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

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

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

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

Claviceps purpurea Ergot of rye

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

Ergot alkaloids Vindoline Vinblastine (Catharanthus)

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

Lysergic acid structure

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

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

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

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

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

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

Ibotenic Acid and Muscimol Muscimol lacks the carboxyl group

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

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

Psilocybin and Psilocin Psilocybe Psilocybe cubensis Conocybe Gymnopilus Panaeolus

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

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

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

Psilocin Serotonin

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