Chapter 15: Hallucinogens Flashcards
LSD is a ____ agonist, and ketamine is a ____ antagonist
LSD is a 5-HT2a agonist, and ketamine is an NMDA antagonist
LSD was derived from ____ fungus
ergot
who discovered LSD
Albert Hoffman
main method of administration of LSD
oral injestion
4 main categories of hallucogenic effects
1) phantasticants
2) psychodelics
3) entactogens
4) psychomimetics
characteristics of a phantasticant
spiritual enlightenment
psychodelic characteristics
manipulation of senses, more intense colors
T/F: psychodelic drugs cause hallucinations
false, everything you see is real, but just more intense. things may be wavy with brighter colors
characteristics of entactogens
feelings of insight
characteristics of psychomimetics
beliefs or seeing things that aren’t there, hallucinations
where does LSD metabolism take place
mostly in the liver
T/F: LSD is a selective serotonin receptor agonist
true. it has a high affinity for 5-HT2a
a common mechanism of action of all hallucinogenic drugs
they almost all increase activity in the prefrontal cortex, and have common downstream effects
Which brain structures are affected, causing more vivid experiences while on LSD?
LSD increases the sensitivity of the thalamus, which is the brain region responsible for relaying external stimuli to the brain
3 primary brain regions (from book)
1) locus coeruleus (limbic system)
2) the cortex
3) raphé nuclei; usually helps filter incoming stimulus. increasing levels of serotonin over activate the raphé and it filters less stimuli
T/F: LSD causes huge stimulation in the mesolimbic dopamine system
false, it gives less stimulation to the mesolimbic dopamine system than caffeine
list some monoamine-like hallucinogens. some dissociative anaesthetcis?
monoamine like: LSD, magic mushrooms, mescaline, MDMA
dissociative anaesthetics: PCP, ketamine
in the cortex, how does LSD and hallucinogens increase activity?
they increase the duration of glutaminergic excitatory action potentials by acting on the excitatory 5-HT2a receptors, turning on the glutamate neurons
hypnogogic states in LSD-like drugs
Hypnogogic states: a state of imagination just before you fall asleep
T/F: people on LSD have increased susceptibility to hypnosis
true
T/F: time speeds up on LSD
false, most people report slowing down while on LSD
T/F: people have increased susceptibility to hypnoses while on LSD
true
entactogenic symptoms while on LSD-like drugs
provideing insight into one’s past and one’s own mind. serious introspection going on.
LSD’s effect on memory
there is a deficit in short-term and working memory
How can LSD like drugs be used as an antidepressant?
LSD is a 5-HT2a agonist and increases amount of serotonin in the brain. increased serotonin incresaes BDNF stimulation, contributing to synaptic remodeling
Why can you not overdose on LSD?
because it is a partial 5-HT2a agonist and will not cause serotonin syndrome
comment on the tolerance effects of LSD
if you take it daily, some tolerance will occur, but sensitization will come back within a week. there is cross tolerance to other mono-amine like drugs like magic mushrooms and mescaline. Tolerance is due to downregulation of serotonin 5-HT2a receptors
T/F: there is cross tolerance from LSD to cannabis
false
withdrawal effects of LSD
none
Is LSD discriminable from saline
heck yes
what other drugs do LSD generalize to?
it generalizes to some other monoamine hallucinogens but not dissociative anaesthetics
are LSD-like drugs readily administered
no, monkeys will even move away from the site of administration. Humans usually only administer it if they’re curious
which monoamine would monkeys readily administer? why?
they would administer MDMA because in addition to the hallucinogenic effect, it acts as a psychomotor stimulant like methamphetamine and activates the reward system. the monkeys begin to associate hallucinations with reward and will thus take MDMA
acute psychotic reaction /psychedelic crises
a “bad trip,” causing terror and anxiety
trailing phenomena
seeing after images as something moves.
what increases the “danger” level of LSD?
if you take MAOI’s with it. In addition to LSD stimulating serotonin release, there is nothing else breaking down the chatecholamines/monamines in the synapse.
combining MAOIS and LSD can lead to ____ toxicity
serotonin toxicity; the death of terminals due to too much monoamine transmission
synthetic MDMA is similar to natural ____, (from a cactus), but is way more potent
MDMA is similar to mescaline but is way more potent
how is MDMA synthesized?
by modifying amphetamine. it thus produces rewarding and hallucinogenic effects
mechanism of MDMA, how is it different than LSD?
MDMA stops the SERT transporters in the presynaptic cell from working, and so serotonin cannot be taken back up into the cell. different than LSD because LSD acts on 5-HT2a receptors POST synaptically like most neurotransmitters.
in addition to disabling the serotonin transporters, how else does MDMA achieve its effects?
it also has effects on dopamine and affects the release of oxytocin.
why is MDMA less safe than LSD
because it has no safety net. it is a full agonist of 5-HT2a unlike LSD, which is impossible to overdose on.
why was MDMA given during therapy?
because it increases therapeutic alliance, people agreed to work more with the therapist and it enhances communication
what does MDMA generalize to?
other serotonin agonists (5HT1A)
T/F: MDMA generalizes to cocaine
false
how does MDMA effect body temp? Why is this risky?
it increases body temp. people often try to drink water to cool down but they end up swelling their brain and causing epileptic-like seizures
main cause of death from MDMA
hyperthermia (over heating) and hypernatremia ( loss of electrolytes)
how do dissociative anaesthetics work
they separate people from sensory experience
disscoiative anaesthetics like ketamine are ____ antagonists
NMDA antagonists
is PCP more potent than ketamine
no, ketamine is more potent than PCP, has stronger effects but lasts a shorter amount of time
how does PCP and ketamine produce rewarding effects?
NMDA antagonist inhibits the GABA interneuron, resulting in increased Dopamine in the mesolimbic dopamine reward system
in what way does PCP and ketamine separate people from sensory experience?
by removing emotional value. people become less bothered by pain.
Why does PCP and ketamine result in memory problems?
because NMDA blockers affect the hippocampus from generating memories, like alcohol
are dissociative anaesthetics lipid soluble?
yes, they are normally injected
how does PCP and ketamine contribute to hallucinogen affects?
it increases cortical activity by blocking the NMDA receptor on GABA neurons in the brain. with no GABA inhibiting the cortex, cortical activity rises.
relationship of ketamine and BNDF
it actually stimulates BDNF
generalizability of dissociative drugs.
animals who can discriminate PCP and ketamine will not generalize them to any other class of drugs, there is some generalization to LSD though, most likely due to commonalities with the 5-HT2a receptors.
withdrawal affects of PCP
teeth grinding, anxiety and confusion
the one drug that generalizes to PCP and ketamine
dextromethorphan. NMDA antagonist
where in the brain is seen to have a reduction in volume upon PCP and ketamine use
there is decreased volume of the frontal gyrus
roboing
taking a bunch of cough syrup that contains dextromethorphan
Salvia is a _____ agonist
kappa opioid receptor agonist
how does salvia counteract kappa agonism resulting in decrease DA?
salvai is also a partial D2 agonist, allowing for hallucinations with no kappa induced DA decrease
What neurotransmitters do GHB modulate?
dopamine and GABA by binding to GHB receptors and GABAb receptors
where are GHB receptors primarily located?
in the cortex and hippocampus, resulting in decrease memory function
what disorder is GHB good at treating?
narcolepsy
T/F: reinforcing effects of MDMA is similar to psychomotor stimulants
false. psychomotor stimulants like amphetamine increase dopamine transmission in the mesolimbic system, but MDMA seems to mediated by its relationship with 5-HT2a receptors.
