Psychoactive PlantsHallucinogens - III: Magic Mushrooms and Other Hallucinogenic Fungi

THE FUNGIKingdom Protista

Div Myxomycota

Div OomycotaKingdom Eumycota

Div Chytridiomycota

Div Zygomycota

Div Ascomycota

Div BasidiomycotaAsexual 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 MuscimolAmanita 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

Serotonin

Psilocin

Symptoms Primary symptom: hallucinations Other possible symptoms:

Fear, agitation, confusion, psychoses Vomiting Prostration Temporary paralysis

Poisoning rarely fatal in adults