Placebo-Controlled Study of Terpenes-Enriched Cannabis Oil T1/C28 for Children With Autism

Phase 2RecruitingNCT07199218

Bazelet Nehushtan LtD.78 enrolled

Overview

The goal of this clinical trial is to determine whether cannabidiol (CBD, 28%) combined with terpenes and a small amount of THC (1%) can help reduce symptoms of autism, and to evaluate the safety of this treatment. The main questions are: 1. Does this treatment improve behavioral challenges in children with autism? 2. Does this treatment improve social difficulties in children with autism? What will happen in the study: 1. Participants take either the study treatment or a placebo (a look-alike substance with no active drug) every day for 2 months. 2. After 2 months, all participants receive the study treatment or a similar treatment without THC for another 2 months. 3. Participants come to the clinic once every 2 months for checkups and tests.

Autism spectrum disorder (ASD) is a condition that affects communication, social interaction, and behavior. Current medications do not treat the core symptoms of autism, and the drugs sometimes prescribed (such as antipsychotics for irritability) can cause significant side effects. Cannabidiol (CBD) is a natural, non-psychoactive compound from the cannabis plant that may reduce brain overactivity and inflammation. Tetrahydrocannabinol (THC), the psychoactive component of cannabis, acts on the endocannabinoid system, which is thought to function differently in people with autism. Research suggests that CBD combined with very small amounts of THC may improve behavior and social functioning. Other plant compounds called terpenes may enhance the effects of CBD and THC, even at low doses. This study tests whether a CBD oil enriched with terpenes and a very small amount of THC is safe and effective for children with autism. Seventy-eight children, ages 4-13, will participate. Half will receive the study oil and half will receive a placebo (an inactive oil that looks the same) for 8 weeks. Afterward, all participants will receive an active treatment for another 8 weeks. The study evaluates whether the treatment improves behavior, social skills, and quality of life. Safety is monitored through regular clinic visits, questionnaires, physical exams, and blood tests.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Interventions

Terpenes-Enriched CBD-Predominant OilDRUG

Oral cannabidiol (CBD; 7.2 mg/kg/day), tetrahydrocannabinol (THC; 0.257 mg/kg/day, equivalent to 1:28 of the CBD dose), and terpenes (0.5 mg/kg/day), administered in two daily doses. The formulation is an olive oil-based solution (CBD/THC: 280/10 mg per g) produced by Bazelet Group, Israel.

PlaceboDRUG

Oral olive oil with added flavors to mimic the appearance, texture, and taste of the study drug, administered in two daily doses.

Terpenes-Enriched CBD Oil (THC-Free)DRUG

Oral cannabidiol (CBD; 7.2 mg/kg/day) and terpenes (0.5 mg/kg/day), administered in two daily doses. The formulation is an olive oil-based solution (CBD- 280 mg per g) produced by Bazelet Group, Israel.

Eligibility

Sex: ALLMin age: 4 YearsMax age: 13 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Children aged 4 to 12 years (after the 4th birthday and before the 13th). 2. Diagnosis of autism spectrum disorder (ASD) according to DSM-5, confirmed by Childhood Autism Rating Scale-Second Edition (CARS-2). 3. Moderate or greater ASD-associated symptoms, defined as a rating of ≥4 ("moderate" or higher) on the Overall Function Clinical Global Impression-Severity (CGI-S). 4. Aberrant Behavior Checklist-Irritability subscale (ABC-I) score ≥18. 5. Social Responsiveness Scale-Second Edition (SRS-2) total T score ≥66. Exclusion Criteria: 1. Body weight \<12.5 kg or ≥57.5 kg. 2. Current or past diagnosis of heart failure, drug addiction, schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder (PTSD), or major depressive disorder (MDD), or diagnosis of schizophrenia in a first-degree relative. 3. Seizure or change in antiepileptic medications within 4 months prior to randomization. 4. Clinically significant abnormalities on physical examination or laboratory testing, including impairment in cardiac, hepatic, or renal function. 5. Change in pharmacological or behavioral treatment, or change in home or school environment (other than school holidays), within 4 weeks prior to randomization or planned during the study. 6. Cannabinoid treatment within 4 weeks prior to randomization. 7. Predicted poor compliance with study procedures (e.g., blood tests). 8. Concurrent use of opiates or alcohol.

Outcomes

Primary Outcomes

Change From Baseline in Aberrant Behavior Checklist-Community (ABC-C): Irritability Subscale raw score (ABC-I)

The ABC-C is a caregiver-completed questionnaire with 58 items, divided into five subscales. The ABC-I (Irritability) subscale includes 15 items that assess emotional and behavioral symptoms of ASD, such as aggression toward others, deliberate self-injury, temper tantrums, depressed mood, and rapidly shifting moods. Scores on this subscale range from 0 to 45, with higher scores indicating greater severity. Change from baseline to Week 8 is reported, with lower scores reflecting clinical improvement.

Time frame: Baseline to Week 8

Secondary Outcomes

Change From Baseline in Vineland™-III Adaptive Behavior Scales (VABS3) Socialization Domain Standard Score

The VABS-3 Socialization domain measures interpersonal relationships, play and leisure, and coping skills, reflecting the individual's ability to engage in age-appropriate social interactions. Higher scores indicate better adaptive social functioning.

Time frame: Baseline to Week 8

Change From Baseline in Social Responsiveness Scale-2nd edition (SRS-II) total raw score

The SRS-2 measures the severity of social impairment associated with autism spectrum disorder. It includes five subscales: Social Awareness (8 items), Social Communication (22 items), Social Cognition (12 items), Social Motivation (11 items), and Restricted Interests and Repetitive Behavior (12 items). Two summary scores are derived: the Total Score (sum of all five subscales) and the Social Communication and Interaction (SCI) score, which combines the four social subscales excluding Restricted Interests and Repetitive Behavior. The SCI and RRB correspond to the two DSM-5 symptom domains of autism spectrum disorder. Raw scores range from 65 to 260; higher scores indicate greater severity of social impairment.

Time frame: Baseline, Weeks 8 and 17

Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)

Participants experiencing at least one adverse event that newly appeared or worsened after treatment initiation. Adverse events are graded as mild, moderate, or severe; hospitalizations are documented as serious adverse events; causality is categorized from not related to definitely related.

Time frame: Baseline to Week 17

Number of Participants With Clinically Significant Abnormal Laboratory Values

Number of participants with clinically significant abnormal values in complete blood count (CBC), liver transaminases, or total bilirubin levels, as determined by the investigator.

Time frame: Week 8

Change From Baseline in Body Mass Index (BMI)

Difference between baseline and week 8 body mass index (kg/m²)

Time frame: Baseline, Weeks 8 and 17

Clinical Global Impressions-Improvement (CGI-I) Score

CGI-I is a clinician rating of overall change from baseline; scores range from 1 to 7, with higher scores indicating worse outcome; anchors: 1 very much improved; 2 much improved; 3 minimally improved; 4 no change; 5 minimally worse; 6 much worse; 7 very much worse.

Time frame: Weeks 8 and 17

Caregiver Global Impression of Change (CGIC or CaGC)

CGIC (CaGC) is a caregiver rating of overall change from baseline; scores range from 1 to 7, with higher scores indicating worse outcome; anchors: 1 very much improved; 2 much improved; 3 minimally improved; 4 no change; 5 minimally worse; 6 much worse; 7 very much worse.