• N&PD Moderators: Skorpio | thegreenhand

The Big & Bangin' Miscellaneous Chemistry/Pharmacology Odds N' Ends Thread: Part 3

Coluracetam has been shown to reverse the loss of choline acetyltransferase production in the medial septal nucleus of rats exposed to phencyclidine (PCP), and is considered a potential therapeutic drug for schizophrenia
Shirayama, Y; Yamamoto, A; Nishimura, T; Katayama, S; Kawahara, R (2007). "Subsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in rats". European Neuropsychopharmacology. 17 (9): 616–26. PMID 17467960. doi:10.1016/j.euroneuro.2007.02.011.

What would be the significance of this? Is this sort of effect of PCP chronic?
How much of bisphenol-A (BPA)-like toxicity are of those naphthoylindole?
I think both of them activates nuclear aromatic receptor somewhat.
(Im not talking about Xenoestrogenic activity)
Solipsis, could be due perhaps to the proglutamatergic effects of GHB. A direction you might want to look down, is the effects of acromelic acid, which acts as a kainate receptor agonist and causes a long lasting, thermally-sensitive allodynia, its naturally present in two fungi (so far as is known, of course) of the genus Clitocybe, namely C.acromelalga and C.amnoelens, could perhaps make sense that kainate sensitive iGLuRs are involved in gating the transduction of noxious stimuli, as they do seem to modulate sensitivity to future stimulation, potentially in the long term, as with, for example, the way acromelate fucks with dorsal root neurons within the spinal cord, a region known to be involved in pain signalling.
1-allyl-3,4-dihydroxybenzene from eugenol / pyridine and AlCl3 plausible?
A quick note about a drug that is not very popular. I had read earlier from some publication that nutmeg oil has been found to contain compounds that inhibit the FAAH enzyme, increasing the amount of endocannabinoids in the body. This could be a reason for it's somewhat cannabis-like effects. I also read that a metabolite of acetaminophen/paracetamol is an anandamide reuptake inhibitor, increasing endocannabinoid activity in another way. So, I thought that taking those two substances at the same time could result in a lot of potentiation (think about how extreme the dangerous effects of an SSRI-MAOI combination can be).

I hadn't taken nutmeg for about 4 years, but yesterday I ingested somewhat less than 10 g of powdered nutmeg and 1000mg of acetaminophen at the same time, and the effects seemed to begin in less than 2 hours, in contrast to the normal 5 hours. The effects were stronger than what a dose of >20g of the spice of the same brand caused when I took it without acetaminophen, and lasted for something like 24 hours. There were also some more visual distortions than in an ordinary nutmeg intoxication.

So, looks like those two things actually potentiate each other. Another possible reason could be the brand of spice containing more actives now than before, but I don't think that is very likely. I'm also on a quetiapine medication now, unlike the last time I took nutmeg, and its antihistaminic effect could probably also potentiate the effect.

Edit: 2 days later, I still feel really stoned after taking another 5 g of nutmeg yesterday, and another 1000 mg of acetaminophen today...
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Still feeling somewhat tired from that... The nutmeg effects can be fun initially, but if you start doing it too often it turns into a terribly depressing and anxious feeling (for some people it's immediately like that, though).

So, either H1 blockage or the acetaminophen's metabolite AM404 has a potentiating effect on this. I hope it's the latter, as this would quite conclusively show that the nutmeg's effect is based on the endocannabinoid system.
I've heard some funky things about Artane (Trihexyphenidyl). So it both can be applied to Parkinson's and extrapyramidal effects of antipsychotics? I've taken it before for extreme restlessness. So it's anti-muscarinic (without affecting the nicotinic receptor), but it must somehow increase dopamainergic action in the neocortex, D1/D5. It always made me sleepy. Are there muscarinic/dopaminergic heteromers? I'm noobish.

A lack of dopaminergic activity will also often cause cholinergic symptoms such as excessive salivation. This is because dopamine and acetylcholine have counteracting effects in the CNS. That's why anticholinergics have an anti-parkinsonian effect.
I'm amazed, as both have been cited as having nootropic effects (dopaminergics and chollinergics). Things get a bit hairy when we talk of nicotinic LGIC's. It's supposed to effect a release of beta-endorphin, dopamine, GABA, serotonin, and more.

Chollinergics like acetylchollinase inhibitors are probably most associated with nootropic effects. More so than stimulants, yet studies exist on amp and nootropic activity, probably just secondary to energy. I know that caffeine has data on it as well. But most evidence, I believe, in spite of the nasty habit researchers have with equating nicotine and cigarettes, is in support of nicotine (by itself) as a pro-cognitive agent.

It seems to be quite complicated, some of the cognitive-decline symptoms in Parkinson's are caused by a loss of cholinergic neurons while some other symptoms are because of change in the dopamine-cholinergic balance.

Doing the nutmeg thing again this week, the 10 g dose didn't seem to produce any dramatic effect either with or without paracetamol... Maybe I just didn't remember how intense the effect can be if you haven't taken any for years.
Nutmeg works best as fresh whole nuts chewed/crushed before ingestion rather than using pre-ground powder. The elemicin etc are volatile after all!
I've never found whole nutmegs on sale where I live, I think it's because it's illegal to import them (or at least used to be). I'm not sure how much of the effect is because of the volatiles like myristicin and how much of it is caused by the effects of less volatile components on the endocannabinoid system.
Nutmeg should not be illegal to import whole; it's just a spice and is not on any sort of watch list. If nutmeg was banned they'd have to ban the powder too, and the essential oil.


Also, cool tidbit: 1-phenylethylamine ("alpha methyl benzylamine") is a MAO-I.[ref]
There are many crazy regulations where I live, and the customs can confiscate just about anything they think will be used as an intoxicant, even when it's not technically a classified substance. Chewing tobacco is banned here, too.

I feel the attempt to make poor drugs better by smart tricks is an interesting endeavour, because if the countries of the West will also develop to a more totalitarian direction like Russia and China, it may be difficult to obtain a large variety of drugs in the future. I just tripped on morning glory seeds today, grinding them first and then mixing with baking soda and keeping the mix in my mouth until the alkaloids had been absorbed. The same trick as with chewing tobacco and coca leaves - the alkaline freebase form passes effectively through membranes. In the case of MG seeds, this also eliminated the nauseating effect. Well, I really don't react to psychedelics in the ordinary way because 20 years of psych med use has altered my serotonin receptors - I only get a feeling of strange atmosphere and some distortions of perception (everything looking like if viewed in a resolution different from usual) without any actual colorful visuals. But a nice energetic mood is left after the comedown.
That brings back memories. Morning glory seeds. I think I might have to revisit those some time, give that transbuccal administration method a crack.

And not only making poor drugs better, but make more routes to extant ones practical with less chemistry skill.

Such as say, (and this is VERY different from the notorious shake'n'bake meth in a coke bottle abomination) using an ethereal suspension of alkali metal, and gaseous anhydrous ammonia (fertilizer and caustic for the NH3, CaO drying tube, continual bubbling into ether, protected by an argon welding gas atmosphere. The blue of solvated electrons takes time to form, but as long as one is comfortable around EtOEt, a damn sight safer than fucking around with liquid anhydrous, for your beginner, and the reducing environment pretty much takes anything unpleasant and peroxide-shaped out of the picture.

Takes 2-3 hours or so, in the case of lithium or sodium, cut up as fine as possible, and a constant stream of NH3 gas passed through the desiccant tube, into a flask of cooled ether. A lot less potential for a massive uncontrollable NH3 gas release, as would happen if a Bircher buggered things up with a flask full of anhydrous NH3 in liquid form. Less concentrated, spread out over more time to form the reductant system, but works just fine. The majority of the anhydrous in a typical Birch-Benkeser is serving as a solvent, rather than the limited quantity which actually serves as a reactant with the alkali metal to form the solvated electron 'soup'

And the more techniques we get out there, such as harvesting benzyl alcohol from the UK's shitty new paint stripper, which now use benzyl alcohol in place of dichlor, benzaldeyde right there. Fermentation techniques, to L-PAC, I've been reading of some rather interesting uses of Brevibacterium linens, for amination, too, this being the red smear limburger cheese bacterium. According to certain bees, such a culture can tolerate up to 10g/liter of benzaldehyde.
It may be best to powder the MG seeds with some machine to get them fine enough and not have pieces of seed stuck between your teeth. Most people will probably not have enough patience to absorb enough of that kind of stuff to trip really hard, but it may be useful in microdosing, cluster headache treatment or as an addition to something else.

Isn't the bitter almond aroma sold in grocery stores 50% benzaldehyde and 50% ethanol? The price per kilogram is of course quite high, I know.
The ones I've seen, I don't know the percentages, but it's in a base of oil, peanut oil I think.

If I ever get both penniless and desperate, I'll adduct it out, cleave, distill under Ar, but otherwise, the 2l ACS grade benz in the reagent fridge is much preferable. Makes the fridge smell absolutely mouthwatering, even with my old man using one shelf to store tubs of maggots and casters under water in there. It still smells like someone carpet-bombed a cherry bakewell tart factory. That, with a slight hint of clean, sanitary-scented iodine, makes even a maggot-lair of a fridge smell nice. And covers up the odor of less pleasant things nicely too.

Crystallize P2NP in there, and the mix of cherry bakewell tarts and fireball-candy....best smelling, most mouthwatering fridge I've ever encountered=D

Edit-electric spice grinder would be perfect for the MGS. That thing will whizz up a handful of dried, cured fly agaric caps, leathery dried peppery boletus, szechuan pepper, which is made from the dried hulls, lacking seeds,of a tough plant seedcase, cubebs, peppercorns,pink pepper after bruising the latter in a mortar to get the oils coming out properly, plus a fair few other tough, brittle or leathery and chitinous ingredients, one quick whirring burst from the blades in that, and it'll reduce the whole lot to a fine dust, just perfect for bottling up for when I fry steaks, or to chuck in chili con carne, as my personal special steak spice blend. Got a few other bits and pieces in it, but the spice grinder renders the toughest, most woody or chitinous and springy ingredients to fluff in moments.

The kinds of things you'd think 'fucking christ...two hours of THIS...' before flopping down on the sofa exhausted with a needle full of morphine in the side of your leg, if having to use a mortar and pestle to grind the blend up.
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I wrote about my MGS/bicarbonate idea on a cluster headache support forum and someone there seemed to agree that it does the trick.

You can probably also extract the seeds with ethanol and evaporate the solvent to get a much smaller mass of stuff with the alkaloids in it. The irritants with the nauseating effect will also be in that extract, but it doesn't matter if it's dosed sublingually/transbuccally.
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