Efficacy and Safety of Black Seed Oil as Adjunctive Therapy in Pediatrics With Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood-onset neurodevelopmental disorder characterized by age-inappropriate levels of inattention and hyperactivity/impulsivity symptoms that interfere with functioning or development. Based on the predominant symptoms, the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-V) classifies ADHD into three subtypes: predominantly inattentive (ADHD-I), predominantly hyperactive/impulsive (ADHD-H), and combined (ADHD-C). To be categorized into one of those subtypes, the diagnostic criteria for ADHD in children requires the presence of six out of nine specified symptoms in either the inattentive or hyperactive/impulsive domains, or both, persisted for at least 6 months prior to the age of 12 and caused impairment in at least two settings. Children and adolescents with ADHD face difficult formative years due to their impulsive behavior and slower rates of processing information, leading to poor performance on exams, lower grades, and higher school dropout rates. In addition, their low self-esteem leads to problems in social relationships and a tendency for substance abuse. This disorder often presents with one or more comorbidities such as anxiety disorders, oppositional defiant disorder, conduct disorder, and major depressive disorder, leading to extra challenges for them.

Attention-Deficit/Hyperactivity Disorder is one of the most prevalent neuropsychiatric disorders affecting children with known persistence into adulthood in about 60% of patients. A meta-analysis of 175 studies worldwide revealed that ADHD prevalence in children and adolescents is 7.2%. In Africa, the prevalence of ADHD in children and adolescents was 7.47%. In Egypt, ADHD prevalence among adolescents has reached as high as 9.4%. The diagnosis of ADHD in boys is approximately double that of girls.

The exact etiology and risk factors for ADHD remain unknown. However, studies showed that multiple genetic and environmental factors interact during early development to create a neurobiological susceptibility to this multifactorial disorder. The pathophysiology related to ADHD is associated with brain abnormalities that lead to cognitive and functional deficits. This disorder extensively addresses a deficit in specific brain regions, primarily the prefrontal cortex (PFC), caudate, and cerebellum together with their linking networks, the dopaminergic and noradrenergic systems, that regulate attention, thoughts, emotions, behavior, and actions.

Oxidative stress (OS) and neuroinflammation along with their role in brain dysfunction have been extensively addressed in ADHD. Brain is particularly susceptible to OS because of its high metabolic rate, high oxygen utilization, high lipid contents, and relatively low antioxidant concentration. A previous study in children with ADHD reported an impairment in serum oxidant/antioxidant balance reflected by lower ratios of serum nitric oxide/melatonin and serum malondialdehyde/melatonin. Numerous studies have shown elevated levels of OS in pediatrics with ADHD, including high levels of urinary 8-hydroxy-2'deoxyguanosine (8-OHdG), plasma malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), and high activity of serum oxidative stress-inducing enzymes such as nitric oxide synthase (NOS) and xanthine oxidase (XO).

According to a previous study, the hyperactivity score on Conners' Teacher Rating Scale increased in correlation with increasing NOS enzyme activity, which can lead to progressive damage to the vulnerable pathways of attention and physical activity due to the production of NO radicals. Decreased antioxidant levels have been observed in pediatrics with ADHD, including low total antioxidant status (TAS), low activity of antioxidant enzymes such as glutathione S-transferase (GST) and paraxonase-1, glutathione peroxidase (GPx), and low serum total antioxidant capacity (TAC).