Hallucinogens Flashcards
What is the inherent rewarding effect of hallucinogens?
Not inherently rewarding; may or may not produce addiction / pleasure etc
No withdrawal / physical dependence at all, generally no increases in DA
What are the 5 groups hallucinogens can be assigned to based on structure?
What do hallucinogens do to these synapses in each group?
1) Ach-like: SYNAPSES BLOCKED
2) 5-HT-like: STIMULATED synapses
3) Catecholamine-like: doesn’t say
4) Glu-like: NMDA BLOCKED
5) Opiate-like: Kappa facilitated
What synapses do LSD/psilocybin generally stimulate?
5-HT2A synapses
How is psychedelic experience generally elicited pharmacodynamically with hallucinogens?
Block cholinergic synapses
Stimulate 5-HT2A
Block NMDA synapses
Facilitate kappa-opiate synapses
What type of hallucinogen is scopolamine?
What receptor does it affect?
What are the phenotypic effects?
Anti-cholinergic; blocks muscarinic Ach
Dry mouth, blurred vision, increased heart rate, dilated pupils
(Jimson weed, belladonna)
What is the ED50/LD50 of jimson weed? TI?
ED50 = .5mg LD50 = 4mg
TI = 8
What drugs do the 5-HT agonists include?
Mescaline / MDMA, LSD/psilocybin
What receptor does belladonna / jimson weed (scopolamine) effect?
Muscarinic Ach receptor
What type of hallucinogen (pharmacodynamic) is mescaline?
5-HT agonist
What is an unpleasant phenotypic effect of mescaline?
Vomiting (even experienced users)
Effect in the stomach
What is the solubility like for mescaline?
Water soluble, not very lipid soluble
What neurotransmitter is mescaline structurally similar to?
NE
How long does it take for mescaline to reach peak CNS levels?
1-2hr
What is the state in the frontal lobes that hallucinogens cause called?
(Specifically right frontal lobe)
‘Hyperfrontal’ state
Hyperactive right frontal lobe; taking info in more
What neurotransmitter is Psilocybin similar to?
5-HT
What dose is psilocybin generally taken at? What is the half-life?
0.25mg/kg; effects within 30min, last 2-6hr; half-life of 3hr
What is the solubility of psilocybin like?
Quite water-soluble
What enzyme breaks down psilocybin?
MAO
What is the TI of psilocybin?
Lethal dose in humans unknown, TI quite high. Estimated 4 digits
What class of hallucinogens has the smallest TI?
Anti-cholinergics
What is the potency of LSD?
Incredibly potent; normal dose is barely visible
What dose is generally taken for LSD?
25-300 micrograms (1x10^-6 g)
How easily is LSD absorbed?
Readily absorbed, peak levels in 1-3hr
Where is LSD metabolized?
Liver, lasts 6-8hr
What is the TI of LSD?
280 (very high)
But the ED50 is super low, so you still have to be careful
What are the effects of LSD?
Slowing of time Change in space perception Color perception Synesthesia Hallucinations
What type of receptors is the locus coeruleus full of?
5-HT2A
Why will some monoaminergic neurons have action potentials on their own?
K+ conductance is high
Sets up K+ shunt
Shunts start to shut themselves off
Sodium leaks in as this happens
You therefore get a spike
How often do these self-firing action potentials in monoaminergic neurons fire?
~1/sec (‘basal LC activity’)
What does NE release in the LC do to glutamatergic excitation in postsynaptic neurons?
Enhances response of postsynaptic neurons to excitation
Where (according to Aghajanian & Marek) do hallucinations come from?
Hallucinogens inhibit basal LC activity
This makes these cells more responsive to sensory inputs
So, sensory system activity is enhanced
What is the ventral striatum involved in doing to experiences?
Adding motivational behavior
According to Vollenweider and Geyer, where do hallucinogens come from?
Increased activity between thalamus, cortical regions, and striatum
What drugs are the NMDA glutamate antagonists?
PCP
Ketamine
What is PCP also an agonist of?
D-2
How is PCP usually taken?
Smoked, but can be taken orally / injected. Aversive effects.
What is the solubility of PCP?
Fat-soluble
LOTS of depot binding
What is the ED50 for PCP?
~1mg/kg dose; LD50 at 70mg/kg
What is the TI for PCP?
High double digits
What is the LD50 for ketamine?
No known (safer than PCP)
What is the solubility of ketamine?
Lipid & water soluble
What effect does salvia have on 5-HT2A and NMDA receptors?
No effect
What receptors does salvia effect?
kappa-opiate receptors, D2 receptors
How fast are the effects of salvia when smoked? How long does it last?
30-60sec, lasts 10 min
What is Ayahuasca?
Hallucinogenic beverage from South America
Has vines with MAO inhibitors to make it psychoactive
How is Ayuhuasca taken into the brain?
Active transport across BBB
What is the active ingredient in Ayuhuasca?
DMT
How else can DMT be taken?
Smoked; no need for MAO inhibition
What brain state do ketamine and PCP produce?
HYPO frontal (as opposed to HYPER frontal)
But they still produce hallucinations!
What brain state exists in schizophrenics?
Hypofrontal
What are two examples of 5-HT agonists?
Catecholamine-like drugs like mescaline or MDMA
Also serotonin-like drugs like LSD or psilocybin
