[Ibogaine] Huge amount of ibogaine press
slowone at hush.ai
slowone at hush.ai
Sat Jan 22 23:38:43 EST 2005
Thanks for pointing that out.
>From a brief look into GDNF, it seems to have both brain and
stomach effects, plus there seems to be a linkage of low GDNF with
insufficient breathing. Here are some items:
"Boucher et al. (2000) demonstrated that glial cell line-derived
neurotrophic factor (GDNF) both prevented and reversed sensory
abnormalities that developed in neuropathic pain models, without
affecting pain-related behavior in normal animals. GDNF reduced
ectopic discharges within sensory neurons after nerve injury.
Boucher et al. (2000) hypothesized that this may arise as a
consequence of reversal by GDNF of the injury-induced plasticity of
several sodium channel subunits, and argued that their findings
provide a rational basis for the use of GDNF as a therapeutic
treatment for neuropathic pain states."
"In rodents, GDNF stimulates an increase in midbrain dopamine
levels, protects dopamine neurons from some neurotoxins, and
maintains injured dopamine neurons. Gash et al. (1996) extended the
rodent studies to rhesus monkey by evaluating the effects of GDNF
injected intracerebrally into monkeys that had had the
symptomatology and pathophysiologic features of Parkinson disease
induced by MPTP. The recipients of GDNF displayed significant
improvements in 3 of the cardinal symptoms of parkinsonism:
bradykinesia, rigidity, and postural instability. "
"Experimental application of growth factors can alter the density
and distribution of axon branches; hence, growth factor release may
be one means by which target cells regulate the number of synaptic
connections they receive. Nguyen et al. (1998) generated several
lines of transgenic mice that overexpress GDNF under a muscle-
specific (myogenin; 159980) promoter. They found that
overexpression of GDNF by muscle greatly increased the number of
motor axons innervating neuromuscular junctions in neonatal mice.
The extent of hyperinnervation correlated with the amount of GDNF
expressed in 4 transgenic lines. Overexpression of GDNF by glia and
overexpression of NTF3 and neurotrophin-4 (NTF4; 162662) did not
cause hyperinnervation. During the period of greatest
hyperinnervation (birth to 3 weeks postnatal), the Myo-GDNF mice
exhibited a tremor. At neonatal ages, the shaking was sufficiently
obvious that transgenic animals could be distinguished from their
littermates without error. The severity of the tremor waned as
multiple innervation diminished. Normal rodent neonates have a
tremor that is most obvious during the first few postnatal days and
gradually subsides over the next week. This tremor may be analogous
to 'jitteriness' in human neonates. Disappearance of tremor
corresponded to the loss of multiple innervation in each transgenic
line, as it did in wildtype animals. "
It looks like some people were administered GDNF directly, but
unlike the announcement, the result is not in the top Google hits.
>From a news announcement on the part of 6 doctors, web page dated
"Developed by Amgen Inc., GDNF is a natural growth factor for
dopamine neurons and is found in low levels in the adult human
brain. It is believed the destruction of these neurons in the mid-
brain causes the symptoms of Parkinsons disease; current FDA-
approved treatments improve the symptoms but do not alter the
underlying disease process. Laboratory studies have demonstrated
that GDNF both protects and promotes regeneration of injured
midbrain dopamine neurons, and thus may directly influence the
degenerative disease process.
"This new investigational treatment uses a version of the Medtronic
SynchroMed® Infusion System, a surgically implantable, programmable
pump developed by Medtronic Inc. and pre-clinically tested at UK.
The system will deliver GDNF directly into the patients brain.
This new therapeutic approach makes possible treatments with drugs
that cannot be used at present because they do not cross the blood
Here's another study which sounds the same but the authors are
"Gill et al. (2003) delivered GDNF directly into the putamen of 5
Parkinson patients in a phase 1 safety trial. One catheter needed
to be repositioned and there were changes in the MRIs that
disappeared after lowering the concentration of GDNF. After 1 year,
there were no serious clinical side effects, a 39% improvement in
the off-medication motor subscore of the Unified Parkinson Disease
Rating Scale (UPDRS), and a 61% improvement in the activities of
daily living subscore. Medication-induced dyskinesias were reduced
by 64% and were not observed off medication during chronic GDNF
delivery. Positron emission tomography (PET) scans of [18F]dopamine
uptake showed a significant 28% increase in putamen dopamine
storage after 18 months, suggesting a direct effect of GDNF on
GenAtlas has an interesting bunch of data:
Looking for possible ibogaine connections (there is much more,
including the DNA sequence):
"physiological period: fetal, pregnancy - developing gut, kidney,
mesenchyma, developing and regenerating peripheral nerves and
central nervous system, gut and kidney
"SUBCELLULAR LOCATION: extracellular
- promoting survival and differentiation of subpopulations of
central and peripheral neurons including several groups;
stimulating Schwann cell migration via NCAM but independently of
- playing an essential role in neural crest stem cell migration"
Brain cells allowed to change sounds familiar.
"cellular process: cell life, antiapoptosis
"text: neurogenesis,development and maintenance of intrahippocampal
circuitry and neuronal function and neuromuscular synapse"
I wonder if 'neuromuscular synapse' could have anything to do with
ibogaine's ataxic effect.
"signaling: signal transduction
- many neurodegenerative disorders
"susceptibility: susceptibility to Hirschsprung disease and to
I wonder if people with these problems would react differently to
ibogaine. Perhaps it would be worth adding a question about this to
any data-gathering on takers of ibogaine.
Random info from other sites:
"Nonmetastatic testicular tumors were regularly formed in older
"This gene encodes a highly conserved neurotrophic factor. The
recombinant form of this protein was shown to promote the survival
and differentiation of dopaminergic neurons in culture, and was
able to prevent apoptosis of motor neurons induced by axotomy."
"Function: Neurotrophic factor that enhances survival and
morphological differentiation of dopaminergic neurons and increases
their high-affinity dopamine uptake."
"Disease: defects in gdnf may be a cause of hirschsprung disease
(hscr) [mim:142623]. In association with mutations of RET gene,
defects in GDNF may be involved in Hirschsprung's disease. This
genetic disorder of neural crest development is characterized by
the absence of intramural ganglion cells in the hindgut, often
resulting in intestinal obstruction.
"Disease: defects in gdnf are a cause of congenital central
hypoventilation syndrome (cchs) [mim:209880]; also known as
congenital failure of autonomic control or Ondine's curse. CCHS is
a rare disorder characterized by abnormal control of respiration in
the absence of neuromuscular or lung disease, or an identifiable
brain stem lesion. A deficiency in autonomic control of respiration
results in inadequate or negligible ventilatory and arousal
responses to hypercapnia and hypoxemia"
"hypercapnia: [n] the presence of an abnormally high level of
carbon dioxide in the circulating blood"
[hypercapnia: not breathing enough]
"Hypoxemia, or reduced oxygen in the blood,"
"On the Aug 2004 Human genome, NCBI 35 version of the human genome:
8 genes relate directly or indirectly to GDNF"
"10 bioalma disease relationships for GDNF are shown
Disease Score Articles
hirschsprung disease 135.29 78
parkinson disease 83.87 171
neurodegenerative diseases 79.31 114
multiple endocrine neoplasia 63.44 31
amyotrophic lateral sclerosis 49.99 49
multiple endocrine neoplasia type 2a 40.92 26
nerve degeneration 31.33 36
other motor neuron diseases 25.89 2
thyroid carcinoma, familial medullary 23.94 5
multiple endocrine neoplasia type 2b 21.82 12 "
"10 bioalma chemical compound relationships for GDNF are shown
Compound Score Articles
tyrosine 69.02 247
heparan sulphate glycosaminoglycan 43.07 3
dopamine 38.88 120
mesencephalic dopamine 34.79 6
neurotoxin 6-hydroxydopamine 33.55 6
6-hydroxydopamine 33.07 27
glycosyl-phosphatidylinositol 29.39 9
ototoxin 24.97 2
rasagiline 24.79 3
phosphatidylinositide 22.84 5 "
There is lots more out there..
>"The paper looks very solid," says Stanley Glick, a
>neuropharmacologist at Albany Medical Center in New York, who has
studied ibogaine for many years. "They may indeed be on to a major
finding." However, both Glick and Ron point out that boosting GDNF
>may be only one of several mechanisms by which ibogaine acts to
>A synthetic ibogaine compound, 18-methoxycoronaridine, which Glick
>has shown can help addicts with fewer harmful side effects than
>ibogaine, may also work by controlling GDNF levels. In preliminary
>studies with cultured nerve cells, Ron's team found that 18-MC
>raises GDNF levels.
I wonder what else may also raise GDNF levels, from antidepressants
>But the team is not pursuing the ibogaine approach. Instead, Ron
>thinks it is time to narrow her focus. "Our idea now is to move
>away from ibogaine and concentrate on GDNF," she says. Her team
>plans to look for ways to stimulate GDNF without side effects.
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