Cheap, Strong, and Oral Immunomodulators, DA/5HT agonists, are Causing Remarkable Clinical Remissions: a New Paradigm
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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
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
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
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
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
BTW, it also stops hangovers in less than 10 minutes!
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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
Copyright 1996, all rights reserved, Pietr Hitzig
9515 Deereco Road
Voice: (410) 560-5733 Fax:(410) 252-5262
fen_phen at internetmci.com
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