Cannabigerol Oil for Adolescents With ADHD (CAN-ADHD)

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by persistent symptoms of inattention, hyperactivity, and impulsivity that interfere with academic performance, emotional regulation, social functioning, and quality of life. ADHD is one of the most prevalent neurodevelopmental conditions worldwide and may persist from childhood into adolescence and adulthood. In addition to the core symptoms, individuals with ADHD frequently present emotional dysregulation, sleep disturbances, anxiety symptoms, impaired executive functioning, and psychosocial difficulties that significantly affect both patients and their families.

Current treatment strategies for ADHD include pharmacological and non-pharmacological interventions, with stimulant medications representing the first-line pharmacotherapy in most clinical guidelines. Although these treatments are effective for many patients, a substantial proportion of adolescents experience insufficient clinical response, limited tolerability, adverse effects, or difficulties with long-term adherence. This scenario reinforces the need for investigating alternative and complementary therapeutic approaches capable of targeting both behavioral and emotional dimensions associated with ADHD.

The endocannabinoid system has emerged as a potential target in neuropsychiatric disorders due to its involvement in emotional regulation, cognition, attention, stress response, sleep modulation, and synaptic plasticity. Cannabis-derived compounds have demonstrated neurobiological effects that may influence pathways relevant to ADHD symptomatology. Among these compounds, cannabigerol (CBG) has attracted increasing scientific interest. CBG is a non-intoxicating phytocannabinoid that acts on multiple molecular targets, including cannabinoid receptors, adrenergic pathways, serotonergic signaling, and transient receptor potential channels. Preclinical and observational evidence suggests potential anxiolytic, neuroprotective, anti-inflammatory, and neuromodulatory properties, although controlled clinical evidence remains scarce, particularly in pediatric and adolescent populations.

This study was designed to evaluate the potential effects and safety profile of a full-spectrum cannabigerol-based formulation in adolescents with ADHD. The study consists of a randomized, double-blind, placebo-controlled clinical trial with a parallel-group design. A total of 60 adolescents aged between 12 and 17 years with a previous diagnosis of ADHD will be enrolled and randomly assigned in a 1:1 ratio to either the intervention group or the placebo group.

Participants allocated to the intervention group will receive a full-spectrum Cannabis sativa extract containing cannabigerol (CBG) 30 mg/mL, cannabidiol (CBD) 30 mg/mL, and tetrahydrocannabinol (THC) 3 mg/mL. The formulation will be administered sublingually according to a structured dose titration schedule beginning with low doses and gradually increasing over the first weeks of treatment. From week six onward, dose adjustments may be performed according to clinical response and tolerability, respecting predefined safety limits established in the protocol. Participants allocated to the placebo group will receive a formulation based on medium-chain triglyceride (MCT) oil matched in appearance, color, viscosity, and administration schedule to preserve blinding conditions.

The total intervention period will last 12 weeks. Participants will undergo clinical assessments at baseline, week 6, and week 12. In addition, weekly remote monitoring will be conducted throughout the study to assess treatment adherence, adverse effects, tolerability, and general clinical evolution. Medical follow-up will be performed by trained physicians involved in the research team.

The primary outcome of the study will be the change in ADHD symptom severity assessed through the SNAP-IV (Swanson, Nolan and Pelham Questionnaire, version IV). Secondary outcomes will evaluate quality of life, emotional symptoms, sleep patterns, and safety profile using validated instruments, including the KINDL (Children and Adolescents Quality of Life Questionnaire), WHOQOL-BREF (World Health Organization Quality of Life - Brief Version), DASS-21 (Depression Anxiety and Stress Scale), and CSHQ (Child Sleep Habits Questionnaire).

This study aims to contribute to the advancement of clinical evidence regarding cannabinoid-based interventions in ADHD, particularly involving CBG-rich formulations in adolescents. By using a randomized, double-blind, placebo-controlled design, the study seeks to generate scientifically rigorous data regarding efficacy, tolerability, and safety, potentially supporting future therapeutic strategies and expanding knowledge about the role of the endocannabinoid system in neurodevelopmental disorders.

• Change in quality of life of legal guardians assessed by the 36-Item Short Form Health Survey [Time frame: Baseline, Week 6, and Week 12]
• Change in emotional symptoms assessed by the Depression Anxiety and Stress Scale for Children [Time frame: Baseline, Week 6, and Week 12]
• Change in sleep patterns assessed by the Children's Sleep Habits Questionnaire [Time frame: Baseline, Week 6, and Week 12]
• Number of participants with treatment-related adverse events assessed by the study adverse effects questionnaire [Time frame: Weekly monitoring during 12 weeks and clinical assessments at Baseline, Week 6, and Week 12]