Naloxone Nasal Spray

[Fractality]

In California without a prescription, one can obtain naloxone in the form of nasal spray designed to save a person who has overdosed on opiates. Has anyone tried it while not overdosed in order to obtain the benefits Peat describes?

 

[Fractality]

Ray Peat's email response to using this drug for neurodegenerative diseases like PSP:

People have discussed that, and I don’t think it’s dangerous, but I think pregnenolone, progesterone, and DHEA are more likely to be helpful.

1. Brain Res. 1987 May 12;411(1):178-82.
Brain neuropeptides in progressive supranuclear palsy.
Taquet H, Javoy-Agid F, Mauborgne A, Benoliel JJ, Agid Y, Legrand JC, Hamon M,
Cesselin F.
No significant alterations in the levels of Met-enkephalin-, Leu-enkephalin-,
cholecystokinin- and substance P-like immunoreactive materials were found in 10
areas of postmortem brains from patients with progressive supranuclear palsy
(PSP) when compared to controls. These results are at difference with the marked
decrease in the levels of enkephalin-, cholecystokinin- and substance P-like
immunoreactive materials previously reported in the basal ganglia of parkinsonian
patients. Since PSP and Parkinson's disease are both characterized by a severe
dopamine nigrostriatal deficit, these results suggest that the decreased brain
peptide concentrations found in Parkinson's disease do not simply result from a
dopaminergic neuronal loss.

2. Brain Res. 1989 Feb 13;479(2):397-401.
Decrease in a proenkephalin peptide in cerebrospinal fluid in Huntington's
disease and progressive supra-nuclear palsy.
Iadarola MJ(1), Mouradian MM.
(1)Neurobiology and Anesthesiology Branch, National Institute of Dental Research,
Bethesda, MD 20892.
The cerebrospinal fluid (CSF) content of Met5-enkephalin-Arg-Gly-Leu
immunoreactivity was found to be significantly decreased in patients with
Huntington's disease and progressive supranuclear palsy. This peptide is derived
from the proenkephalin precursor protein and normally is found in high
concentrations in the basal ganglia. The decrease in CSF from Huntington's
disease patients likely reflects the loss of proenkephalin-containing neurons
seen in postmortem analyses of basal ganglia tissue. The decrease in progressive
supranuclear palsy, a disease in which dopamine neurons degenerate but enkephalin
levels in the basal ganglia are reportedly not decreased, may reflect a
functional decline in enkephalinergic neuronal activity secondary to a striatal
cholinergic deficit. The results suggest that a substantial portion of the CSF
Met5-enkephalin-Arg-Gly-Leu immunoreactivity is derived from the basal ganglia
and that CSF levels of this peptide can serve as an index of functional or
anatomical integrity of proenkephalin synthesizing neurons in the basal ganglia.

3. Acta Neuropathol. 1990;81(1):74-7.
A comparative immunohistochemical study on striatal Met-enkephalin expression in
Alzheimer's disease and in progressive supranuclear palsy.
Matsumoto S(1), Goto S, Hirano A.
(1)Bluestone Laboratory, Division of Neuropathology, Montefiore Medical Center,
Bronx, NY 10467.
Using a sensitive immunoperoxidase technique we examined Met-enkephalin (MEnk)
expression in the striatum and globus pallidus external segment (GPe) from
patients with Alzheimer's disease (AD) and with progressive supranuclear palsy
(PSP). In AD patients strong MEnk-like immunoreactivity was persistent in the
striatum showing so-called "striosomes". In addition, a number of typical "woolly
fibers" were observed in the GPe. MEnk-positive striosomes were also visible in
the striatum of PSP patients and were similar to those of normal controls and of
AD patients. However, the MEnk-positive "woolly fibers" appearance was less well
recognizable in the GPe from all the PSP patients examined.

4. Clin Neuropharmacol. 1985;8(2):198-9.
Naloxone in progressive supranuclear palsy.
Sandyk R, Snider SR.

5. Life Sci. 1985 Nov 4;37(18):1655-63.
The endogenous opioid system in neurological disorders of the basal ganglia.
Sandyk R.
The endogenous opioid peptides have for some time been implicated in the
regulation of motor behavior in animals. Recently, however, there is increased
evidence to suggest a role for these peptides in the control of human motor
functions as well as in the pathophysiology of abnormal movement disorders.
Degeneration of opioid peptide-containing neurons in the basal ganglia has been
demonstrated in Parkinson's disease and Huntington's chorea, but the clinical
significance of these findings is largely unknown. On the other hand, there is
evidence that excessive opioid activity may be important in the pathophysiology
of some movement disorders such as tardive dyskinesia, progressive supra-nuclear
palsy, and a subgroup of Tourette's patients. These findings indicate that
diseases of the basal ganglia are possibly associated with alterations in opioid
peptide activity, and that these alterations may be useful in designing
experimental therapeutic strategies in these conditions.


1. Dis Model Mech. 2013 Sep;6(5):1198-204.
Endogenous progesterone levels and frontotemporal dementia: modulation of TDP-43
and Tau levels in vitro and treatment of the A315T TARDBP mouse model.
Dang TN(1), Dobson-Stone C, Glaros EN, Kim WS, Hallupp M, Bartley L, Piguet O,
Hodges JR, Halliday GM, Double KL, Schofield PR, Crouch PJ, Kwok JB.
(1)Department of Pathology, The University of Melbourne, Victoria 3010,
Australia.
Frontotemporal dementia (FTD) is associated with motor neurone disease (FTD-MND),
corticobasal syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS).
Together, this group of disorders constitutes a major cause of young-onset
dementia. One of the three clinical variants of FTD is progressive nonfluent
aphasia (PNFA), which is focused on in this study. The steroid hormone
progesterone (PROG) is known to have an important role as a neurosteroid with
potent neuroprotective and promyelination properties. In a case-control study of
serum samples (39 FTD, 91 controls), low serum PROG was associated with FTD
overall. In subgroup analysis, low PROG levels were significantly associated with
FTD-MND and CBS, but not with PSPS or PNFA. PROG levels of >195 pg/ml were
significantly correlated with lower disease severity (frontotemporal dementia
rating scale) for individuals with CBS. In the human neuroblastoma SK-N-MC cell
line, exogenous PROG (9300-93,000 pg/ml) had a significant effect on overall Tau
and nuclear TDP-43 levels, reducing total Tau levels by ∼1.5-fold and increasing
nuclear TDP-43 by 1.7- to 2.0-fold. Finally, elevation of plasma PROG to a mean
concentration of 5870 pg/ml in an Ala315Thr (A315T) TARDBP transgenic mouse model
significantly reduced the rate of loss of locomotor control in PROG-treated,
compared with placebo, mice. The PROG treatment did not significantly increase
survival of the mice, which might be due to the limitation of the transgenic
mouse to accurately model TDP-43-mediated neurodegeneration. Together, our
clinical, cellular and animal data provide strong evidence that PROG could be a
valid therapy for specific related disorders of FTD.

 

[Highserotonin90]

what else may be useful intranasal in degenerative diseases reported here ?

 

[ecstatichamster]

Rapamycin maybe.