Receptor down-regulation is responsible for tolerance and is basically the receptor sucking back in to the site in order to stop excessive firing of it's adjoining neuron.

So if serotonin receptors are going in to down-regulation from psilocin then how is that so many people feel very happy, content, peaceful with the world within the first few days after a trip when down-regulation is at it's worst?

The relation between low levels of serotonin and depression is not completely understood yet. SSRI's like prozac are also effective, for instance, against anxiety or compulsive disorders.

The role of serotonin as a neurotransmitter, seems to be, to regulate other neurotransmitters and to regulate brain activity.

Maybe, to have less 'regulation' for a couple of days, isn't as bad as to have less of it for over several weeks or months.

People here on the DMT-nexus often speak about the importance of integrating your experiences. Maybe, if you have decreased serotonergic activity, over longer periods of time, integration is eventually something that's lacking.

Maybe, even feelings of contentness with the world, need integration as much as other feelings.

I think your assumption rests on serotonin being the neurochemical key to wellbeing...i.e. low serotonin levels or serotonin receptor downregulation should, by extension, equate to feeling depressed. This line of thinking is too simplistic and a little scientifically out of date now. For example it seems that SSRI antidepressants work in part by their increasing hippocampal neurogenesis, or blocking the highly detrimental effects of chronic stress hormone cortisol exposure on this process. SSRI's tend to take two or so weeks to start working, which is odd in that they increase serotonin levels rapidly after the first dose. So there is something else going on beyond changes in serotonin levels (interestingly, it apparently takes about two weeks for new hippocampal neurons to sprout, mature and become integrated into brain tissue).

Psilocybin has been found (in research on mice) to increase hippocampal neurogenesis, and a reduction in this process has been linked to depression, anxiety conditions and a number of other disorders. Other research on psilocybin with human subjects has found that the mystical experiences occasioned by large doses can alter human personality and outlook and increase feelings of life satisfaction and wellbeing in the long term. These long term changes seem to reflect a change in the neuroplasticity of the brain. So personally I think this whole scenario is more complex and multifaceted than just the effects of serotonin receptor downregulation.

Woah, thanks for pointing that out. It all seems so obvious now that it is the result of activation of brain structures like those of hippocampus and the default mode network. I wonder if that means SSRI's can be used nootropically then for hippocampal short-term memory improvement

It's always seemed totally obvious me the reason behind Mckenna's such prodigious memory.

I know when I had my own mushroom fever beyond a year ago, taking mircodoses most days going to classes, and then taking 3,4,5 grams interspersed over the course of 6 months, that I basically remembered every conversation I ever had, faces, names, places, and most, if not all, general/specific information that came my way. Partly because of my newly-realized presence, partly because of hippocampal neurogenesis, partly because of meditation, partly because of nootropics, partly because of incredible interest and by implication a laser-focus type of attention developed by the pharmacological aid of the mushroom.

It also seems obvious why these things are illegal. Can't have smart people around. Otherwise, they may derail the stability of the socially, culturally, religious, and ideologically sanctioned systems of control!

Sorry to go on a tangent.

Hippocampal neurogenesis seems to me the best thing that can happen to a brain when we are talking about memory especially, is the point I'm trying to make.

Wow! Amazing post!

We kind of talked about this once. You might like this thread. https://www.dmt-nexus.me...aspx?g=posts&t=70900

Edit - Removed

Blessings
~ND

Related to what ND was saying.


http://www.medicalnewsto...com/articles/312537.php

They don't always make people feel better after.
My friend who has Major depressive disorder (and at the time in hindsight must have had psychotic symptoms) tried mushrooms to treat himself (he had come off ssri a fee months prior and was determined to treat himself with natural means) and it had an interesting initial effect. It brought him out of the psychosis he had been in and he felt and looked quite well in the few hours after. He was determined to do them despite my strong reservations as he was quite unwell at the time, but in a mild psychotic/manic state which he thought was a recovery. So I went to trip sit him on a low dose. I was expecting a tense emotional and unpredictable night but he was very relaxed and cheerful and had a great time.
This is the note of caution, the next day he crashed badly and was terribly depressed, this carried on for weeks and he also became intensely anxious until he was prescribed an anti-depressant and anti-psychotic which made him slightly better.
What to take from this is that depression is a very complex illness and is most probably related to a number of environmental ques, genetics in some cases and imbalanced neurotransmitter systems.
Mushrooms are not the silver bullet fix for it, sure it shows promise and may work for some but it's certainly not a catch-all cure due to the incredibly complex nature of the condition.

Another related topic some may be interested in..
http://www.reddit.com/r/...eddit_im_olivier_george/

[quote=DreaMTripper]Related to what ND was saying.


http://www.medicalnewsto...com/articles/312537.php

They don't always make people feel better after.
My friend who has Major depressive disorder (and at the time in hindsight must have had psychotic symptoms) tried mushrooms to treat himself (he had come off ssri a fee months prior and was determined to treat himself with natural means) and it had an interesting initial effect. It brought him out of the psychosis he had been in and he felt and looked quite well in the few hours after. He was determined to do them despite my strong reservations as he was quite unwell at the time, but in a mild psychotic/manic state which he thought was a recovery. So I went to trip sit him on a low dose. I was expecting a tense emotional and unpredictable night but he was very relaxed and cheerful and had a great time.
This is the note of caution, the next day he crashed badly and was terribly depressed, this carried on for weeks and he also became intensely anxious until he was prescribed an anti-depressant and anti-psychotic which made him slightly better.
What to take from this is that depression is a very complex illness and is most probably related to a number of environmental ques, genetics in some cases and imbalanced neurotransmitter systems.
Mushrooms are not the silver bullet fix for it, sure it shows promise and may work for some but it's certainly not a catch-all cure due to the incredibly complex nature of the condition.

Another related topic some may be interested in..
http://www.reddit.com/r/...ddit_im_olivier_george/[/quote]

These two posts contradict each other.

Nathanial.Dread is saying that when 5-HT2Ar gets firing, it has been correlated with increased risk of depression, anxiety and OCD. Also that mice who have an inhibited or down-regulated 5-HT2Ar system display signs of less anxiety.

DreaMTripper however gives a report of his friend who had LESS psychosis and depression while having his 5-HT2Ar firing but crashed when then 5-HT2Ar was in withdrawal (less active). Are you sure this could not of been caused by something else, like say the withdrawal from the SSRI?

Well like I said depressions a complex illness there must be lots going on in the brain (or not as the case maybe) so it probably doesnt have the same effect on my friend. Neurotransmitter systems could be functioning differently and they don't exist in isolation they interact and moderate each other.

Did you mean that while sober there is a tonic (seizure?) like activity going on with 5ht2a receptors but as soon as it is either activated (via dmt or psilocybin etc.) or downregulated it mediates this and contrary wise, antagonizing them makes it worse? Why would the 5ht2a have a tonic going on?

The psychotherapeutic effects of a meaningful experience might also lead to epigenetic change
http://www.neuropsychoth...s-learn-from-experience/

I see, so perhaps the depressive brain does not adhere to the neurotransmitter science that ND supplied.

[quote=obliguhl]The psychotherapeutic effects of a meaningful experience might also lead to epigenetic change
http://www.neuropsychoth...-learn-from-experience/[/quote]

But is a meaningful experience likely to be encoded in to our genes overnight so as to affect our mood the next morning? A side note though, this would mean that as soon as you impregnate a female or get pregnant then the subsequent life experiences that are encoded in to your genes wont be transmitted to the child thereby making your subsequent experiences after impregnation obsolete (genetically speaking). True?

EDIT - Removed

I've often thought about the impact on psycehdelic experiences on the genes of your offspring. Subsequent experiences might not change your children directly, but indirectly through your behaviour.

Also, a productive experience can affect your mood directly...if you have worked on something that drained your ressources, having more internal ressources available would probably make you more happy.

I find the gradual recovery, after having had some shrooms very statisfying.
Being plunged into the world of shrooms has not always been so pleasent for me, but it taught me alot more to relax and gratitude.

On the other hand, if you have an uplifting & visual trip then ofcourse that sense of awe and wonder will stay with you .

Well sometimes it's not just about serotonin or whatever, like if something gets resolved during the trip or you understood and accepted something you were having trouble with.. a part of what is causing you anxiety and making you unhappy is resolved or at least seen in a better way of course you will feel good peacefull and happy it's not just chemical reactions
I don't know how you can see things just like this
of course any substance can make us feel differently and put you in some state but i believe in normal states the opposite happens your state induce the production of these substances. The substance is the link between the state and its physical existence