MUSCIMOL - WHAT IS IT ?

Muscimol is a substance produced in mushrooms such as fly agaric (Amanita muscaria) and Amanita pantherina and is one of the main psychoactive substances. Its legal and not analysable

The dosage of muscimol is usually not precise, because it is most often taken by consuming mushrooms or mushroom preserves, where its dose is one big unknown. The psychoactive dose of muscimol is between 8 and 15 mg

CHEMICAL STRUCTURE AND BIOLOGICAL ACTION

Muscimol is an alkaloid with a chemical structure similar to GABA (gamma-aminobutyric acid), which is a key neurotransmitter in the brain responsible for inhibiting neuronal activity

Mechanism of action: Muscimol acts as an agonist of GABA receptors, meaning it binds to these receptors and mimics the effects of GABA. GABA is responsible for reducing the excitability of the nervous system, which leads to a calming, relaxing effect and reduced anxiety. As a result, muscimol induces a feeling of deep relaxation, and it can also induce changes in perception and psychedelic experiences

EFFECTS OF MUSCIMOL

The effects of muscimol depend on the dose and the individual reaction of the body. Here are the main effects it can have:

  • Relaxation and calming: Thanks to its action on GABA receptors, muscimol causes a calming effect, reducing stress and anxiety
  • Perceptual alterations: In higher doses, muscimol can induce visual hallucinations, changes in the perception of space and time, and a feeling of „detachment” from reality
  • Drowsiness: Due to its sedative effects, muscimol can induce drowsiness and even put the user into dream-like sleep states (known as oneirogenicity).
  • Low risk of addiction: Muscimol, unlike other psychoactive substances, does not tend to become physically or psychologically dependent, which makes it interesting in the context of research on alternative psychoactive substances
  • The effects of muscimol begin about an hour after ingestion, peak after 3 hours, and last for 10 to 24 hours. Experiences related to its effects include euphoria, a state of mind similar to lucid dreaming, the experience of leaving the body, and synesthesia. Negative effects include mild to moderate nausea, stomach discomfort, increased salivation, and convulsions or muscle tremors. In high doses, you may feel a strong dissociation or delirium

TERAPEUTIC APPLICATIONS AND RESEARCH

Although muscimol is not widely used in conventional medicine, its unique effects on the nervous system are of interest to scientists:

  • Treatment of anxiety and depression: Thanks to its sedative properties, muscimol can potentially be used in the treatment of anxiety, stress and insomnia
  • Research potential: Muscimol is being studied for use in research on the neurobiology of sleep, psychoses, as well as in the context of the treatment of addiction to other psychoactive substances

SAFETY AND TOXYCITY

The mean lethal dose (LD50) of muscimol in mouse studies is 3.8 mg/kg administered subcutaneously (SC) and 2.5 mg/kg administered intramuscularly (i.p.). For rats, the LD50 is 4.5 mg/kg administered intravenously (i.v.) and 45 mg/kg administered orally.

Human death due to muscimol is rare, mainly affecting young children, the elderly, or those with serious, chronic illnesses.

DIFFERENCEES BETWEEN MUSCIMOL AND PSYLOCIBIN

Muscimol is often confused with psilocybin because the two compounds are associated with mushrooms with psychoactive properties, but they differ in many ways:

  • Mechanism of action: Psilocybin works primarily through serotonin (5-HT2A) receptors, producing strong psychedelic effects, while muscimol affects GABA receptors, resulting in more sedative and relaxing effects.
  • Origin: Psilocybin is found in mushrooms of the genus Psilocybe, and muscimol is found in fly agarics.
  • Effects: Psilocybin usually induces intense hallucinations and mystical experiences, while muscimol has a more oneirogenic effect, influencing dreams and sleepiness.
  1. Johnston GA (October 2014). “Muscimol as an ionotropic GABA receptor agonist”. Neurochemical Research39 (10): 1942–1947. doi:10.1007/s11064-014-1245-yPMID 24473816S2CID 13364321
  2. Heiss JD, Walbridge S, Rene’Smith RN, Sato S, Oldfield EH, Lonser RR (August 2012). “174 Convection-Enhanced Delivery of Muscimol to the Epileptic FocusPreclinical and Clinical Research”. Neurosurgery71 (2): E568. doi:10.1227/01.neu.0000417764.02569.dcISSN 0148-396X
  3. Ramawad HA, Paridari P, Jabermoradi S, Gharin P, Toloui A, Safari S, Yousefifard M (2023). “Muscimol as a treatment for nerve injury-related neuropathic pain: A systematic review and meta-analysis of preclinical studies”The Korean Journal of Pain36 (4): 425–440. doi:10.3344/kjp.23161PMC 10551397PMID 37732408
  4. Benkherouf AY, Taina KR, Meera P, Aalto AJ, Li XG, Soini SL, et al. (April 2019). “Extrasynaptic δ-GABAA receptors are high-affinity muscimol receptors”Journal of Neurochemistry149 (1): 41–53. doi:10.1111/jnc.14646PMC 6438731PMID 30565258
  5. DeFeudis F. V. (1980) Physiological and behavioral studies with muscimolNeurochem. Res. 5, 1047–1068.
  6. Krogsgaard‐Larsen P., Hjeds H., Curtis D. R., Lodge D. and Johnston G. A. (1979) Dihydromuscimol, thiomuscimol and related heterocyclic compounds as GABA analoguesJ. Neurochem. 32, 1717–1724
  7. Michelot D, Melendez-Howell LM (February 2003). “Amanita muscaria: chemistry, biology, toxicology, and ethnomycology”. Mycological Research107 (Pt 2): 131–146
  8. Chilton WS (1978). “Chemistry and Mode of Action of Mushroom Toxins”. In Rumack, BH, Salzman, E (eds.). Mushroom Poisoning: Diagnosis and Treatment. Palm Beach: CRC Press. pp. 87–124.
  9. Frølund B, Ebert B, Kristiansen U, Liljefors T, Krogsgaard-Larsen P (August 2002). “GABA(A) receptor ligands and their therapeutic potentials”. Current Topics in Medicinal Chemistry2 (8): 817–832. doi:10.2174/1568026023393525PMID 12171573
  10. Quirk K, Whiting PJ, Ragan CI, McKernan RM (August 1995). “Characterisation of delta-subunit containing GABAA receptors from rat brain”. European Journal of Pharmacology290 (3): 175–181. doi:10.1016/0922-4106(95)00061-5PMID 7589211
  11. Chandra D, Jia F, Liang J, Peng Z, Suryanarayanan A, Werner DF, et al. (October 2006). “GABAA receptor alpha 4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol”Proceedings of the National Academy of Sciences of the United States of America103 (41): 15230–15235. Bibcode:2006PNAS..10315230Cdoi:10.1073/pnas.0604304103PMC 1578762PMID 17005728
  12. Woodward RM, Polenzani L, Miledi R (April 1993). “Characterization of bicuculline/baclofen-insensitive (rho-like) gamma-aminobutyric acid receptors expressed in Xenopus oocytes. II. Pharmacology of gamma-aminobutyric acidA and gamma-aminobutyric acidB receptor agonists and antagonists”. Molecular Pharmacology43 (4): 609–625. PMID 8386310
  13. T. Peredy, R.D. BruceIII, in Encyclopedia of Toxicology (Third Edition), 2014
  14. Goldstein A (2001). Addiction: From Biology to Drug Policy. Oxford University Press. p. 228. ISBN 978-0-19-514664-6
  15. Scotti de Carolis A, Lipparini F, Longo VG (1969-01-01). “Neuropharmacological investigations on muscimol, a psychotropic drug extracted from Amanita muscaria”. Psychopharmacologia15(3): 186–195. doi:10.1007/BF00411168PMID 5389124S2CID 26824149
  16. Hollister LE (1990). “New class of hallucinogens: GABA-enhancing agents”. Drug Development Research. Wiley. 21 (3): 255. doi:10.1002/ddr.430210311ISSN 0272-4391S2CID 143868762
  17. Merck Index; fragment
  18. Spoerke D, ed. (1994). Handbook of mushroom poisoning: diagnosis and treatment. Boca Raton: CRC Press. p. 269. ISBN 978-0-8493-0194-0OCLC 29913834.Preview Google Books