Mood

Nemifitide

Nemifitide (originally coded INN 00835, and briefly called netamiftide) is a synthetic pentapeptide that was developed as an injectable antidepressant. Its sequence is 4-fluoro-L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-arginyl-glycyl-L-tryptophanamide, and it is a structural analog of MIF-1 (melanocyte-inhibiting factor-1, the tripeptide Pro-Leu-Gly-NH2). It was studied by Innapharma, later Tetragenex Pharmaceuticals, and reached Phase II trials in major depressive disorder before development stalled; it was never approved. The interesting thing about it is the mismatch between its pharmacokinetics and its effect: the peptide clears the blood in well under an hour, yet the antidepressant response reported in trials came on within days and lasted weeks to months after a short dosing course. It was given as a subcutaneous injection, not a pill, and its tolerability was consistently good with side effects limited mostly to the injection site.

Phenylalanine

Phenylalanine is an essential amino acid and the first step in making dopamine and noradrenaline: the body converts it to tyrosine, tyrosine to L-DOPA, and L-DOPA to dopamine. That chain is the entire basis for taking it, and it is also the reason to be measured about it, because supplying more of the first ingredient does not reliably speed up a pathway that is regulated further downstream. The best-supported use is not mood at all; L-phenylalanine combined with light therapy has a real if modest evidence base in vitiligo [9][10]. The critical safety fact is short and absolute: anyone with phenylketonuria must not take it [7].

Pregnenolone

Pregnenolone (3β-hydroxypregn-5-en-20-one) is an endogenous neurosteroid and the first steroid synthesized from cholesterol, making it the obligatory precursor of every other steroid hormone, including progesterone, dehydroepiandrosterone (DHEA), cortisol, the sex steroids, and the neuroactive metabolites allopregnanolone and pregnenolone sulfate. Once regarded as a metabolically inert intermediate, it is now recognized as a signaling molecule in its own right, most notably as an endogenous negative allosteric modulator of the type-1 cannabinoid receptor (CB1, the principal brain receptor for THC) and as a ligand for microtubule-associated protein 2 (MAP2, a neuronal cytoskeletal scaffolding protein), through which it promotes microtubule assembly and neurite outgrowth. Synthesized de novo in the brain by neurons and glia, it is investigated as an adjunctive treatment for schizophrenia, mood disorders, and cannabis-related conditions, and is sold over the counter as a nootropic and hormonal supplement.

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Taltirelin

Taltirelin (TA-0910, brand name Ceredist) is a synthetic, metabolically stable analog of thyrotropin-releasing hormone (TRH), the three-residue hypothalamic peptide. It was developed by Tanabe Seiyaku and approved in Japan in 2000 for spinocerebellar degeneration, where it is taken orally to help with ataxia and related symptoms. The interesting thing about taltirelin is that it was engineered to keep the central nervous system effects of TRH while shedding most of the hormonal ones; it is roughly 10 to 100 times more potent than native TRH at driving CNS arousal, yet its effect on thyroid hormone release is much weaker. It also lasts far longer in the body because it resists the enzymes that chew up natural TRH within minutes. Outside its approved use it gets discussed in nootropic and biohacker circles as a wakefulness-promoting, pro-cholinergic "analeptic" and neuroprotective agent, and there is a real preclinical literature behind those claims (Parkinson's models, ischemia, pain, respiratory stimulation). Human data outside spinocerebellar degeneration is thin, so most of what you read about it as a cognitive enhancer is extrapolation from animal work.

Tropisetron

Tropisetron is a prescription anti-nausea drug that blocks the serotonin 5-HT3 receptor, and it is used to stop the vomiting caused by chemotherapy or by surgery; it has been sold for that purpose since 1992 in Europe, Japan, Australia and much of Asia, but it was never approved in the United States. What sets it apart from the other drugs in its class is that it also binds tightly to a brain receptor called the alpha-7 nicotinic acetylcholine receptor, which is why researchers have tested it for fibromyalgia pain, for thinking problems in schizophrenia, and in animal models of Alzheimer's and Huntington's disease. The anti-nausea use is solidly established; every other use rests on small short trials, mostly fewer than 45 people and under two weeks long, or on animal work, and no regulator anywhere has approved it for any of them. Anyone reading the older literature should also know that a large slice of the post-surgical anti-nausea evidence base was fabricated and later retracted, so individual old trials in that area carry very little weight on their own.

Peptide

GB-115

GB-115 is a cleverly designed dipeptide anxiolytic that eases anxiety while keeping the mind clear, a combination almost nothing else in its category manages. Rather than sedating, it blocks the cholecystokinin CCK-1 receptor, a pathway tied specifically to chronic anxiety and panic, and in a clinical study of generalized anxiety disorder it actually sharpened attention and reaction time while it worked. For those seeking calm without the fog, weakness, or dependence of classic sedatives, GB-115 is a genuinely intriguing research anxiolytic.

5-HTP

5-HTP (5-hydroxytryptophan), also known by the international nonproprietary name oxitriptan, is a naturally occurring amino acid and a direct metabolic precursor in the biosynthesis of the neurotransmitter serotonin. Formed in the body from the amino acid tryptophan and then converted onward to serotonin, it is sold widely as an over-the-counter dietary supplement and has also been used medicinally in the management of depression and several other conditions.

7,8-DHF

7,8-Dihydroxyflavone (7,8-DHF), also called tropoflavin, is a naturally occurring flavone studied as a small-molecule mimic of brain-derived neurotrophic factor (BDNF). It is reported to act as an agonist of tropomyosin receptor kinase B (TrkB), the principal BDNF receptor, binding the receptor's extracellular domain to drive its dimerization and activation, and because it is orally active and crosses the blood-brain barrier it has become a widely used tool compound in neuroscience. Its direct activation of TrkB is not fully settled, however, since some quantitative assays have been unable to reproduce it, and it remains an experimental compound studied in models of depression, Alzheimer's, and other neurological conditions.

Apigenin

Apigenin is a naturally occurring flavone, a subclass of flavonoid plant pigment, found in many fruits, vegetables, and herbs, with especially high levels in chamomile, parsley, and celery. It is a yellow crystalline compound studied for antioxidant, anti-inflammatory, and mild calming effects, the last linked to its interaction with receptors in the brain. Apigenin is consumed as part of a normal diet and is also sold as a dietary supplement.

Ashwagandha

Ashwagandha is an adaptogenic herb prepared from the root of Withania somnifera, a small evergreen shrub in the nightshade family (Solanaceae) native to parts of Africa, the Middle East, and the Indian subcontinent. It has been used for centuries in Ayurveda, India's traditional system of medicine, as a rejuvenating tonic. Its main active constituents are steroidal lactones known as withanolides, and it is among the better-studied herbal supplements, with clinical research centering on stress, anxiety, and sleep.

Cacao Powder

Cacao powder is the ground, mostly de-fatted solids of the roasted Theobroma cacao bean. Its active fraction is a group of flavanols (flavan-3-ols), chiefly (-)-epicatechin and catechin plus procyanidins, alongside the methylxanthine theobromine and a little caffeine. The flavanols drive nitric-oxide-dependent vasodilation, which is the best-supported reason people take it: lower blood pressure, better endothelial function, and modestly improved blood flow to the brain. Natural (non-alkalized) cacao keeps far more of these flavanols than Dutch-processed cocoa.

Chromium Picolinate

Chromium picolinate is a coordination compound of trivalent chromium and picolinic acid that is sold as a dietary supplement. It is promoted mainly for blood sugar control, body composition, and weight management, on the premise that chromium supports the action of insulin. Systematic reviews of clinical trials have generally found the supporting evidence weak and inconsistent, and no chromium deficiency state is recognized in otherwise healthy people.

DHEA

Dehydroepiandrosterone (DHEA) is an endogenous androstane neurosteroid and the most abundant circulating steroid hormone in humans, secreted chiefly by the adrenal cortex and also synthesized de novo within the central nervous system. It functions primarily as a precursor to androgens and estrogens, yet exerts direct actions on the brain by acting as an agonist at the sigma-1 receptor (an endoplasmic reticulum chaperone protein that shapes calcium and neurotrophic signaling), as a positive modulator of NMDA receptor (the principal excitatory glutamate ion channel involved in learning) signaling, and, chiefly as its sulfate ester DHEAS, as a negative allosteric modulator of the GABA-A receptor (the brain's main inhibitory ion channel). DHEA additionally behaves as a functional anti-glucocorticoid, buffering the neurotoxic effects of cortisol, and shows neuroprotective and mood-related activity in preclinical and clinical studies. Circulating concentrations peak in early adulthood and decline markedly with age, a phenomenon termed adrenopause that has driven its widespread use as an over-the-counter supplement.

EPA

Eicosapentaenoic acid (EPA) is a long-chain omega-3 polyunsaturated fatty acid, designated 20:5(n-3), found mainly in oily fish, fish oil, and certain microalgae. It is incorporated into cell membranes and serves as a precursor to signaling molecules that regulate inflammation, blood clotting, and immune function. A highly purified prescription form has been shown to lower cardiovascular risk in people with elevated triglycerides.

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.

Hopantenic Acid

Hopantenic acid, best known by the Russian brand Pantogam and as its calcium salt calcium hopantenate, is a naturally occurring homologue of pantothenic acid in which the beta-alanine unit is replaced by GABA [1]. It is used in Russia and formerly in Japan as a gentle nootropic and mild anxiolytic-anticonvulsant, particularly in children with cognitive, behavioral and hyperkinetic problems [1][2]. Its effects are attributed to weak GABA-B-like modulation combined with support of neuronal metabolism, and the bulk of its clinical evidence is Russian rather than from large Western trials [1].

Kava

Kava is a beverage and herbal medicine prepared from the root of Piper methysticum, a shrub in the pepper family native to the islands of the Pacific. For centuries it has been consumed ceremonially and socially across Oceania for its calming, mildly intoxicating effects, and it is used more widely as a remedy for anxiety and tension [1][2]. Its activity comes from a group of compounds called kavalactones, and its safety, particularly concerning the liver, has been the subject of regulatory debate [3][4].

Lemon Balm

Lemon balm, known botanically as Melissa officinalis, is a lemon-scented perennial herb in the mint family, Lamiaceae. Native to the eastern Mediterranean and western Asia, it has been grown for over two thousand years and used traditionally to ease tension, lift mood, and aid digestion and sleep. Its leaves are rich in the polyphenol rosmarinic acid and in fragrant terpenes such as citronellal, geranial, and neral. Modern controlled studies have examined it for anxiety, mood, cognition, sleep, and palpitations, with its calming effect attributed largely to rosmarinic acid inhibiting GABA transaminase and to extract binding at cholinergic receptors.

Lithium Orotate

Lithium orotate is a salt of lithium and orotic acid sold as a low-dose dietary supplement. It provides much less elemental lithium per tablet than the lithium carbonate used as a prescription mood stabilizer, and it is marketed for mood and general wellbeing. It is not approved as a medicine, and rigorous human evidence for its benefits is lacking.

Maca

Maca (Lepidium meyenii) is an edible plant of the mustard family, Brassicaceae, native to the high Andes of Peru. Its starchy root, or hypocotyl, has been eaten and used as a traditional remedy for centuries and is now sold worldwide as a powder or extract. It is best known for claims around libido, sexual function, and energy, although the clinical evidence is modest and mixed.

Magnesium Glycinate

Magnesium glycinate, also called magnesium bisglycinate or magnesium diglycinate, is a chelated compound in which the mineral magnesium is bound to two molecules of the amino acid glycine. It is used as a dietary supplement to raise or maintain magnesium status and is often chosen for being gentle on the digestive tract relative to some other magnesium salts [1][3]. Because it is a chelate, part of the compound appears to be absorbed as an intact magnesium-amino acid complex rather than solely as free magnesium ions [1].

Magnesium Orotate

Magnesium orotate is a salt formed from magnesium and orotic acid, sold as a dietary supplement and, in some countries, as a medicinal product for magnesium deficiency and certain heart-related conditions. It is only sparingly soluble in water, so unlike readily dissociating magnesium salts it produces little laxative effect [1]. Interest in the compound centers on the pairing of magnesium with orotic acid, a pyrimidine precursor proposed to support the energy metabolism of heart muscle [1].

Magnolia Bark

Magnolia bark is a herbal material obtained from the bark of Magnolia officinalis and related magnolia species, long used in traditional Chinese and Japanese medicine, where it is known as houpu or hou po. Its characteristic constituents are the polyphenolic lignans magnolol and honokiol, which are considered responsible for most of its biological activity [1][2]. Modern research has examined the bark and its isolated lignans for neuroprotective, anti-inflammatory, anti-anxiety, and antitumor properties, though most evidence comes from laboratory and animal studies rather than large human trials [1][2].

Dopaminergic

Mucuna Pruriens

Mucuna pruriens, commonly called velvet bean or cowhage, is a tropical climbing legume of the family Fabaceae whose seeds are a rich natural source of levodopa (L-DOPA), the precursor of the neurotransmitter dopamine. Long used in Ayurvedic medicine, its seed extracts are marketed as dietary supplements and have been studied as a plant-based option in Parkinson disease. The plant is also notorious for the fine hairs on its pods, which cause intense itching on contact with skin.

N-Acetyl L-Tyrosine (NALT)

N-Acetyl L-Tyrosine (NALT) is an acetylated, more water-soluble form of the amino acid L-tyrosine, originally introduced as a tyrosine source for intravenous nutrition. It is widely marketed as a nootropic on the premise that tyrosine is the precursor of the catecholamine neurotransmitters dopamine and norepinephrine. However, human and animal studies indicate that N-Acetyl L-Tyrosine is converted to free tyrosine inefficiently, with much of an infused dose excreted unchanged in the urine.

Passionflower

Passionflower usually refers to Passiflora incarnata, a climbing vine native to the southeastern United States and long used in herbal medicine. Its above-ground parts are taken, typically as teas, extracts, or tinctures, to ease anxiety and support sleep. It is thought to act on the brain's GABA system, and while some clinical studies suggest calming and sleep benefits, the overall evidence remains limited.

Pyridoxal-5-Phosphate

Pyridoxal-5-phosphate, often abbreviated PLP or P5P, is the biologically active coenzyme form of vitamin B6. It serves as an essential helper molecule for well over a hundred different enzymes, most of them involved in the metabolism of amino acids and the manufacture of neurotransmitters. The body makes PLP from the various dietary forms of vitamin B6, and it is also sold directly as a supplement marketed as a ready-to-use form of the vitamin.

Rhodiola Rosea

Rhodiola rosea, commonly called golden root or roseroot, is a perennial flowering plant of the family Crassulaceae that grows in cold, high-altitude and Arctic regions. Its root has a long history of use in the traditional medicine of northern Europe and Asia, and it is popularly classed as an adaptogen, an herb said to help the body resist stress and fatigue. Its most characteristic studied constituents are the phenolic compounds rosavin and salidroside, though high-quality clinical evidence for its benefits is limited.

Saffron

Saffron is a spice obtained from the dried red stigmas of the flower Crocus sativus, and it is among the most expensive spices in the world by weight. Beyond its long use in cooking as a coloring and flavoring, it has been investigated as a herbal remedy, most notably for depression and low mood. Its characteristic color, taste, and aroma come from the compounds crocin, picrocrocin, and safranal.

SAM-e

SAM-e is a molecule the body already makes from the amino acid methionine; it is the chemical the body uses to hand a methyl group to hundreds of enzymes, which is how it reaches DNA, brain chemicals such as dopamine, and liver metabolism. It is sold as a dietary supplement in the United States and as a prescription drug called ademetionine in Italy, Germany and Russia, mostly for depression, joint pain and liver problems. The evidence is real but genuinely mixed; the Cochrane review of eight trials found the quality too low to draw a conclusion, the largest United States trial found SAM-e no better than placebo, and two separate 2024 meta-analyses of much the same studies reached opposite answers. It is usually well tolerated apart from stomach upset, but it can trigger mania in people with bipolar disorder and should not be combined casually with antidepressants.

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Stimulant

Theobromine

Theobromine is a bitter methylxanthine alkaloid and the principal stimulant compound of the cacao plant (Theobroma cacao), giving chocolate and cocoa much of their mild pharmacological activity. Chemically it is 3,7-dimethylxanthine, an isomer of theophylline and a close relative of caffeine, and it also forms in the human body as a major breakdown product of caffeine [1][3]. It has gentle effects on the heart, blood vessels, airways, and kidneys, and unlike caffeine produces little central-nervous-system stimulation; it is well tolerated in people but is toxic to dogs and some other animals [1].

TMG

TMG (trimethylglycine, sold as betaine anhydrous) is a methyl donor; a small molecule that carries three methyl groups (CH3 chemical tags) it can hand off to other molecules. It comes originally from beets, and its headline job in the body is recycling homocysteine (an amino acid that damages blood vessels when it builds up too high) back into methionine, using an enzyme called BHMT (betaine-homocysteine methyltransferase). By feeding that reaction, TMG lowers homocysteine and supports the whole methylation system, which touches everything from DNA maintenance to neurotransmitter and mood chemistry. People take it for three main reasons: reliably lowering homocysteine, supporting liver health in fatty liver (NAFLD), and squeezing out a bit more strength and power in training. One point of confusion worth clearing up: TMG is chemically the exact same molecule as betaine, but it is NOT the same product as Betaine HCl; Betaine HCl is the hydrochloride salt people use to add stomach acid for digestion, while TMG/anhydrous betaine is the plain methylation form. Same core molecule, very different job.

Tongkat Ali

Tongkat ali is the common name for Eurycoma longifolia, a flowering shrub of the family Simaroubaceae native to Southeast Asia, whose roots are used in traditional medicine and sold as a dietary supplement [1]. It is widely marketed for claims about testosterone, male fertility, libido, and physical performance, though the supporting clinical evidence is mixed and largely preliminary [1][3]. The plant contains a range of bioactive compounds known as quassinoids, including eurycomanone.

Mood Support

Tryptophan

Tryptophan is an essential, proteinogenic alpha-amino acid used to build proteins and to make several important molecules, including the neurotransmitter serotonin, the sleep hormone melatonin and the vitamin niacin. Because humans cannot synthesise it, it must be obtained from the diet, where it occurs in foods such as meat, fish, eggs, dairy, seeds and legumes. The naturally occurring L-form is also sold as a dietary supplement marketed for mood and sleep, though clinical evidence for those uses is limited [3].

Turmeric (Curcumin)

Curcumin is a bright yellow polyphenol, the principal curcuminoid of turmeric, the spice ground from the rhizome of Curcuma longa in the ginger family. It has long been used as a food colouring and flavouring and is widely sold as a herbal supplement, but it is chemically unstable and very poorly absorbed by mouth. In medicinal chemistry it is regarded as a difficult, likely misleading lead compound, and despite extensive study no rigorous clinical trial has established it as an effective medical treatment [1][2].

Sleep Support

Valerian Root

Valerian is an herbal supplement prepared from the root and rhizome of Valeriana officinalis, a flowering plant native to Europe and Asia. It has a long history of traditional use as a sleep aid and mild sedative and remains one of the more widely used botanicals for insomnia and nervous tension. Clinical evidence for its effectiveness is mixed, and it is sold as a dietary supplement or, in some regions, as an approved traditional herbal medicine.

Vitamin B Complex

Vitamin B complex is a collective term for the group of eight water-soluble B vitamins that act as coenzymes or coenzyme precursors throughout cellular metabolism. The group comprises thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9), and cobalamin (B12), each chemically distinct yet metabolically interrelated. Supplement products that combine all eight are marketed as vitamin B complex, and the vitamins occur together in foods such as meat, eggs, dairy, legumes, and whole grains.

Vitamin B6 (Pyridoxine)

Vitamin B6 is a water-soluble essential nutrient that exists as several interconvertible forms; pyridoxine is the stable form used in most supplements and food fortification. In the body it is converted to pyridoxal-5-phosphate (PLP), the active coenzyme that drives well over a hundred distinct enzyme reactions, most of them in amino acid metabolism and in the synthesis of neurotransmitters such as serotonin, dopamine, and GABA. Because of that reach it is tied to mood, energy metabolism, and the clearing of homocysteine, and it is a first-line remedy for the nausea of early pregnancy and a popular one for premenstrual symptoms. It is cheap and generally safe, but chronic high doses are the one real catch, since they can cause a slowly reversible sensory nerve injury.

Vitamin B8 (Inositol)

Inositol is a naturally occurring sugar alcohol, most abundant as the isomer myo-inositol, that serves as a building block for cell membrane phospholipids and for intracellular signaling molecules. It was once grouped with the B vitamins as vitamin B8, but because the human body synthesizes it, inositol is not considered a true vitamin or an essential nutrient. It occurs in foods such as fruits, beans, grains, and nuts, and myo-inositol together with its isomer D-chiro-inositol has been studied for use in polycystic ovary syndrome and related metabolic conditions.

Vitamin D3

Vitamin D3 (cholecalciferol) is a fat-soluble secosteroid synthesized in the skin under ultraviolet B light and obtained from a few foods, becoming biologically active only after sequential hydroxylation in the liver and kidney to calcitriol (1,25-dihydroxyvitamin D). Beyond its classical control of calcium absorption and bone mineralization, calcitriol acts through the nuclear vitamin D receptor to regulate hundreds of target genes and to epigenetically program monocytes, macrophages and dendritic cells; immune cells can generate the active hormone locally to induce antimicrobial peptides such as cathelicidin and to trigger autophagy against intracellular pathogens including Mycobacterium tuberculosis. In the large VITAL randomized trial, several years of supplementation modestly reduced the incidence of autoimmune disease and of advanced or fatal cancer, while showing largely neutral effects on major cardiovascular events. Prolonged deficiency causes rickets in children and osteomalacia in adults, and the vitamin appears on the World Health Organization list of essential medicines.

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Neurosteroid

Pregnanolone

Pregnanolone (3α-hydroxy-5β-pregnan-20-one, also written 3α,5β-tetrahydroprogesterone) is an endogenous neurosteroid, meaning a steroid that acts rapidly on neuronal ion channels rather than through classical intracellular hormone receptors, formed as a reduced metabolite of progesterone. It is the 5β epimer of allopregnanolone and a potent positive allosteric modulator of the GABA-A receptor (the pentameric chloride channel that carries most fast inhibitory signalling in the brain), giving it sedative, anxiolytic, anticonvulsant and anaesthetic properties. Under the International Nonproprietary Name eltanolone it was developed in the 1990s as an intravenous general anaesthetic, formulated in a soybean-oil emulsion after earlier castor-oil-solubilised steroid anaesthetics proved allergenic; smooth induction and cardiovascular stability were offset by slow recovery and skin reactions, and it was never marketed. Its sulfate and synthetic glutamate esters are studied separately as use-dependent inhibitors of the NMDA receptor, an excitatory glutamate channel implicated in excitotoxicity and neuroprotection.

Amitriptyline

Amitriptyline is a tricyclic antidepressant introduced in the early 1960s, originally for major depression and now used at least as often for chronic pain conditions. It relieves symptoms by increasing the availability of the neurotransmitters serotonin and norepinephrine, while also blocking histamine, acetylcholine, and adrenergic receptors, which accounts for both its sedating quality and many of its side effects [1]. Common uses today include neuropathic pain, fibromyalgia, and the prevention of migraine and tension headaches, in addition to depression [3][4].

Blend

Dextromethorphan + Bupropion

Dextromethorphan/bupropion is a fixed-dose combination medicine used to treat major depressive disorder in adults. Sold under the brand name Auvelity and developed by Axsome Therapeutics, it was approved by the United States Food and Drug Administration in 2022. The product pairs dextromethorphan, which blocks NMDA glutamate receptors and activates sigma-1 receptors, with bupropion, an established antidepressant that also slows the breakdown of dextromethorphan so that useful levels are maintained. It is taken as an extended-release oral tablet and is a prescription medicine that is not a controlled substance.

Duloxetine

Duloxetine is a balanced serotonin-norepinephrine reuptake inhibitor, marketed chiefly as Cymbalta since 2004, approved for major depression and generalized anxiety as well as several chronic pain conditions. Its analgesic action reflects potentiation of descending serotonergic and noradrenergic pathways that dampen pain signaling in the spinal cord, an effect largely separate from its antidepressant activity. Randomized trials support its use in diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain from osteoarthritis and low back pain, and it is the agent with the strongest randomized evidence recommended by oncology guidelines for chemotherapy-induced peripheral neuropathy. Through the same monoaminergic facilitation of pudendal motor neurons in Onuf's nucleus, duloxetine strengthens urethral sphincter tone and is used in some countries for stress urinary incontinence. It is a prescription-only medicine, available generically, and appears on the World Health Organization list of essential medicines.

Anticonvulsant

Lamotrigine

Lamotrigine is a prescription anticonvulsant of the phenyltriazine class that is also widely used as a mood stabilizer. In epilepsy it treats several seizure types, including focal and generalized seizures and those of Lennox-Gastaut syndrome, and in psychiatry it is approved for the long-term maintenance of bipolar I disorder, where it is aimed particularly at preventing depressive episodes. It works mainly by calming overexcited nerve cells, and it is included on the World Health Organization's list of essential medicines.

Hormone

Progesterone

Progesterone (P4; pregn-4-ene-3,20-dione) is an endogenous pregnane steroid hormone best known for its reproductive roles and is the prototypical neuroactive precursor within the neurosteroid system. Although the parent hormone signals principally through classical nuclear progesterone receptors and through membrane-associated receptors such as PGRMC1 and the mPR/PAQR family, most of its rapid effects on neuronal excitability arise only after sequential metabolism to 5-alpha-dihydroprogesterone and then to allopregnanolone, one of the most potent endogenous positive allosteric modulators of the GABA-A receptor (the brain's principal inhibitory chloride channel). Progesterone and its metabolites are synthesized within the nervous system itself, where they regulate myelination, neuronal survival, neuroinflammation, and inhibitory tone. It has been studied extensively as a neuroprotective agent, with strong preclinical support but negative large-scale human trials in acute traumatic brain injury.

Tianeptine

Tianeptine is an atypical antidepressant, chemically related to the tricyclic antidepressants, that has been used since the 1980s to treat major depressive disorder and anxiety, mainly in parts of Europe, Asia, and Latin America under brand names such as Stablon and Coaxil. Long thought to work by an unusual effect on serotonin, it was later shown to be an agonist at the mu-opioid receptor, with weaker action at the delta-opioid receptor, which is now regarded as central to its effects [1][2]. This opioid activity also underlies a growing problem of misuse; sold in some markets as an unapproved supplement and nicknamed gas station heroin, tianeptine can cause opioid-like euphoria, dependence, and withdrawal, and it is not approved as a medicine in the United States [1].

Venlafaxine

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) used for major depressive disorder and several anxiety disorders, and available in immediate-release and extended-release forms. It is distinguished by an ascending dose-response relationship: at low doses it behaves much like a selective serotonin reuptake inhibitor, while progressively higher doses recruit norepinephrine reuptake inhibition, which contributes both to added efficacy and to dose-dependent increases in blood pressure. Beyond monoamine transport, preclinical work implicates sigma-1 receptor modulation in its antidepressant action, and the drug is widely repurposed as an effective nonhormonal treatment for menopausal and cancer-therapy-related hot flashes. Network meta-analyses place it among the more efficacious antidepressants, although tolerability, cardiovascular effects in overdose, and a pronounced discontinuation syndrome temper its use.

ARB

Telmisartan

Telmisartan is an orally active angiotensin II receptor blocker (ARB) of the benzimidazole class, used mainly to treat high blood pressure and to lower cardiovascular risk by blocking the angiotensin II type 1 (AT1) receptor. Unusually for its class it also behaves as a partial agonist of the nuclear receptor PPAR-gamma, the same target as the diabetes glitazones, which underlies its interest in metabolic disease; it also has the longest plasma half-life and highest lipophilicity of the marketed ARBs, giving persistent blood-pressure control and central nervous system penetration that has prompted study of cognitive and neuroprotective effects. It is given once daily.