Anxiety: nootropics and compounds | sci-wiki

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.

2 outlets

Supplement

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.

1 outlet

Nootropic

Etifoxine

Etifoxine (brand name Stresam; also called etafenoxine) is a benzoxazine anxiolytic (an anti-anxiety drug from a chemical family unrelated to the benzodiazepines like Valium). It has been prescribed for the anxious, tense, physical side of stress mainly in France and a handful of other countries since the late 1970s, and it is not approved by the US FDA. What makes it interesting is a dual mechanism: it calms the brain both by directly tuning up GABA-A receptors and by nudging the body to make more of its own calming neurosteroids. In head-to-head trials it eased anxiety comparably to some benzodiazepines while causing less sedation, less memory and psychomotor impairment, and little rebound or dependence when stopped. It has also been explored beyond anxiety for helping injured peripheral nerves heal and for damping neuroinflammation (inflammation inside nervous tissue). The important caveat is safety: rare but serious liver injury and severe skin reactions have been reported.

1 outlet

Anxiolytic

GABA

GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the mature mammalian central nervous system, where it lowers the excitability of nerve cells. The same molecule is sold as a dietary supplement marketed for relaxation, stress, and sleep. A long-standing point of debate is that orally taken GABA does not readily cross the blood-brain barrier, so how supplements produce their reported calming effects is not fully settled and may involve the peripheral nervous system and the gut rather than direct action in the brain.

3 outlets

Nootropic

Selank + Semax

Selank + Semax is a nasal spray pairing two Russian research peptides that are normally sold on their own. Selank is a synthetic relative of the immune peptide tuftsin, studied in Russia as an anxiolytic that does not sedate and does not appear to produce the tolerance or withdrawal that benzodiazepines do. Semax is a shortened fragment of ACTH, cut so that it keeps the behavioural effects without the hormonal ones, and studied for attention, stroke recovery and neuroprotection. Both are reported to raise BDNF, and that shared thread is the usual argument for combining them: one takes the edge off, the other sharpens.

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Analgesic

Tetrahydropalmatine

L-THP (levo-tetrahydropalmatine) is a plant alkaloid from Corydalis and related herbs with a long history in traditional Chinese medicine for its calming, sedative, and pain-relieving properties. Modern research has clarified its mechanism as a dopamine receptor modulator, and it has been carried all the way into a human clinical study for cocaine use disorder, an unusually strong evidence base for a botanical compound. For those exploring natural approaches to relaxation, sleep, and discomfort, L-THP is a genuinely well-studied and intriguing choice.

1 outlet

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.

1 outlet

Anxiolytic

Buspirone

Buspirone is an anxiolytic medication of the azapirone class, used mainly to treat generalized anxiety disorder. It acts chiefly as a partial agonist at the serotonin 5-HT1A receptor and, unlike benzodiazepines, does not cause significant sedation, dependence, or withdrawal. It was approved for medical use in the United States in 1986 and is sold as a generic, formerly under the brand name Buspar.

2 outlets

Anxiolytic

Tofisopam

Tofisopam is an anxiolytic drug of the 2,3-benzodiazepine class, marketed in parts of Europe and Asia under brand names such as Grandaxin [1]. Unlike the familiar 1,4-benzodiazepines such as diazepam, it relieves anxiety without producing sedation, muscle relaxation, memory impairment, or anticonvulsant effects [2]. It is used mainly for anxiety and autonomic symptoms, and it is not approved in the United States or Canada.

2 outlets

Antidepressant

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.

2 outlets

Nootropic

3α-Androstanediol

3α-Androstanediol (5α-androstane-3α,17β-diol) is an endogenous neurosteroid formed as the terminal 3α-reduced metabolite of dihydrotestosterone (DHT, the most potent natural androgen). Despite its androgenic origin it binds the androgen receptor only weakly; its defining pharmacology is potent positive allosteric modulation of the GABA-A receptor (the brain's principal inhibitory chloride ion channel), which produces anxiolytic (anxiety-reducing) and anticonvulsant (seizure-suppressing) effects in animal models. It is widely regarded as the androgenic counterpart of allopregnanolone (the analogous progesterone-derived neurosteroid), and is proposed to mediate much of the influence that testosterone exerts on seizure threshold, anxiety, and mood in males. It additionally acts as a ligand of estrogen receptor beta (ERβ), which may underlie some of its cognitive and neuroprotective actions.

Anxiety

GB-115

Carnosic Acid

Etifoxine

GABA

Selank + Semax

Tetrahydropalmatine

Pregnanolone

Buspirone

Tofisopam

Venlafaxine

3α-Androstanediol

Acaprazine

Allopregnanolone

AZD-2327

AZD-7268

D-Serine

Deoxycorticosterone

Emapunil

MIF-1 (Melanostatin)

MTEP

Rapastinel

Tabernanthalog

THDOC

URB597

Zuranolone

Anxiety

GB-115

Carnosic Acid

Etifoxine

GABA

Selank + Semax

Tetrahydropalmatine

Pregnanolone

Buspirone

Tofisopam

Venlafaxine

3α-Androstanediol

Acaprazine

Allopregnanolone

AZD-2327

AZD-7268

D-Serine

Deoxycorticosterone

Emapunil

MIF-1 (Melanostatin)

MTEP

Rapastinel

Tabernanthalog

THDOC

URB597

Zuranolone