CB1 Receptor: nootropics and compounds | sci-wiki

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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Cannabinoid

HU-210

HU-210 is a synthetic cannabinoid that acts as an ultra-potent full agonist at both the CB1 and CB2 cannabinoid receptors. It is the (6aR,10aR) enantiomer of the 1,1-dimethylheptyl homolog of 11-hydroxy-delta-8-tetrahydrocannabinol, developed in the 1980s by Raphael Mechoulam's group at the Hebrew University of Jerusalem (the source of the "HU" prefix). Structurally a close analog of THC, HU-210 is estimated to be roughly 100 to 800 times more potent than delta-9-THC, with sub-nanomolar affinity at CB1 and a notably long duration of action. It has been used primarily as a pharmacological tool compound to probe the endocannabinoid system in preclinical models, and has also appeared as an adulterant in illicit "herbal incense" (Spice/K2) products. HU-210 is controlled as a Schedule I substance in the United States and is not an approved medicine.

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Cannabinoid

JWH-210

JWH-210 is a synthetic cannabinoid of the naphthoylindole class that acts as a potent agonist at both cannabinoid receptors, CB1 and CB2. It was created during academic research into cannabinoid structure and pharmacology and later appeared as an active ingredient in illicit herbal smoking blends sold as synthetic cannabis [1][2]. It has no approved medical use and is controlled as an illegal substance in many countries [2].

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Synthetic Cannabinoid

MDMB-4en-PINACA

MDMB-4en-PINACA is a synthetic cannabinoid, an indazole carboxamide sold sprayed onto plant material and into vape liquid. ⚠️ It is not strong cannabis. THC is a partial agonist at the CB1 receptor and therefore has a ceiling; this is a full agonist and has none, reaching roughly 2.4 times THC's maximum effect and about 27 times its potency in the same experiment [1]. In the largest clinical series, 81 percent of presentations involved reduced consciousness and 30 percent involved seizures [3].

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Cannabinoid

Nabilone

Nabilone is a synthetic cannabinoid (a structural analog of delta-9-tetrahydrocannabinol) that acts as an agonist at the cannabinoid CB1 and CB2 receptors. Marketed as Cesamet, it is approved in the United States, Canada, the United Kingdom and other countries for the treatment of severe nausea and vomiting associated with cancer chemotherapy that has failed to respond to conventional antiemetics. Unlike inhaled cannabis or plant-derived THC, nabilone is a single, orally administered, pharmaceutically standardized molecule, which gives it consistent dosing and a defined pharmacokinetic profile. Beyond its licensed antiemetic indication, it has been studied off-label for neuropathic and chronic non-cancer pain, fibromyalgia, PTSD-associated nightmares, and agitation in Alzheimer's disease, with mixed but frequently encouraging results. Nabilone is a Schedule II controlled substance in the United States and a prescription-only medicine.

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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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Cannabinoid

Rimonabant

The first CB1 cannabinoid-receptor blocker; a withdrawn anti-obesity drug (Acomplia) that curbed appetite and cleaned up metabolic markers, but was pulled worldwide for serious psychiatric risk.

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Cannabinoid

WIN 55,212-2

WIN 55,212-2 is a synthetic aminoalkylindole cannabinoid receptor agonist that binds and fully activates both the CB1 and CB2 cannabinoid receptors, and is one of the most widely used reference agonists in endocannabinoid pharmacology. Developed by Sterling Winthrop from the aminoalkylindole (pravadoline) series while researchers were pursuing non-steroidal anti-inflammatory analgesics, it is structurally unrelated to plant-derived cannabinoids like THC yet produces overlapping in vivo effects including antinociception, hypothermia, catalepsy and hypomotility. It is a laboratory tool compound rather than an approved medicine, valued because it is a high-potency full agonist with slight CB2 preference and because its two enantiomers (the active R(+) form versus the near-inactive S(-) WIN 55,212-3) allow clean stereochemical control experiments. It has no approved medical use and is a Schedule I controlled substance in many jurisdictions as a synthetic cannabinoid.

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