Sulforaphane and autism

McGuinness G, Kim Y. Sulforaphane treatment for autism spectrum disorder: A systematic review. EXCLI J. 2020 Jun 26;19:892-903. doi: 10.17179/excli2020-2487. PMID: 33013262; PMCID: PMC7527484.

Abstract

Autism Spectrum Disorder (ASD) is defined as a neurodevelopmental condition characterized by social communication impairment, delayed development, social function deficit, and repetitive behaviors. The Center for Disease Control reports an increase in ASD diagnosis rates every year. This systematic review evaluated the use of sulforaphane (SFN) therapy as a potential treatment option for individuals with ASD. PubMed.gov, PubMed Central, Natural Medicines, BoardVitals, Google Scholar and Medline were searched for studies measuring the effects of SFN on behavior and cognitive function. All five clinical trials included in this systematic review showed a significant positive correlation between SFN use and ASD behavior and cognitive function. The current evidence shows with minimal side effects observed, SFN appears to be a safe and effective treatment option for treating ASD.

Zhang X, He Q, Zhu YY, Lorimer GH, Bayram H, Ghiladi RA, Wang J. Emerging Promise of Sulforaphane in Autism: A Comprehensive Review of Its Therapeutic Potential and Mechanisms. ACS Chem Neurosci. 2026 Aug 5;17(15):2880-2892. doi: 10.1021/acschemneuro.6c00282. PMID: 42473985.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that emerges in early childhood and significantly impacts the quality of life for individuals and families. Currently, there are no specific medications available for ASD. Increasing attention is now focused on bioactive compounds with anti-inflammatory and antioxidant properties. Sulforaphane (SFN), a key member of the isothiocyanate family, is abundant in cruciferous vegetables. It exhibits potent antioxidant and anti-inflammatory effects with minimal side effects, while oxidative stress and inflammation are recognized triggers in ASD pathogenesis. As research deepens, SFN's physiological activities─including antioxidant, neuroprotective, and anti-inflammatory properties are gaining heightened attention. Building on prior studies, this review comprehensively summarizes seven potential pathways through which SFN protects neurodevelopment or reverses ASD-related neural damage, including Keap1/Nrf2/ARE; MAPKs; NF-κB; HSR; AhR/CYP1; Sirtuin-FOXO; and mTOR/autophagy signaling pathways, elucidating the potential mechanisms underlying its multifaceted actions. This review offers new insights for the comprehensive utilization of sulforaphane and the treatment of ASD.

Long J, Liao X, Tang Z, Han K, Chen J, Wang X, Liu J, Zhang Y, Zhang H. Investigating the clinical efficacy, safety and molecular mechanism of sulforaphane in autism spectrum disorder: an integrated study combining meta-analysis, network pharmacology, and computational biology. BMC Pharmacol Toxicol. 2025 Nov 22;26(1):217. doi: 10.1186/s40360-025-01052-5. PMID: 41275316; PMCID: PMC12751817.

Abstract

Background: Sulforaphane, a natural antioxidant rich in cruciferous vegetables, has emerged as a promising dietary supplement for autism spectrum disorder (ASD). However, its therapeutic efficacy remains controversial, and the pharmacological mechanisms are not fully elucidated.

Methods: Eligible randomized controlled trials were retrieved from PubMed, Web of Science, Embase, and Cochrane Library databases. Review Manager 5.4 was used for meta-analysis and bias risk assessment. Network pharmacology, Mendelian randomization, GEO data analyses, molecular docking, and molecular dynamics simulation were employed to explore the mechanisms of sulforaphane in ASD.

Results: Six trials involving 333 participants were included in the meta-analysis. Pooled results demonstrated that both 4-5 weeks and 8-10 weeks of sulforaphane supplementation significantly decreased the scores on the Social Responsiveness Scale compared to placebo controls. No significant difference was observed in the incidence of adverse events. Network pharmacology identified 10 core targets of sulforaphane in ASD, including AKT1, EGFR, HSP90AA1, SRC, CASP3, STAT1, MAPK1, MMP9, MAPK8, and JAK2. These targets were implicated in the PI3K-Akt signaling pathway, MAPK signaling pathway, Chemokine signaling pathway, Chemical carcinogenesis - reactive oxygen species, TNF signaling pathway, Th17 cell differentiation, mTOR signaling pathway, and IL-17 signaling pathway. Mendelian randomization further revealed an inverse association between STAT1 levels and ASD risk. GEO transcriptomic data provided independent validation for the network pharmacology predictions. The binding energies between sulforaphane and the top 10 core targets are all ≤ -4.0 kcal/mol. Molecular dynamics simulations further validated the stable interaction between MMP-9 and sulforaphane.

Conclusion: Sulforaphane may serve as an efficacious and safe adjunctive therapy for ASD, mediated by its anti-oxidant and anti-inflammatory effects along with the modulation of autophagy.

Guo J, Wang Y, He W, Lou M, Peng Y, Shi H, Lian A. Effects of sulforaphane on ABC and SRS scales in patients with autism spectrum disorder: a meta-analysis. Brain Dev. 2025 Apr;47(2):104321. doi: 10.1016/j.braindev.2025.104321. Epub 2025 Feb 14. PMID: 39951914.

Abstract

Autism spectrum disorder (ASD) has become an increasingly prominent global health issue. Sulforaphane is a phytochemical with multiple functions that target many of the same biochemical and molecular pathways (biomarkers) associated with ASD. This study aimed to conduct a meta-analysis based on sulforaphane's effect on Aberrant Behavior Checklist (ABC) and Social Responsiveness Scale (SRS) in patients with ASD. We conducted comprehensive searches in the PubMed, Medline, Cochrane, EMBASE, and Web of Science databases from their inception. The modified Cochrane risk of bias tool was used to check the risk of bias of the included studies. Review Manager 5.3 software was used to conduct this meta-analysis. The results of this meta-analysis showed that sulforaphane significantly improved irritability and hyperactivity symptoms, suggesting that sulforaphane has the potential for the combined treatment of autism. Additional studies are needed to confirm and explore the effect of sulforaphane.

Ou J, Smith RC, Tobe RH, Lin J, Arriaza J, Fahey JW, Liu R, Zeng Y, Liu Y, Huang L, Shen Y, Li Y, Cheng D, Cornblatt B, Davis JM, Zhao J, Wu R, Jin H. Efficacy of Sulforaphane in Treatment of Children with Autism Spectrum Disorder: A Randomized Double-Blind Placebo-Controlled Multi-center Trial. J Autism Dev Disord. 2024 Feb;54(2):628-641. doi: 10.1007/s10803-022-05784-9. Epub 2022 Nov 24. PMID: 36427174.

Abstract

Sulforaphane has been reported to possibly improve core symptoms associated with autism spectrum disorders from mostly small size studies. Here we present results of a larger randomized clinical trial (N = 108) in China. There were no significant changes in caregiver rated scales between sulforaphane and placebo groups. However, clinician rated scales showed a significant improvement in the sulforaphane group, and one third of participants showed at least a 30% decrease in score by 12 weeks treatment. The effects of sulforaphane were seen across the full range of intelligence and greater in participants over 10 years. Sulforaphane was safe and well-tolerated even for young children. The inconsistent results between caregiver and clinician rated scales suggest more clinical trials are needed to confirm our findings.

Ecopipam for Tourette syndrome 3

Gilbert DL, Atkinson SD, Kim DJB, Miller MM, Rice PM, Flatt JA, Karkanias GB, Munschauer FE, Bittman RM, Wanaski SP, Cunniff TM, Tomczak KK. Efficacy and Safety of Ecopipam for Tourette Syndrome: A Phase 3 Randomized Clinical Trial. JAMA Neurol. 2026 Jul 1;83(7):645-653. doi: 10.1001/jamaneurol.2026.1431. PMID: 42189524; PMCID: PMC13213590.

Abstract

Importance: Current Tourette syndrome (TS) pharmacotherapy is hindered by adverse effects and high discontinuation rates.

Objective: To evaluate the safety and maintenance of effect of ecopipam, a selective dopamine D1 receptor antagonist, for up to 24 weeks for TS.

Design, setting, and participants: This randomized clinical trial was a phase 3, double-blind, placebo-controlled, randomized withdrawal study conducted between January 31, 2023, and February 4, 2025. Participants were enrolled at 77 sites in 12 countries. Individuals 6 years and older with TS were eligible.

Intervention: In the 12-week, open-label period, ecopipam was titrated over 3 to 4 weeks (target dose, 1.8 mg/kg per day). Responders (≥25% improvement in Yale Global Tic Severity Scale Total Tic Score [YGTSS-TTS] at weeks 8 and 12) were randomized to continue ecopipam or taper to placebo for the 12-week double-blind period.

Main outcomes and measures: Time to relapse (≥50% loss of open-label period YGTSS-TTS improvement) in participants aged 6 to 18 years (primary) and adults (exploratory).

Results: The trial enrolled 216 participants (n = 167 [77.3%] pediatric; 146 [67.6%] male and 70 [32.4%] female) to the open-label ecopipam period. Of these, 43 pediatric participants (mean [SD] age, 14.3 [5.5] years) and 8 adult participants were randomized to receive ecopipam; 47 pediatric (mean [SD] age, 14.0 [5.8] years) and 6 adult participants were randomized to receive placebo. Ecopipam significantly reduced the relapse risk vs placebo in pediatric participants (hazard ratio [HR], 0.47; 95% CI, 0.26-0.84; P = .008; n = 90). In adults, the effect was directionally similar (HR, 0.51; 95% CI, 0.11-2.30; P = .37; n = 14) but not significant. The most frequently reported adverse events with ecopipam (open-label and double-blind periods) were somnolence (n = 24 [11.1%]), anxiety (n = 21 [9.7%]), headache (n = 21 [9.7%]), insomnia (n = 19 [8.8%]), tic (n = 17 [7.9%]), and fatigue (n = 14 [6.5%]). Ecopipam did not have a clinically meaningful impact on weight, metabolic parameters, or psychiatric scale measures. Drug-induced movement disorders were not observed.

Conclusions and relevance: Ecopipam maintained clinically meaningful TS symptom improvements and was well tolerated for up to 24 weeks. Adverse events primarily affected the central nervous system

Panda PK, Panda P, Dawman L, Mishra AS, Kumar V, Sharawat IK. Safety and Efficacy of Ecopipam in Patients with Tourette Syndrome: A Systematic Review and Meta-analysis. CNS Drugs. 2025 Feb;39(2):127-142. doi: 10.1007/s40263-024-01140-w. Epub 2024 Dec 27. PMID: 39730854.

Abstract

Background and objectives: Ecopipam is a selective antagonist of the dopamine D1 receptor, and its efficacy and safety have recently been explored in several clinical trials involving patients with Tourette syndrome (TS). The objectives of this systematic review were to determine the pooled estimate for efficacy [in terms of reduction in tic Yale Global Tic Severity Scale (YGTSS) scores] and safety of oral ecopipam in subjects with TS.

Methods: All clinical trials that explored the efficacy and/or safety of ecopipam in patients with TS were included to determine the pooled estimate for change in YGTSS, Clinical Global Impression (CGI)-TS, and the severity of comorbid attention-deficit hyperactive disorder (ADHD), obsessive compulsion disorder (OCD), and depressive symptoms, as well as the nature and frequency of adverse effects. Case-series, retrospective studies, and case reports were excluded. Databases, such as PUBMED, EMBASE, Cochrane Central Register of Controlled Trials, and SCOPUS were searched to identify these trials using suitable combination of MESH terms/keywords on 15 June 2024. ROB 2.0 and ROBINS-I tool were used to assess the risk of bias in included randomized-controlled trials (RCTs) and non-randomized intervention studies, respectively, and the GRADE system to determine the certainty of the collated evidence.

Results: A total of 96 records were identified in the database search and 31 records were screened after removing duplicates. After excluding 23 irrelevant records, the full-text review included 8 records. Finally, six publications from three completed clinical trials (two RCTs, with one having an open-label extension) and one ongoing clinical trial were included. A total of 251 participants were included. The pooled estimate for mean change in YGTSS-TTS from baseline to the completion of the randomization period was statistically better in the ecopipam group compared with the placebo group [mean difference: - 3.0, 95% (confidence interval (CI) - 4.2 to - 1.9, I2 = 55%, p < 0.0001]. The ecopipam group also fared statistically better in terms of YGTSS-motor tic score, phonic tic score, as well as CGI-TS-S (p < 0.0001). Changes in depressive and obsessive-compulsive symptoms were comparable in both groups, as well as the incidence of adverse effects.

Conclusions: Ecopipam is effective in reducing the severity of tics in subjects with TS and has a good safety profile. However, only a limited number of studies were included in the review, with some having small sample sizes and short duration of follow-up.

Gilbert DL, Budman CL, Singer HS, Kurlan R, Chipkin RE. A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome. Clin Neuropharmacol. 2014 Jan-Feb;37(1):26-30. doi: 10.1097/WNF.0000000000000017. PMID: 24434529.

Abstract

Objectives: Dysregulation of dopaminergic signaling has been hypothesized to underlie the motor and phonic tics in Tourette syndrome (TS). The objective of this trial was to evaluate the safety and tic-reducing activity of the selective dopamine D1 receptor antagonist ecopipam in adults with TS.

Methods: This was a multicenter, nonrandomized, open-label study of 50-mg ecopipam daily (weeks 1-2) and then 100 mg daily (weeks 3-8), taken orally before bedtime. The primary efficacy end point was the change in the Yale Global Tic Severity Scale (YGTSS) total tic score. Comorbid psychiatric symptoms and premonitory urges were rated; weight, serum metabolic studies, and adverse effects were monitored.

Results: Eighteen adults (15 men; 15 white, 2 African American, 1 Asian), with a mean age of 36.2 years (range, 18-63 years), were enrolled, and 15 completed the study. Mean (SD) YGTSS Total Tic score was 30.6 (8.8) at baseline and 25.3 (9.2) at 8 weeks (2-tailed paired t17 = 4.4; P = 0.0004). Mean (SD) YGTSS impairment score was 29.7 (10.9) at baseline and 22.8 (13.7) at final visit (t17 = 2.2; P = 0.04). There was no significant change in premonitory urges or psychiatric symptoms. Mean change in weight was -0.7 kg (P = 0.07). The most commonly reported adverse events were sedation (39%), fatigue (33%), insomnia (33%), somnolence (28%), anxiety (22%), headache (22%), and muscle twitching (22%).

Conclusions: In this open-label study in adults with TS, tics were reduced after 8 weeks of treatment with ecopipam. To confirm safety and efficacy, randomized, double blind, placebo-controlled trials are warranted.