Know all 7 FDA approved drugs for addiction
what addiction they treat (if more than 1, know all of those)
molecular effects (partial agonist, antagonist),
What stage of the addiction do they treat binge/intoxication, etc,
disadvantages vs advantages
treats craving for heroin because it is an agonist for the R = user won’t crave heroin, but it doesn’t happen in the preoccupation/craving period.
have to keep taking it to feel good
decrease in hepatitis C, HIV infection b/c less use in needles
Old stuff: IC self - stim,
acute effects during withdrawal
Hallucinogens - 3 subtypes
3. Phenylethylamines (mixed stimulant and NMDA hallucinogen effects)
Mixture of amphetamine and
• More similar to the INDOLE(5-HT) effects
MESCALINE = more similar to the indole (5-HT)-type effect than the other, similar effects to LSD
HOT TOPIC 3 = Psilocin binds to 5HT-2A R (responsible for spirituality)
Study on correlation b/w 5-HT Rs and Spirituality
out of 1000s of questions/questionnaires-trying to put together the effects of hallucinogens,
the only common factor was spirituality,
they managed to correlate it with use
5-HT-1A. 5-HT2A Rs & spirituality related
inversely related to spirituality. Increase 5-HT R binding = less spirituality
spirituality increase regardless of whether they enjoyed the trip, has anxiety (40% had negative effect)
The 40%-group still wrote down that it was a VERY SUBSTANTIAL experience
Effect during trip vs after = NO relationship
PCP acts on/binds to NMDA R, on PCP site
(like benzo site in GABA R)
blocks 5-ht transpoter causing an antidepressant effect in long-term
--> antidepressant effects are IMMEDIATE
Antidepressant effects on 5-HT system
block the 5-HT transporter
Making more 5-HT available to bind to the 5-Ht Rs
This has a long-term + long-acting antidepressant effect
SINCE 5-HT has an effect on drepression, indirect effect on NMDA Rs?
NOT available to treat depression, b/c can’t make money off it
3 ionotropic, 1 metabotropic,
their distribution: _______
Cross tolerance b/w LSD + psilocybin?
they work on the same R --> cross tolerance in short
Indole = No cross tolerance
NMDA = Yes Cross tolerance
TEST EFFECT in rats b/w the US + CS, if you test a level you want the effect to be w/in 10-20 secs in order for the mice to connect the rewarding effect of lever pressing.
ICSS ∆ - w/acute admin. of NMDA + withdrawal from NMDA****ON EXAM
when happy = need less electricity,
when unhappy = need more electricity
= is not the active ingredient
Psilocin = active ingredient
takes one week for it to break down in the body
Ondansetron = anti-nausea drug given to cancer patients bind to 5-HT3 R, (not traveling nausea) some effect on treatment of alcoholism
Figure 1: see a general dose response curve for drug happiness, ex. fearful experience, in one patient, the higher dose managed to do it, but in others that's not necessarily the case
Figure 3: Ascending + Descending dose
looks at repeated dosing. avoids:
confounding effect of repeated dosing
patients can’t guess what they are getting next, placebo or drug
they are guessing about feeling more/less of the effects
Nice to see a dose response (straight line)
looks at LSD effects, similar to psilocibin
Animal Model: Drug discrimination experiment =
Given Questionnaires to compare ∆ after taking LSD (factors in there) --> so if they answered similarly to the way people answered to LSD = assume the effects are similar
humans DID NOT discriminate b/w LSD and psilocibin,
in study given PSILOCYBIN
with animal it would be more difficult b/c they don’t like LSD effects
- It didn’t matter if there were negative effects during the drug taking = people still rated it as a POSITIVE EXPERIENCE
Psilocibin is NOT that much of an addictive drug
has more longer lasting effects that makes it happen during the effects
LOW amount of side-effects
Treatment and Genetics ppt
- take home messages slide important to know
addiction is multi-factorial trait like height
Ex. Gives a whole area (can have mRNA, microRNA, introns) --> splice ∆es could cause the intron locus to ∆
looked at population for a trait we can quantify. (.e. # of drinks, height)
locate a locus aka QTL (where the gene might be located) in DNA (not a gene).
quantify the trait, gene that is responsible for ___
After running a DNA sequence, we can see differences of DNA in locus --> a maker where for _____ gene exists
is much easier to find it on the genotype that may be appropriate. “this is the locus where the ____ gene is”
For ex. NUMBER OF DRINKS is a Quantifiable trait
Alcoholism: COGA Project ----> QTL mapped in same region as alcohol dehydrogenase (ADH)
Max # of drinks pinpoints locus in the genome to where alcohol (enzyme) dehydrogenase (breakdown) is
Located on mouse chromosome3
Have 2 diff strains of mice: D2 = withdrawal induced convulsions C57 = less convulsions (non-seizure prone strain)
all animals genetically identical --> find locus/gene that cause convulsion
start crossing them toward 1D,
cross non-seizure prone strain to make it a seizure- prone strain
after 1 day, after 1 cross will hit the seizures
cross it once, no seizure, again, no seizure
The amount of time we hit a seizure then we know that in between the generation b4(no seizures) and the generation after(seizures) there was a flip in genes that seemed to be important for seizures
Out of all the genes that ∆d in the split, 1 of them should to be involved in the seizures
b/w the 2 genes we want to pinpoint/mark which locus is responsible for seizures--> a way to isolate gene in locus
mpdz, barrier to treatment in addiction,
Rosetta Stone Cross Validity.
you have animal model and drug.
If you decide to move it to clinical trials + FDA approval + it is used on humans,
if it works get it approved by FDA,
Ex. bupropian (antidepressant, smokeing cesation, helps w/obesity) with depression --> it helps w/sadness but doesn’t help anxiety,
take it back to animal models to see which of them seemed to be ∆ed by this drug that does work on humans
ex. bupropian -> take it back into animal models, it affects depressive measuring animal models but NOT anxiety measure animal models
Validates use of animal models to test drug that will be used to treat humans.
Test in animal models --> take it to humans --> take it back and judge which animal models are actually accurate
Clinical phases = more effective in European vs American
ex. chantex working in Europe not the US
Exam questions over Treatment part
ExtraCredit****Gabapentive = not FDA approved drug, decreases GABAR (increase Ca2+) --> reduces alcohol SA
alcohol works on the GABAR, so it makes sense that GABAR would be able to affect it aka directly correlated
-----> makes sense that withdrawal would cause anxiety and stress --> then modulating anti stress molecules might have an affect as well
None of the FDA approved drugs that treat alcoholism work on GABAR
All drugs of abuse ∆ DA so maybe it makes sense to use some DA ???
7 FDA drugs + nicotine substitute
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