Exploring Hallucinogenic Fungi: Magic Mushrooms & Beyond

1. Psychoactive Plants Hallucinogens - III: Magic Mushrooms and Other Hallucinogenic Fungi

2. THE FUNGI Kingdom Protista Div Myxomycota Div Oomycota Kingdom Eumycota Div Chytridiomycota Div Zygomycota Div Ascomycota Div Basidiomycota Asexual Fungi

3. Kingdom Fungi • Division Ascomycota (ascomycetes) - yeasts, mycelial fungi, morels, cup fungi, truffles • Division Basidiomycota (basidiomycetes) - mushrooms, bracket fungi, puffballs, • Asexual Fungi (imperfect fungi) - artificial group of mycelial fungi with no sexual stage - molds

4. Hallucinogenic Fungi • Hallucinogenic compounds found in many fungi • Ascomycota - Claviceps purpurea - ergot compounds - Lysergic acid alkaloids - LSD • Basidiomycota - several mushrooms • Amanita muscaria, A. pantherina, and others • Psilocybe and related fungi

5. Claviceps purpurea Ergot of rye

6. Ergotism • Ergot contains a number of toxic alkaloids, if harvested with the grain and milled into the flower - it causes a disease called ergotism • During Middle Ages called “Dancing Mania” and “St. Anthony’s Fire” • Many alkaloids found in the ergot • Some constrict blood vessels • Some act on CNS • Ergotism rare today but historically important

7. Ergot alkaloids Vindoline Vinblastine (Catharanthus)

8. The Road to LSD • Late 19th and early 20th centuries chemists began to isolate active principles of ergot • In 1918 Stoll, Swiss chemist, isolated an alkaloid which he named ergotamine • Early 1930's Jacobs and Craig basic structure of all ergot alkaloids - lysergic acid • 1935 – Albert Hofmann – ergobasine • 1938-1943 – Hofmann – LSD-25

9. Lysergic acid structure

10. A new hallucinogen • Hofmann decided to experiment with LSD-25 on himself • On April 19, 1943, he took 0.25 mg of LSD-25 - birth of a hallucinogen • Effects of LSD

11. Mode of Action • Effects mid-brain activity by interfering with action of serotonin and serotonin receptors • In small amounts mimics serotonin but in larger amounts it is antagonistic to serotonin • Hallucinations due to disruptions in the normal pathways of sensory stimulation

12. Hallucinogenic Mushrooms • Two different toxin groups exhibit hallucinogenic properties • Ibotenic acid and Muscimol in the family Amanitaceae (and possibly others) • Psilocybin (psilocin) in several mushroom families • Strophariaceae • Bolbitiaceae • Cortinariaceae • Coprinaceae

13. Ibotenic Acid and Muscimol • Amanita muscaria (fly agaric) • Amanita pantherina (panther cap) • Amanita cothurnata • Amanita gemmata • Amanita smithiana • Amanita strobiliformis • Tricholoma muscarius • Panaeolus campanulatus????

14. Amanita muscaria • Long history of use as an intoxicant • Used by native peoples in many parts of the world • Possibly used in India for 4000 years - Soma hymns of Rig Veda have been interpreted as description of A. muscaria • Used for centuries by tribes in Siberia • Excreted unaltered - so urine collected and drunk for a second dose among the poor

15. Ibotenic Acid and Muscimol • Both substances produce the same effects, but muscimol is approximately 5 to 10 times more potent than ibotenic acid • Ibotenic acid converted to muscimol on drying and cmpds last 5-10 yrs in dried mushrooms • Ibotenic acid may be converted into muscimol in the body • Symptoms of poisoning generally occur within 1 - 2 hours after ingestion of the mushrooms

16. Ibotenic Acid and Muscimol Muscimol lacks the carboxyl group

17. Muscimol • Muscimol's primary action is at GABA receptor sites as a potent GABA-A agonist • GABA - inhibitory neurotransmitter - inhibitor of presynaptic transmission in the CNS and also in the retina • Muscimol has been shown to be active in several parts of the brain including the cerebral cortex, hippocampus, and cerebellum

18. Symptoms • Manic behavior, delirium, inebriation, spasms • Deep sleep full of fantastic images and vivid hallucinations • May progress into more serious symptoms including seizures and possibly coma • Many cases of poisoning in this group of mushrooms are known, but only a few deaths • 10 mushrooms a fatal dose - much more serious in kids - lower doses fatal • No antidotes - stomach pumped

19. Psilocybin and Psilocin • Psilocybe • Psilocybe cubensis • Conocybe • Gymnopilus • Panaeolus

20. Psilocybin and Psilocin Containing Mushrooms • Used for psychoactive effects in religious ceremonies of certain Native American tribes for hundreds of years especially in Mexico and Central America • Aztecs described their sacred mushrooms as Teonanacatl - the flesh of the Gods • Used in religious and healing rites for thousands of years • Suppressed by Spanish but not abandoned • Rediscovered in 20th century

21. Magic Mushrooms • Psilocybe cubensis -magic mushrooms of street use • Active compounds psilocybin/psilocin • Compounds partially similar in structure to LSD - contain an indole backbone • Again act as mimic to serotonin - so effects may be through serotonin receptors

22. Psilocybin • In the body psilocybin is hydrolyzed to psilocin - the phosphate group lost • Psilocin is just as potent as psilocybin and is even closer to the structure of serotonin

23. Psilocin Serotonin

24. Symptoms • Primary symptom: hallucinations • Other possible symptoms: • Fear, agitation, confusion, psychoses • Vomiting • Prostration • Temporary paralysis • Poisoning rarely fatal in adults