Hallucinogens I Flashcards
what are the 4 types of hallucinogens?
- indole hallucingoens
- catechol
- antichiolingerics
- deliriants
what is Phantastica?
it involves indole, and catechol hallucinogens
they are drugs that alter your perception but not by a lot to impair your communication and everything (person remains in communication with present world)
little physiological toxicity mostly psychological effects
new synethic ones can be deadly
what are some examples of indole hallucinogens?
LSD (synthetic), psilocybin (mushrooms), lysergic acid amide (morning glory), bufotenin (toads)
what is an example of catechol hallucinogens?
2-C drugs, MDMA, mescaline
what is an example of anticholinergic hallucinogens?
mandrake
what is an example of deliriant?
PCP
what are some of the structural properties of indoles ?
they all have a indole group and mimic serotonin
what are some structural properties of catechols?
they have a catechol backbone and resemble dopamine
what are ergot and ergot alkaloids?
they are a fungus that infects rye and contains lysergic acid and other complex ergot alkaloids
some ar potent vasoconstrictors and cause uterine contractions and ergotamine is still used to teat migrates via vasoconstriction, it has lysergic backbone
in the Middle Ages, there was outbreaks of ergotisim
there was two forms:
- severely constricted blood flow to limbs made limbs feel like they were burning (st Anthony’s fire)
- lead to gangrene, loss of limbs via vasoconstriction
- other forms led to convulsions, deliriums and hallucinations
How was LSD invented and by who?
albert Hoffman of sand laboratories used ergot alkaloids as a starting point from which to synthesize new respiratory and circulatory stimulant
after testing it on one particular compound, lysergic acid diethyl amine (added nitrogen w double bond oxygen and two carbons to lysergic acid) he felt strange so he administered a 0.25 mg dose on himself which was 7X normal dose and had the first LSD trip ever recorded
what happened after Sandoz synthesized LSD?
they didn’t know how to market it so they gave it away
and it was used to develop psychoses in animal models
- in general therapy it was used to access the subconscious
- as therapy adjust for alcoholics with 50% success rate
- there is some clinical evidence it may be useful in treating cluster headaches
- trials examining its use in treating ends of life anxiety
What was Timothy leary’s contribution to LSD?
Tim and Richard Alpert used graduate students in their research projects and turned to LSD
and experimented with LSD lots in school and got suspended and arrested
how is LSD administered using animals?
animals cannot be trained to self administer LSD
if given the option they will work hard to stop administration
- no evidence that they are reinforcing
- reasons for taking are often very different with other drugs of abuse
how is the normal administration of LSD?
mostly oral
LSD doses range from 10-300 micrograms which is 1/230,000th of alcohol
these hits usually absorbed onto blotting paper and then put on tongue to dissolve
also comes in gel tabs and microdots (candies or small pills)
often taken at a dose that doesn’t produce full blown hallucinations
microdosing is taking sub threshold doses that are supposed to induce creativity
what is the pattern of use of LSD?
LSD does not seem to form habit
- very low on abuse potential scale
- taken when opportunity arises or in certain social situations
- set (expectation of user) and setting (environment_ are more improtant for this drug than others because it can result in good or bad experience depending on the set and setting where you take the drug
how are hallucinogens metabolized?
effect beging at 30-90 minutes after injestion via 1st pass metabolism
only 1% actually makes it to the brain
- extensively metabolized by liver
- half life is approx 110 minutes but effects can last for longer than this (5-12 hours)
what are some psychological effects?
- hallucinations (visual)
- synesthesia
- intense emotion
- time distortion
- distortion of sense of body and object
- mystical experiences
what are some of the physiological effects of LSD?
its sympathomimetic (stimulates sympathetic) so it causes
increase in BP vasoconstriction sweating dilated pupils increased salivation
what is the mechanism for LSD working?
- LSD is a weak partial agonist at central 5HT2A (Hallucinations) and 5HT2B, and 5HT2c receptors
- HTA and HTB are found in nucleus accumbens and prefrontal cortex but does not moderate a rewarding effect
- their activation changes gene expression in these regions
other 5HT dopamine receptors may play a small role
When LSD binds to 5HT2 recpetors, what happens?
LSD increases release of glutamate from glutamergic neurons in the cortex
5HT2 receptors may be presynaptic in this brain region and their activation leads to increased glutamate release in the medial prefrontal cortex (MPC) which is important for perception and information processing
MPC thought to be where emotions and meaning of things is
glutamate effects in the cortex are thought to be on eo fate major contributors to hallucinogen effects
in chronic animal studies, there is dramatic increase in GABA-A receptor levels
glutamate just starts up connections with areas that normally don’t have connection
as part of the fear centre, the LC detects novelty in the environment, LSD enhances the response of the LC to lovely and makes the ordinary seem extremely novel
users report seeing and hearing for the first time
LSD will bind to dopamine type D2 receptors with high affinity and act as an agonist
known that over stimulation of dopamine receptors can lead to hallucinations
what are some hard reported by LSD use?
no reported death
pshyiologically safe
made make person do unsafe things
flashbacks called Hallucinogen Persisting Perception Disorder –> sudden an unexpected return to the druggist state which is short lasting and visual
no one knows why this happens some people say it happen when under stress or taking other drugs
can occur years after last taking the drug
how does tolerance develop?
develops quickly
if taken repeatedly, compete tolerance in 2-3 days, 5ht receptors rapidly disappear and within a week sensitivity returns
tolerance can be cross tolerance to mescaline and psilocybin not just LSD
no withdrawal symptoms ever representorted
addiction has never been occurring
