However, some side effects like headache, dizziness, and drowsiness have been reported, especially at higher doses. ^{1 5 6 7 8}

How does the drug Nabilone differ from other drugs for aggression in intellectual disabilities?

Nabilone is unique because it is a synthetic cannabinoid, which means it mimics the effects of compounds found in cannabis, and it may offer a novel approach to managing aggression in individuals with intellectual disabilities, unlike traditional antipsychotics or other medications that are commonly used but have significant side effects. ^{3 4 9 10 11}

Research Team

Hsiang-Yuan Lin, MD

Principal Investigator

Centre for Addiction and Mental Health, Toronto, Ontario, Canada

Eligibility Criteria

Adults over 25 with intellectual and developmental disabilities (IDD) like autism or Down syndrome, who show severe behavioral problems. They must not have used other cannabinoids recently, be free from certain medical conditions, and women of childbearing age need a negative pregnancy test and must use birth control.

Inclusion Criteria

At least one month must pass from participation in another investigational drug trial

My recent liver tests are within the required limits.

I am a woman who can have children and I use effective birth control.

Exclusion Criteria

Pregnancy

I am a woman who could get pregnant and plan to breastfeed or try for a baby.

I haven't changed my mental health medications in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline

Baseline assessments including severity of behavioural problems, vital signs, cognitive capacity, and anxiety

1 week

1 visit (in-person)

Dose Titration

Nabilone dosage is titrated in 0.25 mg increments every two days to a maximum of 1 mg twice daily

2 weeks

Regular phone calls

Open-label Treatment

Participants receive a stable dose of nabilone for 4 weeks

4 weeks

1 visit (in-person)

Tapering

Nabilone is tapered off over 8 days to prevent withdrawal effects

1 week

Phone calls every other day

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Nabilone

Trial Overview The trial is testing Nabilone, a synthetic cannabinoid, to see if it's safe and can help manage aggression in adults with IDD. It's an open-label study where everyone gets the drug to assess changes in behavior before and after treatment.

Participant Groups

Group I: Open Label Experimental Treatment 1 Intervention

Titration: Nabilone p.o., increased in 0.25 mg increments every 2 days to a maximum of 1 mg b.i.d. Open label: Nabilone p.o. at maximum dose tolerated for 28 days Tapering: Nabilone p.o. decreased in 0.25 decrements per day

Nabilone is already approved in United States, Canada, United Kingdom for the following indications:

Approved in United States as Cesamet for:

• Chemotherapy-induced nausea and vomiting

Approved in Canada as Cesamet for:

• Chemotherapy-induced nausea and vomiting

Approved in United Kingdom as Cesamet for:

• Chemotherapy-induced nausea and vomiting

Who Is Running the Clinical Trial?

Hsiang-Yuan Lin

Lead Sponsor

Trials

1

Recruited

30+

Findings from Research

In a study of 104 male inmates with serious mental illness, nabilone demonstrated significant improvements in PTSD-related insomnia, nightmares, and overall functioning, suggesting it is an effective treatment option for these symptoms.

Nabilone also allowed for the discontinuation of other medications with higher risks of adverse effects, such as antipsychotics and sedatives, indicating its potential to reduce polypharmacy and improve safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a synthetic cannabinoid in a correctional population for posttraumatic stress disorder-related insomnia and nightmares, chronic pain, harm reduction, and other indications: a retrospective evaluation. Cameron, C., Watson, D., Robinson, J.[2022]

Current understanding of the neurobiology of aggression suggests that the roles of neurotransmitters like serotonin, dopamine, and GABA in aggression are complex and not fully understood, making it difficult to predict how drugs will affect aggressive behavior.

There is limited evidence supporting the effectiveness of pharmacotherapy for aggression in individuals with intellectual disabilities, with the exception of risperidone, as most controlled trials have shown negative outcomes for other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neurobiology of aggression: implications for the pharmacotherapy of aggressive challenging behaviour by people with intellectual disabilities. Willner, P.[2014]

Pharmacological treatment for aggression in individuals with mental retardation (MR) is similar to that for individuals without MR, but it is recommended to start with lower doses and increase slowly.

Both conventional antipsychotics like zuclopenthixol and atypical antipsychotics like risperidone have shown effectiveness in managing disruptive behaviors, including severe self-injury, in both children and adults with MR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of disruptive behavior in mentally retarded subjects: A review of the current literature. Hässler, F., Reis, O.[2022]

In a study involving 39 patients with intellectual disabilities, stopping zuclopenthixol treatment after 6 weeks led to increased aggressive behavior, as measured by external raters using the Modified Overt Aggression Scale.

The placebo group (20 patients) exhibited more aggression compared to those who continued the medication (19 patients), suggesting that zuclopenthixol may help manage aggression in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zuclopenthixol in adults with intellectual disabilities and aggressive behaviours: discontinuation study. Haessler, F., Glaser, T., Beneke, M., et al.[2018]

This study proposes the first Phase I pre-pilot clinical trial to evaluate the safety, tolerability, and adherence of nabilone, a synthetic cannabinoid, in adults with intellectual and developmental disabilities (IDD) experiencing severe behavioral problems (SBPs).

The research aims to gather preliminary data that could support future randomized controlled trials, addressing the urgent need for effective and safe treatments for SBPs in this population, where current medications often have limited effectiveness and significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nabilone treatment for severe behavioral problems in adults with intellectual and developmental disabilities: Protocol for a phase I open-label clinical trial. Lin, HY., Abi-Jaoude, E., Desarkar, P., et al.[2023]

In a study of 110 pediatric patients receiving nabilone for preventing chemotherapy-induced nausea and vomiting (CINV), 34% experienced minor adverse effects, with sedation and dizziness being the most common, but all were of low severity.

Nabilone provided only moderate success in controlling acute chemotherapy-induced vomiting, with only about 50% of patients achieving complete control, indicating a need for improved CINV management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nabilone for acute chemotherapy-induced vomiting prophylaxis in pediatric patients: A multicenter, retrospective review. Polito, S., MacDonald, T., Romanick, M., et al.[2019]

In a retrospective review of 7 patients with refractory vomiting due to gastrointestinal dysmotility, nabilone showed symptomatic improvement in 43% of cases, suggesting it may be a useful treatment option for this condition.

However, more than half of the patients (57%) experienced side effects such as headache, dizziness, and hallucinations, indicating that while nabilone can help, its use must be carefully monitored due to potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of nabilone as an antiemetic in persistent vomiting due to refractory gastrointestinal disorders. Olmedo Moreno, C., Holman, R., Naghibi, M., et al.[2023]

In a 14-week study involving 39 patients with moderate-to-severe Alzheimer's disease, nabilone significantly reduced agitation compared to placebo, as measured by the Cohen Mansfield Agitation Inventory.

While nabilone showed promise in reducing agitation and caregiver distress, it also caused more sedation, indicating that monitoring for sedation and cognitive effects is important when using this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease. Herrmann, N., Ruthirakuhan, M., Gallagher, D., et al.[2020]

Aggressive behavior in individuals with developmental disabilities is a significant issue that can lead to negative outcomes such as social isolation and increased reliance on medication, highlighting the need for effective interventions.

Current evidence on pharmacological and psychological treatments for aggression in this population is generally poor or lacking, indicating a gap in high-quality research that could inform better clinical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of aggression in individuals with developmental disabilities. Antonacci, DJ., Manuel, C., Davis, E.[2021]

Opioid antagonists like naltrexone show promising results in managing self-injurious behavior (SIB) and aggression in individuals with mental retardation and autism, although more controlled studies are needed to confirm their efficacy.

The use of neuroleptics is decreasing due to their adverse effects, such as tardive dyskinesia, highlighting the need for safer treatment options and a better understanding of the underlying psychiatric syndromes associated with these behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-injurious behavior in the developmentally disabled: pharmacologic treatment. Osman, OT., Loschen, EL.[2011]

Maladaptive aggression, particularly impulsive aggression (IA), lacks a specific FDA-approved treatment, leading to inadequate management options for patients, as current therapies often do not effectively address IA symptoms.

The investigational drug SPN-810 (extended-release molindone) is being studied as a potential treatment for children with IA and ADHD, suggesting it could be a candidate for a new class of anti-maladaptive aggression agents that would streamline treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A proposed anti-maladaptive aggression agent classification: improving our approach to treating impulsive aggression. Robb, AS., Schwabe, S., Ceresoli-Borroni, G., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Use of a synthetic cannabinoid in a correctional population for posttraumatic stress disorder-related insomnia and nightmares, chronic pain, harm reduction, and other indications: a retrospective evaluation. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The neurobiology of aggression: implications for the pharmacotherapy of aggressive challenging behaviour by people with intellectual disabilities. [2014]

3. United States pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of disruptive behavior in mentally retarded subjects: A review of the current literature. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Zuclopenthixol in adults with intellectual disabilities and aggressive behaviours: discontinuation study. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Nabilone treatment for severe behavioral problems in adults with intellectual and developmental disabilities: Protocol for a phase I open-label clinical trial. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nabilone for acute chemotherapy-induced vomiting prophylaxis in pediatric patients: A multicenter, retrospective review. [2019]

7. Spain pubmed.ncbi.nlm.nih.gov

Usefulness of nabilone as an antiemetic in persistent vomiting due to refractory gastrointestinal disorders. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of aggression in individuals with developmental disabilities. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Self-injurious behavior in the developmentally disabled: pharmacologic treatment. [2011]

11. England pubmed.ncbi.nlm.nih.gov

A proposed anti-maladaptive aggression agent classification: improving our approach to treating impulsive aggression. [2019]