Anandamide: nootropics and compounds | sci-wiki

AM3506

AM3506 is an investigational fatty acid amide hydrolase (FAAH) inhibitor of the sulfonyl fluoride chemical class that raises brain levels of the endocannabinoid anandamide by irreversibly blocking the enzyme that degrades it. Developed at Northeastern University's Center for Drug Discovery (Makriyannis group) and characterized largely in collaboration with the National Institutes of Health, it is a potent, selective, covalent inhibitor of both rat and human FAAH. In preclinical models it normalizes blood pressure in hypertensive rats, promotes fear extinction through the amygdala, and restores endotoxin-disturbed gastrointestinal motility, all via downstream CB1/CB2 receptor signaling. AM3506 has not entered human clinical trials and remains a research compound.

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Cannabinoid

Cannabichromene

Cannabichromene (CBC) is a non-psychotropic phytocannabinoid and one of the six most abundant cannabinoids in Cannabis sativa, biosynthesized from cannabigerolic acid (CBGA) via the enzyme CBCA synthase and decarboxylated from its acidic precursor cannabichromenic acid. Structurally a resorcinol-derived chromene rather than the classic dibenzopyran of THC, it binds the classical cannabinoid receptors only weakly and instead acts primarily as a potent agonist of the TRPA1 ion channel while inhibiting the cellular reuptake and degradation of the endocannabinoid anandamide. Preclinical studies describe anti-inflammatory, gastrointestinal-normalizing, antidepressant-like, analgesic, antimicrobial and neural stem-cell-supporting activity, and CBC is frequently cited as a contributor to the "entourage effect" of whole-plant cannabis. It is not scheduled as a distinct controlled substance in most jurisdictions but is regulated as a cannabis constituent, and its clinical evidence base in humans remains early-stage.

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Cannabinoid

JZL195

JZL195 is a first-in-class, centrally active dual inhibitor of the two principal endocannabinoid-degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), reported with in vitro IC50 values of approximately 2 nM and 4 nM respectively [1]. By simultaneously blocking both catabolic pathways it raises brain and peripheral levels of the two major endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), thereby driving broad, indirect activation of the cannabinoid CB1 receptor [1]. It is a research chemical used to dissect endocannabinoid signalling and is not an approved human medicine.

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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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Cannabinoid

PF-04457845

PF-04457845 is an investigational, orally bioavailable fatty acid amide hydrolase (FAAH) inhibitor developed by Pfizer that raises endocannabinoid tone by blocking the enzyme responsible for degrading anandamide. It is a highly potent, exquisitely selective, covalent (irreversible) inhibitor that carbamylates FAAH's catalytic serine, inhibiting the human enzyme with an IC50 of roughly 7.2 nM. Because it amplifies the body's own cannabinoid signaling rather than directly activating CB1 receptors, it elevates anandamide (and related fatty acid amides) without the intoxication, cognitive impairment, or motor side effects associated with direct CB1 agonists such as THC. In clinical testing it achieved greater than 96% FAAH inhibition and a roughly ten-fold rise in circulating anandamide, and it has been studied for osteoarthritis pain, cannabis use disorder, and stress- and fear-related conditions such as post-traumatic stress disorder. It failed to beat placebo in an osteoarthritis knee-pain trial but showed positive signals for cannabis withdrawal and fear extinction, and it remains a widely used pharmacological tool for probing the endocannabinoid system.

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Cannabinoid

PF-3845

PF-3845 is a highly selective, covalent fatty acid amide hydrolase (FAAH) inhibitor developed by Pfizer as a pharmacological tool to augment endocannabinoid signaling in vivo. By carbamylating the serine nucleophile of FAAH, the enzyme responsible for degrading the endocannabinoid anandamide, PF-3845 raises brain and peripheral levels of anandamide and related N-acylethanolamines for up to 24 hours after a single dose. It is widely used in preclinical neuroscience to probe endocannabinoid contributions to pain, inflammation, anxiety, and nausea, and remains an investigational research compound rather than an approved drug.

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