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.

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.

De-identified individual participant data (IPD) that support the results of this trial will be made available to qualified researchers after study completion and publication of the primary results. Data will include baseline characteristics, outcome measures, and safety data.

Supporting Information:

Data will be shared beginning 12 months after publication and available for up to 5 years. Access will be granted upon submission of a methodologically sound proposal and approval by the principal investigator and institutional ethics committee. A data use agreement will be required to ensure protection of participant confidentiality. Supporting documents such as the study protocol and statistical analysis plan will also be available upon request.

The study protocol, statistical analysis plan (SAP), and informed consent form (ICF) are available prior to enrollment of the first participant. De-identified individual participant data and the clinical study report (CSR) are available beginning 12 months after publication of the primary results and remain available for up to 5 years.

The study protocol, statistical analysis plan (SAP), and informed consent form (ICF) are available to the public prior to enrollment of the first participant. De-identified individual participant data (baseline characteristics, outcome measures, and safety data) and the clinical study report (CSR) are available to qualified researchers beginning 12 months after publication of the primary results. Access requires submission of a methodologically sound proposal, approval by the principal investigator and ethics committee, and execution of a data use agreement.