Repurposing Existing Drugs for Autism
Unlocking the hidden potential of existing, FDA-approved drugs to treat autism
At the BRAIN Foundation we were recently thrilled to announce a groundbreaking collaboration with Every Cure, a nonprofit organization dedicated to identifying new uses for existing drugs to treat various diseases.
Every Cure was co-founded by Dr. David Fajgenbaum. who was diagnosed with Castleman Disease in 2010 and, after nearly dying five times, discovered a new use for an existing drug that led to his remission. David’s personal experience inspired him to embrace this approach to help millions of people who suffer from diseases and conditions without approved treatments, including those impacted by autism.
The focus of The BRAIN Foundation – Every Cure partnership is to unlock the hidden potential of existing drugs and repurpose them specifically for autism, offering hope to mitigate symptoms, enhance functioning, and improve independence and quality of life for every person on the spectrum.
One of the critical steps being taken to achieve this goal is the production and maintenance of a comprehensive list of existing drugs and nutraceuticals that demonstrate the greatest potential therapeutic effects for autism.
Some of these drugs are already in advanced stages of human autism studies, providing a strong foundation for further exploration, while others have been utilized in clinical practices (awaiting formal publications) or investigated in animal models of autism.
The past and ongoing investigations into these therapeutics are varied in scope: some target specific subsets of autism or particular challenges associated with the condition, such as sensory sensitivities or social difficulties, while others aim to address a broader range of core autism symptoms, including communication and behavioral challenges.
| Drug/Supplement | Drug Class/Type | Reported Benefits* | References (PMID) | Mechanisms of action of relevance to autism |
|---|---|---|---|---|
| Agmatine /Arginine | Nutritional supplement | Reduced core symptoms in three different animal models of autism | 38624050 (P) 38333751 (P) 36057317 (P/ FXS) | A metabolite of amino acid arginine, nutritional/sports energy supplement. Improves brain energy metabolism, insulin sensitivity and cognitive function. 6-8g per day significantly reduced seizures in people with refractory epilepsy. |
Branched Chain | Nutritional supplement | Improved communication; Reduced stereotypy and hyperactivity. | 37424284 38265552 | BCAAs are essential amino acids |
| Carnitine | Nutritional supplement | Improved sleep and energy; Reduced apraxia; Reduced hyperactivity and irritability | 31766743 30622681 37551601 18286595 (FXS) | Transports long-chain fatty acids into mitochondria for ATP energy production. Stimulates glycogen synthesis and glucose utilization in the brain. |
| Coenzyme Q10 (Ubiquinone) | Nutritional supplement | Improved communication, social interaction; | 24707344 29684771 | Antioxidant, supports mitochondrial energy production. Can increase activity of brain mitochondria. |
| Creatine | Nutritional supplement | Research in progress | 35267907 | Regulates glycogen and energy metabolism in the brain, has antioxidant and |
| Dimethylglycine (DMG) | Nutritional supplement | Improved communication and sociability; Improved sensory & cognitive awareness | 34823458 21417812 | Amino acid with anti-inflammatory, antioxidant and NMDA-modulating effects. |
| Lithium | Nutritional supplement | Improved cognition and sociability; Reduced repetitive behaviors | 31308580 25093602 18698192 (FXS) 39633007 (P) 20497624 (P/FXS) | Reduces excitatory and increases inhibitory GABA neurotransmission. Restores brain insulin sensitivity, stimulates glycogen synthesis and improves glucose metabolism in the brain |
| Magnesium & Vitamin B6 | Nutritional supplement | Improved interaction & communication; Reduced repetitive behaviors | 16846101 21417812 | |
| Methylcobalamin (MB-12) | Nutritional supplement | Improved communication & living skills; Improved sleep, reduced hyperactivity | 34442428 35631176 26889605 | Improves cell oxidation status & methylation capacity. |
| N-Acetyl Cysteine (NAC) | Nutritional supplement | Improved social awareness, hyperactivity Reduced irritability & aggression; Reduced self-injurious behaviors | 32900213 22342106 26541950 (CR) 23826003 (CR) 24815193 (CR) | Precursor to glutathione. Strong anti-oxidant action. Cognition & attention improvement linked to enhanced cerebral blood flow and glucose metabolism by NAC (32117038, 34377857) |
| Omega-3 Fatty Acids | Nutritional supplement | Improved communication; Reduced hyperactivity & inattentiveness | 37654990 34577816 35013866 | Wide range of effects, including anti-inflammatory action. |
| Probiotics | Nutritional supplement | Improved gastrointestinal symptoms; Reduced anxiety | 39265200 39702309 38902804 | |
| Sulforephane | Nutritional supplement | Improved irritability and hyperactivity | 39951914 33013262 30790585 (P) | Sulfur-based phytochemical found in cruciferous vegetables such as broccoli. Activates Nrf2, which upregulates antioxidant and detoxification enzymes. Can increase cerebral blood flow by acting as a vasodilator. |
| Taurine | Nutritional supplement | Research in progress | 37711998 (P) 38830122 31141786 | Affects GABA/NMDA calcium channels, Nrf2 and NF-κB pathways. Regulates brain insulin sensitivity/glucose uptake. Can improve cerebral blood flow, reduce edema and intracranial pressure. |
| TMG (betaine) | Nutritional supplement | Research in progress | 30821067 (P) | Natural compound present in many foods. Anti-inflammatory & anti-oxidant. Osmoprotectant and a methyl donor. Decreases homocysteine levels. |
| Vitamin D3 | Nutritional supplement | Reduced stereotypical behaviours; Reduced hyperactivity | 37119216 32893747 35010901 | Antiinflammatory and antioxidant effects. Regulates energy metabolism & inflammation in astrocytes/microglia. Impacts neurotransmitter synthesis and brain plasticity. |
| Fluconazole | Antimicrobial | Research in progress | Antifungal medication. Crosses the blood-brain barrier. Has neuroprotective effects via interactions with insulin growth factor-1 receptor signaling. | |
| Itraconazole (Sporanox) | Antimicrobial | Complete dissolution of autism symptoms (CR) | 33132781 | Itraconazole is an anti-fungal medication. |
| Minocycline | Antimicrobial | Research in progress | 32198305 37441807 (P) 38102393 23572165 (FXS) 35058813 (FXS) | Broad-spectrum antibiotic. Anti-inflammatory action likely due to inhibiting the activity of microglial cells. |
| Niclosamide | Antimicrobial | 39153648 (P) | Anthelmintic medication. Has a wide range of biological effects, regulates aspects of metabolism and immunity. | |
| Vancomycin | Antimicrobial | Improved interaction, communication, behavior | 10921511 | Antibacterial action against gram-positive bacteria. |
| Intravenous Immunoglobulin (IVIG) | Immunomodulatory | Improved social interaction; Improved irritability and hyperactivity. | 34070826 29427532 30097568 | Immunomodulator. Lowers TNF-α and microglial inflammation. Improves brain glucose/energy metabolism, primarily in parietal and frontal brain regions. |
| Methotrexate | Immunomodulatory | Research in progress | 24020679 (P/ FXS) | Immune-modulation and anti-inflammatory action. NF-κB inhibitor. |
| Mercaptopurine (6-MP) | Immunomodulatory | Research in progress | ||
| Prednisone | Hormone | Improved speech & communication; Improved behaviors, reduced sterotypy | 32330433 24885033 32168067 7545148 (CR) 30804752 (P/ FXS) | Binds to the glucocorticoid receptor. Modulates blood brain barrier permeability, reduces brain edema. |
| Anakinra (Kineret) | Antiinflammatory | Research in progress | 38979496 | MABs/JAK Inhibitor, IL-1 receptor antagonist. |
| Baricitinib (Olumiant) | Antiinflammatory | Research in progress | 38979496 | MABs/JAK Inhibitor. Affects pathways of several pro-inflammatory cytokines. Crosses the blood brain barrier. Affects sensory neurons. Protective against inflammation-induced metabolic dysfunction. |
| Adalimumab (Humira) | Antiinflammatory | Research in progress | 38979496 | MABs/JAK Inhibitor. Human monoclonal IgG1 antibody, TNF-α blocking anti-inflammatory action. |
| Infliximab | Antiinflammatory | Improved hyperactivity; Improved stereotypical behavior. | 38979496 10.37321 | MABs/JAK Inhibitor. TNF-alpha antagonists. Reduces depression in a subgroup of patients: "Antidepressant response...which involved regulation of metabolic & inhibition of genes related to innate immune activation." 23624296 |
| Upadacitinib (Rinvoq) | Antiinflammatory | Research in progress | 38979496 | MABs/JAK Inhibitor. Anti-inflammatory action via JAK-STAT pathway. |
| Tofacitinib (Xeljanz) | Antiinflammatory | Research in progress | 38979496 | MABs/JAK Inhibitor. Anti-inflammatory action via JAK-STAT pathway. |
| Dapagliflozin | Antidiabetic | Research in progress | 39004410 (P) 36364000 (P) | Sodium-glucose cotransporter-2 (SGLT2) inhibitor. Decreases GSK3β. Affects cholinergic system, important in memory and cognition. SGLT-2 inhibitors may have ketogenic effect, increasing ketone body production. |
| GLP-1 /semaglutide | Antidiabetic | Reduced agitation and aggression; Reduced obsessive and compulsive behavior. | 30881319 (CR) 6405420 (P) | From case report: "Also obsessions, compulsions and behavioral problems not related to food, including aggressive behavior, decreased in a significant way at home."(30881319) |
| Intranasal Insulin | Antidiabetic | Improved cognition and communication; Improved social and motor skills; Reduced irritability & aggression. | 31104364 (FXS) 33757860 (FXS) 27577546 (PMS) 39329976 (P) | "Following insulin administration, a substantial reduction in autism symptoms was observed in all three social behavior tests... insulin exhibited noteworthy capabilities in decreasing brain MDA, IL-2, IL-17, and TNF-α levels." 39329976 |
| Metformin | Antidiabetic | Reduced irritability; Reduced core autism symptoms (FXS) Ameliorates core symptoms in several animal models | 39676223 31520524 (FXS) 35222739 (P) 30555309 (P) | Improves insulin resistance IR in the brain (see 33879765) Neuroprotective effects via regulation of brain glucose uptake. NFκB inhibitor - immuno-modulating & anti-inflammatory effects. |
| Pioglitazone (Actos) | Antidiabetic | Reduced social withdrawal; Reduced repetitive & externalizing behaviors | 30498564 17207275 301762v1 (P/ FXS) 39179196 (P) 31128204 (P) | Thiazolidinedione, PPARγ agonist, modifies brain energy metabolism. Reduces oxidative stress and neuroinflammation. "TZDs can modify astrocyte metabolism and mitochondrial function, which could be beneficial in neurological conditions where glucose availability is reduced.” |
| Acamprosate (Campral) | Addiction medicine | Improved social behaviour; Reduced aberrant behavior and hyperactivity; Markedly improved communication in FXS-autism | 22136091 24052275 20213249 (CF/FXS) 23436129 (FXS) 29317220 (P/FXS) | Structural analogue of GABA, affects calcium channels and modifies transmission along GABA and glutamine pathways in the brain. |
| Adrenocorticotropic hormone (ACTH) | Hormone | Reduced core autism symptoms; Increased social interaction; Reduced irritability & hyperactivity | 1326339 1331023 27645286 12478882 (CR) | Improves brain energy metabolism by increasing |
| Amantadine | Glutamatergic | Improved speech; Reduced aggression and hyperactivity | 11392343 34456474 27483360 | Dopaminergic agent and NMDA receptor antagonist. Increases glucose metabolism in prefrontal cortex. Inhibits release of proinflammatory cytokines. |
| Arbaclofen | Addiction medicine | Improved socialization; Reduced irritability, agitation | 27748740 24272415 25754761 (P) | Activates GABA-B receptors in the brain, modulates glutamate levels. |
| Bumetanide | Diuretic | Improved cognitive abilities | 36626004 33336381 23647528 (CR/ FXS) 38950809 (P/ FXS) | Inhibits NKCC1 transporter, which transports sodium, potassium, and chloride ions into neurons. Affects GABA signaling. |
| CBD/THC | Cannabinoid | Improved social interaction; Reduced aggression, anxiety, hyperactivity | 34043900 35617670 38226593 | Wide range of effects on inflammatory and metabolic pathways |
| Citalopram (Celexa) | Antidepressant | Normalisation of brain activation | 31712584 35948343 | Selective serotonin reuptake inhibitor (SSRI). Increases serotonin activity in the brain. Increases brain-derived neurotrophic factor (BDNF) levels. |
| Clonidine | Vasodilator | Improved social interaction; Improved sensory dysfunction; Improved sleep | 18280681 1548248 39269569 | Alpha-2 adrenoceptors agonist. Improved brain energy metabolism by stimulating glycogen synthesis in astrocytes |
| Famotidine (Pepcid) | Antihistamine | Improved socialisation and behaviors | 9185122 | GSK-3 inhibitor. Stimulates glycogen synthesis, increases uptake of glucose into cells |
| Fluoxetine | Antidepressant | Reduced restricted/repetitive behavior; Reduced irritability and self-injurious behavior. | 30002940 15602505 35948343 | Selective serotonin reuptake inhibitor (SSRI). Inhibits inflammation via a GSK-3β-dependent pathway. Affects brain energy metabolism by modulating mitochondrial function. |
| Guanfacine | Vasodilator | Reduced hyperactivity and inattentiveness; Reduced irritability, agitation, impulsivity | 30125242 39269569 | Stimulates alpha-2A adrenergic receptors, increases blood flow and glucose energy metabolism in the brain, primarily in prefrontal cortex. |
| Leucovorin (Folinic acid) | Folate analogue | Improved social behaviour Reduced hyperactivity & irritability Reduced frequency of seizures | 32892962 34834493 39243316 38248763 | High dose folic acid/leucovorin supplementation reverses abnormalities in brain |
| Melatonin | Hormone | Improved sleep | 30148039 24050742 | Regulates sleep-wake cycles by binding to receptors in the brain. Has anti-inflammatory and anti-oxidant effects. |
| Memantine (Namenda) | Dementia drug | Reduced social withdrawal; Reduced anxiety and inattentiveness | 36006807 17016714 35315131 | NMDA receptor antagonist with glutamate blocking action. Reduces mitochondrial oxidative stress and dysfunction. In AD it slows the decline in glucose metabolism in the brain. |
| Microbiota Transplant Therapy (MTT) | MTT | Reduced core autism symptoms; Improved GI symptoms and sleep | 30967657 39677507 38783921 38715916 | |
| Naltrexone | Addiction medicine | Reduced hyperactivity and irritability | 7896655 9394942 8780837 | Opioid antagonist, binds to mu opioid receptors. Likely anti-inflammatory properties. Used for reduction of chronic pain, neuro-inflammatory conditions. |
| Oxytocin | Hormone | Improved social responsiveness; Reduced repetitive behaviors | 27798253 38461957 39944132 37540265 | Human hormone, modulates social bonding and sexual behavior. Involved in regulation of stress response. Has anti-inflammatory and anti-psychotic effects. |
| Propranolol | Anxiolytic | Improved world fluency; Improved aggression and irritability; Reduced anxiety; | 21487259 39174017 32134849 38086927 | Beta-adrenoreceptor antagonist. Lowers sympathetic activation and nervous system 'fight or flight' response by blocking stress hormones adrenaline/noradrenaline. Helps to reduce anxiety, palpitations, sweating. |
| Tianeptine (Stablon) | Antidepressant | Reduced restrictive/repetitive behavior; Reduced aggression and irritability; Reduced self-injurious behavior; | 31425465 33608048 35948343 12858327 | Atypical tricyclic antidepressant. Acts as opioid receptor agonist and PPAR activator. Increases serotonin reuptake. Modulates glutamate and NMDA receptor activity. |
| Vasopressin | Hormone | Improved socialisation; Reduced anxiety, repetitive behaviors | 31043522 37892977 | Stimulates release of adrenocorticotropic hormone (ACTH) (see entry for adrenocorticotropic hormone for autism) |
| Canagliflozin | Antidiabetic | Improved all biochemical & behavioral abnormalities in animal models: enhanced sociability, reduced stereotypy | 37242552 (P) 36909191 (P) 36364000 | SGLT2 inhibitor. Improves brain glucose utilisation and energy metabolism in the brain, esp in astrocytes. Anti-inflammatory effects. Modulates PPAR-γ and mTOR pathways. Suppresses activation of T cells from autoimmune patients via 'metabolic reprogramming'. |
| Luteolin/ Quercetin/ Rutin (Flavonoids) | Nutritional supplement | Improved adaptive functioning and daily living skills. Improved communication and social relatedness. | 23688534 26418275 22697063 27701827 (CR/P) | Plant flavonoid. Anti-inflammatory and anti-oxidant action. Luteolin and other flavonoids improve brain insulin resistance, reduce microglial activation. |
| Amoxicillin | Antimicrobial | Improved eye contact and speech; Reduced ‘rigidity' - insistence for routine | 25808801 (CR) | Wide spectrum antibiotic. |
| Cycloserine (Seromycin) | Antimicrobial | Improved social responsiveness | 28138381 28733898 (P) 23685206 (P) | Antibiotic, NMDAR partial agonist, GABA transaminase inhibitor |
| Celecoxib | Antiinflammatory | Improved irritability and social withdrawal; Reduced stereotypic behavior (combined with risperidone) | 22782459 | COX-2 inhibitor, nonsteroidal anti-inflammatory |
| Palmitoylethanolamide (PEA) | Nutritional supplement | Improved speech; Improved social and nonsocial behaviors | 33919499 26491593 29807317 30193877 (P) | Naturally occurring fatty acid. Endocannabinoid. "Potential neurobiological underpinnings include immune modulation, neuroinflammation...neurogenesis, neuroplasticity, mitochondrial function, and microbiota activity, possibly through PPAR-α activation." |
| Ketamine | Analgesic | Improved social cognition: Improved social relatedness | 38766674 (CR) 35651653 (CR) | NMDA receptor antagonist. Potentializes GABA inhibition. Binds to opiate receptors. Stimulates release of norepinephrine, dopamine & serotonin. |
| Tetrahydrobiopterin /Sapropterin (BH4) | Enzymatic cofactor | Improved social awareness and stereotypy; Improved hyperactivity & inappropriate speech | 23782126 23462988 | Cofactor that's essential for biosynthesis of dopamine, noradrenaline and serotonin. Important for production of nitric oxide. |
| Gastrin-Releasing Peptide (GRP) | Neuropeptide | Improved social interaction; Improved irritability and hyperactivity; | 27332629 26893210 28452904 | Regulates gastric acid secretion. Influences astrocyte functions related to neuroinflammation, synaptic plasticity, regulation of neurotransmitter homeostasis, esp. in response to stress or injury. |
| Donepezil | Cholinesterase inhibitor | Improved receptive language, irritability, lethargy, stereotypy, hyperactivity, inappropriate speech | 31230222 37637783 22937405 (CR) 25202686 31264943 (FXS) | Acetylcholinesterase inhibitor. Reduces levels of proinflammatory cytokines TNF-α and IL-1β. Improves glucose energy metabolism in the brain. |
| Galantamine | Cholinesterase inhibitor | Improved irritability and social withdrawal; Reduced emotional lability and inattention | 24132248 17069550 | Acetylcholinesterase inhibitor, nicotinic receptor agonist. Improves brain perfusion & brain glucose/energy metabolism. |
| Steroid therapy | Hormone | Improved language and social interaction; Improved motor skills & gestural stereotypies; Reduced hyperactivity, irritability and echolalia | 24884537 24885033 7545148 (CR) 10802504 (CR) 18625572 (CR) | Glucocorticoids reduce inflammation, improve BBB integrity, facilitate storage and utilization of brain carbohydrate reserves and lead to diversification of available sources of energy in the brain. |
| Cyproheptadine | Antihistamine | Improved verbal communication; Improved social relatedness; Reduced aberrant behaviours | 15068403 12231270 (CR) | Histamine receptor antagonist. Modulates serotonin & acetylcholine |
| Insulin-like growth factor 1 (IGF-1) | Hormone | Improved social impairments, reduced restrictive behaviors (PMS) | 32591005 (P) 39188438 (P) 25613838 (P/ FXS) 25685306 (PMS) 35395866 (PMS) 27643697 (FXS) | Promotes protein synthesis, bone and tissue growth. Involved in brain development, glucose and lipid metabolism. Has antioxidant and anti-inflammatory effects. Protects the brain from glucose deprivation and neuroinflammation via mTOR modulation |
| Pentoxifylline | Vasodilator | Improved lethargy/social withdrawal, stereotypy; Improved irritability, hyperactivity/noncompliance; Reduced inappropriate speech | 19772883 31824351 39520226 (P) 30184549 | Activator of PPAR-γ, involved in regulating inflammation, (brain) insulin sensitivity and glucose homeostasis. |
| Lenalidomide | Immunomodulatory | Improved language expression and receptive speech; Improved socialization | 22997574 | Antiinflammatory, TNF-α inhibitor. Increases levels of antiinflammatory molecule IL-10. |
| Suramin | Antimicrobial | Improved language, social interaction; Reduced restricted and repetitive behaviors | 28695149 37932739 31904357 (P) 23516405 (P) | Purinergic receptor antagonist. Potent anti inflammatory and anti oxidant effects. Reverse transcriptase inhibitor. |
| Sirolimus (Rapamycin)/ Everolimus | Immunomodulatory | Reduced hyperactivity and stereotypy (ASD); Improved cognition, attention, sociability, and language development (TSC) | 34491961 (CR/ASD) 24295733 (P) 30621732 (P) 30060984 (TSC) 27216612 (CR/TSC) 39727664 (CR/TSC) | Antiinflammatory effects via mTOR inhibition. Modulates BBB integrity. Affects 'energy sensing' mechanism via mTOR: brain energy metabolism incl. uptake and utilization of fuel sources for the brain |
Atovarstatin / | Statins | Reduced irritability and hyperactivity (ASD); | 28719227 | Statins are cholesterol lowering drugs with secondary anti-inflammatory and anti-oxidant effects, esp. in endothelium. Possible effects on mitochondrial function and ATP production. Possible effects on GSK-3β/mTOR signaling pathway in the brain. |
| Nimodipine | Calcium channel blocker | Reduced neurobehavioral abnormalities in valproic acid model of ASD | 36263647 (P) | Voltage gated calcium channel antagonist. Reduces neuroinflammation and oxidative stress in valproic acid animal model. Rescues brain energy/glucose metabolism. |
| Dapagliflozin | Antidiabetic | 39004410 (P) 36364000 | Sodium-Glucose Transport Protein 2 (SGLT2) inhibitor. Increases levels of growth factors BDNF, IGF-1. Modulates brain energy metabolism, oxidative stress & inflammation via TNF-a, IL-17, AMPK/mTOR, Nrf2. | |
| Modafinil | Wakefulness promoter | Reversed abnormal behaviors and neuroinflammation in propionic acid animal model of autism | 37043086 (P) | Neuroprotective & anti-inflammatory effects, particularly in astrocytes. Reduces immune cells infiltration and glial activation during neuroinflammation. Improves adrenergic sensitivity and cognitive function in glucose-deprived brain. Has possible glutamatergic /GABA modulating effects. |
| Torasemide | Diuretic | Improved behavioral and neuro-inflammatory markers in an animal model of autism. | 36879996 (P) | Affects NKCC1 transporter, which plays a crucial role in maintaining chloride homeostasis in astrocytes and neurons. Modulates GABA signalling. |
| Insulin-like growth factor 2 (IGF-2) | Hormone | Reversed cognitive and behavioral deficit in two different animal models of autism | 29217683 (P) 38298376 (P) 28352664 (P/ FXS) 27643697 (P/ FXS) | A protein hormone, plays a role in growth and development. Modulates mTOR pathways. Has antioxidant, neuroprotective and neuroplasticity-enhancing effects in the brain. |
| Papaverine | Vasodilator | Improved social behaviour, corrected repetitive behaviour, anxiety, locomotor, and nociceptive changes (P) | 33127361 (P) 33480092 (P) | Increases BDNF levels. Lowers oxidative stress and inflammation, increases blood flow and glucose energy metabolism in the brain. |
| Vinpocetine (Cavinton) | Vasodilator / Nutritional Supplement | Reversed autism-related behaviors and pathological markers in different animal models | 34415116 (P) 35451422 (P) 37434477 (CR) | PDE1 inhibitor & sodium channel antagonist. Increases BDNF. Antioxidant & anti-inflammatory effects. Cerebral metabolic enhancer: improves oxygen & glucose uptake to increase brain ATP production. |
CR = case report; FSX = Fragile X Syndrome; P = preclinical/animal study; PMS = Phelan-McDermid/22q13.3 deletion syndrome
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