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psy383_Phenethylamines_Cognitive_Enhancement

also includes info on caffeine
by

Will Moore

on 5 September 2013

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Transcript of psy383_Phenethylamines_Cognitive_Enhancement

Nobel Laureate (1933)
Father of Quantum Mechanics
Entropy
The amount of information an event provides
- An infrequently occurring event provides more information that a frequently occurring event
The uncertainty in the outcome of an event
- Systems with one common event have less entropy than systems with many equally probable events
The dispersion in the probability distribution
- An image of a single amplitude has a less disperse histogram than an image of many grayscales
Potential murderer of imaginary cats
error: variance in y that cannot be predicted by x
What does this have to do with drugs?
this is what Friston says...
...he's probably right
basal ganglia
striatum
caudate
putamen
dorsal
nucleus
accumbens
ventral
(not part of the striatum)
SN
substantia nigra
synapse
neurotransmitter cycle
dopamine synthesis
amphetamine
methamphetamine
methylphenidate
cocaine
Ritalin
(methylphenidate)
Methylphenidate
(Ritalin)
1885: ephedrine isolated

1887: amphetamine synthesized

1893: methamphetamine synthesized from ephedrine

1919: methamphetamine synthesized in crystal form

1927: Merck patents MDMA

1932: Smith, Kline & French market Benzedrine inhaler

WWII: (meth)amphetamine widely used by Japanese, Nazis, Allies

1965: Drug Abuse Control Ammendments tighten controls on amphetamine

1965: Shulgin synthesizes MDMA

1970: Comprehensive Drug Abuse and Prevention Control Act (Controlled Substances Act) places cocaine, methamphetamine and amphetamine on Schedule II

1984: DEA 'Emergency Schedules' MDMA to Schedule 1 for 1 year

1986: Justice Francis Young decides (after over a year of hearings) that because MDMA is safe to use under medical supervision, has little potential for addiction, and has legitimate medical applications, it cannot legally be scheduled higher than Schedule III.

1986: The DEA completely ignores the evidence and permanently declare MDMA a Schedule I controlled substance.

1988: After a protracted legal battle in which a collective of doctors and scientists sued the DEA, the courts affirmed Justice Young's decision, remove MDMA from Schedule I, and order the DEA to reassess its decision.

1988: Again, the DEA ignores not only science and the law, and 're-evaluates' its decision by permanently returning MDMA to Schedule I.

1991: Shulgin publishes Phenethylamines I Have Known and Loved (PIHKaL)

2002: Ricaurte et al., publish an article in Science on the neurotoxic effects of MDMA on dopaminergic neurons in primates

2003 (April): Illicit Drug Antiproliferation Act passed by congress, largely as informed by the aforementioned study

2003 (September): Ricaurte et al., publish a retraction, claiming that their vials of 'MDMA' had mistakenly been switched with vials containing methamphetamine

2004: MAPS finally administers first dose of MDMA in PTSD study
Lazår Edeleanu
Nagai Nagayoshi
Akira Ogata
Phenethylamine Timeline
catecholamine
action
Kristian Wilson, 1989
VMAT:
DAT:
vessicular monoamine transporter
dopamine transporter
normal
w/ drug
cocaine can also cause seizures...
methamphetamine is available by prescription in the US
adderall
racemic amphetamine aspartate monohydrate
racemic amphetamine sulfate
dextroamphetamine saccharide
dextroamphetamine sulfate
?
nigrostriatal path
ventral tegmental area
mesolimbic path
- crucial for motor behavior
- disrupted in Parkinson's
- to amygdala, hippocampus, nAcc
- 'reward' pathway?
- to neocortex (mostly prefrontal)
- attention, working memory
- additcion?
downstream effect
receptor type
low-potency/partial agonists
antagonists
receptor location
D
1
D
2
dopamine receptors
post-synaptic
'excitatory'
decrease cAMP
increase cAMP
pre- & post-synaptic
'inhibitory'
family
family
what sort of drugs are these?
So now that we know how the phenylethylamines work, what are these drugs for?
midbrain
VTA
nAcc
hippocampus
(you can't actually see it here)
amygdala
mesocortical path
dopaminergic pathways
“[c]ognitive enhancement may be defined as the amplification or extension of core capacities of the mind through improvement or augmentation of internal or external information processing systems”
“[e]ducation and training, as well as the use of external information processing devices, may be labeled as “conventional” means of enhancing cognition. They are often well established and culturally accepted”
2004
2011
MDMA leads to long term cognitive deficits in heavy users
No cognitive differences b/w subjects who had used MDMA and those who had not
Same Lab!!!
Bostrom & Sandberg (2009)
cognitive measures
cognitive enhancement
& stimulant addiction

"Alan Leshner, former director of the National Institute on Drug Abuse (NIDA) and chief executive of the American Association for the Advancement of Science, which publishes Science, agreed. This says even a single evening's use is playing Russian roulette with your own brain, he said."
Washington Post, 9/30/2002
"Ricaurte's findings were widely quoted when Congress was lining up support for the Illicit Drug Anti-Proliferation Act, also known as the Rave Act, which makes it easier to prosecute club owners and event promoters for the drug use of their customers. Congress passed the Rave Act on April 10, 2003. And tax dollars pay for public service announcements declaring that one hit of Ecstasy can destroy your brain"
E-fer Madness, Salon.com, 2003
"The retracted paper left the public with the impression that ecstasy is far more hazardous than it may actually turn out to be. This perception may have influenced the fate of the Reducing Americans' Vulnerability to Ecstasy Act. The act, which was appended to another bill and signed into law in April, holds club owners responsible for drug use on their premises. Critics say it is unlikely to reduce ecstasy use, but may discourage club owners from voluntary measures to protect users, such as cool-off rooms for the dangerous overheating that can occur with ecstasy, as these are tantamount to admission that drug use is going on. The legislation might have passed anyway, even if Ricaurte' s study had never been published, but the news certainly lent it urgency."
Nature, 2003
Cognitive Enhancement?
MDMA effects on cognition
Is ecstasy... bad?
Greely, et al. (2008)
Caffeine
half life:
LD :
50
192 mg/kg
rat
3-5 hr*
adenosine receptors:
nonselective antagonist
most widely used stimulant, often considered benign
~100 mg caffeine
stimulant
(but unlike nicotine OR the dopaminergics)
estimated for humans at ~ 3-20 grams, oral
single-shot espresso
24 oz. Mountain Dew
1/2 tablet of NoDoz
stomach
small intestine
readily crosses
(oral)
caffeine crystals
dissolved in solution w/ glucose
caffeine is both lipid- and water-soluble
adenosine
hippocampal A1
Goethe encouraged Runge to isolate caffeine
moral: put sugar in your coffee?
moral: drink coffee if you plan to disengage?
mechanism of action
role of expectation
(ADORA2A)
striatal A
2A
basal ganglia
contemporary
glutamate
acetylcholine
dopamine
epinephrine
norepinephrine
serotonin
downstream consequences:
concentration & turnover
GABA
The world's favorite psychostimulant!
increases activity of dopaminergic cells in the nucleus accumbens
findings
*wide variability based on drug interactions, developmental stage, hormonal state, etc.
"We have become convinved that contemporary efforts to educate people about the effects of alcohol and other drugs are inadequate and misdirected."

-Buzzed, p.17
Full transcript