N&PD Moderators: Skorpio | thegreenhand
There's plenty. When have you last researched this? There's been a lot going on in the past 3 years. I'll try to post some articles tonight or maybe tomorrow if I have the energy. There really is no reason to believe DMT would not be endogenous. It's transported to the brain extremely quickly where it binds to at least 3 different receptors (5HT2r, vesicular monoamine transporter 2, sigma1r, in that order) and is apparently being stored for quite some time. Why would the body do this with an exogenous monoamine? We definitely express enzymes needed for DMT synthesis, too. We have also found DMT being excreted in urine without the subject having previously consumed it, haven't we?
Low dose DXM seems to exhibit the antidepressant effects which are partially based on s1r agonism. It's extremely cheap over here and available in otc capsules. It is also an NMDA agonist (and many other things) as you will probably know. Definitely the best starting point for an antidepressant other than SNRI's/SSRI's (though I think DXM is an ssri too lol). If there is going to be a new class of antidepressants, I'm sure we will hear about that, but I personally wouldn't mess with these experimental compounds for the time being. As far as I know none of the s1r agonists that have been clinically used have been very promising.
Basically it's a receptor that's located on the endoplasmic reticulum and which seems to regulate a lot of ion channels, it's very far upstream and does a wide range of things, most of which we don't understand very well. It's dysfunction also seems to be involved in many pathological behavioural phenomena like addiction, gambling, depression, schizophrenia, but also sigma receptors are abundantly expressed outside the brain, e.g. in the heart or on cancer cells (the latter s2r if I'm not mistaken). It's very abundant in the brain and therefore seems to be pretty important, but there isn't much scientific effort being focussed on understanding it. There has been a clinical studie for comorbid depression and coronary heart disease if I am not mistaken and with improved affective status the changes the heart had undergone became reversed to some degree as well (I found that one impressive).
It is certainly not an agonist, but you are correct.
While s1r activity indeed has an impact on the function of almost every ion channel, a lot of receptors' activity is actually reduced. There's an excellent review on sigma receptors, which unfortunately I couldn't find when I just looked for it. I ought to try again tomorrow, since I'll be going back to bed in a sec.
