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Addiction Protocol (Hypothetical)


topiramate 50mg daily x 30 days then 25mg daily at bedtime

namenda xr 28 mg daily in PM (this is an optional medicine)
minocycline 50mg --2 daily in AM x 3 months then 1 every AM
lithium 100mg daily in AM (could use the OTC version lithium orotate 120mg )
valproic acid 250mg daily ( take with the lithium)
N-acetyl cysteine 600mg bid
EGCG/green tea-- 1 cup drank warm and slow over 30 min twice a day or green tea gum.
Theanine 400mg at bedtime
Curcumin Phytosome 1000mg daily

The protocol is meant to be taken for 3-5 years .

For all addictions any PTSD and any borderline personality: The low dose topiramate is used for
lifetime and at 25mg at bedtime it is a pretty benign substance.
Taking the curcumin phytosome, theanine and the geen tea for lifetime would be well advised , but not
All of the agents are inexpensive except for the namenda and the namenda is an optional agent.
Check the homocysteine level. If elevated then check MTHFR status and consider adding 5-methyl
folate 400mcg daily.
While one could use all of the agents for every patient , it would not be necessary.
For the average alcoholic-use the topiramate and the N-acetyl cysteine and the theanine.
For the opioid addiction, using topiramate , theanine, n-acetyl cysteine,minocycline,
Low dose lithium and low dose valproic acid , green tea.
Stop the low dose lithium/vpa combo after 4 months.
For the average PTSD person-- topiramate and the curcumin and the theanine and green tea.
You have to use the curcumin phytosome because it really improves bioavailability .
For the average borderline personality--topiramate, curcumin and the theanine and green tea along with
their normal meds should help.
For the person who has multiple drug addictions or really severe single drug addictions or who has
severe borderline or severe PTSD issues, one could use all the agents for 3-5 yrs and then wean off
some of them as able.( still need to think about this may change some things)

The 3-5 yrs is to allow time for neuronal restructuring and then to strengthen those new neural
connections- ie deepen the new 'nonaddiction' learning pathways in and between the various
subsystems in the affected brain areas of the nucleus accumbens, ventral tegmentum , prefrontal cortex,
amygdala,locus cerules..etc.
The goal is to allow for 'normality' to be re-established and then deeply ingrained/reinforced as new
learning pathways ( ie neural connections) in these affected brain areas(ie nucleus accumbens, ventral
tegmentum , medial prefrontal cortex, amyggdala, hippocampus, ventral pallidum... etc) over that 3-5
yr period. Also all of these folks should abstain from HFCS containing substances .
The high fructose corn syrup will upregulate AMPA receptor expression and I suspect it would put
them at higher risk for relapse. That is why topiramate helps the most as wt loss agent in obese
situations where the person has a dependance on HFCS.
Time is the friend of topiramate . The longer the patient is on the topiramate , the more 'normalization'
of the neuronal connections occurs in those with AMPA driven neuronal distortions.

http://www.ncbi.nlm.nih.gov/pubmed/12452551 topiramate inhibits ampa locus cerules interaction in
opioid withdrawl
http://www.ncbi.nlm.nih.gov/pubmed/12858324 interesting but not surprising
http://www.ncbi.nlm.nih.gov/pubmed/17719565/ NAC help prevent relapse in heroin
http://www.ncbi.nlm.nih.gov/pubmed/8747753 role of ampa receptors and lc in opioid withdrawl
http://www.ncbi.nlm.nih.gov/pubmed/?term=curcumin+and+ptsd curcumin impairs fear memory
reconsolidation--- this is a good thing fyi there are versions of curcumin that cross bbb .
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1479803/ interesting , but not surprising..
I think one could consider the proximal agent of most conditions with an obsession component will be
found to be upregulated AMPA receptor expression. No surprise then that topiramate downregulates the
AMPA receptor expression and so would weaken the obsessions.
http://www.ncbi.nlm.nih.gov/pubmed/8914123 Ampa antagonist can suppress many of the withdrawl
sx of morphine

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754842/ theanine acts on nmda bdnf and gaba to help

minimize withdraw effects of opioids

http://www.ncbi.nlm.nih.gov/pubmed/12559125 selective ampa antagonism helps

http://www.ncbi.nlm.nih.gov/pubmed/1839935 NMDA competitive inhibitors help in narc withdrawal

http://www.ncbi.nlm.nih.gov/pubmed/8994212 pathways of withdrawal

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075088/ glutamatergic system and gambling

/addiction and topiramate
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154511/ a good one on topiramate and
ampa receptors containing the GluR5 subunit and it is this subunit that causes addictive like behaviors.
Topiramate inhibits this subunit ---this is an effect that is unique to topiramate.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2239014/ discusses glutamatergic substrates that help

to drive addiction behaviors. This is a very good article.....
http://www.ncbi.nlm.nih.gov/pubmed/25515789 curcumin effect on opioid dependance via modulation
of calmodulin protein kinase II alpha activity.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792955/ the role nucleus accumbens plasticity plays
in addictiontake note if the increase in expression of ampa receptors in maintaining and reinstating
problems .. their expansion is crucial to the addiction and they upregulate during withdrawl to place
person at risk for failure --- this is why pace on topiramate for 3-4 months before stop and for 3 yrs
after.=== and why if on opioid for chronic pain then maybe keep on small dose of topiramate to
prevent ampa expansion in the first place. This is fantastic article.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2601563/ interesting one on ampa receptors in the NA

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365010/ ampa effect in opioid abuse.

Ampa expansion is a problem.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063512/ topiramate pharmacokinetics and effects on

etoh---good article.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964903/ a very nice article on the intricacies of
AMPA NMDA and KA receptors. I need to put this one to text to speech yet.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1575064/ topiramate as carbonic anhydrase inibitor.

http://www.ncbi.nlm.nih.gov/pubmed/10768293 topiramate effect on KA receptors.

http://www.ncbi.nlm.nih.gov/pubmed/22920535 mu and nmda interactions

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034717/ mu and topiramate

http://www.ncbi.nlm.nih.gov/pubmed/21508625 morphine and reward pathways

http://www.ncbi.nlm.nih.gov/pubmed/12522725 tolerance
http://www.ncbi.nlm.nih.gov/pubmed/11387385 narc withdrawal in locus cerules
-----------------------------------------------------------------------------------------------------------------------http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302770/ just discusses the some mechanisms of
topiramate in sci.
http://www.ncbi.nlm.nih.gov/pubmed/9757028/ just mentions the NMDA effects of topiramate.

http://www.ncbi.nlm.nih.gov/pubmed/15244111 another one on mechanisms of topiramate on KA,

AMP and gaba and Na channels.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1838561/ mmp in addiction
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842477/ mmp 9 is needed for opioid physical
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428329/ mmp9 in ltp

http://www.ncbi.nlm.nih.gov/pubmed/18792988 mmp 9 is important for reinstating addiction memory

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4241163/ mmp2 and mmp9 are required for relapse
from cocaine

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228456/ nr2b is crucial in heroin addiction

http://www.ncbi.nlm.nih.gov/pubmed/25623036 epigenetics of addiction
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718567/ epigenetics of addiction good one
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368896/ epigenetic issues and etoh control
http://www.ncbi.nlm.nih.gov/pubmed/18616668 epigenetic in etoh
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670307/ nicotine and GABAergic neurons
http://www.ncbi.nlm.nih.gov/pubmed/9716929 mole mech of relapse
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549070/ reward and antireward mechanisms
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651846/ reward systems in brain

http://www.ncbi.nlm.nih.gov/pubmed/17072591 dopamines role in 'wanting ' drugs

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549070/ rewards systems discussion/review
http://www.ncbi.nlm.nih.gov/pubmed/18469802/ cue-reward learning and thalamo-amygdala

http://www.ncbi.nlm.nih.gov/pubmed/10420169 interesting one on nmda and ampa and corticoamygdala interations----------- fyi same as thalamo-amygdala interactions

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545669/ neurobiology of 12 step program

http://www.ncbi.nlm.nih.gov/pubmed/9768547/ etoh and limbic system

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131314/ reward and incentive and hedonistic drivers

http://www.ncbi.nlm.nih.gov/pubmed/16354936/ mu narcs stimulate hedonic areas in the nucleus

accumbensso do sweetness , food and drug reward

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606924/ role of ventral pallidum in reward and


http://www.ncbi.nlm.nih.gov/pubmed/26276628 from reward to addiction

http://www.ncbi.nlm.nih.gov/pubmed/20730946 addiction overwhelms the brains control mechanisms

http://www.ncbi.nlm.nih.gov/pubmed/15987950/ Conditioned nicotine withdrawal profoundly

decreases the activity of brain reward systems.
http://www.ncbi.nlm.nih.gov/pubmed/16738231 Conditioned withdrawal drives heroin
consumption and decreases reward sensitivity.

http://www.ncbi.nlm.nih.gov/pubmed/15388289 The results indicate that neuroadaptation within brain

reward circuitry results in significant reward deficits after a single morphine pretreatment, and this deficit increases
rapidly with repeated morphine and naloxone-induced withdrawal experience.

http://www.ncbi.nlm.nih.gov/pubmed/25583178 emotions and addictions

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730086/ addiction is reward deficit and stress surfeit
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830720/ this is a very good article

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637927/ neuro substrates for compulsion addictions

http://www.ncbi.nlm.nih.gov/pubmed/23883567 effects of theanine on nmda receptors and ltp
http://www.ncbi.nlm.nih.gov/pubmed/17182482 theanine in neuroprotection/cognition improvement
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009342/ NAC in addictions
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003018/ retrieval induces reconsolidation of fear
extinction memory
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407613/ glutamate uptake in etoh disorders
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542613/ DNMT activity is critical for cocaine
memory reconsolidation .so make a good argument for DNMT inhibitors ie sulfurophane,
resveratrol, egcg, valproic acid etc.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2080837/ discusses how NMDA receptors in the
basolateral amygdala are crucial for longterm memory consolidation in cocaine abuse and drive the risk
for relapse over the long term.,,,, I think it makes the argument for long term low dose topiramate and
maybe curcumin phytosome.
http://www.ncbi.nlm.nih.gov/pubmed/12724166 I think strengthens the argument having a sodium
channel blocker on board for the long term in the form of low dose topiramate.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429636/ interesting effects of fructose on cognition
http://www.ncbi.nlm.nih.gov/pubmed/20800122 discusses how fructose acts like ETOH --- very
interesting article fructose induces habituation and mild dependence .. using the same brain
systems as alcohol ---just to milder effect. THAT is why topiramate helps best as wt loss agent in obese
people who have an AMPA receptor upregulation driven habituation /dependence on fructose and
HFCS(worse version of fructose).
That is why if addicted to etoh or narcs , then abstain from fructose and high fructose corn syrup.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649103/ fructose is alcohol without the buzz--this is a great article and helps one to understand why fructose and High fructose corn syrup causes so
many problems and why the food companies put it in everything from chicken soup to cola ...it helps
create a habituation situation/dependence to their product.
I think the PhD folks in the food industry figured all this out in the early 1980s ---- hence the start of
the obesity epidemic....and worsening of the narc/etoh /other AMPA driven problems in society..
Because the AMPA system is a survival system meant to help one survive a famine, those populations
with a famine history or feast or famine lifestyle are going to be at greatest risk for AMPA manipulation
via chemicals , and so at most risk for AMPA driven addictions /habituation/ dependence.
What happened historically to the Native Americans, the Russians, the Irish and other recurrent famine
exposed populations places them at much greater risk for fructose related obesity, alcoholism narcotic
use, smoking etc...etc.