There are further complications to overcome if any bid to replicate and sustain full-spectrum E-like consciousness is to succeed. MDMA triggers the release of the neurotransmitter acetylcholine via a histaminergic H1 mechanism. MDMA is also a weak agonist of the acetylcholine muscarinic M1 receptors. MDMA's modest cholinergic activity may contribute to the exquisite lucidity of consciousness characteristic of pure MDMA taken in a therapeutic setting. For the cholinergic system is vital to memory, higher thought-processes and verbal fluency. Cholinergics such as piracetam (Nootropil) are used as nootropics or "smart drugs"; and acetylcholinesterase inhibitors like galantamine (Reminyl), rivastigmine (Exelon), tacrine (Cognex) and donepezil (Aricept) are used as palliative treatments of Alzheimer's disease. Acetylcholine-release and muscarinic receptor activation probably play no direct role in the rewarding hedonic effects of MDMA. Yet their subtle contribution to the texture of the magic can't be discounted. "Dumb-drug" antimuscarinic agents commonly induce mild euphoria via their indirect enhancement of dopamine function. Their mood-brightening effect stands in contrast to many cholinergic (e.g. muscarinic M4 receptor) agonists and cholinesterase inhibitors which have a tendency to subdue mood. A wide range of cholinergics is now under development for the palliative treatment of Alzheimer's disease, a progressive neurodegenerative disorder characterised by profound cholinergic deficits. Some depressives, however, may actually benefit from the antimuscarinic anticholinergic effects that more intellectually fastidious clinicians would call an adverse side-effect of the older tricyclics. While a great many depressed people report intellectual sluggishness and poverty of thought, other melancholic and introspective depressives endure "hypercholinergic frenzy", possibly owing to dysregulation of the cholinergic-adrenergic axis. Sadly, innumerable depressives among life's walking wounded today find the examined life scarcely worth living: they cope with life only by "just getting on with it". By contrast, MDMA allows introspection to become insightful and enjoyable even to the naturally angst-ridden. On MDMA, both philosophising and emotional self-honesty can be illuminating and fun. It's a shame that such self-insight can't more readily be prolonged.
Another enigma is the role of DHEA. MDMA causes a rise in the adrenal corticosteroid dehydroepiandrosterone (DHEA). DHEA is the precursor to testosterone, progesterone, estradiol and other steroids. The rise and peak physiological values of DHEA between around 1 to 2½ hours post-MDMA administration is correlated with user-reported euphoria, though DHEA's precise contribution to the mood-elevation is unclear. In general, levels of DHEA decline with age after early adulthood. Long-term supplementation with DHEA seems to have beneficial effect on libido, immune function and some forms of cognition. However, in spite of a wealth of research, no firm conclusions have yet been reached on the advisability of taking DHEA supplements, or an optimal dosage if taken. Nor is it known what role enhanced DHEA might play in sustaining enriched quality of life over the longer term. Taken on its own, DHEA may brighten mood; but it's scarcely an E-like effect.
One unwanted effect of MDMA, especially when taken at higher doses, is its tendency inhibit to tryptophan hydroxylase by triggering a rapid oxidation of the enzyme's sulphydryl sites. Tryptophan hydroxylase is the rate-limiting enzyme in serotonin synthesis. Even though the acute functional loss of tryptophan hydroxylase in the cell terminal is reversible, the axon's vulnerability to oxidative stress is increased. In order sustainably to enhance our capacity for empathetic bliss, and certainly to prevent any functional serotonergic deficit, tryptophan hydroxylase function must be enhanced, not inhibited. However, to date no stimulator (or inhibitor) of the biosynthesis of serotonin has been commercially marketed. Interestingly, the use of interventions to increase the biosynthesis of serotonin prior to MDMA use tends to trigger an increased synaptic release of dopamine, thereby enhancing the user's euphoria. Unfortunately, increased serotonin synthesis also aggravates post-E neurotoxicity. The two mechanisms are separable in principle. In the meantime, restraint is prudent.
http://72.14.205.104/search?q=cache...0+2D6+piracetam+mdma&hl=en&ct=clnk&cd=2&gl=us
If that makes any sense. So this speculates nootropics do not contribute significantly to the major euphoria... but who knows. We'll try it. By other accounts there is some sort of potentiating effect. Alternatively, pre-loading 5-htp should be done with restraint?
There actually is a lot of info out there but it is inconclusive and extremely challenging to interpret.
