Sleep: nootropics and compounds | sci-wiki

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.

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Supplement

Magnesium Acetate

Magnesium acetate is the magnesium salt of acetic acid, with the formula Mg(CH3COO)2. It forms white, water-soluble, moisture-absorbing crystals and is used as a food additive, a laboratory buffer, and a source of magnesium. As a dietary ingredient its role is simply to deliver magnesium, an essential mineral, in a soluble form.

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Peptide

Sermorelin

Sermorelin is a synthetic analogue comprising the first 29 amino acids of growth hormone-releasing hormone (GHRH), the shortest fragment that retains full biological activity at the pituitary GHRH receptor. Rather than supplying growth hormone directly, it stimulates the somatotrophs to secrete the body's own hormone, preserving the natural pulsatile rhythm and leaving intact the negative feedback that guards against overexposure. Once approved for the diagnosis and treatment of growth hormone deficiency, it is now used chiefly in compounding and research settings, where interest centers on recovery, body composition, and sleep. The broader GHRH-receptor family it belongs to is under active study for effects well beyond the pituitary, including agonist protection in heart failure and antagonist activity against prostatic hyperplasia, fibrosis, and tumor growth.

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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.

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Antidepressant

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.

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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.

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Sleep Support

Oleamide

Oleamide (cis-9,10-octadecenoamide) is an endogenous fatty acid primary amide, the simple amide of oleic acid, and the prototypical member of a family of brain lipids that function as biological signaling molecules [1]. It first drew attention when it was isolated from the cerebrospinal fluid of sleep-deprived cats, where it accumulates in proportion to the sleep debt and, when injected into rats, induces physiological sleep [1]. Mechanistically it is a substrate of fatty acid amide hydrolase (FAAH), the same enzyme that degrades the endocannabinoid anandamide, and it modulates cannabinoid, serotonergic, GABAergic, and gap-junction signaling [2][3][4][5]. In the supplement market it is sold as a sleep and relaxation aid, although controlled human evidence remains thin and most of what is known derives from cell and rodent work [6][13].

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Neurosteroid

THDOC

THDOC (3-alpha,5-alpha-tetrahydrodeoxycorticosterone) is an endogenous neurosteroid (a steroid that acts rapidly on neuronal membrane receptors rather than on classical nuclear hormone receptors) and the fully reduced 3-alpha,5-alpha metabolite of the adrenal steroid deoxycorticosterone. It is one of the most potent naturally occurring positive allosteric modulators (compounds that amplify a receptor's response to its own transmitter) of the GABA-A receptor, the brain's principal inhibitory chloride ion channel, where it enhances both fast synaptic and sustained extrasynaptic inhibition. Because its synthesis is driven by adrenocorticotropic hormone and by acute stress, THDOC is regarded as a stress-responsive inhibitory neurosteroid that provides negative feedback on the hypothalamic-pituitary-adrenal axis and transiently raises the seizure threshold. Alongside allopregnanolone, it is a prototypical member of the stress-derived GABAergic neurosteroid family.

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Hypnotic

Zolpidem

Zolpidem is the most prescribed sleeping pill in the world, sold as Ambien and Stilnox. It is not a benzodiazepine chemically, being an imidazopyridine unrelated to the cyclopyrrolones zopiclone and eszopiclone, but it acts at the same site on the same receptor. ⚠️ Its famous alpha-1 selectivity is about 375-fold over alpha-5 and alpha-6 but only sixfold over alpha-2 [1]. Its half-life of about two hours is roughly a third of eszopiclone's [4].

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Antidepressant

Zuranolone

Zuranolone (development code SAGE-217; marketed as Zurzuvae) is an orally bioavailable synthetic analog of allopregnanolone (a naturally occurring neurosteroid derived from progesterone) that acts as a positive allosteric modulator (a compound that amplifies a receptor's response to its own transmitter) of the GABA-A receptor (the brain's principal inhibitory chloride channel). It was engineered by Sage Therapeutics from the same neurosteroid scaffold as the intravenous agent brexanolone, but with a modified 3-hydroxy pyrazole substitution that confers metabolic stability suitable for once-daily oral tablets rather than a continuous infusion. In August 2023 the United States Food and Drug Administration approved zuranolone for postpartum depression (a major depressive episode arising in the weeks after childbirth), making it the first oral drug indicated specifically for that condition. It is notable for producing an antidepressant response within days when given as a short, fixed two-week course, in contrast with the weeks-long onset of conventional monoamine antidepressants.

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Hypnotic

Zopiclone

Zopiclone is a nonbenzodiazepine hypnotic of the cyclopyrrolone class, one of the Z-drugs, used for the short-term treatment of insomnia. Marketed under names such as Imovane and Zimovane, it was introduced in the 1980s and helps with both falling asleep and staying asleep. Although chemically unrelated to benzodiazepines, it acts on the same receptor site and carries similar risks of tolerance and dependence.

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Hypnotic

Eszopiclone

Eszopiclone is a sedative-hypnotic medication used to treat insomnia. It belongs to the nonbenzodiazepine group of sleep drugs often called Z-drugs, and chemically it is the active S-enantiomer of the older hypnotic zopiclone, in the cyclopyrrolone class. Marketed principally under the brand name Lunesta, it helps people fall asleep and stay asleep by enhancing the activity of the brain's main inhibitory neurotransmitter. It is a prescription medicine and, in the United States, a controlled substance.

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