Viewing a single comment thread. View all comments

rjmsci OP t1_j8tpods wrote

Reply to comment by bannedPosts in Psychedelics activate the same receptors as serotonin, so why aren't we always tripping? Psychedelics may cause neuronal plasticity and relieve depression by activating intracellular serotonin receptors that serotonin itself cannot, suggests a new study. by rjmsci

I think quoting the Moncrieff paper is a mistake here - that's an article with an agenda. Depression is not caused by lowered serotonin activity, sure, but compounds that primarily modulate the serotonin system do relieve it. It's up to the field to unravel the mechanisms behind this. Do these intracellular 5ht2as kick off pathways that surface receptors don't? How do different serotonin agonists affect these receptors? This is exactly the kind of research the field needs to answer these questions.

32

The-Crawling-Chaos t1_j8u9m24 wrote

> Depression is not caused by lowered serotonin activity, sure, but compounds that primarily modulate the serotonin system do relieve it.

Which isn’t surprising when their response rate is only ~10% higher than the placebo- controlled response rates for depression of ~40% on average.

source 1 Source 2 Source 3 (another Moncrieff)

14

peer-reviewed-myopia t1_j8wac9x wrote

I think it's a mistake to say compounds that primarily modulate the serotonin system relieve depression.

Considering the delayed 'time of effect' of the therapeutic actions of compounds targeting the serotonin system, it's clear the adaptive structural / functional changes are not specific to serotonergic signaling — be it at the synaptic, or intracellular level.

For example, underlying these changes in plasticity are interactions with the BDNF system, as pretty much all effective antidepressant therapies lead to increases in levels of BDNF mRNA.

There are plenty of other systems at play, and they interact via a variety of feedback mechanisms to regulate the circuits involved in affective behaviors.

3

nickyfrags69 t1_j8x8ysr wrote

>but compounds that primarily modulate the serotonin system do relieve it

That's not necessarily accurate though. First off, Ketamine has a much higher success rate, suggesting at the bare minimum that other mechanisms can relieve depression without touching serotonin receptors. Second, most of the benefit of SSRIs seem to be indirect/downstream, which is why they take so long to kick in.

1