Muscimol, GABA Agonists, and GABA

Papers broadly covering the Amanita genus.
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socalgirl723
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Muscimol, GABA Agonists, and GABA

Post by socalgirl723 » Tue Oct 27, 2020 12:10 am

Muscimol, GABA Agonists, and GABA

Muscimol (also known as agarin or pantherine) is one of the principal psychoactive constituents of Amanita muscaria and related species of mushroom. Muscimol is a potent, selective agonist for the GABAA receptors, and displays sedative-hypnotic, depressant and hallucinogenic psychoactivity. Muscimol is a potent GABAA agonist, activating the receptor for the brain's principal inhibitory neurotransmitter, GABA. Muscimol binds to the same site on the GABAA receptor complex as GABA itself, as opposed to other GABAergic drugs such as barbiturates and benzodiazepines which bind to separate regulatory sites. GABAA receptors are widely distributed in the brain, and so when muscimol is administered, it alters neuronal activity in multiple regions including the cerebral cortex, hippocampus, and cerebellum. Muscimol is a non-addictive GABA agonist.

A GABA receptor agonist is a drug that is an agonist for one or more of the GABA receptors, producing typically sedative effects, and may also cause other effects such as anxiolytic, anticonvulsant, and muscle relaxant effects. There are three receptors of the gamma-aminobutyric acid. The two receptors GABA-α and GABA-ρ are ion channels that are permeable to chloride ions which reduces neuronal excitability.

Gamma-Aminobutyric acid, or γ-aminobutyric acid or GABA, is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GABA is a chemical that is made in the brain. GABA is taken for relieving anxiety, improving mood, reducing symptoms of PMS, and treating ADHD. It is also used for promoting lean muscle growth, burning fat, stabilizing blood pressure, and relieving pain. GABA is also used for increasing sense of well being, relieving injuries, improving exercise tolerance, decreasing body fat, and increasing lean body weight. GABA works by blocking brain signals (neurotransmissions). Neurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors in the adult vertebrate. As the brain develops into adulthood, GABA's role changes from excitatory to inhibitory.

Besides the nervous system, GABA is also produced at relatively high levels in the insulin-producing β-cells of the pancreas. The β-cells secrete GABA along with insulin and the GABA binds to GABA receptors on the neighboring islet α-cells and inhibits them from secreting glucagon (which would counteract insulin's effects). GABA can promote the replication and survival of β-cells and also promote the conversion of α-cells to β-cells, which may lead to new treatments for diabetes.
GABA has also been detected in other peripheral tissues including intestines, stomach, Fallopian tubes, uterus, ovaries, testes, kidneys, urinary bladder, the lungs and liver, albeit at much lower levels than in neurons or β-cells. GABAergic mechanisms have been demonstrated in various peripheral tissues and organs, which include the intestines, the stomach, the pancreas, the Fallopian tubes, the uterus, the ovaries, the testes, the kidneys, the urinary bladder, the lungs, and the liver. Experiments on mice have shown that hypothyroidism induced by fluoride poisoning can be halted by administering GABA. The test also found that the thyroid recovered naturally without further assistance after the Fluoride had been expelled by the GABA. Immune cells express receptors for GABA and administration of GABA can suppress inflammatory immune responses and promote "regulatory" immune responses, such that GABA administration has been shown to inhibit autoimmune diseases in several animal models.

Sources:
https://en.wikipedia.org/wiki/GABA_receptor_agonist.
https://en.wikipedia.org/wiki/Muscimol.
https://www.webmd.com/vitamins/ai/ingre ... -acid-gaba.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020178/.
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Re: Muscimol, GABA Agonists, and GABA

Post by Gjayy » Mon Nov 02, 2020 3:57 pm

Hey Socal, found your write up super interesting. I posted a few days ago saying I had recently come across the possible benefits of AM, and wondered if it worked on the same receptors as benzodiazepines how could it help with withdrawal/recovery? I’m 7 years off, and still have issues with solid refreshing deep sleep. I think it’s not an issue with gaba per say but an issue with limited receptors due to the benzos.

To clarify what they’re saying is that the Muscimol works on a different part of the receptor that does not cause tolerance or down-regulation like benzos?
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Re: Muscimol, GABA Agonists, and GABA

Post by socalgirl723 » Thu Nov 12, 2020 5:10 pm

Honestly I'm not a scientist by any means, but it sounds to me that since it binds to the brains receptors themselves, it is non addictive and also seemingly difficult to build a tolerance to. Ive been microdsing 2 to 3 times a week and I havent noticed a tolerance at all, in fact I've been taking less and less. Possibly this is due to the fact that I started ordering my amanitas from another supplier and they might be more potent, but I think my mind is just needing less to get the desired anti-anxiety effects. It almost feels like its balancing things out for me and since I have an extremely addictive personality (ive managed to quit cigarettes, heroin and alcohol over the years) im super cautious now when it comes to anything mind altering. I have always found psychedelics to be beneficial for me, now I trip on psilocybin a few times a year usually although it used to be more. Muscimol is very different from other psychedelic compounds from what ive found. It makes me feel better even on the days I dont microdose, I havent felt burnt out at all and my anxiety is minimal compared to what it used to be.
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