Psychoactive Plants Flashcards
Hallucinogen
any agent that causes alterations in perception, cognition and mood as its primary psychobiological actions in the presence of an otherwise clear sensorium
Psychedelic
from the greek meaning: “mind manifesting” or “mind expanding”
psychotomimetics
-‘ induce psychotic states’
- compared to symptoms of schizophrenia
Traditional use of Hallucinogenic plants
- used worldwide by indigenous peoples for magic, medical and religous purposes
- early societies believe that the plants are gifts from the gods
- are used to mediate between man and the supernatural
Albert Hofmann
- 1949
- synthesis of LSD
Aldous Huxley
- author
- documents uses
- “doors of perception” (portrayal of his mescaline experiences)
- “Brave new world” (‘soma’ is the new social drug of the future)
Psychoplastogen
small molecules that produce rapid and sustained structural and functional neural plasticity
Modern use of Hallucinogens
are being considered therapeutics for depression, addiction and PTSD
Hallucinogens in clinical development
- MDMA: in conjunction with psychotherapy for PTSD, anxiety and eating disorders
- psilocybin: for treatment of a variety of disorders including anxiety and depression
- LSD: cluster headaches and anxiety
- ibogaine: addiction
Monoamine Hallucinogens
- indole and catechol hallucinogens
- target serotonin related pathways
- vivid sensory effects
- perception is altered while maintaining contact with real world
- low toxicity (no overdose)
Indole group
N-H
Claviceps purpurea: Ergot
- parasitic fungus
- fungal spores grow hyphae into ovaries of grain to obtain nutrients
symptoms of Ergotism
gangrene, nervous spasms, psychotic delusions, convulsions
Salem witch trials and Ergotism
- suggested that the trials may have resulted from and outbreak of ergotism
- suggested that the ‘great fear’ of peasant revolt in 1789 where many ‘lost their heads’ may have occurred due to ingestion of ‘bad flour’
Chemical compounds of Ergot effects on receptors
show both antagonistic and agonist effects on serotonin, dopamine and adrenergic receptors
Ergot Compounds
ergoline, ergotamine, lysergic acid, ergine
Modern Uses of Ergot
- uterine contractions
- treat migraine
- reduce prolactin levels resulting from pituitary tumors
- reduce postpartum hemorrhage
- treat senility and Alzeimer’s dementia
Where is LSD derived from?
- is a synthetic compound derived from Ergoloids
- acts as a model for plant-derived psychedelic’s mechanism of action
LSD characteristics
- most potent example of a hallucinogenic lysergic acid derivative
- odorless and tasteless
- small doses intensify perception and large doses cause hallucination
- rapid and complete tolerance develops for behavioral effects after 4-7 days, lasting for 3 days
- not addictive, no withdrawal symptoms
LSD mechanism of Action
- LSD and related indole hallucinogenic alkaloids regulate serotonin pathways
- LSD binds to multiple serotonin receptor subtypes
- has both agonist and antagonist effects
- tolerance due to downregulation of certain serotonin receptors
Good trips vs. Bad trips
- good trip: profound perceptual distortions and hallucinations, heightened awareness of sensations and altered sense of self
- bad trip: panic episode brought on by dislike of drug’s effects and fear that the experience will not end
Morning Glories
- possess lysergic acid
- found in seeds called ololiuqui
- aztecs use these for divination
- modern use by indigenous mexicans ( ground into flour, soaked in cold water, filtered and drunk)
Examples of Historical religous uses of Psilocybe species
- Mexico and Central Americla
- mushroom is called Teonancatl (God’s flesh)
Characteristics of Psilocybe mushrooms
- structurally similar to serotonin
- effects similar to lysergic acid and LSD
Timeline of Effects of Psilocybe Compounds
- 30 min: dizziness, weakness and twitching
- 30-60 min: visual effects seen, colors, patterns, wave motions, and dreaminess, sense of euphoria develops
- 180 mins: normalcy returns
Indole hallucinogens
- lysergic acid
- psilocybin
catechol hallucinogens
- mescaline
- myristicin
Peyote Cactus: Lophophora williamsii
- small, spineless cactus
- over 56 difference alkaloids identified in peyote
- mescaline is the primary psychoactive alkaloid
Pharmacology of Mescaline
- similar to indole hallucinogens
- contains catechol group
- readily absorbed by body (poorly passes through bbb)
- hallucination lasts 6-10 hours
psychoactive dose of mescaline
- dilation of pupils
- increase in pulse rate and bp
- elevation in body temp
Cathechol Hallucinogenic structures mechanism of action
- resembles catecholamine neurotransmitters (norepinephrine and dopamine)
- effects suggested to mirror mechanism of indole hallucinogens
- pharmacological activity is very similar to LSD
History of Peyote
- used by Aztecs (traditionally eaten during religious ceremonies, used by priests and their congregation
- used in Texas 1760 (spread among regional indigenous tribes by 1880
- native American Church (founded in 1918, groups practice ceremonial peyote use)
preparation of Peyote
- only the above ground portion is edible
- crown is sliced into small discs
- mescal buttons
- can be eaten green or made into tea for drinking
- dried and then eaten
- dried mescal buttons remain psychoactive indefinitely
Mytistica fragrans
- nutmeg
- contains a catecholamine hallucinogen (myristicin)
Powdered nutmeg uses
- used as hallucinogen in Old world
- in Asia, often added to tobacco and chewed or snuffed
- aphrodisiac powers
- mace is also used
Myristicin
- terpenoid
- hallucinogenic effect, similar to peyote
- mix 1-6 tablespoons in water (serve hot)
- toxic compounds result in hangover
Plant hallucinogenic compounds that have amino acid targets and pathways
- ibotenic acid
- muscimol
Amanita muscaria
- fly agaric mushroom
- widespread in NA and Asia
- amino acid targets and pathways
historical uses of Fly agaric
- may be the oldest and most widely used hallucinogenic drug
- the soma cult of the Indus valley
- soma is a hallucinogenic plant thought to be a God
Compounds from Amanita muscaria
- muscimol, muscarine, ibotenic acid
Ibotenic Acid
- activates glutamate receptors
- glutamate is an endogenous excitatory neurotransmitter
- binds to receptors that act as ion channels or that are G-protein coupled
Muscimol
- thought ot be the most active compound in Fly agaric
- GABA receptor agonist
- produces state of confusion, disorientation, sensory disturbances
Muscarine
- does not seem to have a role in the psychoactive effects of Fly agaric
- binds to muscarinic acetylcholine receptors
Effects of ingesting Fly agaric
- onset is 15 min to an hour after ingestion
- derangement of senses, then manic behavior
- delirium and altered perception of size
- desire for exaggerated physical activity
- visual and acoustic hallucinations
- general inhibition of motor function
- after 12 hours, deep sleep
Plant hallucinogenic compounds with cholinergic targets and pathways
- scopolamine
- also atropine, hyoscyamine
History of scopolamine use
- used clinically by 1910 (pre-anesthetic medication)
- world was II (doctors prescribe it for American GIs to combat seasickness)
- Gauss, german doctor, early 20th century (use drug to allow for “twilgiht sleep” for women during childbirth)
- used as a tranquilizer in alcohol and drug withdrawal treatment
- used in combination with morphine as a truth serum
Modern Scopolamine Use
- post-operative nausea
- motion sickness
- GI spasms
- to aid in GI radiology and endoscopy
- irritable bowel syndrome
- eye inflammation
Scopolamine
- alkaloid
- anti-muscarinic
- hallucinogenic at higher doses
CNS effects of scopolamine
- as dosage increases, a behavioral pattern emerges
- delirium, mental confusion, loss of attention, drowsiness, loss of memory for recent events, death
What has been used as an antidote for scopolamine
phytostimine
Source of Scopolamine
- corkwood tree
- Australia, Queensland and north and central new south wales
- leaves have concentration of atropine and scopolamine
- aborigines submerged branches of tree into eel populated pools
- eels become lethargic and easy prey
Other sources of scopolamine
- other solanaceae species
- hyoscyamous niger (Henbane)
- atropa belladona
Production of Scopolamine
- 10 fold higher commercial demand for scopolamine than for hyoscymine and atropine combined
- plants produce less scopolamine that the other alkaloids
How to meet the demand for medicinal plant compounds?
- cultivation
- cell culturing approaches (callus, hairy root cultures
- genetic engineering approach
Hyoscyamous niger
- henbane
- high levels of H6H enzyme
- active H6H gene (transcribed at high rates, produces larger amount of H6H mRNA
- difficult to grow
Atropa Belladonna
- hyoscamine producer
- lower amount of H6H enzyme produced
- easy to grow, good candidate for cultivation
