Mind Enhancing.pdf

8/14/2019 Mind Enhancing.pdf

1/14

Nootropics - reviewing piracetam and analogues

by James South M.A.

Over 30 years have passed since the Nootropic !evolution "uietly began with the

development o# $iracetam in the late medical e##icacy with a virtual absence o# to%icityand side e##ects& something rarely seen with more standard medical drugs.

More importantly' they o##ered promise not only in the realm o# #ighting disease' but alsoin the virtually une%plored realm o# drugs that could not only postpone or even reverse

normal brain aging' but could even ma(e normal brains wor( better)

*he $iracetam-nootropics have been e%haustively researched& since the #irst scienti#icstudies on $iracetam in the late +,0s over +000 scienti#ic papers on $iracetam'

O%iracetam' $ramiracetam' and Aniracetam have been published with about two thirds o#

them on $iracetam.

*he action o# the $iracetam-nootropics has been studied in a broad range o# animals&

gold#ish' mice' rats' guinea pigs' rabbits' cats' dogs' marmosets' mon(eys and humans.

*he to%icity o# $iracetam and its cousins is ama/ingly low- almost non-e%istent. n

acute to%icity studies' intravenous doses o# $iracetam given to rats 12g 4g bodyweight5and oral doses given to mice' rats' and dogs 1+0g 4g or more5 produced no to%icity.

*his would be e"uivalent to 60-700 grams 1+.83 to +.69 pounds5 #or a +69 pound

human. !ats given +00-+000mg 4g orally #or months and dogs given +0'000mg 4gorally #or one year showed no to%ic e##ect' a teratogenic 1birth de#ect causing5 e##ects

were #ound' either 1*acconi and :urtman +,25.

*he $iracetam-nootropics are among the to%icologically sa#est drugs ever developed.

*he #our main commercially available racetam nootropics all share a pyrrolidinenucleus' while $iracetam' O%iracetam' and $ramiracetam' also share an acetyl group.

*he racetams 1especially $iracetam and O%iracetam5 are closely related in structure to the

amino acid $yroglutamic Acid. $yroglutamic Acid has been shown in some studies to

have wea( nootropic activity 1;ouliaev and Senning +,,95. $yroglutamic Acid isnaturally present in many human #oods' as well as the mammalian brain.

*he concept and de#inition o# a nootropic drug was #irst proposed in +,78 by


2/14


3/14

maintaining Ialiums anti-an%iety e##ects. $iracetam and Aniracetam have ameliorated

the amnesia produced by the protein synthesis inhibitor


4/14

n the Allobarbital e%periment' one o# the two surviving control rabbits actually presented

a more normal electroconvulsive shoc( treatment a#ter Allobarbital than did one o# the

survivors eleven $iracetam survivors..

Ket an electroconvulsive shoc( treatment recorded the ne%t morning 1about +2 hours

later5 showed that the control was still asleep' and it was not aroused by a loud noise.*he $iracetam rabbit' however' was well awa(e' behaved normally' moved around and its

electroconvulsive shoc( treatment was normal.

*hus' whether given .I. or orally' and be#ore or a#ter general lethal 1to controls5

barbiturate in#usion' $iracetam served to protect both li#e and brain structure and

#unction' as evidenced by electroconvulsive shoc( treatment records and post recovery

behavior.

*he rabbit e%periments @ust described are hardly unusual. *he $iracetam-nootropics

routinely show an ability to stabili/e or normali/e the electroconvulsive shoc( treatments

o# humans and animals under a broad range o# e%perimental and medical conditions.

*he electroconvulsive shoc( treatment records the electro-chemical activity o# largegroups o# cortical neurons' and thus provides a macro picture o# brain activity. Aging'

dementia' hypo%ia and ben/odia/epines all promote a similar shi#t in electroconvulsive

shoc( treatment #re"uency patterns.

Low #re"uency delta waves 10-9 cycles per second5 and theta waves 19-2 cps5 are

increased' while alpha waves 12-+8 cps5 and beta waves 1beta-+& +8-80 cps' beta 8& 80-38

cps5 diminish. *he average #re"uency o# the delta and alpha waves also drops' ascompared to healthy normal sub@ects.

Nootropics - clinical studies

;iaguinto and colleagues 1+,25 gave +8 healthy humans 6mg Ialium orally at +0$M the

night be#ore their e%periment. *he ne%t morning they were given either .I. O%iracetamor saline in a double blind crossover e%periment. O%iracetam strongly decreased the

e%cessive delta activity while simultaneously strongly increasing alpha activity' and also

induced a modest increase in beta activity. *hus O%iracetam restored the

electroconvulsive shoc( treatment to a pattern indicating increased vigilance andalertness' yet without destroying Ialiums anti-an%iety e##ect.

til and co-wor(ers 1+,25 treated #our groups o# +6 patients su##ering mild to moderatedementia with either O%iracetam or placebo #or three months. *he double blind study

used O%iracetam in doses o# 200' +00 and 8900mg daily. uantitative electroconvulsive

shoc( treatment data indicated that in patients with dementia' O%iracetam had a mode o#action similar to other vigilance enhancing compounds. *he ma@ority o# patients who had

abnormal slow electroconvulsive shoc( treatment patterns be#ore treatment showed a

normali/ation o# their brain waves- i.e. a decrease in slow 1delta and theta5 and an

increase in alpha waves. Saletu and colleagues 1+,265 conducted a #our wee( double


5/14

blind trial o# O%iracetam 18900 mg per day5 or placebo in 90 patients 1mean age& 20

years5 su##ering #rom the organic brain syndrome o# late li#e. *heir results showed a

clear trend towards a decrease in delta and theta wave activity' an increase in alpha andbeta wave activity' as well as an increase in the dominant #re"uency and the centroid o#

alpha activity a#ter O%iracetam treatment. *heir report notedG *he attenuation o# the

slow activity and the elevation o# the alpha andor slow wave beta activity a#terBO%iracetam - other studies have shown similar results with $iracetam and AniracetamC

re#lect


6/14

!esults o# a series o# paper and pencil tests' as well as computeri/ed tests to measure

perceptual motor reactions' showed a clear bene#it o# $iracetam over placebo.

*he three di##erent paper and pencil tests showed superior e##ects on per#ormance

compared to placebo' with con#idence levels o# $.00+' $.00+ and $.06. n #our o# thesi% computeri/ed tests $iracetam showed a signi#icant e##ect over placebo' with

con#idence levels o# $.06 #or three and $.08, #or the #ourth.

A #i#th test showed a clear trend in #avor o# $iracetam' with $.+0. :ilsher and co-

wor(ers 1+,7,5 related their results with 9.2 grams per day $iracetam in a double blind'

crossover trial to study the bene#its o# $iracetam #or dysle%ic students.

nterestingly' the +9 healthy student controls' matched #or with the dysle%ic sub@ects'

demonstrated a signi#icantly better result on a test measuring ability to memori/e

nonsense syllables while using $iracetam as compared to placebo.

*heir improvement #rom baseline was a +,.6 decrease in the number o# trials needed to

learn the nonsense syllables while using $iracetam' versus a +0., decrease #rombaseline while using placebo. $.06. $iracetam-nootropics may increase learning and

memory in healthy individuals' where they are not merely attenuating or reversing

pathology' through their distinctive power to promote what has been termed hemisphericsuper-connection.

*he cerebral corte% in humans and animals is divided into two hemispheres- the le#t and

right corte%. n most humans the le#t hemisphere 1which controls the right side o# thebody5 is the language center' as well as the dominant hemisphere. *he le#t corte% will

tend to be logical' analytical' linguistic and se"uential in its in#ormation processing' while

the right corte% will usually be intuitive' holistic' picture oriented and simultaneous in itsin#ormation processing. !esearch has shown most people #avor one hemisphere over the

other' with the dominant corte% being more electrically active and the nondominant

corte% relatively more electrically silent 1when the person is being tested or as(ed tosolve problems' or respond to in#ormation5. *he two cortical hemispheres are lin(ed by a

bundle o# nerve cables& the corpus callosum and the anterior commisure. n theory

these two structures should unite the #unction o# the two hemispheres& in practice they act

more li(e a wall separating them. *his #unctionally-split neurology produces a parallelset o# dichotomies in consciousness& logic vs. intuition& reason vs. emotion& analysis vs.

synthesis& parts vs. whole& words vs. pictures& science vs. art and religion' etc. As noted

earlier' the word nootropic is derived #rom the ;ree( word nous 1the more standardphilosophical spelling5. Ket in the philosophy o# $lato and Aristotle' nous did not

simply mean mind. n ancient ;ree( philosophy' nous re#erred to the #aculty o#

higher mind or reason' as opposed to the more concrete' sensory oriented mind whichhumans share even with the lower animals. And reason did not merely mean logic or

analysis.


7/14

*he ;ree( philosophers saw the role o# philosophy to be a method o# developing and

per#ecting nous reason. *hey understood nous reason to be the integrative mind' where

logic wor(s complementarily with intuition' and reason and emotion are in harmony.:ith a developed nous' one could clearly see and understand the #orest and the trees

simultaneously. Erom a modern neurological perspective it is obvious that the cerebral

basis #or a well-#unctioning nous would be the e##ective' complementary' simultaneousintegrated #unction o# cortical hemispheres' with neither hemisphere being automatically

dominant or silent.

*his in turn would re"uire the corpus callosum and anterior commisure to optimi/e

in#ormation #low between the two hemispheres. !esearch has shown the $iracetam-

nootropics to #acilitate such intercebral in#ormation trans#er- indeed' its part o# the

de#inition o# a nootropic drug.

;iurgea and Moyersoons reported in +,70 that $iracetam increased by +00 the

transcallosal evo(ed responses elicited in cats by stimulation o# one hemisphere and

recorded #rom a symmetrical region o# the hemisphere.

?uresova and ?ures 1+,75 in a comple% series o# e%periments involving monocular1one-eye5 learning in rats' demonstrated that ...$iracetam enhances transcommisural

encoding mechanisms... and some #orms interhemispheric trans#er...

imond 1+,7' +,7,5 used a techni"ue called dichotic listening to veri#y the ability o#

$iracetam to promote interhemispheric trans#er in humans. n a dichotic listening test'

di##erent words are transmitted simultaneously into each ear by headphone. n most

people the speech center is the le#t corte%' because the nerves #rom the ears cross over tothe opposite side o# the brain' most people will recall more o# the words presented right

ear than the le#t ear. :ords received by the right ear directly reach the le#t corte% speech

center' while words presented to the le#t ear must reach the le#t corte% speech centerindirectly' by crossing the corpus callosum. imonds e%periments with young healthy

volunteers showed that $iracetam signi#icantly improved le#t ear word recall' indicating

$iracetam increased interhemispheric in#ormation trans#er.

O(uyama and Aihara 1+,225 tested the e##ect o# Aniracetam on the transcallosal response

o# anaesthetised rats. *he transcallosal response was recorded #rom the sur#ace o# the

#rontal corte% #ollowing stimulation o# the corresponding site on the opposite corticalhemisphere. Aniracetam at two di##erent .I. doses 1+0 mg and 30mg per 4g5

signi#icantly increased the amplitude o# the negative wave compared to its level prior to

drug' $.0+ and $.00+. *he researchers stated that the present results indicate thatAniracetam.. increased the amplitude o# the negative wave' thereby #acilitating

interhemispheric trans#er... *hus' it is considered that the #unctional increase in

interhemispheric neurotransmission by nootropic drugs may be related to theimprovement o# the cognitive #unction.

n spite o# the many and diverse neurological and psychological bene#its they have shown

in human' animal and cell studies' the $iracetam-nootropics are generally considered


8/14

NO* to be ma@or agonists or inhibitors o# the synaptic action o# most neurotransmitters.

*hus' ma@or nootropic researchers $epeu and Spignoli 1+,,05 state& the pyrrolidinone

derivatives B$iracetam-nootropicsC show little or no a##inity #or


9/14

Moglia and co-wor(ers 1+,25 concluded #rom a study o# 93 organic syndrome patients

that side e##ects during BO%iracetamC treatment headache 13 cases5' constipation 1+ case5'sleep disturbances 1+ Side e##ects during placebo treatment were headache 18 case

constipation 1+ case5. *he side e##ects spontaneously disappears re"uired neither

medication nor treatment interruption. No signi#icant BadverseC change in neurologicaland laboratory e%1 lions' =


10/14

$iracetam-nootropics have been combined in many clinical and e%perimental situations

with other drugs' almost always with a positive' synergistic e##ect. Many clinical

e%periments have demonstrated $iracetam and O%iracetam to synergi/e with anti-epileptic medications' especially carbama/epine 1*egretol5. A simultaneous enhancement

o# the anti-epileptic drugs anti-sei/ure activity' combined with improvement or

elimination o# the memory' alertness and comprehension cognitive de#icits induced +Ganti-epileptic drug' have been #ound in multiple studies 1


11/14

goal directed and purposive behavior 1?ranconnier +,235. A#ter trying $ramiracetam in

my regimen several years ago. did notice an increase in my tendency to "uic(ly ta(e

care o# routine household' auto and personal maintenance chores habitually tended toignore' avoid or postpone.

have ta(en $iracetam #or eight years' $ramiracetam and Aniracetam #or the past twoyears and O%iracetam #or about , months. uring the past year' my li#elong severe

writers bloc( has gradually disappeared' and my writing output o# the past year has

e%ceeded that o# the previous decade. Some studies on dementia comparing $iracetamand O%iracetam 1the two most nearly identical racetams5. have suggested that O%iracetam

may be more e##ective in restoring the cognitive de#icits o# dementia 1decreased memory'

concentration and alertness5' while $iracetam may be more e##ective at normali/ing the

emotional problems o# dementia 1agitation' tension-an%iety' hostility' insomnia'uncooperativeness5.

uantitatively' $iracetam is the least potent racetam' with clinical doses typically being

8900 mg to 9200 mg per day' occasionally even 000 mg to 0'000 mg per day.

O%iracetam is usually given 600 mg to 8900 mg per day. Aniracetam doses are typically760 mg to +600mg per day' while $ramiracetam has shown bene#it even at +60 mg to 600

mg per day' although 00 mg to +600 mg per day is more typical.

$iracetam and O%iracetam are highly water soluble 1,-,25' while Aniracetam and

$ramiracetam are more #at soluble. *heir lipophilicity may allow #or less #re"uent dosing

1once or twice daily5 with Aniracetam and $ramiracetam' compared to 3 to 9 doses a day

with $iracetam and O%iracetam.

Aniracetam is #avored by the Japanese' who have contributed much research on it. t is

widely used there as an agent to rapidly promote clarity o# thought.

Nootropics - uses and conclusion

uring the past 30 years' the $iracetam-nootropics have been used to treat an ama/ingly

broad range o# human ailments and conditions' either or with other drugs' with moderate

to ma@or bene#it. $iracetam-nootropics have been used to treat various #orms o# dementia

and organic brain syndrome. *hey have been used success#ully to treat dysle%ia'epilepsy and age-associated memory impairment. $iracetam-nootropics have success#ully

treated post-concussional syndrome' vertigo' alcohol withdrawal' cerebrovascular

insu##iciency and hypo%ia. *hey have shown bene#it in normali/ing blood #low parametercreased platelet aggregation' increased red blood cell 1!?


12/14

*he racetams are cerebral homeostatic normali/ers' neuroprotectants' cerebral metabolic

enhancers and brain integrative agents. *hey enhance brain energy' especially under

de#icit conditionG hypo%ia' chemical to%icity or impaired cerebral microcirculation. *heypreserve' protect and enhance synaptic membrane and receptor structure and plasticity.

*hey enhance brain integration- hori/ontally' by increased coupling o# the cerebralhemispheres& and vertically by enhancing cerebral connection with and tonic control o#

the limbic system' through nootropics e##ects on the hippocampus- a ma@or lin( between

cerebrum and system.

*his vertical integration increase may help to integrate reason 1cerebrum and emotion

1limbic system- sometimes called the horse brain5. *he increased tonic cortico-

subcortical control and regulation may prevent our limbic passions and desires #romrunning away with us as in crimes o# passion.

n middle aged and older individuals who do not yet su##er any speci#ic neural malady or

ma@or mental impairment' nootropics may not only slow down or postpone entropic brainaging' but they may even reverse mild neural mental decline. *hus a person at 60 might

be smarter' have better memory' "uic(er re#le%es and greater vigilance and alertness thanwhen they were 90. *he racetams may literally be sa#e and e##ective pharmacologic tools

to enhance' protect and optimi/e truly normal' #ully human neuropsychological structures

and #unction' well into old age.

HOM= to order

!=E=!=N


13/14

7. S.J. imond' =. ?rouwers 1+,75 ncrease in the power o# human memory in normal

man through the use o# drugs $sychopharmacol 9,' 307-0,.

2. S.J. imond et al 1+,7,5 Some e##ects o# $iracetam on chronic schi/ophrenia

$sychopharmacol 9'39+-92.

,. S.H. Eerris et al 1+,285


14/14

88. L. $arnetti et al 1+,265 Haemorheological pattern in initial mental deterioration&

!esults o# a long term study using $iracetam and $e#ylline Arch ;erontol. ;eriatr9'

+9+-66.

83. ;. $epeu. ;. Spignoli 1+,,05 Neurochemical actions o# nootropic drugs in

Advances in Neurology I6+& Al/heimerFs disease. !. :u ed. 897-68' !aven $ress.

89. ?. Saletu et al 1+,265 O%iracetam in the organic brain syndrome o# late li#e

Neuropsychobiol +3' 99-68.

86. 4. Scha##ler' :. 4lausnit/er 1+,225 Antihypo%idotic e##ects o# $iracetam using

psychophsiological measures in healthy volunteers Ar Eorsch. rug !es. 32' 822-,+.

8. M. *acconi' !. :urtman 1+,25 $iracetamG physiological disposition and

mechanism o# action in Advances in Neurology I93& Myocio Eahn' ed. 76-26' !aven

$ress.

87. $. :ester 1+,275 Magnesium Am. J. L NO* !=$LA4.

Mind Enhancing.pdf

Documents

Transcript of Mind Enhancing.pdf