Cannabidivarin for Autism Spectrum Disorder

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of cannabidivarin (CBDV) for children with Autism Spectrum Disorder (ASD). Researchers compare CBDV to a placebo (a non-active substance) to determine its impact on symptoms like irritability and social challenges. Children diagnosed with ASD who experience significant irritability or social difficulties might be suitable candidates. The trial aims to discover new ways to manage ASD symptoms in children. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that cannabidivarin (CBDV) is likely to be safe for children with autism spectrum disorder?

Research shows that cannabidivarin (CBDV) is under investigation for safety in children with autism spectrum disorder (ASD). Previous studies have found that CBDV is generally well-tolerated by children and young adults with ASD. Most side effects are mild, such as drowsiness or changes in appetite. Importantly, no serious side effects have been linked to CBDV in these groups.

CBDV has also been studied for epilepsy, which often occurs with ASD. In these studies, CBDV was well-tolerated, suggesting it might be a promising treatment option. However, more research is needed to fully understand its safety and effectiveness for ASD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for autism?

Unlike the standard treatments for Autism Spectrum Disorder, which often include behavioral therapy and medications like antipsychotics or stimulants, Cannabidivarin (CBDV) offers a unique approach. CBDV is derived from cannabis plants and acts on the body's endocannabinoid system, which is thought to regulate mood and behavior. Researchers are excited about CBDV because it might offer benefits without the side effects commonly associated with current medications. Additionally, its potential to target specific pathways in the brain opens up new possibilities for managing symptoms of autism more effectively.

What evidence suggests that cannabidivarin might be an effective treatment for autism spectrum disorder?

Research has shown that cannabidivarin (CBDV), which participants in this trial may receive, might help treat Autism Spectrum Disorder (ASD). Early animal studies found that CBDV can reduce behaviors similar to those seen in autism. It helps balance brain signals, which can be uneven in people with ASD. Other studies suggest that CBDV might also help with epilepsy, a condition that sometimes occurs with ASD. Although research on humans remains limited, these findings indicate that CBDV could be a potential treatment for ASD. ^{1 2 5 6 7}

Who Is on the Research Team?

Eric Hollander, MD

Principal Investigator

Montefiore Medical Center/Albert Einstein College of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03202303

Cannabidivarin (CBDV) vs. Placebo in Children With ... Although VPA is efficacious for pediatric epilepsy and some symptoms of ASD, it also has significant side effects, including weight gain, sedation and nausea.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31748505/

Effects of cannabidivarin (CBDV) on brain excitation ... - PubMed Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03849456

Safety and Tolerability of Cannabidivarin (CBDV) in ... To determine the safety and tolerability of GWP42006 (cannabidivarin, CBDV) in children and young adults with autism spectrum disorder (ASD) and to examine the ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0163725821000802

Therapeutic potential of cannabidivarin for epilepsy and ... Preclinical results collected so far raise the intriguing possibility that CBDV could represent a promising compound for the management of epilepsy and ASD.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6696797/

Cannabidivarin Treatment Ameliorates Autism-Like Behaviors ... We investigated the ability of CBDV treatment to reverse or prevent ASD-like behaviors in male rats prenatally exposed to valproic acid.

6. aesnet.org aesnet.org/abstractslisting/safety-and-tolerability-of-gwp42006-(cbdv)-in-subjects-with-drug-resistant-epilepsy-and-autism

Safety-and-Tolerability-of-GWP42006-(CBDV) Rationale: Epilepsy and autism have been estimated to coexist in 20-30% of patients with either disorder.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9024565/

Clinical Data on Canabinoids: Translational Research in the ... Translational research made with Cannabis sativa L. and its biocompounds provides data for some targeted diseases, as also symptoms associated with Autism ...