I opened this notification while I was rather busy but I’mma find the paper when I have the time/tomorrow if I forget before going to sleep.

Feel free to respond again calling me out if I don’t do that. I just have ADHD and autism so it’s easy for stuff like this to slip my mind

I don’t know why you brought up dissociatives. Those NMDA receptors - whilst yes, typically activated by glutamate, are located on GABAergic neurons, preventing the release of GABA in to the synapses.

Additionally the effects of psychedelics are more closely linked to changes in endocrine hormone distribution and GABA, glutamate and acetylcholine balance. The 5-HT2A, 2C and 1A receptor complexes which are thought to be the starting point for psychedelic effects all regulate the distribution of these compounds, along with dopamine and norepinephrine. Many do not seem to understand that inhibition of the NMDA receptor is a core mediator of effects from classical psychedelics. The activation of the 5-HT2A receptor directly prevents the activation of any NMDA receptors located on the same neuron.

It is also worth noting that SSRIs stimulate neuroplasticity and neurogenesis as well - through the same mechanism (inhibition of mTOR, mGlu2,3,7 and various cortisol functions and subsequent release of NGF and BDNF in to various brain regions).

MDMA does this as well, although the dose and frequency makes the poison. Same can be said, perhaps more surprisingly, about other amphetamines such as methamphetamine and mixed amphetamine salts. All these compounds are also capable of producing neurotoxicity as well, however this effect is only paradoxical with methamphetamine. The neurotoxicity of MDNA and things like Adderall appears to disconnected from the direct effects of the chemicals themselves (even in high doses, MDMA injected straight in to the brain does not cause toxicity - for example)

Also as of like, last month, “we don’t know how psychedelics induce this neuroplastic change” is an outdated statement. They trigger a highly novel mechanism through penetration of the cell membrane, rather than activating surface receptors. Similar to how dopamine receptors server different functions depending on their location on or within the cell, so too do serotonin receptors.

I have a lot more I want to say but I am high as balls right now. I will leave this by saying that it is unlikely that the NMDA receptor plays any role whatsoever on the antidepressant effects that have been discovered in ketamine and DXM. In fact, despite both being dissociatives with similar MoAs, it is likely the antidepressant effects are being cause by entirely different mechanisms from eachother (DXM with sigma-1 activation, ketamine has a strong link with its stimulation of adenosine release and AMPA receptor activation).

SSRIs also cause downregulation of certain serotonin receptors, namely 5-HT1A, which tends to be over active in people with anxiety and has even be speculated to play a role in the development of neural inflammation in chronic amphetamine, nicotine and alcohol abusers. It also regulates the distribution of glutamate and stress hormones like cortisol, vasopressin and epinephrine. But since having too much glutamate is linked to neural inflammation and excitoxicity, it is likely that this mechanism plays a strong role in their effects

It seems, however, tat most of the role serotonin plays in depression has more to do with its relationship with glutamate than any specific function of serotonin itself.

That is to say that too much glutamate activity is linked to depression symptoms and certain serotonin receptors modulate glutamate levels in the brain. So by increasing serotonin activity, you can decrease glutamate activity and this helps with depression symptoms in some people.

Actually it sounds like withdrawal. Alcohol relieves anxiety, your body adjusts and now requires alcohol to handle anxiety when it didn’t before.

Self-medication implies the problem was there before the drinking go started. A lot of people get addicted to things like weed and alcohol by mistaking withdrawal symptoms for personal symptoms that the drug is actually helping.

Yeah let’s not encourage people that we don’t know to take benzodiazepines. They are overprescribed as it is and we are on the verge of an epidemic.

I know you’re just trying to help, but I don’t know if this is the move