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"What are your thoughts on 4-FA being a strong neurotoxic compound due to its similarity
with 4-CA?"
This isn't something that currently concerns me.
4-FA was studied in rats and initial signs of neurotoxicity weren't seen relative to
the chloro and bromo substituted alternatives.
Even at high concentrations, only a temporary decline in serotonin was observed.
This is quite distinct from 4-CA.
Obviously I'd like to see more studies, but the available data doesn't suggest everyone
needs to stay away from it.
It wouldn't shock me if a number of serotonin releasers are capable of being somewhat neurotoxic,
but with reasonable use, I don't currently see a reason to be worried about 4-FA.
"This model, that model, "might," "maybe," "could," -- they have no idea how any of these
SSRI/SNRI drugs work or even if they work."
Critiques of psychopharmacology like this never seem particularly well-informed.
Essentially what's being said is that the brain is complex.
Until we have a better understanding of the brain, of course we're not going to have a
full mechanistic explanation of how SSRIs exert their effects.
It's far easier to investigate a drug's efficacy than its mechanism.
That being said, clinical trials are frequently problematic, and can easily end up underestimating
or overestimating a drug's utility.
The populations studied often aren't ideal and pharmaceutical companies may not even
publish trials that showed minimal effect.
But when we take the available data and combine it with countless clinical reports, it's pretty
clear SSRIs and SNRIs work for at least a portion of patients.
As to how they work, yes, we don't fully know.
Some basic explanation of depression like "oh, this patient has too little serotonin"
is almost certainly false.
That doesn't mean serotonin isn't involved, but it's seeming quite clear that efficacy
arises from neuroadaptations, like serotonin receptor downregulation and neuroplasticity
facilitated by BDNF.
If you're not fine with terms like "might" "maybe" and "could," you're probably not going
to be happy with any area of medicine.
We don't have a full understanding of the liver, much less the brain.
Shall we avoid treating cancer until we know every tumor suppressor gene, oncogene, and
environmental influencer.
Evolution didn't equip us with some inherent understanding of how G-protein coupled receptors
work or how psychological states arise from their material substrate.
But that's fine, it's a work-in-progress.
"What causes the brain to be delusional?
Is there a relationship between scopolamine and diphenhydramine?"
There are multiple paths towards delirium.
The anticholinergics you mentioned aren't going to produce delirium as other drugs and
the delirium may also present differently.
Because there are so many drugs, especially in overdose, that can potentially generate
delirum, I'm just going to focus on the anticholinergic pathway.
Scopolamine and diphenhydramine share a mechanism.
Namely, they prevent a neurotransmitter, acetylcholine, from interacting with a subtype of cholinergic
receptors, the muscarinic acetylcholine receptors.
In the brain, we know this can produce memory loss, hallucinations, and a highly confused
state.
Given acetylcholine activity plays a role in memory and possibly sensory information,
disturbing cholinergic transmission in the brain can generate a delirious state.
The details of how this take place aren't entirely clear.
It's interesting to note that dementia, like Lewy Body Dementia and Alzheimer's disease,
is associated with a significant decline in cholinergic activity.
Some of these deficits may been even greater in Lewy Body Dementia, which is also more
likely to present with hallucinations.
So based on the activity of anticholinergic drugs and the symptoms of disorders affecting
cholinergic activity, it appears proper acetylcholine activity is vital for accurate memory and
perception.
Here's a nice comment from my 5-MeO-DMT video...
"This is a propaganda video!
This is a sacred medicine which requires respect and is not for everyone."
I wonder if we'll one day move beyond terms like "sacred medicine."
It's fine if people use them, but personally they've never seemed useful.
This is 2017, not 500 BC.
We know enough about drugs nowadays to be fairly certain your 5-HT2A-mediated hallucinations
are coming from the Gods or another dimension.
If you happen to find psychedelics improve your life without impairing your critical
thinking, that's awesome.
Sadly, it seems a lot of people practically worship drugs like 5-MeO-DMT, DMT, ayahuasca,
and psilocin.
Just because hallucinations feel good or give you something to believe in doesn't mean they
tell you anything about reality.
So, I'd caution against turning the Bufo alvarius toad into the next Jesus or Buddha figure.
Elevating drugs to that level leads to situations like this, where factual content is viewed
as antagonistic or sacrilegious.
If the facts disturb your beliefs, you may need to update how you think about things.
I can't change reality to fit your beliefs.
"I suffer from really bad anxiety, what would you recommend?"
There's no way for me to give an exact answer and I'm not a physician or psychologist, so
you're best off visiting either.
The treatment that's best for you will depend on a few things.
What kind of anxiety do you have: general anxiety, social anxiety, performance anxiety,
a specific phobia, etc.
Is your anxiety co-occurring with depression or another condition?
And what's your lifestyle like, such as with diet, exercise, and sleep?
Depending on factors like these, the treatments will range from lifestyle improvements to
psychotherapy to pharmacotherapy.
Psychotherapy is a good first step.
A lot of people obtain significant and lasting benefits from cognitive behavioral therapy,
mindfulness, and other techniques.
And then sometimes medications are helpful, whether that's SSRIs, benzodiazepines, beta-blockers,
or something else.
If you have any questions, feel free to put them in the comments.
You can also email me.
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