Serotonin

Selank

Selank is a synthetic peptide anxiolytic and nootropic derived from the immune peptide tuftsin, developed in Russia as a non-sedating, non-addictive alternative to conventional anti-anxiety drugs. It eases anxiety while supporting memory and attention, and animal research links these effects to modulation of GABA, serotonin, and brain-derived neurotrophic factor. Typically given as a nasal spray, it offers calm and cognitive support without the dependence or withdrawal associated with benzodiazepines.

7 outlets

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].

4 outlets

Bacopa Monnieri

Bacopa monnieri is a creeping wetland herb of the family Plantaginaceae, known in Ayurvedic tradition as brahmi and used for centuries as a remedy for memory and mental clarity. Its characteristic compounds are a group of triterpenoid saponins called bacosides, and standardized extracts are marketed as dietary supplements aimed at cognition. Clinical trials suggest it may modestly aid memory in some settings, though the overall evidence is mixed and it is not an approved medicine.

Memantine

Memantine (brand names Namenda and Ebixa) is an NMDA receptor antagonist approved for moderate to severe Alzheimer's disease; it calms excess glutamate signaling to protect neurons while leaving the normal signaling needed for memory and learning intact [1][2]. What makes it unusual is its voltage-dependent, fast-off-rate binding; it blocks the constant, low-level 'noise' of glutamate but steps aside when a real learning signal arrives, so it doesn't cloud cognition the way stronger blockers (like ketamine) do. It is also more than a pure NMDA blocker; at or near therapeutic brain concentrations it reaches a spread of remote targets, agonizing the high-affinity state of the dopamine D2 receptor, antagonizing 5-HT3 serotonin receptors and several nicotinic acetylcholine receptors (alpha-7, alpha-4/beta-2, alpha-3/beta-4 and alpha-9/alpha-10), and weakly engaging sigma-1 receptors; see the affinity table below for the full fingerprint. Beyond Alzheimer's it is being investigated for a range of conditions; it shows the most promise for the negative symptoms of schizophrenia (social withdrawal, apathy, blunted motivation) and as a mood stabilizer in bipolar disorder, with earlier signals in ADHD (often as an adjunct to a stimulant), anxiety and OCD, and autism.

BPAP

BPAP is an experimental laboratory compound created in the late 1990s by the Hungarian and Japanese team behind selegiline; it has never been approved as a medicine in any country. It is described as a "monoaminergic activity enhancer", meaning that in animal tissue it makes dopamine, noradrenaline and serotonin neurons release more transmitter when they fire, rather than forcing transmitter out the way amphetamine does; at higher concentrations it also blocks dopamine and noradrenaline reuptake. Essentially all the evidence comes from rats, mice and cell cultures, and almost all of it was produced by the two groups with a stake in the compound, namely Knoll's Semmelweis University laboratory and Fujimoto Pharmaceutical Corporation. No clinical trial in humans has ever been run or even registered, so claims about memory, mood, longevity or anti-aging benefit in people rest on no human evidence at all.

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.

Agomelatine

Agomelatine is a first-in-class antidepressant that acts through a mechanism unlike conventional agents, combining agonism at the melatonin MT1 and MT2 receptors with antagonism of the serotonin 5-HT2C receptor. This dual action resynchronizes disrupted circadian rhythms and increases dopamine and noradrenaline in the frontal cortex, and it is the only marketed antidepressant to work through the melatonergic system rather than monoamine reuptake. Approved in Europe as Valdoxan, it is noted for a relatively favorable tolerability profile, with fewer sexual side effects and less weight gain than SSRIs, though it requires monitoring of liver enzymes because of a risk of hepatotoxicity.

3 outlets

Tesofensine

Tesofensine is a triple monoamine reuptake inhibitor, originally investigated for Parkinson's and Alzheimer's disease, that produced some of the largest weight losses reported for an appetite-suppressing drug. By simultaneously blocking the reuptake of dopamine, noradrenaline, and serotonin it curbs hunger and increases satiety, and it additionally silences appetite-driving GABAergic neurons in the hypothalamus. In a phase 2 obesity trial it produced weight loss roughly twice that of the obesity medications approved at the time, though that trial has carried an expression of concern over its adverse-effect reporting since 2013; it remains investigational, with cardiovascular effects among the safety considerations.

Dapoxetine

Dapoxetine (marketed as Priligy) is a fast-acting selective serotonin reuptake inhibitor developed specifically as the first on-demand medication for premature ejaculation [1]. In large Phase III trials it roughly tripled the time to ejaculation and improved control and satisfaction, working from the very first dose and clearing the body quickly to suit as-needed use [1][2]. Approved across Europe and much of Asia, dapoxetine is the best-evidenced pharmaceutical option for premature ejaculation available today.

4 outlets

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.

Amisulpride

Amisulpride is a second-generation (atypical) antipsychotic of the benzamide class, used chiefly to treat schizophrenia and, at low doses in some countries, depressive conditions such as dysthymia. A low-dose intravenous form is also used to prevent and treat postoperative nausea and vomiting. It works as a selective blocker of dopamine D2 and D3 receptors, with additional antagonism of the serotonin 5-HT7 receptor that is thought to contribute to its mood effects [1][3].

Antipsychotic

Cariprazine

Cariprazine, sold as Vraylar (and Reagila in Europe), is a third-generation antipsychotic. Rather than simply blocking dopamine, it is a dopamine D3-preferring D2/D3 receptor partial agonist, meaning it partly activates those receptors and buffers dopamine signaling up or down toward a middle setpoint; it is also a 5-HT1A partial agonist and a 5-HT2B antagonist. It is used for schizophrenia and for bipolar disorder, including bipolar depression, and its standout feature is an unusually high affinity for the D3 receptor that is thought to help the negative and cognitive symptoms ordinary antipsychotics tend to leave untouched.

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.

Clomipramine

Clomipramine is a tricyclic antidepressant (TCA), sold chiefly under the brand name Anafranil, best known as one of the most effective drug treatments for obsessive-compulsive disorder [1][2]. It also treats major depression, panic disorder and cataplexy, and is used off-label for conditions such as premature ejaculation and chronic pain [1][2]. Introduced by the Swiss firm Geigy in the 1960s as a chlorinated relative of imipramine, it is the most strongly serotonergic of the older tricyclics and appears on the World Health Organization's list of essential medicines [1][2].

Escitalopram

Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, sold under brand names such as Lexapro and Cipralex. It is the active left-handed (S) form of the older drug citalopram, isolated to concentrate the therapeutic activity in a single molecule. Taken by mouth, it is used mainly to treat major depressive disorder and generalized anxiety disorder, and in some countries other anxiety-related conditions. It is a prescription medicine and one of the most widely used antidepressants.

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.

Fluvoxamine

Fluvoxamine is an antidepressant belonging to the selective serotonin reuptake inhibitor (SSRI) class, sold under brand names such as Luvox. Introduced in the 1980s, it was among the earliest SSRIs to reach the market and is used mainly for obsessive-compulsive disorder, depression, and several anxiety disorders. Unlike most other SSRIs, it is also a strong activator of the sigma-1 receptor, a feature that has drawn research interest well beyond psychiatry, including studies of its use in COVID-19. It is known for interacting with many other medicines because it inhibits certain liver enzymes.

L-Theanine

L-Theanine is a non-proteinogenic amino acid found almost exclusively in the tea plant Camellia sinensis, where it contributes part of brewed tea's savory taste. Chemically it is N-ethyl-L-glutamine, a structural analog of the neurotransmitter glutamate that crosses the blood-brain barrier and interacts with glutamate receptors, weakly modulating NMDA receptors and inhibiting binding at AMPA/kainate sites, while also raising dopamine and other monoamines; on EEG it increases alpha brain-wave activity, the signature of a relaxed but alert state. It is widely used as a supplement for relaxation, attention, and sleep, and is often paired with caffeine, with which it shows a well-studied synergy on attention, although the overall strength of the clinical evidence is still debated.

Neuroprotection

Lithium

Lithium is the lightest metal, taken not as the pure metal but as a salt such as lithium carbonate, citrate, or orotate. It is the long-standing gold-standard mood stabilizer for bipolar disorder, with unusually strong anti-suicidal and neuroprotective properties that other mood drugs do not match. It works largely by damping down two intracellular enzymes, GSK-3 and inositol monophosphatase, which nudges the brain toward neuroprotective, growth-promoting signaling.

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.

Nortriptyline

Nortriptyline is a secondary-amine tricyclic antidepressant and the active metabolite of amitriptyline, distinguished among tricyclics by its relative selectivity for norepinephrine reuptake inhibition over serotonin. It is notable for a well-defined curvilinear therapeutic plasma window, an early landmark in therapeutic drug monitoring, and it is generally better tolerated than tertiary-amine tricyclics in older patients. Beyond depression, it is widely used off-label for neuropathic pain and migraine prophylaxis, effects attributed partly to blockade of voltage-gated sodium channels that also underlies its local-anesthetic activity and, in overdose, its cardiotoxicity. It has additionally demonstrated efficacy as an aid to smoking cessation. Approved in the United States in 1964, it remains an inexpensive generic.

Paroxetine

Paroxetine is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, first approved in the early 1990s and sold under brand names including Paxil. It raises serotonin activity in the brain by strongly blocking its reuptake, and it is used for depression and a range of anxiety-related disorders. Among the SSRIs it is noted for a relatively high rate of discontinuation symptoms when stopped.

Prokinetic

Prucalopride

Prucalopride is a selective, high-affinity agonist of the serotonin 5-HT4 receptor used to treat chronic idiopathic constipation. By stimulating this receptor in the wall of the gut, it promotes the coordinated muscular contractions that move stool through the colon, and it is generally reserved for people whose constipation has not responded adequately to laxatives. It was approved in the European Union in 2009 and by the United States Food and Drug Administration in 2018, and is sold under brand names including Resolor and Motegrity.

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.

Antipsychotic

Risperidone

Risperidone is a second-generation (atypical) antipsychotic used for schizophrenia, bipolar mania and irritability in some conditions. Like other atypicals it blocks both dopamine D2 and serotonin 5-HT2A receptors, which broadens its effect and, at moderate doses, softens the movement side effects seen with older drugs. It is not recreational; it tends to feel sedating and flattening rather than pleasant.

Adaptogen

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.

Sertraline

Sertraline is a selective serotonin reuptake inhibitor (SSRI) prescribed mainly as an antidepressant. It is approved for major depressive disorder together with several anxiety-spectrum conditions, including obsessive-compulsive disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, and premenstrual dysphoric disorder. Introduced by Pfizer in the early 1990s and sold most widely under the brand name Zoloft, it is among the most frequently prescribed medicines of its class.

Tranylcypromine

Tranylcypromine is an antidepressant of the monoamine oxidase inhibitor (MAOI) class, used mainly for major depression that has not responded to other treatments [1][2]. It works by irreversibly blocking monoamine oxidase, the enzyme that breaks down mood-related neurotransmitters, and it is chemically related to amphetamine [1]. Introduced around 1960 and sold under the brand name Parnate, it requires a tyramine-restricted diet because of the risk of dangerous blood pressure spikes.

Sleep Support

Trazodone

Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor (SARI) class, used for major depression and very widely, if off-label, as a sleep aid [1][2]. Chemically a phenylpiperazine, it combines blockade of certain serotonin receptors with weak inhibition of serotonin reuptake and sedating actions at histamine and adrenergic receptors [1]. Developed in Italy in the 1960s and approved in the United States in 1981, it is sold under names such as Desyrel and Oleptro.

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].

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.

Vortioxetine

Vortioxetine is an antidepressant used to treat major depressive disorder in adults, often described as a serotonin modulator because it combines several actions on the serotonin system. It both blocks the serotonin transporter, like conventional serotonin reuptake inhibitors, and acts directly on a range of serotonin receptors as an agonist, partial agonist, or antagonist. Approved in the United States and Europe in 2013, it is taken once daily by mouth and has drawn particular interest for possible effects on the cognitive symptoms of depression.

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

Avanafil + Dapoxetine

Avanafil + Dapoxetine is a fixed-dose combination that pairs avanafil, a fast-acting PDE5 inhibitor for erectile dysfunction, with dapoxetine, a short-acting selective serotonin reuptake inhibitor used to delay ejaculation. It is marketed in some countries as an on-demand treatment for men who have both erectile dysfunction and premature ejaculation. Each ingredient is well studied on its own, but the combination product itself has little dedicated clinical trial data.

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.

Anxiolytic

Flibanserin

Flibanserin is a serotonergic medication approved to treat hypoactive sexual desire disorder (HSDD) in premenopausal women, sold under the brand name Addyi. It was first developed as an antidepressant but was repurposed after it appeared to influence sexual desire. Unlike drugs for erectile dysfunction, it is taken daily and acts on the brain rather than on blood flow. Its 2015 approval by the United States Food and Drug Administration was controversial, following two earlier rejections and a debate over whether its modest benefits justified its risks.

Mirtazapine

Mirtazapine is a tetracyclic antidepressant, often classified as a noradrenergic and specific serotonergic antidepressant (NaSSA), used primarily to treat major depressive disorder. Rather than blocking the reuptake of neurotransmitters like most modern antidepressants, it works by blocking a set of receptors, which increases noradrenaline and serotonin signaling and produces marked sedative and appetite-stimulating effects. Introduced in the 1990s and sold under brand names such as Remeron, it is a prescription medicine available as a generic.

Blend

Sildenafil + Fluoxetine

Sildenafil plus fluoxetine is the combined use of a phosphodiesterase type 5 (PDE5) inhibitor and a selective serotonin reuptake inhibitor (SSRI) in men with both erectile dysfunction and premature ejaculation. Sildenafil improves erectile function, while fluoxetine, a long-acting SSRI antidepressant, delays ejaculation as a side effect that is used off-label for premature ejaculation. Studies suggest the pairing can outperform either agent alone in appropriately selected men.

Cannabinoid

CBD

CBD (cannabidiol) is a non-intoxicating phytocannabinoid, one of the many active compounds found in the cannabis plant. Unlike THC, it does not produce a high, and a purified pharmaceutical form is approved to treat certain severe childhood epilepsies. It is also widely sold as an unregulated supplement and studied for anxiety, pain, and inflammation, though high-quality evidence for most of those uses remains limited.