Microdosed LSD: Finally A Breakthrough For Alzheimer’s Disease?

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
Microdosed LSD: Finally A Breakthrough For Alzheimer’s Disease?

But I read the work of Professor Charles Nichols at Louisiana State University, who found that some psychedelics potently reduced inflammation at levels that would be predicted not to be psychoactive or even perceptible, via activation of the serotonin 2A receptor, which besides being expressed in the brain, is also highly expressed throughout the body. And this got me very excited.

I continued to dig into the literature, and found that the same receptor that mediates the psychoactivity of psychedelics is also implicated in the effects these compounds have in terms of providing protection against oxidative stress, enhancing neuroplasticity, and alleviating depression and anxiety. And because these compounds are anti-inflammatory, they address a constellation of dysregulated functions in aging.

Digging further, I found research indicating that this receptor, if it was engaged by a psychedelic drug, would also reduce the amount of toxic amyloid that was produced in an organism. And I thought that was interesting, because at the time, and certainly for the prior decade, amyloid was the primary target for Alzheimer's disease.

When I put together the entire picture of what psychedelics were doing, it became quite clear that this could be a therapy to modify the course of Alzheimer's disease. LSD in particular seemed like an attractive candidate for such a therapeutic approach, as it is capable of potent and prolonged activation of the serotonin and dopamine neurotransmission receptors implicated in Alzheimer’s disease, and specifically the serotonin 2A receptor.

If you look at the symptoms of Alzheimer's and the disease progression, not only is the loss of 2A receptor expression correlated with cognitive impairment and toxic amyloid burden, but you also have a significant increase in the incidence of depression and anxiety, which are psychiatric conditions known to be significantly influenced by serotonin 2A receptor function.

Given the extensive clinical evidence of LSD’s efficacy in treating alcoholism, depression, anxiety, and other indications, could all this just be a coincidence?

When you combine all of the effects which LSD or other psychedelics have been observed to have, in vitro, in animal models, and in patients, they check all the boxes for an attractive multi-target drug candidate with the potential to halt the progression of Alzheimer’s disease. It was based on this revelation that I decided to found Eleusis, with the mission to develop the full therapeutic potential of psychedelics.
 

rei

Member
Joined
Aug 6, 2017
Messages
1,607
not only is the loss of 2A receptor expression correlated with cognitive impairment and toxic amyloid burden

So what would cause the body to downregulate receptor expression? Hmm, could it be excessive activation?
 
OP
L

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
Yes, everything is a question of balance. The 5-HTs can be activated by many substances, not only Sero though Sero is the main endogenous ligand.
There is an evolutionary reason for its existence, the existence of serotonin as its ligand and for its capacity to give contextual good or bad effects.

The importnat question is, why does LSD interact in such a way that modulates a longterm pthological development that it can be reversed or treated?
 

rei

Member
Joined
Aug 6, 2017
Messages
1,607
It causes long-lasting functional antagonism towards the chronic serotonin excess the population suffers from.
 
OP
L

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
So because of pathological or unhealthy overactivation for a long-time (due to stress, bad nutrition etc.) 5-HT2a downregulates.

Good to reduce the damaging overactivation (why is chronic overactivation bad?)
but bad because it gives way to other impairments like Alzheimer’s.

Enter LSD. It doesn’t reverse downregulation (or does it) but improved sero transmission on the remnant receptors -> a state not similar to a healthy homeostasis, where more receptors would handle less sero activation


My rationalization
 

Samya

Member
Joined
Feb 22, 2017
Messages
187
I wouldn't be surprised if improving glucose utilization in the brain is a part of it as well as this tends to be impaired in Alzheimers and the brain (ime) definitely requires glucose for LSD to work optimally.
 
OP
L

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
Cell energy / respiration is always part of the equation. Question is always hen and egg, upstream/downstream
 

Kingpinguin

Member
Joined
Aug 14, 2019
Messages
586
I wouldn't be surprised if improving glucose utilization in the brain is a part of it as well as this tends to be impaired in Alzheimers and the brain (ime) definitely requires glucose for LSD to work optimally.

Yeah. The whole brain energy connection to serotonin. Chronic fatigue and serotonin has a strong relation. Anything that helps the brain work better, burn energy more efficiently and supplies energy will have a positive effect. Glucose is energy just like fat is also energy. But glucose is prefered and burned more easily by the brain. When you don’t supply enough glucose its the exact same as not giving the brain energy. Serotonins job is to fatigue the brain. Fatigue you. Specially when you’re exercising. Once the glucose runs out serotonin goes up to signal to you. Hey stop exercising coz you are out of fuel. You need to lay down and eat. If you don’t listen to that signal. What will happen? Serotonin increase. Affinity for 5-ht2c receptor increase. That receptors job is to further lower dopamine/motivation. And cause anxiety / fight or flight response by significantly boosting cortisol and adrenaline. Both those hormones are emergency stress hormones to help your body keep running a bit further in the time of danger. But if you chronically elevate serotonin and keep glucose low that will cause chronic adrenaline and cortisol release. That will over time break down tissue, break down organs. You will start displaying symptoms of autoimmune disease because of this body breakdown (antibodies are produced to clean up the toxic breakdown products) But all it is doing is breaking down tissue to supply fuel to your brain while you are starving. The brain eats the body and eventyally eats itself for you to survive. Thats exactly how PUFA works aswell. It inhibits glucose metabolism much more effectivly simulating a state of starvation to your body. And that exact same cascade starts again. This is exactly what ray peats stuff is all about.
 

Pointless

Member
Joined
Apr 13, 2016
Messages
945
The in vitro results are tempered by the unfortunate reality that LSD very quickly produces a tolerance. So LSD can only go so far.
 

Samya

Member
Joined
Feb 22, 2017
Messages
187
LSD does produce a tolerance but it appears to be dose-dependent, so a sub-perceptual 'microdose' could have less of a tolerance effect. I also believe LSD makes permanent or at least long lasting changes in the brain, so the effects could continue even after usage has ceased.
 

Anders86

Member
Joined
Feb 7, 2017
Messages
355
Doesn't amyloids accummulate? By limiting the expression you would have long lasting benefits. This is one of the main effects of Glycine. Lowering innflammation, lowering the expression of amyloids and antagonising NMDA.

What really cleans up/remove beta amyloids? Atleast the more excitatory state of the brain, the more the accumulation of amyloids.
 

Kingpinguin

Member
Joined
Aug 14, 2019
Messages
586
Doesn't amyloids accummulate? By limiting the expression you would have long lasting benefits. This is one of the main effects of Glycine. Lowering innflammation, lowering the expression of amyloids and antagonising NMDA.

What really cleans up/remove beta amyloids? Atleast the more excitatory state of the brain, the more the accumulation of amyloids.

amyloid build up is just a side effect of reduced BDNF and other neurosteroids like progesterone, pregnenolone and allopregnenolone.
 

Similar threads

Back
Top Bottom