New Human Study With Pregnenolone For Treating Autism

haidut

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It is to be held at Stanford University and is set to last 14 weeks. No word on dosing but the explanation is that downstream metabolites of pregnenolone are inhibitory in the CNS and can balance the excessive neuroexcitation that is a feature of autism. Given that serotonin is the likely main mechanism of the autistic spectrum pathology, if pregnenolone works then it would mean it opposes serotonin at least functionally.

Autism researchers seek teens, young adults for drug trial

"...Some scientists hypothesize that individuals with autism have too much excitatory signaling or too little inhibitory signaling, or both, in their brain circuits. Metabolites of pregnenolone have been shown to increase inhibitory signaling. Thus, pregnenolone may benefit people with autism by “normalizing” the imbalance between excitatory and inhibitory signaling; it could possibly help treat mood dysregulation, sensory abnormalities and social deficits. “Pregnenolone is very benign and usually very well-tolerated,” Hardan said. “Patients should know that the potential for benefit is modest, but we think it is still worth exploring its value in treating individuals with autism.”
 

DaveFoster

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I find autists and people with ASD's tend to gravitate toward gabergic, anti-anxiety drugs, such as alcohol and benzosidazepines. It just anecdotally suggests that the underlying cause exists as excessive nerve excitation promoted by serotonergic and glutamergic transmission.

Indeed, maybe all kinds of neurotic personality disorders involve elevated serotonin as the main player, which would be in line with what Dr. Peat has said about serotonin promoting excessive verbalization, and in some cases of extreme energy deficits, schizophrenia and related paranoid/anxiety complexes.
 

dookie

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@haidut

I have to say I would be very cautious with giving pregnenolone to any young person, even if they have autism. When I hear phrases such as "Pregnenolone is very benign and usually very well-tolerated", I automatically think of how the same exact thing is said of highly toxic drugs, such as the aromatase inhibitors, which are disastrous for many people.

For me, a small dose of pregnenolone gave me anxiety, depression, insomnia, depersonalization lasting for weeks. Not something you'd want a teen to go through, especially if they have another disorder too.
 
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haidut

haidut

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@haidut

I have to say I would be very cautious with giving pregnenolone to any young person, even if they have autism. When I hear phrases such as "Pregnenolone is very benign and usually very well-tolerated", I automatically think of how the same exact thing is said of highly toxic drugs, such as the aromatase inhibitors, which are disastrous for many people.

For me, a small dose of pregnenolone gave me anxiety, depression, insomnia, depersonalization lasting for weeks. Not something you'd want a teen to go through, especially if they have another disorder too.

Well, given their autism and the lack of inhibitory neurotransmission they are probably deficient in pregnenolone to start with so for them it is probably benign as it would just normalize their levels. Point taken, but it is their words not mine.
 

Dragon

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well, could be, even probably is, but...

As it happens, just yesterday I stumbled across this interesting hypothesis...

Note the over-INHIBITING. He posits that the 'visible' over-excitation is a -homeostatic- response...the body's attempt to balance an -original- state of over-inhibition. Has some pretty good arguments for it too. Yet, as always in medicine, I seriously doubt that EVERY similar condition can be lumped under a single cause. Still, I found it provocative of thought.

Overstimulation of the inhibitory nervous system plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis. - PubMed - NCBI

Version 2. F1000Res. 2016 Jun 20 [revised 2016 Aug 19];5:1435. doi: 10.12688/f1000research.8774.2. eCollection 2016.
Overstimulation of the inhibitory nervous system plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis.
Tuk B1.
Author information
1
Leiden Academic Center for Drug Research (LACDR), Leiden University, Leiden, 2333 CC, Netherlands; Ry Pharma, Hofstraat 1, Willemstad, 4797 AC, Netherlands.
 

Frankdee20

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Probably is not the same as definitely
 

DavePalumbo

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Evidence points to pregnenolone and other neurosteroids being elevated in autism as well. At least they are testing it.
 

Frankdee20

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Yeah, Stewie Griffin tried using his gene splicer.
 

cs3000

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one here small study, used big doses by the end "Pregnenolone was initiated at a dose of 50 mg twice daily for the first 2 weeks and was increased by 50 mg twice daily every 2 weeks until reaching the maximal dosage of 250 mg twice daily from weeks 9 to 12. If subjects could not tolerate a specific dose, s/he would be maintained at the highest tolerated dose"

��
Clinical measures​
Baseline​

Week 12a​

Paired t test​

Effect size Cohen’s d​
Mean​
SD​
Mean​
SD​
t​
p
Aberrant behavioral checklist
ABC-Irritability​
17.4​
7.4​
11.2​
7.0​
2.5​
0.028*​
−0.86​
ABC-lethargy/social withdrawal​
18.1​
8.0​
12.8​
8.7​
2.3​
0.046*​
−0.63​
ABC-stereotypy​
9.8​
5.5​
8.7​
6.5​
0.7​
0.522​
−0.18​
ABC-hyperactivity​
20.5​
16.1​
16.1​
8.9​
1.8​
0.098​
−0.34​
ABC-inappropriate speech​
5.8​
4.3​
4.8​
4.4​
1.0​
0.356​
−0.23​
Short sensory profile—total score​
137.7​
21.5​
147.6​
15.3​
−3.2​
0.009*​
0.53​
Social responsiveness scale—total score​
84.9​
8.1​
84.5​
9.2​
0.2​
0.848​
−0.05​
Vinelandb—adaptive behavior composite score​
37.3​
13.1​
42.9​
16.5​
−1.3​
0.224​
0.38​

big effect on the ABC measures. and results were still similar 4 weeks after stopping.

trying it out over time in many doses ranging 12.5mg - 150mg i couldn't land on one that felt good. often caused irritability / anxiety. which felt like it was getting worse like a buildup effect, similar to gaba agonist rebound when i tried gaba herbs. but sometimes re-starting gave a noticeable antidepressant chill effect acutely, but didn't replicate with the same dose. its a weird one.

edit: maybe this is why (helpful info thanks) How To Start On Pregnenolone? & How Pregnenolone And Progesterone Raise Metabolism so gonna try 5mg - 10mg instead

in this study that high dose would probably be a concern for tanking cholesterol though (& too much progesterone probably). this person mentioned a huge fast drop from 300mg a day for a week High dose pregnenolone so i wonder if low dose is helpful too just from a bit of extra pregnenolone without extra conversion
 
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