Cheap, Strong, and Oral Immunomodulators, DA/5HT agonists, are Causing Remarkable Clinical Remissions: a New Paradigm

Pietr Hitzig 0202319473539538 at 109KMS5JC0II
Sun Jan 21 19:50:42 EST 1996


Are the Monoamines Dopamine and Serotonin Neurotransmitters the Primary 
Regulators? A Paradigm-shifting Hypothesis  Version 1.1

The serotonin (5HT) agonists, fenfluramine (FEN), and the dopamine (DA) 
agonist,phentermine (PHEN), when given in tandem, cut an extremely broad 
therapeutic swath.  It has alreadu been well-established that FEN/PHEN is 
a superior anorectic agent compared to either of these substituted 
amphetamines taken alone.  Furthermore, not only is there a superior 
weight loss result, but also tachyphylaxis does not develop(1).

FEN/PHEN abolishes not only alcohol and alcohol craving(2,3) but also 
resolves all psychoneuroses in nineteen severely depressed alcoholics, 
seven of them cocaine co-addicted(4).

Over the last 39 months, 582 patients with affective and/or 
obsessive/compulsive disorders (OCD) with (166) or without (416) alcohol 
or substance addiction have enjoyed relief of depression, obsession and 
craving.  More than 300 alcoholics and 100 cocaine-addicted individuals 
had experienced craving relief, very nearly always in less than 2 hours 
if craving at the time of the first visit.

These monoamines, acting reciprocally, are TH1 and TH2 modulators(5).  
Dopamine is a TH1 agonist and an inhibitor of TH2.  Serotonin is a TH2 
agonist and a TH1 antagonist(6,7).

Patients suffering from immediate and delayed hypersensitivity disorders 
(IHD, DHD), had a resolution of their immune disorders.  At least 
thirty-nine asthmatics,more than twelve of them refractory to traditional 
treatment, savored the resolution of symptoms. Their previously 
prescribed sympathomimetics, antihistamines and corticosteroids became 
redundant.  Persistence of allergic rhinitis, urticaria, or asthma is an 
indication to increase DA in the FEN/PHEN protocol.  The response is 
universal.

A forty-three year old registered nurse with not only refractory asthma 
but also idiopathic and shellfish anaphylaxis had a resolution of her 
asthma despite the cessation of multiple medications, had no reaction 
when she ate shellfish and reduced her markedly elevated histamine levels 
to normal. 

Response to TH2-driven conditions also respond. More than 20 refractory 
psoriasis patients, two out of three with Crohn's disease(2/3), 
individuals with cutaneous lupus and Sjogren's enjoyed a total or near 
total resolution.  Both IHD and autoimmune patients were able to 
discontinue all other medications.

A patient suffering from amyotrophic lateral sclerosis lost his extensive 
fasciculations and severe fibromyalgia-like pain within 60 minutes of 
initiation of therapy and continues without them two months later. The 
only patient with multiple sclerosis, previously experiencing 
exacerbations every three to four months, she not only had had no attacks 
in the eighteen months she has been taking FEN/PHEN but also the amount 
of physical exertion she was capable of doing during the recent blizzard 
couldn't have been done by her before therapy. The response rate in all 
these conditions has been greater than 75%.

Three HIV+ patients have had clinically significant improvement.  All   
three showed impressive psychological and physical improvement when 
treated with FEN/PHEN.  In two of these cases, CD4+ counts increased with 
FEN/PHEN (170 to 480,480 to 900).  They had relief of severe depression 
and cocaine craving.  The third patient, suffering from advanced AIDS, 
had a CD+ count of five.  He suffered from oral and esophageal thrush, 
wasting, depression, anxiety, abdominal pain with diarrhea, anorexia and 
wasting. 

Treatment with FEN/PHEN  was initially directed toward relief of his 
affective disorders.  This goal was realized after three days of 
treatment.  By the fifth day, his thrush and all the other symptoms had 
resolved.  Appetite returned with a 2.5 kg. Weight gain for the six weeks 
he continued the protocol.  Abdominal pain and his chronic diarrhea 
resolved. Unfortunately, he expired two weeks after his AIDS physician 
stopped FEN/PHEN therapy.
 
Many patients report a marked decrease in viral illnesses and that an 
increase in the DA agonist dose results in a marked decrease of symptoms. 
Patients with frequent or chronic candidiasis have found relief.  

There is increasing belief that a balance of TH1 and TH2 promotes health 
and homeostasis eerily similar to Hippocrates's balance of the humors or 
the chinese Yin/Yang(8-11).  Serotonin, in relative excess, presumably 
triggers immediate hypersensitivity disorders.. Excessive TH1, associated 
with dopamine relative excess causes organ-specific autoimmunity(12). 
Conversely, those with psoriasis or Crohn's respond when the TH1 
antagonist FEN dose is increased.

Dopamine and 5-HT deficiencies are not only found in HIV but also in  
chronic stress(13) and during alcohol withdrawal(14,15).  These monoamine 
deficiencies have been considered the etiology of stress-induced 
behavioral and immunological pathology(13,16).  The HIV and murine 
immobilization stress induce excessive TNF-alpha and interferon-gamma  
production and start a cascade resulting in DA and 5-HT deficiency(17). 

TH1 cytokines increase indoleamine 2,3 dioxygenase (IDO)(18).  This 
enzyme shunts tryptophan towards the kynurenic pathway thereby decreasing 
5HT production. Marked increases in kynurenate and quinolinate(19) and   
deficiencies of tryptophan, 5-hydroxytryptophan and 5-HT result(17).    
Excessive quinolinic acid being a dopaminergic cell neurotoxin, DA   
production and DA levels decrease.  

A similar tyrosine depletion secondary to an increase in tyrosine 
aminotransferase activity occurs with chronic stress(20).  A similar 
mechanism may be occurring in HIV.

Clinicians have been utilizing this monoamine immunomodulating effect 
unknowingly.  Pentoxifylline, a methylxanthine, is a DA and 5HT 
agonist(21) and is effective against both endotoxic shock(22) and HIV in 
vitro replication(23).  Methylxanthines and cannabis, both effective 
against asthma(24), are DA and 5-HT agonists(25,26).  Bromocriptine, a DA 
agonist, combined with cyclosporine, a 5-HT agonist(27), increases murine 
and human cardiac transplant survival(28,29). Finally, fluoxetine and 
other SSRI's, the "panaceamycins" of the 90's, promote 5-HT and DA(30).  
It is likely that thalidomide, with its ever-increasing therapeutic 
efficacy, is also a combined monoamine agonist.

FEN/PHEN's ability to reverse psychiatric, craving, and immediate and 
delayed hypersensitivity disorders suggests that DA and 5HT, both only 
one precursor away from amino acids may be not only Selye's "first 
mediators of stress," but also the primary regulatory neurotransmitters 
formed coincident or shortly after life began. The hypothesis is that all 
other controlling mechanisms are derived from the DA-HT interaction.  
Multiple intricate mediators, developed along the way, have, up to now, 
obscured their primacy.  

 Further studies, especially if done expeditiously, are eagerly awaited 
by  the author who, in his  primary internist role in, is neither 
practically nor ethically able to proceed alone with these mandatory 
studies.  

Unpublished murine studies by Bart Hoebel at Princeton and Hans Fisher at 
Rutgers confirm FEN/PHEN's cessation-of-craving ability.  In the works 
are alcohol and cocaine studies at the Kansas City VA, a Persian Gulf 
illness and fibromyalgia study at the U. of Wisc. and an asthma study at 
Mass General.

BTW, it also stops hangovers in less than 10 minutes!

Bibliography

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NOTE OF EXPLANATION

  In this advanced era clinicians, unable to pass through all the hurdles 
imposed by IRB's, cannot do double-blind studies studies.  The catch-22 
is that the prestigious and most peer-reviewed journals, oriented towards 
the laboratory, demand placebo-controlled work.  Despite a wealth of 
clinical data, the author has been unable to expose his ideas to the 
harsh glare of his contemporaries.  It doesn't help that he has done his 
work without institution or government funding.  

In the late nineteenth century, Baron von Humboldt once commented, and I 
paraphrase, that revolutionary ideas go through three stages.  In the 
beginning these ideas are ignored, next they are ridiculed, and, finally, 
the experts say they knew it all along. 

Fortunately, I have had strong allies.  Dr. Richard Rothman, a research 
psychiatrist at NIDA, for three years carried the FEN/PHEN crusade 
forward.  Despite murine confirmatory work, the byzantine politics of 
NIDA was stronger.  

I suppose it should be a signal honor that Dr. Alan Leschner, the chief 
at NIDA, pulled the trigger on the alcohol and cocaine studies himself.  
Despite wide-spread use of the self-same drugs for obesity, he was able 
to say with a straight face that the toxicity of these medications, out 
in the marketplace for thirty years, was in question.  Whether he is 
involved in the alternative work being done at NIDA, Hopkins, and 
Guilford Pharmaceuticals is not known yet.  Fortunately, Jan Campbell, 
Rothman, and I are collaborating in the VA Kansas City.

Dr. Dan Malone, a University of Wisconsin based rheumatologist, his 
interest whetted by my claim that FEN/PHEN treated fibromyalgia, and his 
scepticism vanishing when he reproduced the findings, has been pushing 
for a fibromyalgia study.  That multi-center study should start in the 
very near future.  His advocacy has been a God-send.  

Dr. Bernard Hitzig, a second cousin once removed and a Harvard research 
pulmonologist, has had an informal approval from Mass. General's 
pulmonary division.  Now, when we get the money........

I would appreciate any potential researcher or clinician acknowledge the 
fact that the basic concepts of FEN/PHEN have been covered by patents and 
FEN/PHEN is trademarked.

Sorry for the length.  I would have preferred NEJM, Nature, SCIENCE, 
JAMA, or Lancet, but they are not interested in clinical findings 
anymore.

Copyright 1996, all rights reserved, Pietr Hitzig 

9515 Deereco Road
Suite 810
Timonium, MD
21093-1132
Voice: (410) 560-5733              Fax:(410) 252-5262  
fen_phen at internetmci.com




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