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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a synthetic cannabinoid called nabilone to determine if it can safely reduce severe behavioral problems in adults with intellectual and developmental disabilities, such as autism or Down syndrome. Participants will take the medication for a set period to monitor its effects on aggressive and self-injurious behaviors. The trial seeks adults with intellectual disabilities who frequently experience these challenging behaviors. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that nabilone is likely to be safe for humans?

Research shows that nabilone, a synthetic cannabis-like drug, might safely manage severe behavior issues in adults with intellectual and developmental disabilities. While its safety for this specific group remains uncertain, its use for other health problems suggests it might be well-tolerated. Previous studies with different populations generally reported few serious side effects from nabilone. However, as this is an early-stage trial, the primary goal is to assess how well adults with intellectual disabilities tolerate it. This initial trial will gather important safety information for future research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nabilone is unique because it offers a new approach to managing aggression in individuals with intellectual disabilities. While most current treatments focus on antipsychotics or mood stabilizers, which primarily target neurotransmitter systems like dopamine and serotonin, nabilone is a synthetic cannabinoid that engages the body's endocannabinoid system. This could provide a different pathway for reducing aggression, potentially with fewer side effects. Researchers are excited about nabilone because it may offer a more targeted and effective treatment option, especially for those who don't respond well to existing medications.

What evidence suggests that nabilone might be an effective treatment for severe behavioral problems in intellectual disabilities?

Research has shown that nabilone, a synthetic form of cannabis, may help with serious behavior issues like aggression. In past studies, nabilone improved symptoms such as restlessness and overall behavior in similar situations. It also reduced stress for caregivers, which is a significant advantage. Although it might cause drowsiness in some individuals, the overall benefits make it a promising option for managing behavior problems. This potential is why researchers are further studying it in this trial for adults with intellectual and developmental disabilities. ^{1 3 5 6 7}

Who Is on the Research Team?

Hsiang-Yuan Lin, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1064748119303550

Randomized Placebo-Controlled Trial of Nabilone for ... Nabilone was shown to improve agitation, overall behavior, and caregiver distress compared to placebo. While sedation was greater in nabilone treatment group, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10096227/

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

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05273320

Clinical Trial of Nabilone for Aggression in Adults With ... Innovative treatments are urgently needed for severe behavioural problems (SBPs) in adults with intellectual and developmental disabilities (IDD).

4. trialx.com trialx.com/clinical-trials/listings/249283/clinical-trial-of-nabilone-for-aggression-in-adults-with-intellectual-and-developmental-disabilities/?&radius=50

Clinical Trial of Nabilone for Aggression in Adults With ... The investigators propose to conduct this first-ever Phase I pre-pilot open-label clinical trial to collect data on the tolerability and safety ...

5. biologicalpsychiatryjournal.com biologicalpsychiatryjournal.com/article/S0006-3223(25)00700-0/fulltext

364. Nabilone for Severe Aggression in Adults With Profound ... Current medications for severe aggressions in adults with intellectual disabilities (ID) show equivocal effectiveness and are associated with a high risk of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37043511/

Protocol for a phase I open-label clinical trial We hypothesize that nabilone has favorable tolerability and safety profile for adults with IDD. The preliminary results will inform the next- ...

7. journals.plos.org journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0282114&type=printable

Nabilone treatment for severe behavioral problems in adults ... To enhance the current state of evidence for nabilone use to treat SBPs and aggression in adults with IDD, we propose to conduct the first phase ...