NESC 3237 Lecture Notes - Vasodilation, Methylphenidate, Nicotinic Acetylcholine Receptor

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Published on 18 Apr 2013
School
Dalhousie University
Department
Neuroscience
Course
NESC 3237
Professor
March 12th, 2013
March-12-13
2:33 PM
Addictive potential for hallucinogenic drugs
Very rapid tolerance seen in hallucinogenic drugs
o If LSD taken again the next day, not very large effects seen
o Because of this, these drugs are not very likely to be compulsively used
Maximum effects obtained at very low doses (LSD in particular)
o Once all receptor sites occupied, you may have longer duration of effects if you take more,
but you will not have a greater high
Often just used for a period of a few years
Not usually self-administered by animals
o Because effects take so long to onset
Epidemiology
Gained popularity in the 60s
Goes through cycles of popularity
Tend to be fairly inexpensive
MDMA
Gained popularity in the 90s
Associated with raves often times
Has characteristics of hallucinogenic drugs and has psychostimulant properties
o So a cross from amphetamine and hallucinogen
Increased feeling of well being, heightened feeling of connectedness
o Connectedness from affect on oxytocin
Neuropharmacology
DA, 5HT and NE agonist
o A reuptake inhibitor
o Also facilitates release
Some evidence that there's a risk of 5HT neurotoxicity associated with repeated use
o Depression, memory and attention problems, anxiety, impulsivity
Causes an increase in body temperature
o Some evidence that neurotoxic effects associated with its hyperthermic effects
Hard drug to study because its so often used in conjunction with other drugs
Pharmacokinetics
Normally administered orally
Peak levels after a couple hours
Half life is around 8 hours, 95% gone in 40 hours
Lingering effects which last for several days
Has a therapeutic index of 15, so it's a fairly safe drug
But much more dangerous in terms of lethal effects when compared to LSD, cannabis
Effects of other drugs on it
o Alcohol may make it worse in terms of dehydration
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o Cannabis may help in terms of body temperature
***Polysubstance abuse***
Polysubstance use
Often no distinction made between concurrent and simultaneous polysubstance use
o DSM-IV has a category for concurrent substance use
This allows you to be classified as having a drug abuse without meeting the criteria for
one drug individually
Simultaneous polysubstance use
o More interesting in understanding drug action
o Because you can look at interaction between two drugs
Simultaneous polysubstance use
In general associated with poorer prognosis in treatment-seeking drug users
o Use of one substance may be associated with relapse to misuse of the other
Coke and alcohol example
Most drugs that are commonly coadministered usually produce combined positive effects
o Functional aspects to the combination of substances usually
o In some cases it may actually reduce the level of harm associated, however in most cases it
cause an increase in risk of harm
It's not only what drugs you're mixing that matters, the order of administration is also important
o Coke first than alcohol does not cause the increased plasma levels of cocaine because there
is not alcohol metabolism competition present yet to cause it, because the alcohol has not
made it to the liver before the cocaine. But using alcohol first does cause the increase in
plasma cocaine levels
o Neurotoxic effects of MDMA when coadministered with amphetamine are more
pronounced when MDMA administered prior to amphetamine
In terms of determining how people coadminister drugs, best to tie their administration to a
specific memory
o Once done, you can develop lab based models of polysubstance abuse
o 97.5% of people who use cannabis coadminster when at rave in study
Orders of administration
Alcohol very commonly coadminstered with other drugs
o When administered first, it often causes increased plasma levels of other types of drugs
because of competition for metabolism
o Quite often produces novel metabolites when mixed with other drugs
o Unclear most times why people mix alcohol with other drugs
Possibly related to decrease in negative affect
So people are drinking, and are just like fuck it, I'll try some ecstasy
Amphetamine very often administered first when coadminstered with MDMA
Cannabis pattern of use much more unpredictable, no reliable order of administration
o Except with hallucinogens, people more likely to smoke weed after using mushrooms
Barret's new paper
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Document Summary

Very rapid tolerance seen in hallucinogenic drugs. If lsd taken again the next day, not very large effects seen: because of this, these drugs are not very likely to be compulsively used. Maximum effects obtained at very low doses (lsd in particular: once all receptor sites occupied, you may have longer duration of effects if you take more, but you will not have a greater high. Often just used for a period of a few years. Not usually self-administered by animals: because effects take so long to onset. Has characteristics of hallucinogenic drugs and has psychostimulant properties: so a cross from amphetamine and hallucinogen. Increased feeling of well being, heightened feeling of connectedness: connectedness from affect on oxytocin. Da, 5ht and ne agonist: a reuptake inhibitor, also facilitates release. Some evidence that there"s a risk of 5ht neurotoxicity associated with repeated use: depression, memory and attention problems, anxiety, impulsivity.

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