Biochemically speaking.

the brief version..5-HT3 signaling in the gut.
the remedy: 5-HT3 antagonist.

related: https://www.dmt-nexus.me...aspx?g=posts&t=24003

Thanks for the reply Benzyme.
and thanks for digging up that 2011 thread Ufo. This will serve for now.

Goings to acquire some Lemon balm pretty soon. I may come back later to discuss the full explanation.
I was thinking of Bacteria/immune response in my initial post.

Various pathogens in the GI tract can produce chemicals that initiate an intracellular response leading to a large amount of water in the illuem/jejeunum/duednom ( otherwise known as diarrhoea). This is usually accompanied by abdominal pain and nausea.

A lot of psychedelics are relatively indiscriminate 5-HT agoninsts (at least tryptamine-based ones, like psilocybin), so you often get nausea even using pharmaceutical grade pure compounds, just because some of your dose hooks into those pesky 5-HT3s.

Blessings
~ND

As an example, if one ingests psilocybin, is some potency lost because some of it is activating 5-HT3 sites which cause nausea instead of tripping? If one blocked the 5 HT3 sites would that lead to a stronger trip?...in theory at least?

I imagine that the loss in potency is negligible. Only a fraction of your total dose actually makes it across the blood-brain barrier to tickle the brain receptors - a lot is lost to first-pass metabolism (that's why drugs tend to have lower doses when injected as opposed to eaten or insufflated).

Taking a 5-HT3 agonist would probably also be a good idea anyway.

Blessings
~ND

There is extensive evidence that there are numerous 5 ht2 neurons in the gut/enteric nervous system, and that the brain and the gut have an extensive communication. The gut is considered the second brain. It is conceivable that a significant portion of the tryptamine is activated at receptor sites in the gut...In fact, i would say highly likely.

Whether activation of those 5-HT2Rs contributes to the psychoactive effect of magic mushrooms is unclear. We know that ginger/other antinausea agents don't alter the experience much, but I don't know how many of those compounds also bind to the 2Rs. And even if you loose some to enteric receptor binding, that doesn't change the fact that you still loose a lot to 1st Pass Metabolism.

Blessings
~ND

I believe that this may be one of the reasons that I find pharmahuasca to have a much more profound healing effect than inhaling dmt or changa. The former also strongly involves the gut brain and the periferal nervous system, while the latter mostly affects the central nervous system only.

IMHO the role of the body is severely undervalued in modern culture and by extension, in psychology and psychiatry in particular.

What is the gut brain is really our first brain?

I find it rather ironic, on an almost daily basis these days (I manage an acupuncture clinic & herbal pharmacy), that the ancient Chinese physicians knew that the gut was an integral part of the brain 2000+ years ago & that modern, Western science has just recently started to figure this out.

I've said very similar things before, and I feel very strongly that this is the case. Pharmahuasca stimulates multiple energetic systems (mainly the brain and the enteric nervous system) which are both inextricably linked to themselves and to our thoughts, emotions, habits, desires, etc. So by engaging multiple systems in one major system (mind, body, soul, spirit system) one has an increased ability to do numerous things, healing being one of them.

Unfortunately we are still a ways off from being able to verify some of this as facts.

Exactly! And irony is an understatement..lol The gut and the skin are part of the same ''organ''..which is such an important ''organ''. We are toruses.....

Yes!! The Lung/Large Intestine/Skin system. You know it!!

Not to mention the Heart/Small Intestine/Pericardium system.

The above is one of the main reasons I almost always take harmalas orally, even if I'm going to be smoking changa. That, and because it lasts much longer.

I recently read The Second Brain, by Dr. Michael Gershon. He was one of the main people involved in convincing the resistant scientific community at the time that serotonin was an enteric neurotransmitter. Pretty interesting book.

And with the enteric nervous system there is no blood/brain barrier like with the head's brain...It really makes you wonder what the implications of filling it with junk food 24/7/365 for generations has had. And of that "gut feeling"...