Psychoactive Plants

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Psychoactive Plants

• Hallucinogens - III Magic Mushrooms and Other
  Hallucinogenic Fungi

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Fungi

• Generally have a thread-like body
• Hypha - single filament or thread
• Mycelium - all the hyphae of a colony
• Reproduce by spores - usually airborne
• Fungal-like organisms in Kingdom Protista
• True fungi in the Kingdom Fungi

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Fungal-like organisms in Kingdom Protista

• Slime molds - Division Myxomycota
• Slimy (animal-like) feeding stage
• Reproduce by spores
• Water molds - Division Oomycota
• Many in fresh water others on land
• Important plant pathogens in this group

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Kingdom Fungi

• Divison Zygomycota (zygomycetes) - simple
  mycelial 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

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Fungi include molds and mushrooms
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Fungal Life Styles

• Fungi can be pathogens, symbionts, or saprobes
• Most fungi are saprobic and recycle organic
  material
• Many symbionts lichens and mycorrhizae
• Many pathogens
• Most pathogens are plant pathogen
• Some human and animal pathogens

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Fungi and Human Health

• Human Pathogens
• Allergenic spores
• Fungal toxins
• Mushroom toxins
• Mycotoxins
• Antibiotics
• Yeast -gt alcohol production

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Hallucinogenic Fungi

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

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Claviceps purpurea

• Cause of ergot or rye
• Ascospores are produced in the spring at about
  the same time rye is flowering
• Ascospores land on flower, invades the ovary and
  destroys it - produces conidia in a sticky, sweet
  material that attracts insects - spread spores to
  other flowers
• As season progresses, mycelium in ovary develops
  into a hard, dark structure called an ergot
  (technically it is a sclerotium - hardened fungal
  tissue)

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Claviceps purpurea Ergot of rye
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Ergot Overwinters

• Ergot replaces the grain - it may be harvested
  along with the grain or it may fall to the ground
  and overwinter
• In the spring, the ergot produces several stroma
  each containing perithecia
• Ascospores are long and thin and start the
  infection cycle all over when they are released
  from the perithecia

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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. Anthonys Fire
• Ergotism can also occur in grazing animals that
  forage on contaminated grain
• Many different alkaloids --- cause many
  different effects

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Alkaloids in Ergot

• Some of the ergots constrict blood vessels and
  impair circulation - in extreme conditions can
  result in gangrene - limbs may drop off or
  require amputation
• Other toxins affect the CNS resulting in
  hallucinations and convulsions - loss of mental
  function
• Feelings of burning in calves or intense cold

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Ergotism

• With modern milling techniques, ergotism rare
• Outbreak in France in 1951 - 4 deaths and 150
  hospitalized
• 1977 in Ethiopia on contaminated barley
• Salem Witches may have been ergotism
• Belief in werewolves may be due to hallucinations
  from ergotism
• Many potent alkaloids present in the ergot

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Ergot alkaloids
Vindoline Vinblastine (Catharanthus)
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The Road to LSD

• Late 19th and early 20th centuries chemists began
  to isolate active principles of ergot
• In 1918 Swiss chemist Stoll isolated an alkaloid
  which he named ergotamine
• Early 1930's Jacobs and Craig of Rockefeller
  Institute in NY isolated and characterized the
  nucleus common to all ergot alkaloids
• They named it lysergic acid

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Lysergic acid structure
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The road continues

• In 1935 Albert Hoffman of Sandoz Pharmaceuticals
  began synthesizing natural ergot alkaloids
• By combining lysergic acid with the amino alcohol
  propanolamine, Hoffman obtained a compound
  identical to the natural ergot alkaloid,
  ergobasine - found to stimulate uterine
  contractions

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LSD synthesized

• Encouraged by his success, Hoffman began to
  synthesize other lysergic acid compounds,
  believing that other derivatives might also have
  interesting pharmacological properties.
• In 1938 he produced lysergic acid diethylamide,
  abbreviated LSD-25 (25th cmpd he had synthesized)

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LSD-25

• LSD-25 didn't appear to have any particularly
  useful medical properties
• Although Hoffman noted "the experimental animals
  became restless"
• For 5 yrs, nothing more was done with LSD-25 but
  in 1943 Hoffman remembered it and went back to
  reinvestigate
• He resynthesized it but developed strange
  feelings of restlessness and dizziness

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A new hallucinogen

• Hoffman decided to experiment with LSD-25 on
  himself
• On April 19, 1943, he took 0.25 mg of LSD-25 -
  birth of a hallucinogen

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Hoffmans description

• A demon had invaded me, had taken possession of
  my body, mind, and soul. I jumped up and
  screamed, trying to free myself from him, but
  then sank down again and lay helpless on the
  sofa...I was seized by a dreadful fear of going
  insane.

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Effects of LSD

• Users feel several different emotions at once or
  swing rapidly from one emotion to another
• If taken in a large enough dose, the drug
  produces delusions and visual hallucinations
• Sense of time and self changes
• Sensations seem to "cross over," giving the user
  the feeling of hearing colors and seeing sounds

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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

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From MSDS for LSD

• A temporary psychotic state with sensory
  illusions, distortions or visual hallucinations
  consisting of shimmering intensification of color
  and texture, brightly colored lights, geometric
  designs, animals and occasionally human images
  may occur.
• Hearing or tasting colors and seeing sounds
• Rarely, anxiety, fearful auditory, visual and
  tactile hallucinations, panic states and paranoid
  delusions, suspiciousness, intense depression,
  loss of control, suicidal ideation and self
  destructive
• Deaths have resulted from hallucinatory effects
  leading to accidental death.

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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

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Ibotenic Acid and Muscimol

• Amanita muscaria (fly agaric)
• Amanita pantherina (panther cap)
• Amanita cothurnata
• Amanita gemmata
• Amanita smithiana
• Amanita strobiliformis
• Tricholoma muscarius
• Panaeolus campanulatus????

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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

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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

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Ibotenic Acid and Muscimol
Muscimol lacks the carboxyl group
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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

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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
• No antidotes - stomach pumped

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Psilocybin and Psilocin

• Psilocybe
• Psilocybe cubensis
• Conocybe
• Gymnopilus
• Panaeolus

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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

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Magic Mushrooms

• 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

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Psilocybin
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Psilocybin and psilocin

• 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

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Psilocin
Serotonin
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Symptoms

• Primary symptom hallucinations
• Other possible symptoms
• Fear, agitation, confusion, psychoses
• Vomiting
• Prostration
• Temporary paralysis

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Poisonings

• Onset of symptoms is usually rapid and the
  effects generally subside within 2 hours
• Poisonings by these mushrooms are rarely fatal in
  adults and may be distinguished from ibotenic
  acid poisoning by the absence of drowsiness or
  coma
• Most severe cases of psilocybin poisoning occur
  in small children, where large doses may cause
  hallucinations accompanied by fever, convulsions,
  coma, and death.