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the sci-wiki/effects/Neurotrophins

Neurotrophins

Every compound in the sci-wiki that affects neurotrophins; the ones you can source are floated to the front, then the reference-only entries. Tap any for the full entry, mechanism, and outlets.

24 sourced · 71 reference

←neurotrophins95/95filter this drawer by compound name

Dihexa

Dihexa is a small angiotensin IV analogue engineered at Washington State University to do something most peptides cannot, which is survive oral dosing and cross into the brain. Where most cognitive compounds nudge neurotransmitter levels, it was designed to act on the machinery that physically builds connections between neurons, and the preclinical reports are striking: reversed amnesia in animal models, restored spatial learning in Alzheimer's-model mice, and measurable growth of new synapses. The mechanism originally proposed for that effect, amplification of the HGF and c-Met growth-factor system, no longer rests on its original evidence; the central paper was retracted in 2025 after image manipulation was found, two supporting papers from the same laboratory were retracted alongside it, and the paper that first introduced Dihexa carries an expression of concern that is still in force. What the compound does is therefore an open question rather than a settled one. It has never been through a registered human trial, and the clinical programme built on the same mechanism, using an injectable modified version, missed its main Alzheimer's endpoint in 2024.

Semax

Semax is a synthetic peptide nootropic and neuroprotective agent based on a fragment of adrenocorticotropic hormone (ACTH), developed in Russia and used there clinically for cognition, stroke, and brain injury. It rapidly raises the brain's own growth factors, BDNF and NGF, and modulates dopamine and serotonin, underpinning its reputation for sharper focus, memory, and mental drive. Delivered as a nasal spray and stripped of any hormonal activity, it pairs cognitive support with genuine neuroprotection.

Cerebrolysin

Cerebrolysin is a neuropeptide preparation that mimics the brain's own neurotrophic factors to support neuronal protection, repair, and plasticity. Widely used across Europe and Asia for stroke, dementia, and traumatic brain injury, it is one of the most established neurotrophic therapies in clinical practice. For those focused on brain health and neuroregeneration, Cerebrolysin is a uniquely biologically active peptide preparation.

P21

P21 (P021) is a small, orally active neurotrophic peptide mimetic derived from ciliary neurotrophic factor, engineered to deliver the brain-building benefits of a neurotrophic factor without the drawbacks that stalled earlier protein therapies. It enhances hippocampal neurogenesis and raises BDNF while lowering the tau-driving kinase GSK-3beta, and in Alzheimer's models it reduced tau pathology and rescued cognition and synaptic plasticity [1][2]. Its blood-brain-barrier permeability and clean design make it a genuinely exciting frontier compound for neuroprotection.

PE-22-28

PE-22-28 is a fast-acting mood peptide with a genuinely clever mechanism, engineered from the natural antidepressant peptide spadin to be more potent and stable. It blocks the TREK-1 potassium channel that sits in mood circuits and dampens serotonin signaling, and animals bred without TREK-1 are naturally resistant to depression [2]. In rodent studies its shortened design achieved dramatically stronger TREK-1 inhibition than spadin, produced antidepressant-like effects within days, and boosted neurogenesis, making it one of the more exciting frontier tools in the mood space [1].

Adamax

Adamax is a research peptide built from Semax by capping it with an adamantane group, a bulky lipophilic cage intended to improve stability and passage into the brain. No published study examines Adamax itself, so everything on this page about how it works is reasoned from the Semax literature rather than measured for this compound; the claim that it is more potent than its parent has never been tested. For readers who already know the Semax family, it is best understood as an untested modification of a well-documented peptide rather than an upgraded version of one.

Noopept

Noopept is one of the most extensively researched dipeptide nootropics, a proline-containing compound designed as a peptide analog of piracetam with far greater potency by weight. Its standout quality is neuroprotection; in cellular models it guarded neurons against oxidative and amyloid-related damage more effectively than piracetam or classic antioxidants, while attenuating tau hyperphosphorylation [1][3]. Studied for memory restoration and neuroprotection, it also raises endogenous NGF and BDNF and activates adaptive stress-response pathways.

Cortexin

Cortexin is a polypeptide preparation made from the cerebral cortex of cattle, consisting of a mixture of low-molecular-weight peptides, amino acids, and trace elements. Marketed as a neuroprotective and nootropic medicine, it is registered and prescribed mainly in Russia and other post-Soviet countries, where it is given by intramuscular injection for stroke recovery, cognitive disorders, and other neurological conditions. It is not approved by Western drug regulators, and most clinical evidence for it comes from Russian-language literature.

Sabroxy

Oroxylin A is a plant flavonoid from the bark of the Indian trumpet tree (Oroxylum indicum) and from Chinese skullcap; consumers almost never buy the pure compound, they buy Sabroxy, a standardised bark extract in which oroxylin A is one of three flavonoids. It is marketed for memory and focus, and the animal work points to two mechanisms: it blocks the benzodiazepine site on the GABA-A receptor, releasing the brain's main braking signal, and it slows dopamine reuptake in roughly the way ADHD stimulants do. Human evidence is thin and rests on a single 12-week trial in 82 older adults with memory complaints; that trial was paid for by the ingredient's manufacturer, had a company founder as a co-author, found gains on some memory tasks but not most other measures, and applied no statistical correction for testing many outcomes at once. A separate Phase I study showed pure oroxylin A is tolerated up to 2400 mg in healthy volunteers, but no trial has ever shown the pure compound improves cognition in people.

TAK-653

TAK-653, also called osavampator or NBI-1065845, is an experimental oral drug that makes the brain's main excitatory receptor, the AMPA glutamate receptor, respond more strongly to glutamate the brain is already releasing; crucially it cannot switch the receptor on by itself, a design choice intended to avoid the seizure risk that stopped earlier drugs of this type. It is being developed as a fast-acting antidepressant for people whose depression has not responded to standard antidepressants. A 183-person Phase 2 trial found that 1 mg once daily beat placebo on a standard depression rating scale while 3 mg did not reach statistical significance, and five Phase 3 trials are now enrolling; those Phase 2 results have not yet been published in a peer-reviewed journal. It is approved nowhere in the world, it is not a legal supplement, and the entire published literature amounts to about ten papers, most of them written by employees of the companies that own it.

9-Me-BC

9-Me-BC is a small synthetic molecule from the beta-carboline family, chemically close to compounds that occur naturally in coffee, cooked meat and tobacco smoke; it is sold online as a nootropic and has never been approved as a medicine anywhere. In cell cultures and in rodents it raises dopamine levels, protects and partly regrows dopamine-producing neurons, and improved maze learning in rats, which is why it was proposed as a possible Parkinson's disease drug. The evidence is entirely preclinical; there is no human trial, no human dosing study and no human safety data at all, and almost every positive finding comes from a single research group in Germany. Two specific concerns remain unresolved: it inhibits the enzyme MAO-A at low concentrations, the same mechanism that makes prescription MAOI antidepressants risky with certain foods and drugs, and enzymes in the brain can convert it into a closely related molecule that is itself an established nerve toxin.

NSI-189

NSI-189 is a first-in-class neurogenic compound built on a genuinely novel premise; rather than manipulating monoamines like conventional antidepressants, it stimulates the birth of new neurons in the hippocampus. This small, orally active molecule promotes neurogenesis of human hippocampus-derived neural stem cells and, in clinical testing for major depressive disorder, produced encouraging antidepressant and pro-cognitive signals [1][3]. Its dual mood and cognition profile makes it one of the more distinctive investigational compounds in the space.

J-147

J147 is an experimental neuroprotective compound that grew out of a curcumin-like scaffold, designed at the Salk Institute through phenotypic screens that mimic the aging brain rather than any single Alzheimer's protein. In mice it is potent, orally active, and brain-penetrant: it enhances memory, raises the neurotrophic factors BDNF and NGF, and can rescue cognition even when given late, after pathology is already advanced. Its molecular target was a mystery for years until 2018, when it was identified as the mitochondrial ATP synthase; gently modulating that enzyme flips on the AMPK/mTOR longevity pathway, tying Alzheimer's and ordinary brain aging to a shared mechanism. Crucially, essentially all of this is preclinical; a phase 1 safety study was reportedly initiated but no human efficacy results have been published. Treat J147 as a promising research compound, not a proven drug.

BPN14770

BPN14770, also known as zatolmilast, is an investigational drug that inhibits the phosphodiesterase-4D (PDE4D) enzyme through an allosteric mechanism, binding a regulatory domain rather than the catalytic site so that inhibition is only partial. This partial, subtype-selective action raises the signaling molecule cyclic AMP in the brain to enhance memory while avoiding the nausea and emesis that limited earlier pan-PDE4 inhibitors. It has been studied for Fragile X syndrome, where it improved cognition in a phase 2 trial, and for Alzheimer's disease; it reached phase 2 trials but is not approved for medical use.

SANA

SANA, also identified as MVD-1, is an orally active, non-stimulant thermogenic being explored for obesity and metabolic disease. As a salicylate-derived small molecule, it is designed to switch on creatine-dependent thermogenesis in fat cells, driving a futile creatine cycle that raises energy expenditure and releases energy as heat rather than blunting appetite. This mechanism-first approach, aimed at reducing body fat and liver fat while improving glucose control and preserving lean mass, represents one of the more novel ideas in the metabolic pipeline.

Pinealon

Pinealon is a synthetic tripeptide bioregulator (Glu-Asp-Arg, also called the EDR peptide) from the Russian Khavinson family of short peptides, developed to support the brain and target age-related cognitive decline [1][5]. In laboratory and animal studies it acts as a neuroprotective agent that shields neurons from oxidative stress and hypoxia, promotes healthy dendrite growth, and helps regulate the genes that keep neurons functioning [1][3]. Marketed as a peptide geroprotector for memory and healthy brain aging, it is one of the best known members of the short-peptide nootropic class [4][5].

Artichoke Extract

Artichoke extract is a botanical preparation made from the leaves of the globe artichoke (Cynara cardunculus var. scolymus), a cultivated thistle in the family Asteraceae. It is standardized for polyphenols such as cynarin, chlorogenic acid, and the flavone luteolin, and has a long history of use as a digestive aid and bile stimulant. Modern research has focused mainly on its modest cholesterol-lowering and liver-supportive effects, while a niche nootropic interest stems from luteolin's ability to inhibit phosphodiesterase enzymes.

Carnosic Acid

Carnosic acid is a phenolic diterpene found in the herbs rosemary (Salvia rosmarinus) and common sage (Salvia officinalis), where it is one of the main compounds responsible for their antioxidant activity. Together with its oxidation product carnosol, it is used commercially as a natural antioxidant food preservative, labeled as rosemary extract (E392). It has been studied extensively for antioxidant, anti-inflammatory, and neuroprotective effects, which are largely attributed to its ability to activate the cell's Nrf2 defense pathway.

Eutropoflavin

Eutropoflavin is a synthetic flavonoid studied as a selective agonist of TrkB, the receptor for brain-derived neurotrophic factor (BDNF). Chemically known as 4'-dimethylamino-7,8-dihydroxyflavone, it is a modified and more potent derivative of tropoflavin (7,8-dihydroxyflavone). In animal experiments it activates TrkB more strongly and for longer than its parent compound and shows neuroprotective, neurogenic, and antidepressant-like effects. It is not an approved medicine, although it has been sold online as a nootropic.

Fluoxetine

Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, best known by the brand name Prozac. Developed by Eli Lilly and approved in the United States in 1987, it was the first of the SSRIs to become a commercial success and helped make this class the leading treatment for depression. It is prescribed for major depression, obsessive-compulsive disorder, panic disorder, bulimia nervosa, and premenstrual dysphoric disorder, and it appears on the World Health Organization's List of Essential Medicines. A distinctive feature is its unusually long stay in the body, owing partly to a long-lived active breakdown product.

Gotu Kola

Gotu kola is the common name for Centella asiatica, a small creeping herbaceous plant of the family Apiaceae that grows in wetlands across Asia and other warm regions. It has a long history in Ayurvedic and traditional Chinese medicine, where it has been used for wound healing, skin conditions, and as a tonic said to support memory and mental clarity. Its activity is attributed to a group of pentacyclic triterpenoid compounds, including asiaticoside, madecassoside, and their related acids.

Nicergoline

nicergoline (sermion) is a semisynthetic ergoline nootropic-vasodilator; a potent alpha-1 blocker that also boosts cholinergic/neurotrophic tone, with modest but real cochrane-backed benefit in age-related and vascular cognitive decline, tempered by ergot-class fibrosis risk on long timelines.

Retinalamin

Retinalamin is a peptide preparation made from water-soluble polypeptide fractions extracted from cattle retina, developed and used mainly in Russia and some neighboring countries. Classed as a peptide bioregulator, it is given by injection as a neuroprotective treatment for retinal diseases such as diabetic retinopathy, retinal dystrophies, and glaucoma. It is not approved in the United States or the European Union.

Lion's Mane

Lion's Mane is the common name for Hericium erinaceus, an edible and medicinal mushroom recognized by its cascade of long, white, icicle-like spines. Native to North America and Eurasia, it grows on hardwood trees and has long been used as food and in traditional Chinese medicine. It is now sold widely as a dietary supplement marketed for brain and nerve health, though human evidence remains limited.

reference shelf; no outlet carries these yet

(2R,6R)-Hydroxynorketamine

(2R,6R)-Hydroxynorketamine is a downstream metabolite of ketamine, and it is the compound at the centre of the most interesting open question in rapid-acting antidepressant research: whether the mood effect can be separated from the dissociation. In mice, a single dose produces the same antidepressant-like changes as ketamine itself [1], yet at the concentrations that produce them it does not measurably block the NMDA receptor [2]. If that holds, the antidepressant action and the anesthetic, dissociative, abuse-prone action are two different drugs wearing one molecule. The catch is that the behavioural finding has not replicated cleanly, and no human efficacy trial has reported out.

522-054

522-054 is a laboratory research compound built in Kelvin Gee's group at the University of California, Irvine to do two opposite things to the hippocampus at once: strengthen α7 nicotinic acetylcholine receptors and block the α5-subunit-containing GABA-A receptors that hold pyramidal cells under constant inhibition. In rats the combination potentiated synapses, lowered the threshold for long-term potentiation, and restored learning and attention that had been disrupted either by scopolamine or by a traumatic brain injury months earlier. The whole published record is two primary papers, both in rats and rat tissue, plus one review that summarises them. No human has been given it and no clinical trial exists.

A4 Amyloid Beta

Amyloid beta (Aβ), historically called the A4 peptide, is a short peptide of roughly 36 to 43 amino acids best known as the principal constituent of the amyloid plaques found in the brains of people with Alzheimer's disease. It is produced naturally in the body through enzymatic cleavage of a larger membrane protein, and its accumulation and aggregation are central to the leading theory of how Alzheimer's disease develops.

ACD856

ACD856 is an experimental drug from the Swedish company AlzeCure Pharma designed to make the brain's own growth factors work harder rather than replacing them; it attaches to the Trk receptors that BDNF and NGF normally act through and amplifies their signal. In animals it improved memory and produced antidepressant-like effects, and in healthy volunteers it was well absorbed, reached the brain, and caused few side effects at single doses up to 150 mg. The evidence stops there; ACD856 has never been tested for effectiveness in anyone with Alzheimer's disease or any other condition, and every published study on it was written by employees of the company that owns it. It is not approved as a medicine anywhere and is currently sold only as a laboratory chemical labelled not for human use.

Adamantyl Carbonyl Proline

Adamantyl carbonyl proline is an obscure synthetic compound that links a rigid adamantane cage to the amino acid proline through a carbonyl, or amide, bond. It has circulated in nootropic circles as a putative cognitive enhancer, but it is essentially uncharacterized in the peer-reviewed literature, with no published human trials. Much of what is claimed about it is inferred from the general chemistry of adamantane-containing drugs and from unrelated proline-based peptides rather than from direct study of the molecule itself.

AMN082

AMN082 is the first identified selective allosteric agonist of the mGlu7 receptor, a group III metabotropic glutamate receptor that is the most abundant and evolutionarily conserved of the family and is concentrated at presynaptic terminals. It became the primary pharmacological tool for probing mGlu7 function in stress, anxiety, fear, addiction and depression. Because mGlu7 sits at active synaptic zones and requires high glutamate concentrations for physiological activation, an allosteric agonist offered a unique way to engage it directly. AMN082 is significant as the compound that opened experimental access to mGlu7 pharmacology, though its off-target effects require careful interpretation.

Amycenone

Amycenone is a standardized bioactive extract obtained from the Yamabushitake mushroom (Hericium erinaceus), studied as an anti-inflammatory antidepressant. In a lipopolysaccharide-induced mouse model of inflammatory depression, oral amycenone blocked the rise in tumor necrosis factor-alpha, increased the anti-inflammatory cytokine interleukin-10, and reduced depression-like immobility in the tail-suspension and forced-swim tests, with effects comparable to the SSRI paroxetine. It is investigated as a natural supplement for inflammation-related mood disorders.

Arketamine

Arketamine is the R-enantiomer of ketamine, the half that was not developed. It binds the NMDA receptor about four times more weakly than esketamine, and on the standard account that should make it the weaker antidepressant. A large body of rodent work says the opposite: arketamine produces antidepressant-like effects that are more potent and longer lasting, with less dissociation-like behaviour and less abuse-related response [1]. That contradiction made it one of the most anticipated compounds in the field. Then the human trials arrived, and they have not shown an advantage over placebo [2]. It is the clearest example on this site of preclinical promise failing to carry across.

Basimglurant

Basimglurant (developmental codes RG7090 and RO4917523) is a potent, selective negative allosteric modulator of the mGlu5 receptor developed by Roche as a once-daily modified-release medicine for psychiatric disorders. It was advanced principally as an adjunctive treatment for major depressive disorder and for fragile X syndrome, based on preclinical evidence that mGlu5 blockade produces broad anxiolytic and antidepressant-like effects. A phase 2b depression trial missed its clinician-rated primary endpoint but showed consistent improvement on patient-rated measures, while a fragile X trial did not meet its primary behavioural outcome. Basimglurant is notable for its favourable drug-metabolism profile and its position as one of the most clinically advanced mGlu5 negative allosteric modulators.

Bilobalide

Bilobalide is a sesquiterpene trilactone, a plant compound found almost exclusively in the leaves of the ginkgo tree (Ginkgo biloba). It is one of the characteristic terpene trilactones that, together with the ginkgolides, define standardized ginkgo extracts [1]. In laboratory research it has drawn attention as a neuroprotective agent and as a negative modulator of GABA-A receptors, though its full range of actions in the brain is not completely understood [3][4]. It reaches people mainly as a minor constituent of ginkgo leaf supplements rather than as an isolated product.

CE-158

CE-158 is an investigational, highly selective atypical dopamine transporter inhibitor developed by academic groups in Vienna, Salzburg, and Cagliari as a modafinil-derived cognitive enhancer. In rodents it raises prefrontal and hippocampal dopamine, restores age-related synaptic and cognitive decline, and improves behavioral flexibility without signs of abuse liability. It is a preclinical research compound with no human data.

Celastrus Paniculatus

Celastrus paniculatus is a woody climbing shrub of the family Celastraceae, native to India and known in English as the intellect tree or black oil plant [1][2]. Its seeds and the oil pressed from them have a long history in Ayurvedic, Unani, and Siddha traditional medicine, where they are counted among the memory-supporting 'Medhya Rasayana' tonics and used for a range of nervous-system complaints [2][3]. Modern laboratory and animal studies have examined the seed oil and extracts for antioxidant, neuroprotective, and nootropic activity, though controlled human trials are lacking [2][4].

Cerebroprotein Hydrolysate

Cerebroprotein hydrolysate is a mixture of low-molecular-weight peptides and free amino acids extracted from porcine brain tissue and used as a neuroprotective preparation, chiefly for cognitive impairment and dementia [2][4]. It is closely related to Cerebrolysin, a similarly prepared brain peptide product, and is marketed mainly in China and other parts of Asia rather than in Western countries [1][3]. Laboratory and animal studies attribute neurotrophic and antioxidant actions to the preparation, though rigorous human evidence remains limited [2][4].

Clitoria Ternatea

Clitoria ternatea is a perennial climbing legume of the family Fabaceae, widely known as butterfly pea or blue pea for its vivid blue flowers [1][5]. Native to equatorial Asia, it is now grown across the tropics as an ornamental, a nitrogen-fixing cover crop, and a source of natural blue food colouring [1][5]. In the traditional medicine of South Asia it has long been used as a memory tonic, and modern laboratory studies have examined its extracts for effects on cognition and the nervous system [2][6].

Colivelin

Colivelin is a synthetic 26-amino-acid hybrid peptide built by fusing a short activity-dependent neurotrophic factor fragment (ADNF-9, SALLRSIPA) to the N-terminus of a potent humanin derivative, AGA-(C8R)HNG17. It was engineered to protect neurons from the kinds of insults tied to Alzheimer's disease and other neurodegeneration, and it does so in cell models at femtomolar concentrations, far below its parent peptides. Researchers look at it mainly as a neuroprotective tool compound rather than an approved drug.

Convolvulus Pluricaulis

Convolvulus pluricaulis is a small perennial herb of the morning glory family (Convolvulaceae), native to India and best known in Ayurvedic medicine as shankhpushpi [1][2]. It has long been used as a brain tonic to support memory and to calm the mind, and it is one of several plants traditionally sold under the shankhpushpi name [2][4]. Modern laboratory research has examined its extracts for memory-enhancing, anxiety-reducing and neuroprotective effects, although evidence in humans remains limited [2][3].

Corallocin A

Corallocin A is an isoindolinone natural product first isolated from the coral tooth mushroom Hericium coralloides and subsequently found in Hericium erinaceus fruiting bodies. It induces both nerve growth factor and brain-derived neurotrophic factor expression in human astrocytes, making it one of the dual-neurotrophin inducers of the Hericium genus. Its ability to raise BDNF as well as NGF distinguishes it from the classic NGF-focused hericenones and links it to memory-relevant signaling.

Corallocin B

Corallocin B is a benzofuranone natural product isolated from the mushroom Hericium coralloides alongside corallocins A and C. It induces nerve growth factor and brain-derived neurotrophic factor expression in human astrocytes and, unusually for this class, also shows antiproliferative activity against endothelial and cancer cell lines. This combination of neurotrophic and antiproliferative properties makes it a distinctive dual-activity member of the Hericium neuroactive metabolites.

Cutamesine

Cutamesine (SA4503) is a selective agonist of the sigma-1 receptor, an endoplasmic reticulum chaperone protein that modulates calcium signaling, mitochondrial function, and multiple neurotransmitter systems. Preclinical work shows that sigma-1 activation enhances neurite and axon outgrowth, protects neurons from oxidative and excitotoxic stress, and improves functional recovery when given days after experimental ischemic stroke, acting through neuroplasticity rather than acute neuroprotection. A phase 2 clinical trial in acute ischemic stroke found cutamesine safe and well tolerated, with a post hoc signal of greater neurological improvement among more severely affected patients. The same sigma-1 mechanism has drawn interest for depression, cognitive impairment, and motor neuron disease, and the carbon-11 labeled compound has been used as a PET radiotracer to quantify sigma-1 receptor occupancy. It has reached human testing but is not an approved drug.

CX-546

CX-546 is a benzoxazine ampakine developed by Cortex Pharmaceuticals as a positive allosteric modulator of AMPA-type glutamate receptors. It is a first-generation, high-impact ampakine that markedly slows receptor deactivation and desensitization, boosting excitatory transmission, long-term potentiation, and neurotrophin expression in the hippocampus. Widely used as a laboratory tool compound, it has illuminated how AMPA modulation drives synaptic plasticity, astrocyte energetics, and BDNF signaling. It never became a clinical product but remains an important reference ampakine.

CX-614

CX-614 is a benzoxazine ampakine from the Cortex Pharmaceuticals program and a positive allosteric modulator of AMPA-type glutamate receptors. It is best known as the compound that first demonstrated ampakines can chronically elevate brain-derived neurotrophic factor without permanently down-regulating AMPA receptors, provided dosing is spaced. This made it a foundational tool for the concept of using AMPA modulators to sustain neurotrophin signaling for neuroprotection. It was never a clinical product but remains one of the most cited experimental ampakines.

Immunomodulator

Dapansutrile

Dapansutrile (OLT1177) is an orally active beta-sulfonyl nitrile small molecule that selectively inhibits the NLRP3 inflammasome, blocking maturation and release of the pro-inflammatory cytokines interleukin-1 beta and interleukin-18. Developed by Olatec Therapeutics, it is investigational and has completed early-phase human trials in gout and systolic heart failure with a favorable safety profile.

DHA

Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid, designated 22:6(n-3), that serves as a major structural lipid in the brain, retina, and wider nervous system. It is obtained chiefly from fatty fish, fish oil, and algae-derived oils, and the human body can form only small amounts of it from the shorter omega-3 precursor alpha-linolenic acid. DHA is widely used in dietary supplements and infant formulas and is studied for roles in neurodevelopment, cognition, and cardiovascular health.

Eglumegad

Eglumegad (developmental code LY354740) is a potent, selective orthosteric agonist of group II metabotropic glutamate receptors (mGlu2 and mGlu3) developed by Eli Lilly as a novel anxiolytic. By activating presynaptic autoreceptors that restrain glutamate release, it produced robust anti-anxiety effects in animal models and, through its prodrug LY544344, showed efficacy in human generalized anxiety disorder and experimental panic. Development was halted after preclinical convulsion findings, but eglumegad remains a foundational tool compound for group II metabotropic glutamate pharmacology. It is historically important as one of the first metabotropic glutamate agonists to reach human anxiety trials.

Elunetirom

Elunetirom (ABX-002) is an investigational thyromimetic prodrug designed to deliver selective thyroid hormone receptor beta (TR-beta) activation preferentially to the central nervous system while limiting the systemic thyroid effects that make native thyroid hormone unsuitable as a drug. It belongs to the same CNS-penetrating prodrug class as sobetirome and its amide prodrug Sob-AM2, for which preclinical studies have shown brain-targeted TR-beta engagement that stimulates oligodendrocyte differentiation, promotes myelin repair, and lowers very long chain fatty acids in models of demyelination and X-linked adrenoleukodystrophy. By recreating thyroid hormone action in the brain without body-wide hyperthyroidism, such agents are being explored as add-on treatments for mood disorders and neurological disease. As of the mid-2020s elunetirom remained in clinical trials and had not been approved for any use.

Erinacine A

Erinacine A is the flagship cyathane diterpenoid produced by the mycelium of the culinary-medicinal mushroom Hericium erinaceus (Lion's Mane). It is the single most pharmacologically characterized Lion's Mane metabolite in the central nervous system, acting as a potent low-molecular-weight inducer of nerve growth factor (NGF) synthesis. Unlike the larger hericenones of the fruiting body, erinacine A is small and lipophilic enough to cross the blood brain barrier, giving it central activity after oral dosing in rodents. Preclinical work reports benefit across Alzheimer-type pathology, Parkinsonian models, ischemic stroke, metabolic-driven cognitive decline, and colorectal cancer models.

Erinacine C

Erinacine C is a cyathane diterpenoid from Hericium erinaceus mycelium and one of the more potent members of the erinacine series for inducing nerve growth factor synthesis. Beyond neurotrophic activity, it is distinguished by a well-characterized anti-neuroinflammatory profile: in microglial models it suppresses nitric oxide and pro-inflammatory cytokine production while activating the cytoprotective Nrf2/HO-1 pathway. It is investigated as a natural neuroprotective lead for conditions driven by microglial activation and oxidative stress.

Erinacine P

Erinacine P is a cyathane diterpenoid isolated from liquid cultures of Hericium erinaceus and is best understood as a biosynthetic precursor within the erinacine pathway that leads to erinacine A and erinacine C. Despite its precursor role it is itself neuroactive, promoting neurite outgrowth in PC12 cells at low micromolar concentrations. It is of particular interest to metabolic engineers seeking to raise erinacine A yields, since the pathway flows through erinacine P.

Esketamine

Esketamine is the S-enantiomer of ketamine, the half of the racemic mixture that binds the NMDA receptor several times more tightly, and it is the only member of the ketamine family approved as an antidepressant. As the nasal spray Spravato it is licensed for treatment-resistant depression alongside an oral antidepressant, and for depressive symptoms in adults with active suicidal ideation. Administration is supervised: the dose is taken in a certified setting and the patient is observed for two hours afterwards, because sedation, dissociation and a transient rise in blood pressure are expected rather than rare. It is a real antidepressant with a real effect size and a genuinely inconvenient delivery model.

Fenobam

Fenobam is an imidazole small molecule originally developed in the 1970s as a non-benzodiazepine anxiolytic whose mechanism was unknown until it was later identified as a selective mGlu5 negative allosteric modulator. This retrospective mechanistic discovery made fenobam an early prototype for mGlu5-based anxiolytics and a candidate for fragile X syndrome. A pilot single-dose trial in adults with fragile X syndrome reported no significant adverse effects and improvements in prepulse inhibition, a marker of sensory gating, in half of the participants. Fenobam holds historical importance as the first clinically studied mGlu5 negative allosteric modulator in humans.

Foliglurax

Foliglurax (developmental code PXT002331) is an orally active, brain-penetrant positive allosteric modulator of the mGlu4 receptor, a group III metabotropic glutamate receptor enriched at inhibitory synapses of the basal ganglia. It was developed by Prexton Therapeutics, later acquired by Lundbeck, as a non-dopaminergic treatment for Parkinson's disease, aiming to restore basal-ganglia balance and reduce both off time and levodopa-induced dyskinesia. In a phase 2 trial it produced dose-dependent reductions in daily off time that did not reach statistical significance on the primary endpoint. Foliglurax is a notable clinical test of the mGlu4 positive allosteric modulator concept for movement disorders.

Galanin-like Peptide (GALP)

Galanin-like peptide, or GALP, is a 60-amino-acid neuropeptide isolated from porcine hypothalamus whose central region is identical to the biologically active N-terminus of galanin. It preferentially activates galanin receptor 2 and is expressed in a discrete population of arcuate nucleus neurons, where it integrates signals of energy status such as leptin and insulin. GALP regulates feeding, body weight, and reproductive and neuroendocrine function, producing a pattern of brain activation distinct from galanin itself. It is an endogenous signaling peptide of ongoing research interest rather than a therapeutic.

Galanin(1-15)

Galanin(1-15) is an active N-terminal fragment of galanin that behaves as a distinct signaling entity through galanin receptor 1 and receptor 2 heteroreceptor complexes. On its own it produces strong anxiogenic and depression-like effects in rodents, often exceeding those of full-length galanin, yet paradoxically it enhances the antidepressant action of fluoxetine and can reverse fluoxetine-induced memory impairment. These effects depend on GalR1-GalR2 complexes interacting with serotonin 5-HT1A receptors in the raphe, hippocampus, and prefrontal cortex. It is a preclinical fragment of interest as both a mood modulator and an adjunct concept for antidepressant therapy.

Galanin(2-11)

Galanin(2-11), also known as AR-M1896, is a short galanin fragment corresponding to residues two through eleven of the peptide and is widely used as a galanin receptor 2 preferring agonist. As one of the few subtype-biased galanin tools, it has been central to dissecting which effects of galanin are mediated by GalR2 rather than GalR1, particularly in pain, mood, and neuroprotection. In the spinal cord and periphery it can be pronociceptive through GalR2, while GalR2 activation at the dorsal raphe is linked to increased serotonin and potential antidepressant effects. It is a preclinical research peptide.

Galmic

Galmic is a macrocyclic nonpeptide galanin receptor agonist built on a rigid protein-surface-mimicking scaffold that displays galnon's pharmacophores in a fixed spatial arrangement. It has micromolar affinity for GalR1 and essentially no affinity for GalR2, and after systemic administration it blocks seizures, produces antidepressant-like effects, and reduces inflammatory pain behavior in rodents. Galmic is a preclinical chemical tool that helped establish that galanin receptors can be engaged by drug-like macrocycles. It has not advanced to human studies.

Galnon

Galnon is a low-molecular-weight, systemically active nonpeptide galanin receptor agonist and one of the first small molecules shown to activate galanin receptors in vivo. It was designed from the known pharmacophores of galanin and displaces radiolabeled galanin from brain membranes with micromolar affinity while inhibiting adenylate cyclase, consistent with agonist action. In rodents it is anticonvulsant, anxiolytic, and modulates reward circuitry, making it a foundational pharmacological tool for probing the galaninergic system. Galnon remains a preclinical research compound with no human development.

GDF-11

GDF-11, or growth differentiation factor 11 (also called bone morphogenetic protein 11), is a secreted signaling protein of the transforming growth factor beta (TGF-beta) superfamily. It is closely related to myostatin, sharing much of its structure and using the same receptors, and during embryonic development it helps pattern the skeleton and other tissues [1][5]. GDF-11 became widely known through contested research that proposed it as a blood-borne rejuvenation factor, a claim later studies called into question [2][5].

Ginsenoside Rg1

Ginsenoside Rg1 is one of the most abundant and extensively studied saponins found in ginseng, particularly Panax ginseng and Panax notoginseng. It belongs to the protopanaxatriol group of dammarane-type triterpene glycosides and is a major contributor to the pharmacological profile attributed to ginseng. In laboratory and animal research, Rg1 has drawn attention chiefly for antioxidant, anti-inflammatory, and neuroprotective effects, and it is investigated as a candidate agent in models of neurodegenerative and cognitive disorders.

HER-096

HER-096 is a brain-penetrating peptidomimetic derived from human CDNF (cerebral dopamine neurotrophic factor), developed by Herantis Pharma as a candidate disease-modifying therapy for Parkinson's. It mimics CDNF's cytoprotective biology in a small, stable molecule; it eases endoplasmic-reticulum stress by modulating the unfolded protein response, protects dopaminergic neurons, reduces alpha-synuclein aggregation, and calms neuroinflammation. Unlike the full CDNF protein, which had to be infused directly into the brain, HER-096 reaches the brain after a simple subcutaneous injection.

Hericene A

Hericene A is a hydrophobic hericerin-derived isoindoline compound from Hericium erinaceus that activates a pan-neurotrophic signaling pathway distinct from the classic NGF mechanism. In cultured hippocampal neurons it and its precursor N-de-phenylethyl isohericerin promoted extensive axon outgrowth and neurite branching even without serum, acting partly through a TrkB-independent route that converges on ERK1/2. Mice fed Hericium extract and hericene A showed increased neurotrophin signaling and significantly enhanced hippocampal memory, making hericene A a standout modern discovery in Lion's Mane neurobiology.

Hericenone C

Hericenone C is an aromatic fatty-acid ester isolated from the fruiting body of Hericium erinaceus and one of the classic small-molecule inducers of nerve growth factor synthesis identified from Lion's Mane. Together with hericenones D and E it helped establish the scientific basis for the mushroom's traditional reputation as a nerve tonic. Unlike the mycelial erinacines, hericenones are relatively large and lipophilic and are thought to act largely peripherally rather than crossing the blood brain barrier efficiently.

Hericenone D

Hericenone D is an aromatic fatty-acid ester from the fruiting body of Hericium erinaceus, one of the original nerve growth factor-inducing hericenones described from Lion's Mane. It is closely related to hericenones C and E and contributes to the neurotrophic activity attributed to fruiting-body extracts. Like its congeners it is considered to act predominantly in the peripheral nervous system rather than crossing the blood brain barrier.

JNJ-40411813

JNJ-40411813 (also known as ADX71149) is an orally active positive allosteric modulator of the mGlu2 receptor, developed jointly by Janssen and Addex Therapeutics as a potential treatment for schizophrenia and mood disorders. Unlike full agonists such as pomaglumetad, it enhances the receptor's response to endogenous glutamate only where and when glutamate is released, an approach intended to preserve physiological signalling patterns. It reached phase 2 testing for schizophrenia and for anxious depression, showing an acceptable safety profile and secondary-endpoint signals despite missing primary endpoints. The compound is a leading example of the shift from mGlu2/3 agonism to subtype-selective allosteric modulation.

Ketamine

Ketamine is a dissociative anesthetic that turned into the most important antidepressant discovery in fifty years. It blocks the NMDA glutamate receptor, which is what produces anesthesia without suppressing breathing and made it a battlefield and emergency drug from 1970 onward [1]. The finding that matters now came around the turn of the century: a single sub-anesthetic dose can lift severe, treatment-resistant depression within hours rather than weeks, an effect no monoamine antidepressant produces [3][4]. Its S-enantiomer, esketamine, is approved for that use as a nasal spray. Cognition is the more nuanced half of the story; repeated supervised infusions have not been shown to impair it and several measures improve as depression lifts, while heavy unsupervised use is reliably associated with memory problems [28][30]. It remains a controlled substance with real dependence and bladder toxicity risk outside clinical use.

LY341495

LY341495 is a potent and selective orthosteric antagonist of group II metabotropic glutamate receptors (mGlu2 and mGlu3) developed by Eli Lilly, widely used as the standard pharmacological tool for blocking these receptors. By preventing autoreceptor-mediated suppression of glutamate release, it enhances excitatory transmission and produces rapid antidepressant-like effects in animal models, mechanistically overlapping with ketamine. It has become a key probe for research into fast-acting antidepressants and stress resilience. LY341495 is significant as the reference mGlu2/3 antagonist against which newer compounds are compared.

LY379268

LY379268 is a highly potent and selective orthosteric agonist of group II metabotropic glutamate receptors (mGlu2 and mGlu3) developed by Eli Lilly as a research tool and neurotherapeutic candidate. It became one of the most influential probes for studying how presynaptic glutamate autoreceptors regulate addiction, neuroprotection and excitatory signalling. In animal models it robustly suppresses drug-seeking and cue-induced relapse for cocaine, nicotine and other substances, and it protects neurons against excitotoxic and demyelinating insults. Although never developed as a marketed drug, LY379268 remains a cornerstone compound in metabotropic glutamate neuroscience.

M617

M617 is a synthetic chimeric galanin analog that acts as a galanin receptor 1 preferring agonist and is used as a subtype-selective research tool. Built from the galanin N-terminus fused to a bradykinin-derived segment, it engages GalR1 to produce antinociception in central pain circuits and to improve glucose handling in diabetic rodents by enhancing insulin signaling and glucose-transporter activity in muscle. As one of the more GalR1-selective agonists available, M617 has been valuable for isolating GalR1-specific functions in pain and metabolism. It is a preclinical peptide with no clinical use.

Mavoglurant

Mavoglurant (developmental code AFQ056) is an orally active, selective negative allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGlu5). It was advanced by Novartis primarily for levodopa-induced dyskinesia in Parkinson's disease and for fragile X syndrome, where excess mGlu5 signalling is implicated in synaptic pathology. Randomized trials demonstrated a measurable anti-dyskinetic signal in Parkinson's disease without worsening motor control, but pivotal fragile X and language-learning studies failed to separate from placebo. It remains an important pharmacological probe of group I metabotropic glutamate signalling and a case study in the difficulty of translating mGlu5 blockade into clinical benefit.

Immunomodulator

MCC950

MCC950 is a potent, highly selective small-molecule inhibitor of the NLRP3 inflammasome that blocks canonical and noncanonical NLRP3 activation at nanomolar concentrations, reducing interleukin-1 beta and interleukin-18 release. Originally discovered at Pfizer as CP-456773 (CRID3), it is one of the most widely used research tools for probing NLRP3 biology but remains preclinical and is not approved for human use.

Mibampator

Mibampator (LY451395) is a biarylpropylsulfonamide positive allosteric modulator of AMPA receptors developed by Eli Lilly as a cognition- and behavior-focused clinical candidate. It slows AMPA-receptor deactivation, with an efficacy strongly shaped by the auxiliary TARP proteins associated with the receptor. It reached a randomized controlled trial for agitation and aggression in Alzheimer's disease, where it did not separate from placebo on the primary outcome but showed a signal on a secondary frontal-behavior measure. It is an instructive example of a clinically tested AMPA potentiator.

NAX 810-2

NAX 810-2 is a second-generation galanin analog engineered to prefer galanin receptor 2 over receptor 1, developed to preserve the anticonvulsant and analgesic benefits of galanin signaling while avoiding the hyperglycemia caused by GalR1-preferring predecessors. It has roughly fifteen-fold selectivity for GalR2, blocks seizures in multiple rodent models after intravenous dosing, and is analgesic across inflammatory and neuropathic pain assays. Crucially, it does not impair insulin secretion or raise growth hormone, giving it a cleaner metabolic profile than NAX-5055. It was framed as a first-in-class analgesic and antiseizure candidate.

NAX-5055

NAX-5055, also known as Gal-B2, is a systemically active, metabolically stable galanin analog engineered to cross the blood-brain barrier by combining cationization with position-specific lipidization. It is a GalR1-preferring agonist with low-nanomolar receptor affinity and potent anticonvulsant activity in multiple rodent seizure models, including models of pharmacoresistant epilepsy. It was positioned as a potential first-in-class antiepileptic neuropeptide therapeutic. NAX-5055 also engages peripheral GalR1 to raise blood glucose, which shaped subsequent development toward GalR2-preferring successors.

Neurotrophin-3

Neurotrophin-3 (NT-3) is a naturally occurring protein belonging to the neurotrophin family, which also includes nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). It supports the survival, growth, and differentiation of developing neurons and helps maintain certain nerve cells in the mature nervous system. Because of these roles, recombinant NT-3 has been investigated as a therapy for nerve and gastrointestinal disorders, although it is not an approved or consumer product.

P7C3

P7C3 is an investigational neuroprotective compound of the aminopropyl carbazole class, studied only in laboratory and animal research. It is proposed to work by boosting cellular NAD+ through activation of the enzyme NAMPT, which helps preserve the survival of newly formed and stressed neurons. In animal models it has shown protective effects in conditions such as stroke, traumatic brain injury, and neurodegeneration, but it is not an approved medicine.

PACAP

PACAP, short for pituitary adenylate cyclase-activating polypeptide, is a naturally occurring neuropeptide that acts as a hormone, neurotransmitter, and neuromodulator. Encoded by the ADCYAP1 gene and closely related to vasoactive intestinal peptide, it signals through G protein-coupled receptors to raise cellular cAMP and takes part in the stress response, circadian timing, and neuroprotection. It has become a prominent target in migraine research, since infusing PACAP can trigger migraine-like attacks in susceptible people.

PF-04995274

PF-04995274 is a selective, brain-penetrant 5-HT4 receptor partial agonist originally developed by Pfizer that has become the leading clinical probe for pro-cognitive and antidepressant effects of central 5-HT4 activation in humans. It advanced into experimental medicine studies in major depressive disorder, where short courses altered emotional and memory-related brain circuitry in ways distinct from a conventional selective serotonin reuptake inhibitor. In the RESTAND programme it increased hippocampal and parietal activity during memory encoding and produced early signals of mood improvement without the classic negative-bias shift seen with citalopram. It remains an investigational compound and is not approved for any indication.

Pomaglumetad methionil

Pomaglumetad methionil (developmental code LY2140023) is the methionine amide prodrug of LY404039, a selective orthosteric agonist of group II metabotropic glutamate receptors (mGlu2 and mGlu3). Developed by Eli Lilly, it represented a bold attempt to treat schizophrenia by normalizing glutamate rather than blocking dopamine. An early phase 2 trial reported antipsychotic efficacy comparable to olanzapine without the weight gain, prolactin elevation or extrapyramidal effects of dopamine antagonists, but larger confirmatory trials failed to replicate the benefit. Pomaglumetad is a landmark case study in glutamatergic antipsychotic development and the challenges of reproducing early proof-of-concept results.

Psilocin

Psilocin (4-hydroxy-N,N-dimethyltryptamine) is the active tryptamine responsible for the effects of psilocybin mushrooms, formed in the body when psilocybin is dephosphorylated after ingestion. Structurally a close relative of serotonin, it acts as an agonist or partial agonist at serotonin 5-HT2A receptors, the defining target of the classic psychedelics, with additional activity at 5-HT2C and 5-HT1A subtypes. Its lipophilicity lets it cross the blood-brain barrier readily and reach the brain within minutes, producing a psychedelic experience lasting several hours. Beyond acute receptor signaling, psilocin promotes markers of neuronal plasticity, and a compelling recent finding is that lipophilic psychedelics like psilocin can reach intracellular 5-HT2A receptors that serotonin itself cannot access, a mechanism proposed to underlie their durable therapeutic effects. It is the molecule that ultimately mediates psilocybin's clinical antidepressant activity.

Rapastinel

Rapastinel (originally GLYX-13) is a tiny four-amino-acid peptide (Thr-Pro-Pro-Thr with an amidated tail) that acts as a functional partial agonist at the glycine site of the NMDA receptor. It was the lead candidate in the wave of rapid-acting antidepressants inspired by ketamine, meant to lift mood within a day without ketamine's dissociation; it looked promising through phase 2 but failed its phase 3 depression trials in 2019.

RS-67333

RS-67333 is a selective, high-affinity partial agonist of the serotonin 5-HT4 receptor that has become the reference pharmacological tool for probing the pro-cognitive and disease-modifying potential of 5-HT4 activation in the central nervous system. Unlike the marketed gastrointestinal 5-HT4 agonists, RS-67333 crosses the blood-brain barrier readily and has been studied almost exclusively in preclinical models of learning, memory, and Alzheimer's disease. Its signature finding is that chronic 5-HT4 stimulation shifts amyloid precursor protein processing toward the non-amyloidogenic alpha-secretase pathway, increasing release of the neurotrophic sAPPalpha fragment while lowering amyloid-beta. RS-67333 is an investigational research compound with no human clinical development and no approved use.

Sapunifiram

Sapunifiram (MN-19) is an investigational piperidine cognition-enhancer developed by the medicinal chemistry group at the University of Florence as a close structural relative of sunifiram (DM235). Like its parent scaffold, it produces potent antiamnesic and procognitive effects in rodent avoidance paradigms at very low doses, with reported potency exceeding that of piracetam. It is best understood as an ampakine-like glutamatergic and cholinergic facilitator rather than a classical racetam, and it has never advanced beyond preclinical characterization. It remains a purely research-grade compound of interest to structure-activity chemists and the nootropic community.

SL65.0155

SL65.0155 is a selective 5-HT4 receptor partial agonist developed as a cognition-enhancing candidate, notable for producing robust improvements in learning, memory, and attention in rodents at very low doses. It reversed associative learning deficits after hippocampal damage and enhanced attentional performance comparable to nicotine in the five-choice serial reaction time task. Alongside RS-67333, it is one of the classic experimental 5-HT4 agonists used to establish the receptor as a pro-cognitive and potential anti-dementia target. SL65.0155 is an investigational research compound without approved use.

Souvenaid

Souvenaid is a medical food, taken as a once-daily nutritional drink, that is intended to support the formation of synapses in people with early Alzheimer's disease. It contains a patented mixture of nutrients called Fortasyn Connect, combining omega-3 fatty acids, uridine monophosphate, choline, phospholipids, and several vitamins. Clinical trials have produced mixed results, and systematic reviews have found little convincing effect on cognitive decline, although the product is generally well tolerated.

Tau Peptide

Tau peptide is a loosely used name for short peptide preparations marketed for brain and cognitive support, usually grouped with so-called bioregulator peptides. The label is not well standardized, and the sequences sold under it vary between vendors, so the name says little about the precise contents of a given product. Any connection to tau, the microtubule-associated protein of the nervous system, is largely nominal, and rigorous human data are scarce.

Tremella

Tremella fuciformis, commonly called snow fungus or silver ear, is a gelatinous white jelly fungus in the family Tremellaceae, valued as both a food and a traditional remedy in East Asia [1]. It is cultivated widely and used in Chinese and other Asian cuisines, typically in sweet dessert soups, and it is studied for bioactive polysaccharides linked to effects on skin hydration, immunity, and cognition [2][3]. As a food-derived fungus, it is generally treated as a culinary or supplemental ingredient rather than a drug.

TRH

Thyrotropin-releasing hormone (TRH), whose pharmaceutical form is called protirelin, is a small peptide hormone made by neurons of the hypothalamus. Its best-known role is to signal the pituitary gland to release thyroid-stimulating hormone and prolactin, placing it at the top of the hormonal axis that controls the thyroid. TRH and its more stable analogues have also been studied for effects on mood, alertness, and the nervous system.

Trofinetide

Trofinetide is a synthetic analog of the neuroprotective tripeptide glycine-proline-glutamate, the N-terminal fragment of insulin like growth factor 1, and is the first FDA approved treatment for Rett syndrome. It is thought to improve neuronal morphology and synaptic function and reduce neuroinflammation.

Usmarapride

Usmarapride is an experimental small-molecule drug that acts as a selective partial agonist of the serotonin 5-HT4 receptor. Developed by Suven Life Sciences under the code SUVN-D4010, it has been studied as a candidate treatment for the cognitive symptoms of Alzheimer's disease and schizophrenia. As of the mid-2020s it had advanced to early-phase clinical testing and is not an approved medicine.

Vitamin B9 (Folate)

Folate, or vitamin B9, is a water-soluble vitamin that acts as a coenzyme in one-carbon metabolism, supplying the single-carbon units needed for DNA synthesis and for converting homocysteine to methionine. Folic acid is the stable synthetic form used in supplements and food fortification, while natural folates occur in leafy greens, legumes, and liver. A deficiency causes megaloblastic anemia, and a shortage around the time of conception raises the risk of neural tube defects such as spina bifida, which is why many countries fortify staple grains with folic acid.

Neotrofin

Neotrofin is the brand name for leteprinim potassium (development code AIT-082), a small purine derivative of hypoxanthine that was investigated as a neurotrophic and memory-enhancing agent. Developed by the company NeoTherapeutics, it works indirectly by prompting the brain to make more of its own neurotrophic factors, such as nerve growth factor. It was tested in Alzheimer's disease but the program was discontinued after only modest results, and it never reached approval.

LSD

LSD (lysergic acid diethylamide) is a semisynthetic ergoline psychedelic and one of the most potent hallucinogens known, with active oral doses on the order of tens to a few hundred micrograms. Its effects are mediated chiefly through agonism at the serotonin 5-HT2A receptor; a landmark crystal structure showed that the diethylamide moiety is capped by an extracellular-loop "lid" that traps the molecule in the binding pocket, explaining LSD's unusually slow receptor dissociation and correspondingly long duration of action. Human neuroimaging links the drug to altered effective connectivity within cortico-striato-thalamo-cortical circuits and to a serotonin-2A-dependent loosening of sensory gating, while controlled trials document acute changes in emotional processing, empathy, and self-referential experience that scale with plasma concentration and set and setting. First synthesized by Albert Hofmann at Sandoz in 1938 and central to twentieth-century counterculture, LSD is a controlled substance in most countries and is again under investigation as a potential adjunct to psychotherapy, including for anxiety associated with life-threatening illness.