#94

I didn’t test it “properly”. I was anxious and depressed when I tried it so I hoped to see improvements in mood and sleep but didn’t see any. I think I used it daily (or a few times per week?) for 1 to 2 months.

Meditation, CBT-I and low-dose lithium seemed to be more effective for me. (I also feel like dapagliflozin has positive effects on my mood, but it could be placebo…)

2 Likes
#95

My goals are to achieve deeper and possibly longer sleep. Currently, my average sleep is around 7 hours, but I often need an extra hour in the morning to feel fully awake. Despite this, I still feel tired. I suspect my low blood pressure upon waking (usually around 99/60) may be a contributing factor, as I feel more alert when it rises to 110-115/65. Additionally, having a husband who works as a surgeon and wakes up in the middle of the night doesn’t help.

I’m also aiming to increase my heart rate variability (HRV). It initially improved from 38 (average over a few months) to 45 with a consistent exercise routine. When combined with rapamycin, it increased further to 54. However, following a surgery in January, it has dropped back to around 45. I plan to try Nurosym for 30 days, and if I don’t see any meaningful improvement, I’ll return it.

5 Likes
#96

I have used my Pulsetto everyday since I received it several months ago. It has an amazing effect on my HRV. I am very happy with it.

7 Likes
#97

What protocol are you using for the Pulsetto now?

1 Like
#98

I do 12 minutes (the max allowed for a single session) on the SLEEP setting at level 9 (max) right before bed. I simultaneously do deep breathing while I do HRV biofeedback.

4 Likes
#99

Gyertyán István just answered:

first, I apologize for not responding so long; your first letter actually sank in a stack of unread e-mails. Sorry for that.
Regarding deprenyl, the work is going on with it even after the death of professor Knoll (see 10.1016/j.ejphar.2019.172793;10.3390/ijms22062853;10.1016/j.neuint.2022.105404;10.3390/ijms23158543;10.3390/ijms241713334).
The longevity studies offered by the NIA ITP have already been done with the compound, not only in rodents but other species as well. We also referred them in our paper. A human study would bear a significant value, however, we think, it is currently unfeasible.

The papers he cites are:

Three of them were published by the International Journal of Molecular Sciences, considered predatory/low quality: List of all MDPI predatory journals (*Updated)

Others don’t reproduce the amazing previous life extension claims.

In any case, I don’t understand his point “The longevity studies offered by the NIA ITP have already been done with the compound, not only in rodents but other species as well.”

3 Likes
How Selegiline ((-)-Deprenyl) Slows Brain Aging
#100

In 1999 / 2000 I started to have mental health problems. I would not have labeled the once in a rare moment “crazy ideas” as hallucinations or dementia, but… by 2003 I had really bad depression. I lost my job in Silicon Valley(Dir of Bioinformatics killed a VP, after being terminated for stealing corporate data) and with it my bride to be and quite a bit of money. Talk about a tailspin! I hit rock bottom pretty hard.

In any case, I muddled on until 2006 where I had full blown psychosis. I’d like to think that the shock to my system of the events in 2002/2003 led me to where I was in life in 2006. Psychiatrists and therapists don’t pull out the diagnostic manual and go, “There you are!” There is a lot that goes into a diagnosis…and after 6 to 12 months of guessing and discussions, we arrived at schizoaffective disorder type 1, depressive.

I take 2.5mg of haldol and sertraline. If I take the full 5mg of haldol I start to have problems with the dose after 3 to 5 days. “Anxieties.” I’ve tried a number of drugs(geodon, respiradol, …) and the best for me is the combination of haldol and sertraline. The other medications are impossible, and overmedicated me to the point of not being able to function at all. I do not like sleeping all day.

3 Likes
#101

Even though I’ve never been depressed, I take 10 mg of tranylcypromine and 0.5 mg of roflumilast daily.

#102

PDE4 inhibition enhances hippocampal synaptic plasticity in vivo and rescues MK801-induced impairment of long-term potentiation and object recognition memory in an animal model of psychosis | Translational Psychiatry.

#103

Finally, in order to determine whether our 2c cocktail could also impact biological aging in vivo, we tested the effect of 2c treatment on the lifespan of a commonly used aging model organism, the nematode Caenorhabditis elegans . Towards this goal, we monitored survival in C. elegans treated with either 2c, Repsox, or TCP at three different concentrations (50, 100, or 200 μM) alongside a vehicle control. Strikingly, we observed that 2c treatment at 50 μM was sufficient to extend C. elegans median lifespan from 19 to 27 days, corresponding to a 42.1% increase relative to vehicle control ([Fig. 4a, e]. To a lesser extent, Repsox or TCP alone at 50 μM also increased C. elegans median lifespan to 25 days, a 31.6% increase over vehicle control ([Fig. 4a, e]. These results indicate that Repsox and TCP are each able to extend median lifespan in C. elegans , and when combined as part of the 2c cocktail, can lead to an even greater increase in median lifespan.

#104

Another new story on Flow Neurosciences headset:

2 Likes
#105

Could be just some random noise, but two of us here noticed that telmisartan 40 mg increased our motivation and decreased our apathy / low-grade depression. One small paper in PD suggests the same effect for candesartan 8 mg (equivalent in terms of dose to telmisartan 40 mg):

So if your BP is not optimal (24h average > 115/75 mmHg) then treating it with telmisartan might come with this welcome side effect.

5 Likes
#106

Let’s say your SBP ranges from 105-130 (depending on the day/time/machine) and DBP is between 60-80. Are there any downsides to having a potentially too-low BP from telmisartan.

Kind of like how you don’t mix viagra and BP meds?

1 Like
#107

Telmisartan has a safety profile similar to placebo so the risk is hypotension:

image

You don’t want to faint after standing up and hit your head on the corner of the table…

According to the FDA notice: “Following once daily administration of telmisartan, the magnitude of blood pressure reduction from baseline after placebo subtraction was approximately (SBP/DBP) 6-8/6 mmHg for 20 mg, 9-13/6-8 mmHg for 40 mg, and 12-13/7-8 mmHg for 80 mg.”

With your numbers, even telmisartan 20 mg might cause hypotension, but you can try and stop if you ever feel dizzy.

5 Likes
#108

Do we know the potential mechanism of action?

It’s probably not homocysteine-lowering as “The findings argue against a causal role for homocysteine in the development of depression.” (Plasma homocysteine concentrations and depression: A twin study 2021)

Wikipedia says: “The exact mechanisms involved in the development of schizophrenia and depression are not entirely clear, but the bioactive folate, methyltetrahydrofolate (5-MTHF), a direct target of methyl donors such as S-adenosyl methionine (SAMe), recycles the inactive dihydrobiopterin (BH2) into tetrahydrobiopterin (BH4), the necessary cofactor in various steps of monoamine synthesis, including that of dopamine and serotonin. BH4 serves a regulatory role in monoamine neurotransmission and is required to mediate the actions of most antidepressants.”

Also: at which dose do the antidepressant effects start? Solgar sells metafolin 400 μg. Metafolin is the active ingredient of Deplin (15 mg). It’s just a branded version of levomefolate calcium, a calcium salt of levomefolic acid (aka L-5-MTHF or L-methylfolate).

I found this: “Folate supplements especially levomefolic acid (L-5-methylfolate) demonstrated improvement in clinical outcomes in certain mental health conditions, such as in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Daily dosage range is 50 microgram to 15 mg orally daily depending on the clinical diagnosis and clinical presentation.” (The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review 2022)

And this: “Meta-regression analysis demonstrated that there is no evidence of a significant linear relationship between dose and duration of folic acid supplementation and changes in HAM. Also, based on the non-linear dose response, no evidence of a relationship between dose and duration of folic acid supplementation and changes in HAM was found. […] Folic acid supplementation could possibly have an effect on lowering depression in patients. However, the clinical trials thus far are insufficient for clinical guidelines and practice.” (The effects of folic acid supplementation on depression in adults: a systematic review and meta-analysis of randomized controlled trials 2023)

However, most clinical trials looked at high-dose L-methylfolate (> 2.5 mg/day) and only as an adjunct to antidepressants: Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis 2021: “Adjunct therapy with l-Methylfolate or folic acid improves depression scale scores, patient response, and remission rates.”

And also iron deficiency.

3 Likes
#109

Company Website:

2 Likes
#110

Some of the 17 million US Americans who suffer from major depressive disorder each year may soon receive a surprising new prescription from their doctor:
Have fun with a virtual reality device!

5 Likes
#111

It sounds like the Flow neuroscience NHS trial was successful - but I haven’t seen an official report from the NHS:

2 Likes
#112

Any updates, did you keep taking selegiline since January?

1 Like
#113

I stopped a few weeks ago to try methylene blue instead. No perceived mood change in either direction, but I might try it again soon.

Lithium is more noticable for me.

1 Like