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Ketamine salts solubility

That's a little odd. While I certainly don't doubt the findings of that ayahuasca study, I have also certainly never noticed one of us drug addicts quit using drugs after running across (or more usually, extracting a batch of DMT from mimosa hostilis which I, as a dumb ass, even managed to fuck up the extraction of) a sizable cache of pure DMT or ayahuasca. I could see how it would be a valuable antidepressant though, with fewer side effects than I would get from ketamine, which invariably has a tendency to induce months long psychosis in my mentally ill self even after a single use (though I generally went through about 1.2 grams per session). As it is, I have only vaporized about 30 to 40mg of presumably pure, yellow DMT powder, and I was, just as I expected, impressed by the results. Maybe Ganesha can send me a gram or two of DMT too this year if I place myself in the right circles (at raves in Atlanta) with a little cash? So yeah, that would be great.
 
A Case Report of Clonazepam Dependence

Clonazepam is long-acting benzodiazepine agonist used in short-acting benzodiazepine withdrawal; however, recent observations suggest the existence of its abuse.

We demonstrate a 40-year-old man with a 20-year history of psychiatric care with recently benzodiazepine dependence (daily intake of ∼60 mg of clonazepam and 10 mg of alprazolam). High serum levels of both drugs were analyzed 3 weeks before admission to hospitalization (clonazepam 543.9 ng/mL, alprazolam 110 ng/mL) and at the time of admission (clonazepam 286.2 ng/mL, alprazolam 140 ng/mL) without any signs of benzodiazepine intoxication.

Gradual withdrawal of clonazepam with monitoring of its serum levels and increase of gabapentin dose were used to minimize physical signs and symptoms of clonazepam withdrawal. Alprazolam was discontinued promptly. Clinical consequences of the treatment were controllable tension, intermittent headache, and rarely insomia.

It is the first case report showing utilization of therapeutic drug monitoring during withdrawal period in the patient with extreme toleration to severe benzodiazepine dependence.

NSFW:
The patient used clonazepam 4 mg 3 times daily first 8 days after admission and then the dosage was wind down using a rate of taper off by ∼2 mg/2–3 days with almost daily therapeutic monitoring of its level. Changes in clonazepam concentrations and pharmacokinetic parameters during gradual withdrawal period are summarized in Table ​Table2.2.

The clearance was decreased from the 1st to the 4th day of hospitalization and then remained similar to healthy volunteers.7 The elimination half-life was increased to the 4th day and then was stable similar to general population.5–7Figure ​Figure11 shows differences between serum levels of clonazepam during tapering dosage (when the serum level in the therapeutic range was achieved in ∼2 weeks) and within hypotetical abrupt cessation (when the upper limit of therapeutic range should be reached in 2 days and a nondetectable serum level in 1 week).

The patient only suffered from controllable tension and headache namely at the beginning of hospitalization and rarely insomnia at the end. He has not experienced any other withdrawal symptoms (such as tremor, irritability, sweating, hallucinations, aggressiveness) during hospitalization, but his weight decreased by ∼3.6 kg.

However, 1 mg of alprazolam was administrated 2 times early after admission in the case of anxiety and/or tension and then alprazolam was discontinued. A total of 400 mg of ibuprofen (1 or 2 times daily) was administered at headache and 10 mg of zolpidem in the case of insomnia. The dosage of gabapentin was increased to 900 mg 3 times daily (as prevention of epileptic seizures during reduction of benzodiazepines) and the dosage of citalopram and betaxolol was not changed.

The blood pressure was measured 3 times daily with the values 110–120/70–80 mm Hg. The patient used clonazepam 5 mg daily (2 mg in the morning, 1 mg at noon, and 2 mg at evening), gabapentin 900 mg 3 times daily, citalopram 20 mg once a day, and betaxolol 10 mg once a day at the end of hospitalization.

He was discharged 16th day with the dose of clonazepam 5 mg daily (2 mg in the morning, 1 mg at noon, and 2 mg at evening), the clonazepam serum level 81.3 ng/mL (i.e. in upper limit of therapeutic range) and without clinical signs of withdrawal. Admission in psychiatric sanatorium to detoxification was planned at the same day.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782857/
 
Clonazepam proven effective for individuals suffering from sleep-related painful erections (SRPEs)

INTRODUCTION:
As specialists in male genital problems, urologists and sexologists will most likely to be involved in the treatment of males presenting with sleep-related painful erections (SRPEs). This means that this phenomenon needs to be recognized by urologists and sexologists, and that they should have knowledge of the current diagnostic and therapeutic approaches. Aim. To review the literature on SRPE and to find the best pharmacological treatment. Methods. Four personal clinical observations from two clinics and 29 other cases with SRPE found in PubMed were analyzed, especially regarding the results of pharmacological treatment.

MAIN OUTCOME MEASURES:
The results of pharmacological treatment.

RESULTS:
Many of the various treatments proved to be ineffective and only a few showed efficacy for a few weeks or months. The only effective drugs in the long term were baclofen, clonazepam, and clozapine.

CONCLUSIONS:
Until now, the phenomenon of SRPE is not well understood. The rarity of the published cases undoubtedly does not reflect the actual occurrence of SRPE. Controlled double-blind pharmacological trials are needed, and long-term follow-up including polysomnography coupled with nocturnal penile tumescence and rigidity monitoring may provide further information about SRPE.
http://www.ncbi.nlm.nih.gov/pubmed/17971102
 
Great, so Klonopin or Clozaril or baclofen appears to be a great way to diminish your virility. No thanks! I need all the biggest, hardest, long lasting erections I can get! Viagra doesn't help me.
 
benzos seem to be the first line treatment for both stiff person syndrome and a savagely stiff erection.
 
The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state.

The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time.

Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness.

It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.

*This article is from early 2014 and i figured it would have been posted but my search did not return any results.*

full:http://journal.frontiersin.org/article/10.3389/fnhum.2014.00020/full
 
On a side note, I am also curious about Sodium Acetate Tri-Hydrate as a catalyst instead of Sulfuric/ Phosphoric acid.
Click to expand...

Some of them have appreciable affinities at other sites (mainly DAT and sigma receptors), a 10-fold selectivity isn't really considered very selective.
 
My 18 year access to Uni journals will be coming to an end within the next year. It's going to kill me to not be able to just read whatever I fancy, but anyway if anyone lacking this luxury is itching to read a full paper they can't find elsewhere, please post a link and I'll see if we're subscribed.
 
Interesting Nature paper on the mechanism of Ketamine's antidepressant effects:

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

Major depressive disorder affects around 16 per cent of the world population at some point in their lives. Despite the availability of numerous monoaminergic-based antidepressants, most patients require several weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive, glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist (R,S)-ketamine exerts rapid and sustained antidepressant effects after a single dose in patients with depression, but its use is associated with undesirable side effects. Here we show that the metabolism of (R,S)-ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant-related actions in mice. These antidepressant actions are independent of NMDAR inhibition but involve early and sustained activation of AMPARs (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors). We also establish that (2R,6R)-HNK lacks ketamine-related side effects. Our data implicate a novel mechanism underlying the antidepressant properties of (R,S)-ketamine and have relevance for the development of next-generation, rapid-acting antidepressants.
Click to expand...

To sum up briefly: the effectiveness of ketamine as an antidepressant stems not from its action as an antagonist of NMDA receptors, as was previously thought, but rather those of one of its metabolites (blocking the metabolic step blocked the beneficial effects of ketamine). The metabolite is non-psychoactive, and turns out to act on AMPA receptors (it activates them, and preventing their activation blocks the antidepressant effects). Quite a turn up for the books!
 
I just started getting into it, used one of those links (thanks!) for the free journal downloads..

This is for MDPV and about the two isomers one causing side effects/psychosis the other causing stim effects is what it looks like on the surface.

I think its even more crazy with certain other compounds like 4-CL-PVP will make you see UFO's and aliens while you can fall asleep (atypical of stimulant psychosis.. the 4-cl doesn't feel stimulating)

I wonder if just the S isomer / dextro versions would be awesome stimulants with medical use.

http://onlinelibrary.wiley.com/doi/10.1002/chir.22423/full

article available free through those websites.
 
A nontoxic pain killer designed by modeling of pathological receptor conformations

Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral m-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide–binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3′,5′-monophosphate inhibition in vitro. It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential.

http://science.sciencemag.org/content/355/6328/966

Another non-toxic, non-addictive, "perfect" opioid ... 8) maybe instead of fucking with random fent analogs people could make the one described in the paper?
 
I feel dumb but I gotta ask my current state of minds, well curious about everything. The cat joke? I dont get it.
Also dont know exactly who that guy is just heard his name... We'll I just realized its time to pick up a book.
But really ya gotta explain the cat to me please? :p
 
Enzymatic synthesis of psilocybin
http://onlinelibrary.wiley.com/doi/10.1002/anie.201705489/abstract

Abstract

Psilocybin is the psychotropic tryptamine-derived natural product of Psilocybe carpophores, the so-called "magic mushrooms". Although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure. We characterized four psilocybin biosynthesis enzymes. These include i) PsiD which represents a new class of fungal l-tryptophan decarboxylases, ii) PsiK, that catalyzes the phosphotransfer step, iii) the methyl transferase PsiM, catalyzing iterative N-methyltransfer as terminal biosynthetic step, and iv) PsiH, a monooxygenase. In a combined PsiD/PsiK/PsiM reaction, psilocybin was synthesized enzymatically in a step-economic route from 4-hydroxy-l-tryptophan. Given the renewed pharmaceutical interest in psilocybin, our results may lay the foundation for its biotechnological production.
 
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