Cannabidivarin for Autism Spectrum Disorder

Overseen By Casara Ferretti, MS, MA

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Montefiore Medical Center

Must not be taking: Endocannabinoids

Disqualifiers: Genetic disorders, Bipolar, Schizophrenia, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to study the efficacy and safety of cannabidivarin (CBDV) in children with ASD.

Will I have to stop taking my current medications?

The trial requires that participants have stable medication doses for at least four weeks before joining and throughout the study, so you should not change your current medications during this time.

What data supports the effectiveness of the drug Cannabidivarin for Autism Spectrum Disorder?

Research suggests that cannabinoids like Cannabidivarin (CBDV) may help manage symptoms of Autism Spectrum Disorder (ASD), as similar compounds have shown promise in improving social interaction, communication, and reducing other symptoms in both epileptic and non-epileptic patients with ASD. ^{1 2 3 4 5}

Is Cannabidivarin (CBDV) safe for humans?

Cannabidivarin (CBDV) has been studied for its potential therapeutic effects in neurological conditions like epilepsy and autism spectrum disorder. While specific safety data for CBDV in humans is limited, studies on similar compounds like cannabidiol (CBD) suggest that they are generally well-tolerated with mild side effects. More research is needed to fully understand the safety profile of CBDV in humans. ^{1 3 6 7 8}

How is the drug Cannabidivarin (CBDV) unique in treating Autism Spectrum Disorder?

Cannabidivarin (CBDV) is unique because it is a non-intoxicating compound derived from the Cannabis sativa plant that may modulate brain systems involved in autism, specifically affecting the balance of excitatory and inhibitory neurotransmitters like glutamate and GABA. Unlike other treatments, CBDV's potential to improve core symptoms of autism is still being explored, and it shows promise with low adverse effects. ^{1 2 3 9 10}

Research Team

Eric Hollander, MD

Principal Investigator

Montefiore Medical Center/Albert Einstein College of Medicine

Eligibility Criteria

This trial is for children aged 5-18 with Autism Spectrum Disorder, confirmed by specific diagnostic criteria. They must have stable treatments and a caregiver to consent and assess their behavior. Excluded are those with recent drug use, certain medical conditions, medication changes within the last month, or known allergies to sesame oil.

Inclusion Criteria

Aberrant Behavior Checklist (ABC) - Irritability Subscale (ABC-I) score of 18 or greater at screening visit

Physical exam and laboratory results within normal range for individuals with ASD

I have a guardian who can consent for me and I can understand and agree to the study if I'm 7 or older.

Exclusion Criteria

I have been on long-term treatment with CBD or similar.

I haven't changed my medications or their doses in the last 4 weeks.

I haven't changed my therapy or educational interventions in the last 4 weeks, except for school holidays.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weight-based dosing of 10 mg/kg/day of CBDV or placebo for 12 weeks

12 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cannabidivarin
• Matched Placebo

Trial Overview The study tests Cannabidivarin (CBDV) against a placebo in children with ASD to evaluate its effectiveness and safety. Participants will be randomly assigned to receive either CBDV or an inactive substance that looks the same as CBDV.

Participant Groups

Group I: Cannabidivarin (CBDV) Experimental Treatment 1 Intervention

Weight-based dosing of 10 mg/kg/day of CBDV for 12 weeks

Group II: Matched Placebo Placebo Group 1 Intervention

Weight-based dosing of 10 mg/kg/day of placebo for 12 weeks

Cannabidivarin is already approved in European Union for the following indications:

Approved in European Union as Cannabidivarin for:

• Orphan designation for Rett Syndrome and Fragile X Syndrome

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

GW Pharmaceuticals Ltd

Industry Sponsor

Trials

14

Recruited

1,700+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

Cannabidivarin (CBDV), a non-psychotomimetic cannabinoid, is gaining attention for its potential therapeutic effects in managing neurological conditions, particularly epilepsy and autism spectrum disorder.

This review compiles both animal and human studies to provide a comprehensive overview of CBDV's therapeutic potential, highlighting its promise as a treatment option alongside the more widely studied cannabidiol (CBD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of cannabidivarin for epilepsy and autism spectrum disorder. Zamberletti, E., Rubino, T., Parolaro, D.[2022]

Cannabinoids, especially cannabidiol (CBD), show promise in improving symptoms associated with Autism Spectrum Disorders (ASDs) and may help with common comorbidities, offering a potential alternative to conventional therapies that often have limitations.

Cannabinoid therapy is associated with low adverse effects and may reduce the need for other medications, but further large-scale and long-term clinical trials are necessary to fully understand its efficacy and safety in treating ASDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Data on Canabinoids: Translational Research in the Treatment of Autism Spectrum Disorders. Carreira, LD., Matias, FC., Campos, MG.[2022]

In an observational study of 18 autistic patients treated with a CBD-enriched Cannabis sativa extract, most showed significant improvements in various symptoms of Autism Spectrum Disorders after 6-9 months, particularly in areas like seizures, attention deficit/hyperactivity disorder, and communication.

Despite some patients experiencing mild adverse effects leading to discontinuation, the majority of those who adhered to the treatment reported improvements, with many able to reduce or stop other medications while maintaining these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of CBD-Enriched Cannabis sativa Extract on Autism Spectrum Disorder Symptoms: An Observational Study of 18 Participants Undergoing Compassionate Use. Fleury-Teixeira, P., Caixeta, FV., Ramires da Silva, LC., et al.[2020]

A case report of a 15-year-old boy with autism spectrum disorder showed that a low dose of a cannabidiol-based extract improved his core social deficits and overall functioning, which is a novel finding since traditional treatments often do not address these core issues.

This suggests that cannabidiol may have potential benefits for behavioral symptoms and comorbid conditions like anxiety and sleep difficulties in autism spectrum disorder, warranting further research to understand its mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pediatric patient with autism spectrum disorder and epilepsy using cannabinoid extracts as complementary therapy: a case report. Ponton, JA., Smyth, K., Soumbasis, E., et al.[2021]

Current research indicates that cannabis and cannabidiol may offer potential therapeutic benefits for some individuals with autism spectrum disorder (ASD), particularly for associated noncore symptoms and comorbidities.

The available data suggest that these treatments are generally well tolerated, but further studies are needed to identify which patients might benefit the most and to ensure safety without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autism Spectrum Disorder and Medical Cannabis: Review and Clinical Experience. Mostafavi, M., Gaitanis, J.[2021]

In a study using Fmr1-knockout mice, CBDV showed limited effectiveness when administered during adulthood, only improving some acoustic responses and neurotrophin levels.

However, when given during adolescence, CBDV significantly prevented cognitive, social, and sensory issues in adult Fmr1-KO mice, suggesting that early treatment may be crucial for its therapeutic benefits in Fragile X syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Administration of the Phytocannabinoid Cannabidivarin Prevents the Neurobehavioral Abnormalities Associated with the Fmr1-KO Mouse Model of Fragile X Syndrome. Premoli, M., Fyke, W., Bellocchio, L., et al.[2023]

In a long-term open-label extension trial involving 264 patients with Dravet syndrome, add-on cannabidiol (CBD) treatment resulted in significant reductions in seizure frequency, with a median reduction of 38% to 44% for convulsive seizures and 39% to 51% for total seizures over 48 weeks.

The safety profile of long-term CBD use was acceptable, with 93.2% of patients experiencing adverse events, mostly mild to moderate, and 85% of patients or caregivers reporting an improvement in the patient's overall condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial. Devinsky, O., Nabbout, R., Miller, I., et al.[2020]

In a long-term study involving 315 patients with Dravet syndrome, add-on cannabidiol (CBD) treatment resulted in significant reductions in seizure frequency, with a median reduction of 45%-74% for convulsive seizures and 49%-84% for total seizures over a treatment duration of up to 156 weeks.

The safety profile of long-term CBD use was generally acceptable, with 97% of patients experiencing adverse events, mostly mild to moderate, and 22% reporting liver enzyme elevations, particularly among those taking valproic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Add-on cannabidiol in patients with Dravet syndrome: Results of a long-term open-label extension trial. Scheffer, IE., Halford, JJ., Miller, I., et al.[2022]

In a study involving 34 children aged 4-10 with Dravet syndrome, purified cannabidiol (CBD) was found to be generally well-tolerated, with a dose-proportional increase in exposure to CBD and its metabolites, indicating effective pharmacokinetics.

While CBD treatment resulted in more adverse events (AEs) compared to placebo, such as pyrexia and sedation, no significant safety concerns were identified, and all patients recovered from any elevated liver enzymes without meeting criteria for drug-induced liver injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Devinsky, O., Patel, AD., Thiele, EA., et al.[2022]

In a study involving 34 healthy men (17 with autism spectrum disorder and 17 without), the compound cannabidivarin (CBDV) was found to significantly increase levels of glutamate and glutamine (Glx) in the basal ganglia, indicating its potential to modulate brain excitatory-inhibitory systems relevant to autism.

The response to CBDV varied among individuals, particularly in the ASD group, where changes in Glx levels were negatively correlated with baseline concentrations, suggesting that individual biochemistry may influence the effectiveness of CBDV as a treatment for autism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy. Pretzsch, CM., Voinescu, B., Lythgoe, D., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Therapeutic potential of cannabidivarin for epilepsy and autism spectrum disorder. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Data on Canabinoids: Translational Research in the Treatment of Autism Spectrum Disorders. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of CBD-Enriched Cannabis sativa Extract on Autism Spectrum Disorder Symptoms: An Observational Study of 18 Participants Undergoing Compassionate Use. [2020]

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

A pediatric patient with autism spectrum disorder and epilepsy using cannabinoid extracts as complementary therapy: a case report. [2021]

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

Autism Spectrum Disorder and Medical Cannabis: Review and Clinical Experience. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Early Administration of the Phytocannabinoid Cannabidivarin Prevents the Neurobehavioral Abnormalities Associated with the Fmr1-KO Mouse Model of Fragile X Syndrome. [2023]

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

Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial. [2020]

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

Add-on cannabidiol in patients with Dravet syndrome: Results of a long-term open-label extension trial. [2022]

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

Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. [2022]

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

Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy. [2021]