Psychiatry · Medical Literature
Efficacy and safety of ashwagandha root extract in children and adolescents with mild attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled trial.
Abstract
This study investigated the effects of ashwagandha root extract (ARE) supplementation on core attention-deficit/hyperactivity disorder (ADHD) symptoms, executive functioning, and patient-reported outcomes in children and adolescents with mild ADHD. Fifty-eight children and adolescents with clinically diagnosed mild ADHD were randomly assigned to either the ARE group (ARE; n = 29) or a placebo group (PLA; n = 29) in a prospective, randomized, double-blind, placebo-controlled, parallel-group design. Participants received 150 mg of ashwagandha root extract or a matched placebo gummies twice daily for 56 days. Primary outcomes were changes in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) total score. Secondary outcomes: ADHD-RS-IV inattention and hyperactivity-impulsivity subscales, Behavior Rating Inventory of Executive Function-2 (BRIEF-2) scores and Patient-Reported Outcomes Measurement Information System (PROMIS) scores. Safety markers, including routine clinical laboratory parameters, were assessed at baseline and Day 56. At Day 56, ADHD-RS-IV inattention, hyperactivity-impulsivity, and total scores were significantly lower in ARE than in PLA (P < 0.001). Significant improvements were also observed in the BRIEF-2 behavioral, emotional, and cognitive regulation indices and the global executive composite in ARE (P < 0.001). PROMIS sleep disturbance and anxiety scores improved significantly in ARE relative to PLA (P < 0.001). No significant between-group differences or clinically meaningful changes were observed in safety markers across the intervention period. No serious adverse events were reported. Supplementation with 300 mg/day of ashwagandha root extract for 56 days significantly improved ADHD symptom severity, executive functioning, and selected patient-reported outcomes in children and adolescents with mild ADHD, with a favorable safety profile.
Clinical relevance
Does 56-day supplementation with ashwagandha root extract (300 mg/day, administered as 150 mg twice daily) improve core ADHD symptom scores, executive functioning, and patient-reported outcomes compared to placebo in children and adolescents with clinically diagnosed mild ADHD? __SNAPSHOT__ {"studyDesign":"Randomized, double-blind, placebo-controlled, parallel-group trial","setting":"Not fully reported in abstract; consistent with single-center Indian academic clinical setting based on affiliated investigator institutions","sampleSize":"n = 58 (ARE: n = 29, Placebo: n = 29)","population":"Children and adolescents with clinically diagnosed mild ADHD (DSM-IV criteria), aged approximately 5–12 years, males and females; excluded were those with comorbid psychiatric diagnoses (e.g., OCD, major depressive disorder), hypersensitivity to study product, or concurrent use of supplements or medical foods within 30 days","intervention":"Ashwagandha root extract (KSM-66®; standardized aqueous extract, >5% withanolides), 150 mg per chewable gummy administered twice daily (total 300 mg/day) for 56 days","comparator":"Matched placebo gummies (pectin and honey base), identical in appearance, color, shape, and size, administered on the same dosing schedule","primaryOutcome":"Change from baseline in ADHD Rating Scale-IV (ADHD-RS-IV) total score at Day 56","followUp":"56 days (8 weeks); no post-treatment follow-up reported","fundingSource":"KSM-66 product supplied by Ixoreal Biomed Inc. (Los Angeles, CA, USA); industry involvement in product supply confirmed; independence of statistical analysis and study conduct not reported in abstract"}
Key findings
At Day 56, the ARE group demonstrated statistically significant reductions versus placebo in all three ADHD-RS-IV domains: inattention subscale (–37.28%), hyperactivity-impulsivity subscale (–36.24%), and total ADHD-RS-IV score (–36.6%), all reported at P < 0.001. Within-group placebo change was not statistically significant (P = 0.217). Absolute baseline and endpoint scores, between-group mean differences, 95% confidence intervals, and effect sizes (e.g., Cohen's d) are not reported in the abstract. NNT cannot be calculated from available data. On the BRIEF-2, the ARE group showed significant improvements (P < 0.001) across all three executive function indices: Behavioral Regulation Index (BRI, –47.9%), Emotional Regulation Index (ERI, –38.7%), and Cognitive Regulation Index (CRI, –45.7%), with a Global Executive Composite (GEC) reduction of approximately 44.2%. On the PROMIS parent-reported outcomes, ARE was associated with reductions in sleep disturbance (–39.5%) and anxiety (–40.9%), with an overall PROMIS score reduction of –40.1% (all P < 0.001). On the Clinician Global Impression (CGI) scale, 100% of ARE recipients reported improvement, compared with 65.5% reporting no change and 34.5% reporting minimal deterioration in the placebo arm. Safety: one participant in each arm experienced a single minor adverse event (fever in placebo; cough in ARE); both were described as minor and resolved. Routine laboratory safety markers (hepatic and renal parameters) were assessed at baseline and Day 56; no significant abnormalities were reported. No serious adverse events occurred. All percentage reduction figures are derived from industry-associated secondary communications and should be interpreted cautiously, as they are not independently verifiable from the published abstract alone.
Practice implications
This RCT provides preliminary evidence that an 8-week course of standardized ashwagandha root extract (KSM-66®, 300 mg/day) may reduce clinician-rated ADHD symptom severity and caregiver-reported executive dysfunction in children aged approximately 5–12 years with mild ADHD. The study established statistically significant within-arm and between-arm differences on all prespecified outcome scales, and no serious safety signals were observed over the 56-day observation window. However, the study did NOT establish: long-term safety or efficacy beyond 8 weeks; generalizability to children with moderate-to-severe ADHD, those on concurrent pharmacotherapy, or those with comorbid psychiatric or neurodevelopmental conditions; whether improvements were clinically meaningful at the individual patient level (minimal clinically important difference thresholds for ADHD-RS-IV are not addressed); or non-inferiority or superiority to established ADHD pharmacotherapy. The population was limited to a mild ADHD phenotype, excluding those with psychiatric comorbidities, which significantly restricts generalizability to typical child psychiatry caseloads where comorbidities are the norm. All outcomes relied on caregiver and clinician ratings rather than objective cognitive performance measures, introducing reporter bias. Importantly, this summary is based solely on an abstract and secondary industry-linked sources; full peer-reviewed text with complete statistical tables is not yet available, precluding independent verification of reported effect magnitudes. The supply of the study product by Ixoreal Biomed Inc. (the commercial manufacturer of KSM-66®) represents a potential conflict of interest that requires critical appraisal of the reported findings. Practice should NOT change on the basis of this single small study; confirmation in larger, independently funded trials with longer follow-up is required. __LIMITATIONS__ Very small sample size (n = 58 total; n = 29 per arm), likely underpowered to detect rare adverse events or to adequately characterize effect heterogeneity across age subgroups,Short follow-up (56 days) precludes any conclusion about durability of benefit or long-term safety, including endocrine effects (ashwagandha has known thyroid and gonadal hormonal activity),Exclusively mild ADHD phenotype with exclusion of comorbid psychiatric disorders, reducing generalizability to real-world pediatric psychiatric populations,All primary and secondary outcome instruments rely on caregiver and clinician-rated scales, with no objective neuropsychological performance data reported; susceptible to expectation and reporter bias,Product supply and presumed partial financial support from Ixoreal Biomed Inc. (commercial manufacturer of KSM-66®), raising potential industry conflict of interest,Baseline ADHD-RS-IV scores, between-group mean differences, standard deviations, confidence intervals, and effect sizes are not reported in the abstract, preventing independent appraisal of clinical significance,Restriction to a single age stratum (5–12 years), with the published title referencing 'children and adolescents'; adolescent-specific data are not separately reported,No active comparator arm (e.g., methylphenidate or amphetamine salts); comparison is solely against placebo,Concurrent behavioral, educational, or pharmacologic co-interventions are not described and may not have been controlled,Assessment based on abstract only; full peer-reviewed publication data were not available at the time of this summary, limiting critical appraisal __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ In this small, 8-week, industry-product-supplied RCT of children with mild ADHD, ashwagandha root extract (KSM-66®, 300 mg/day) was associated with statistically significant reductions in ADHD symptom ratings and caregiver-reported executive dysfunction compared to placebo, with no serious adverse events. Clinicians should regard these findings as hypothesis-generating only: the sample is small, follow-up is short, the population excludes typical comorbid presentations, and industry involvement in product supply warrants scrutiny. Independent replication in larger trials with objective outcome measures, longer follow-up, and active comparator arms is required before this intervention can be considered for routine clinical recommendation.