Could Cortisol be the responsible factor in MDMA serotonin receptor downregulation?

[Jabberwocky]

MDMA users that also exerted themselves physically had cortisol levels 800% of controls

[h=1]MDMA, cortisol, and heightened stress in recreational ecstasy users.[/h]
http://www.ncbi.nlm.nih.gov/pubmed/25014666

It is well known that chronically high levels of cortisol can damage hippocampal cells, and also causes serotonin dysfuntion:

The fact that patients with major depression exhibit decreased brain serotonin (5-hydroxytryptamine, 5-HT) function and elevated cortisol secretion has reached the status of textbook truism. More recent formulations have suggested that elevated cortisol levels, probably caused by stressful life events, may themselves lower brain 5-HT function and this in turn leads to the manifestation of the depressive state (see Dinan, 1994). This elegant proposal neatly ties abnormalities of cortisol secretion and 5-HT function into a causal chain in which cortisol is the key biological mediator through which life stress lowers brain 5-HT function, thereby causing depression in vulnerable individuals."

http://bjp.rcpsych.org/content/180/2/99


Of note is that Vitamin C block cortisol release

"In the animal studies, vitamin C fed to rats undergoing stress not only prevented the expected increase in cortisol levels, it prevented the animals from exhibiting the known signs of physical and emotional stress, including loss of body weight. Animals that did not receive vitamin C had three times the level of stress hormones."

https://www.psychologytoday.com/articles/200304/vitamin-c-stress-buster


Perhaps this explains the multitude of reports from people that swear antioxidants and Vitamin C in large doses maintains the magic.

 

[N0 W4RN1NG]

Possibly, but don't forget that down regulation of a receptor, is an extremely normal response to habitual "flooding" of the receptor in question.

Even MDAI should cause notable internalisation of 5HT receptors after habitual use.

 

[Jabberwocky]

Possibly, but don't forget that down regulation of a receptor, is an extremely normal response to habitual "flooding" of the receptor in question.

Even MDAI should cause notable internalisation of 5HT receptors after habitual use.

Agreed,

And cortisol is almost always involved in situations where serotonin floods receptors -- naturally or drug induced.

There is very credible evidence that a significant sub-population of frequent chronic MDMA, MDXX, and psychedelic/hallucinogenic users (all serotonin based) never experience the loss of effect.

Many of these people attribute the phenomenon to religious use of antioxidants before, during, and after empathogen use.


But it is interesting that after chronic flooding due to serotonin release by MDMA -- the serotonin based effects of other drugs -- like MDA, 2-CB, LSD etc -- are not attenuated at all.

In Pihkal, Shulgin illustrates a tolerance study where complete tolerance to a 160 mg dose of MDMA was facilitated by daily dosing for 6 days, on day 7, 120 mg of MDA was administered to the same subjects and the expected effects of MDA intoxication were observed.