Hallucinogens 1 Flashcards
What is phantastica
phantas&ca are drugs capable of altering percep&ons
person remains in communica&on with present world
aware of both fantasy and reality simultaneously
liAle physiological toxicity, mostly psychological effects
What are the 4 types of hallucinogens
indole hallucinogens catechol hallucinogens -amphetamine deriva&ves an&cholinergics deliriants
What is indolent hallucinogens
serotonin has an indole backbone as does: LSD (synthe&c) psylocybin (mushrooms) lysergic acid amide (Morning Glory) bufotenin (toads)
What are catechism hallucinogens
dopamine and noradrenaline have catechol backbones as do: mescaline (peyote cactus) MDA and MDMA (ecstasy) MDA - 3,4 methylenedioxyampehtamine an entactogen and pyschodelic other amphetamine deriva&ves
What is ergot
a fungus that infects rye - contains lysergic acid
in the Middle Ages in Europe, outbreaks of ergo&sm from
consuming infected grains
severely constricted blood flow in limbs made the limbs feel like
they were burning (St Anthony’s Fire)
lead to gangrene, loss of limbs (via vasoconstric&on)
other symptoms included convulsions, delirium, hallucina&on
in 944, an outbreak killed 40,000 people
in 1951 a small French town “went mad overnight.” - including pets
lysergic acid is a component of ergot fungus
What is LSD
lysergic acid was know to cause uterine contrac&ons
Albert Hoffman of Sandoz Laboratories used it as a star&ng point from which to synthesize new medicines for childbirth
aYer tes&ng one par&cular compound, lysergic acid diethylamide, felt very strange
decided to deliberately administer a very small dose of 0.25 mg
turns out it’s about 7 &mes normal dose
had first LSD trip ever recorded
How to use LSD
drug companies were unsure how to market LSD
gave it away in hopes someone could find a use for
it
used to develop psychoses in animal models
in general therapy to access the subconscious
as a therapy adjunct for alcoholics (50% success rate claimed
Explain LSD in the 1959s and 60s
CIA contacted Hoffman regarding large-scale produc&on
his company was offered $240,000 for 10 kg of LSD in 1953
equivalent of 100 million doses (the deal never went through)
the “hippy” movement of the 1960’s was a vocal proponent of LSD use
they were an&-Vietnam war and an&-government
one of the reasons LSD was targeted by the US government
Who is Timothy Leary
in the middle of all this, a Harvard professor of psychology became the poster child of LSD use
Timothy Leary had originally experimented with hallucinogenic mushrooms as part of a legi&mate research project
Leary and Richard Alpert used graduate students in their research projects and eventually turned to LSD
Leary and Alpert were dismissed from Harvard
Leary started the League of Spiritual Discovery
had to take LSD to join
was eventually jailed - escaped - then jailed again
Explain the animal results with LSD
animals cannot be trained to self- administer LSD or other hallucinogens (with some excep&ons)
if given the op&on, will work hard at performing tasks that will stop the administra&ons
no evidence that LSD or other hallucinogens are reinforcing (excep&on with deliriants)
the reasons for taking are oYen very different than with other drugs of abuse
What is the most common route of administration of LSD
mostly oral
LSD doses range from 10 - 300 micrograms
consider one ounce ethanol = 23 g
if dose is 100 ug, then 1/230,000th of alcohol
these “hits” usually absorbed onto blogng paper
gel tabs - LSD in gela&n (windowpanes)
microdots - on candies or small pills
oYen taken at a dose that doesn’t induce full-blown hallucina&ons
What are the patterns of use of LSD
LSD does not seem to habit-forming
very low on the abuse poten&al scale
taken when opportunity arises or in certain social situa&ons (eg. concerts)
set (expecta&on of user) and segng (environment) perhaps more important for this drug than any other - results in good or bad experience
What s the metabolism and excretion of LSD
effects begin 30 - 90 min aYer inges&on
only 1% actually enters the brain
extensively metabolized by liver
half-life of approx 110 minutes but effects can last for longer than this (5 - 12 hours)
What are the psychological effects of LSD
visual hallucina&on synesthesia (mingling of senses) intense emo&on &me distor&on (&me passes slowly) distor&on of sense of body and objects mys&cal experiences
What are the physiological effects of LSD
because it is sympathomime&c it causes autonomic responses increased blood pressure vasoconstric&on swea&ng dilated pupils increased saliva&on
What is the mechanism of LSD on receptors
LSD is a weak par&al agonist at central 5HT2A, 5HT2B and 5HT2C receptors
5HT2A and B are found in the nucleus accumbens and prefrontal cortex
their ac&va&on changes gene expression in these regions
other 5HT and dopamine receptors may play a small role
What are the effect of LSD on NTs
LSD increases the release of glutamate from glutamatergic neurons in the cortex
5HT2 receptors may be presynap&c in this brain region and their ac&va&on leads to increased glutamate release
especially in the medial prefrontal cortex (MPC) which is important for percep&on and informa&on processing
MPC thought to be where emo&ons and meaning of things is experienced - interface between cogni&ve and emo&onal systems
glutamate effects in the cortex thought to be one of the major contributors to hallucinogenic effects
Explain the effects of LSD on fear
as part of a fear centre, the locus coeruleus detects novelty in the environment
LSD enhances the response of the LC to novelty and makes the ordinary seem extremely novel
users report truly seeing or hearing for the first &me when using the drug
Explain LSD effects in D2 receptors
LSD will bind to dopamine type 2 (D2) receptors with high affinity and act as an agonist
shown in the human striatum (part of brain containing the nucleus accumbens)
known that over-s&mula&on of dopamine receptors can lead to hallucina&ons
What are the harms of LSD
no reported death from a true LSD overdose
actually physiologically safe
but may do unsafe things under the influence
flashbacks - a sudden and unexpected return to the drugged state - usually only short las&ng, visual
release from body fat? other theories?
most prevalent when taking other drugs or under stress
What are the tolerance effects if LSD
develops quickly
if taken repeatedly, complete tolerance in 2 - 3 days -
5HT2 receptors rapidly disappear
within a week, sensi&vity returns
become cross-tolerant to mescaline and psylocybin
no withdrawal symptoms have ever been reported
addic&on has never been shown to occur with LSD