Pharmacology of the fly agaric
There are several types of fly agaric. While some species are deadly poisonous, others are even edible.
The fly agaric (Amanita muscaria) contains 3 active ingredients:
-muscimol https://en.wikipedia.org/wiki/Muscimol
– ibotenic acid https://en.wikipedia.org/wiki/Ibotenic_acid
-muscarine https://en.wikipedia.org/wiki/Muscarine
None of these substances are on the list of prohibited substances in any country. So you can happily show the police how you have collected fly agaric mushrooms. Moreover, it is not a protected species.
(But even in the case of psilocybin mushrooms, there is no need to worry, because the police are forbidden to search a vehicle without the prosecutor's permission, they are forbidden to search pockets, bags, etc. In the event that the police did so illegally, it would be invalid evidence for the court, as the evidence was obtained illegally. In such a case, the accused would be released. These legal matters were discussed by JUDr. Adam Puškár – lawyer (criminal law), in a broadcast on Slobodný Vysielač https://www.youtube.com/watch?v=rBV_5tmt79g )
Muscimol
The psychoactive effect is attributed only to muscimol , which is an agonist at GABA receptors. The effects of muscimol are hallucinatory, psychedelic, and dissociative. Unlike sedatives, in my opinion, tolerance to it develops much more slowly because it acts on GABA receptors through a different mechanism, a much more direct way. (A sedative/benzodiazepine increases the activity of GABA receptors based on allosteric modification, so in a narrower sense, it is not perceived as a direct agonist at GABA receptors).
https://en.wikipedia.org/wiki/Muscimol
Ibotenic acid
It is an agonist of NMDA, glutamate receptors. It is also a weaker agonist of excitatory AMPA receptors. 10-20% of ibotenic acid is later converted in the body to muscimol, as they have a very similar chemical structure to muscimol. It is not certain whether muscimol alone would be sufficient for a psychedelic effect. Perhaps the presence of ibotenic acid is also necessary for the psychedelic activity of muscimol. NMDA and GABA receptors are in mutual interaction. While NMDA receptors are excitatory, GABA receptors are inhibitory. By increasing the activity of the excitatory NMDA receptor, they will also send strong signals to the GABA receptors. NMDA receptors increase the inhibitory activity of the GABA receptor.
Ibotenic acid itself would also be suitable as an additional treatment for schizophrenics – by increasing the activity of NMDA receptors, the symptoms of schizophrenia could be suppressed.
In case of hospitalization (if there is an extreme overdose), ketamine should be administered several times and later memantine for a maximum of 3 days to counteract the excitatory toxicity of ibotenic acid.
https://en.wikipedia.org/wiki/Ibotenic_acid
Muscarine
https://en.wikipedia.org/wiki/Muscarine
Muscarine is responsible for the negative side effects of fly agaric. It is a substance of a neurological nature. The name muscarinic acetylcholine receptors (abbreviation MAR) is also derived from muscarine. Muscarine is a strong agonist for these receptors.
Increased activity of muscarinic acetylcholine receptors improves memory, while their low activity causes memory problems. General anesthesia reduces the activity of these receptors, so after surgery, drugs are sometimes administered to increase the activity of these receptors (called acetylcholinesterase inhibitors) to increase the secretion of juices in the stomach and intestines (postoperative ileus). Acetylcholinesterase inhibitors are also used by Alzheimer's patients.
Increased activation of muscarinic acetylcholine receptors results in the following:
increased secretion of all glands: salivary, sweat, ocular, sebaceous, gastric, intestinal,
cramps in the stomach and intestines,
low blood pressure, slowed heart rate, diarrhea, accelerated bowel movements. It probably also affects the muscle tone of the rectum, which can cause a person to be unable to hold their stool.
Other side effects include the inability to hold urine, frequent urge to urinate, tearing, decreased body temperature with the risk of hypothermia due to excessive sweating, muscle cramps and tremors, constricted pupils, blurred vision, decreased intraocular pressure, polyuria (excessive urine production), bronchoconstriction (shortness of breath, asthma attack), vomiting.
Of course, these are symptoms of a lethal dose; with a normal recreational dose of fly agaric, not all of these side effects may manifest, nor to a strong degree.
https://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptor
https://en.wikipedia.org/wiki/Muscarinic_agonist
Drugs that increase MAR activity are probably the best weight loss drugs. And it's not for nothing that smoking also leads to weight loss. Very similar to MAR receptors are nicotinic acetylcholine receptors, which act very similarly.
(I once saw a person suffering from advanced Alzheimer's disease who was obese. The obesity of this person is proof that they either did not take any MAR-acting drugs at all, or only in too low doses. First of all, it was the doctor's failure)
I read an unpleasant story in English about someone who consumed fly agaric. I laughed a lot (I found it very funny) at the story when several people in a group consumed fly agaric, couldn't hold it in, and pooped on the carpet -:). Muscarine was responsible for this. The amount of muscarine in fly agaric is highly dependent on the environment in which the mushroom grew, the soil, the time of harvest, etc. Many people have also had positive experiences without significant side effects.
In case of hospitalization, if there is a more serious muscarine poisoning, atropine or another antagonist/blocker for MAR is used as an antidote to muscarine.
When used recreationally, it is advisable to use fly agaric together with the berries of deadly nightshade, or with a drug that reduces MAR activity (e.g. urological drugs for incontinence – urinary leakage). This will prevent the side effects of fly agaric.
Apparently, muscarine also has very similar effects to drugs used for blood clots and stroke (cyclic adenosine monophosphate (cAMP)). It does not only act on MAR. Thus, it very effectively dilates blood vessels, acts on adenosine receptors, which are responsible for blood pressure, heart performance and frequency, and the width/diameter of blood vessels. Muscarine in low doses would be suitable as a preventive treatment for cardiovascular diseases.
Green fly agaric
I'll just digress a little from the topic, but it's somewhat related, since we're on the subject of fly agarics.
What makes it poisonous?
The toxic active substances in the green fly agaric are strong inhibitors of RNA polymerase, thus almost completely stopping the synthesis/creation of proteins. This causes cell death and failure of entire organs. This mainly concerns the internal organs and kidneys. A person who survives poisoning must have all their internal organs replaced (transplanted).
By the way, it just occurred to me that low doses of some active ingredients of the green fly agaric could probably stop cancer growth, i.e. suppress the symptoms of cancer, which would still be a better drug than the controversial most commonly used type of chemotherapy after which, according to official statistics, 50% of people die (but this is just my speculation, I admit that I don't understand cancer that much, whether the active ingredients of the fly agaric would really be suitable for these things).
Other active substances, in turn, cause hemolysis, i.e. the death of red blood cells.
Antidotes for fly agaric certainly exist, but it seems that they are all only at an experimental level.
https://en.wikipedia.org/wiki/Amanita_phalloides
https://en.wikipedia.org/wiki/Alpha-Amanitin
https://en.wikipedia.org/wiki/Beta-Amanitin
https://en.wikipedia.org/wiki/Phalloidin
https://en.wikipedia.org/wiki/Phallolysin