• N&PD Moderators: Skorpio | thegreenhand

⫸STICKY⫷ The N&PD Recent Journal ARTICLE Club

An animal model of schizophrenia based on chronic LSD administration: old idea, new results.
Marona-Lewicka D, Nichols CD, Nichols DE.
Neuropharmacology. 2011 Sep;61(3):503-12. Epub 2011 Feb 23.
http://dx.doi.org/10.1016/j.neuropharm.2011.02.006

Anyone that has the whole article? Post here or, if you hesitate to post it here, send me a PM please! I 'm highly interested in this as large acid doses were mainly to blame for my psychosis...
 
The Norepinephrine Transporter Inhibitor Reboxetine Reduces Stimulant Effects of MDMA ("Ecstasy") in Humans.
Hysek CM, Simmler LD, Ineichen M, Grouzmann E, Hoener MC, Brenneisen R, Huwyler J, Liechti ME.
Clin Pharmacol Ther. 2011 Aug;90(2):246-55. doi: 10.1038/clpt.2011.78. Epub 2011 Jun 15.

This study assessed the pharmacodynamic and pharmacokinetic effects of the interaction between the selective norepinephrine (NE) transporter inhibitor reboxetine and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in 16 healthy subjects. The study used a double-blind, placebo-controlled crossover design. Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE, increases in blood pressure and heart rate, subjective drug high, stimulation, and emotional excitation. These effects were evident despite an increase in the concentrations of MDMA and its active metabolite 3,4-methylenedioxyamphetamine (MDA) in plasma. The results demonstrate that transporter-mediated NE release has a critical role in the cardiovascular and stimulant-like effects of MDMA in humans.

No big review because NPG is a dick and I have no access -- but I wonder what happens if you administer MDAI with a noradrenaline only releasing agent such as ethcathinone?
 
^that is interesting. I did some experimentation a couple years ago with MDAI & a few varied DARI's/releasing agents, some with greater affinity for NE than others. Buphedrone+MDAI was quite MDMA-like, but was lacking in some regards, which i thought odd. Granted, i don't think there is definitive info on buphedrone's pharmacology, but everything i could find seemed to indicate it was mostly dopaminergic. MPH+MDAI was also quite interesting. d-amph & M1 (separately) + MDAI were nearly indistinguishable from MDMA.

I've been attempting to find the full text to the following article, but both colleges whose library i have access to don't have it. Sure some of you guys would be interested as well. Here's the citation:
International Journal of Neuropsychopharmacology. 2011 May 5:1-5. [Epub ahead of print]
A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department.
Larkin GL, Beautrais AL.
Department of Emergency Medicine, Yale University School of Medicine, New Haven, CT, USA

feel free to pm or email me.
 
nuke said:
No big review because NPG is a dick and I have no access -- but I wonder what happens if you administer MDAI with a noradrenaline only releasing agent such as ethcathinone?

I'm guessing that you'd end up with something that feels remarkably similar to MBDB (given that the latter has significant affinity at SERT and NET, but little at DAT).

ebola
 
Effects of MDMA on Extracellular Dopamine and Serotonin Levels in Mice Lacking Dopamine and/or Serotonin Transporters.
Curr Neuropharmacol. 2011 Mar;9(1):91-5.
Hagino Y, Takamatsu Y, Yamamoto H, Iwamura T, Murphy DL, Uhl GR, Sora I, Ikeda K.

3,4-Methylendioxymethamphetamine (MDMA) has both stimulatory and hallucinogenic properties which make its psychoactive effects unique and different from those of typical psychostimulant and hallucinogenic agents. The present study investigated the effects of MDMA on extracellular dopamine (DA(ex)) and serotonin (5-HT(ex)) levels in the striatum and prefrontal cortex (PFC) using in vivo microdialysis techniques in mice lacking DA transporters (DAT) and/or 5-HT transporters (SERT). subcutaneous injection of MDMA (3, 10 mg/kg) significantly increased striatal DA(ex) in wild-type mice, SERT knockout mice, and DAT knockout mice, but not in DAT/SERT double-knockout mice. The MDMA-induced increase in striatal DA(ex) in SERT knockout mice was significantly less than in wildtype mice. In the PFC, MDMA dose-dependently increased DA(ex) levels in wildtype, DAT knockout, SERT knockout and DAT/SERT double-knockout mice to a similar extent. In contrast, MDMA markedly increased 5-HT(ex) in wildtype and DAT knockout mice and slightly increased 5-HT(ex) in SERT-KO and DAT/SERT double-knockout mice. The results confirm that MDMA acts at both DAT and SERT and increases DA(ex) and 5-HT(ex).
Free fulltext: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137209/?tool=pubmed

This flies in the face of all the people who've been saying that DAT and SERT have been instrumental in the release of monoamines from MDMA. That dopamine release still occurs despite the KO of DAT is surprising, though SERT KO produced ablation of 5HT release activity. This is yet more confusing information about the psychopharmacology of MDMA, since it has been shown in a couple of studies to also not be a substrate for human SERT. I would have been more pleased if they included the effects of NET knock-out too, but making mice with genes knocked out is probably not a trivial matter.
 
This flies in the face of all the people who've been saying that DAT and SERT have been instrumental in the release of monoamines from MDMA.

This would include everyone, right? Holy shit...

ebola
 
This would include everyone, right? Holy shit...

ebola

Well, to be fair, SERT knockout produced the expected results.. but how to explain the catecholamine release? VMAT2?

And if MDMA/MDA doesn't bind to SERT in humans, what stimulates 5HT release?

Lots of questions now about MDMA's mechanism of action, I guess.
 
It probably has more to do with metabotropic glutamate, NAChR's, and VMAT2 than anything else judging by all the other amphetamine studies that have popped out recently. MDMA might have a lot to do with 5HT2A as far as 5HT release goes to quote my pharmacology prof.
 
Let's keep em coming fellas.

Long-Lasting Neuroprotective
Effect of Sildenafil Against 3,4-
Methylenedioxymethamphetamineinduced
5-Hydroxytryptamine Deficits
in the Rat Brain

Elena Puerta,1 Lucia Barros-Min˜ ones,1 Isabel Hervias,2
Violeta Gomez-Rodriguez,1 Lourdes Orejana,1 Neus Pizarro,3
Rafael de la Torre,3,4 Joaquı´n Jorda´n,5 and Norberto Aguirre1*

Sildenafil, given shortly before 3,4-methylenedioxymethamphetamine (MDMA), affords protection against 5-hydroxytryptamine (5-HT) depletions caused by this amphetamine derivative by an acute preconditioning-like mechanism. Because acute and delayed preconditionings do not share the same mechanisms, we investigated whether sildenafil would also protect the 5-HT system of the rat if given 24 hr before MDMA. For this, MDMA (3 × 5 mg/kg i.p., every 2 hr) was administered to rats previously treated with sildenafil (8 mg/kg p.o.). One week later, 5-HT content and 5-HT transporter density were measured in the striatum, frontal cortex, and hippocampus of the rats. Our findings indicate that sildenafil afforded significant protection against MDMA-induced 5-HT deficits without altering the acute hyperthermic response to MDMA or its metabolic disposition. Sildenafil promoted ERK1/2 activation an effect that was paralleled by an increase in MnSOD expression that persisted 24 hr later. In addition, superoxide and superoxide-derived oxidants, shown by ethidium fluorescence, increased after the last MDMA injection, an effect that was prevented by sildenafil pretreatment. Similarly, MDMA increased nitrotyrosine concentration in the hippocampus, an effect not shown by sildenafil-pretreated rats. In conclusion, our data demonstrate that sildenafil produces a significant, long-lasting neuroprotective effect against MDMA-induced 5-HT deficits. This effect is apparently mediated by an increased expression of MnSOD and a subsequent reduced susceptibility to the oxidative stress caused by MDMA

I guess if you want to beat the neurotoxicity of MDMA, it's best to pop a boner-pill...
 
Alkamides and a neolignan from Echinacea purpurea roots and the interaction of alkamides with G-protein-coupled cannabinoid receptors
Judit Hohmanna, , , Dóra Rédeia, Peter Forgoa, Pál Szabób, Tamás F. Freundc, József Hallerc, Engin Bojnikd, Sándor Benyhed
-From various on Universities/Institutes in Hungary

doi:10.1016/j.phytochem.2011.06.008
http://www.sciencedirect.com/science/article/pii/S0031942211003037#sec3.2

Multiple chromatographic separations of the CHCl3-soluble extract of the roots of Echinacea purpurea led to the isolation of 19 compounds. Four natural products, three alkamides and nitidanin diisovalerianate, were identified, and five further compounds were detected for the first time in this species. Additionally, 10 known E. purpurea metabolites were isolated. The structures were determined by mass spectrometry and advanced 1D and 2D NMR techniques. The bioactivity of the isolated compounds was studied in [35S]GTPγS-binding experiments performed on rat brain membrane preparations. Both partial and inverse agonist compounds for cannabinoid (CB1) receptors were identified among the metabolites, characterized by weak to moderate interactions with the G-protein signaling mechanisms. The G-protein-modulating activities of the Echinacea compounds are rather far from the full agonist effects seen with the CB1 receptor agonist reference compound arachidonyl-2′-chloroethylamide (ACEA). However, upon coadministration with ACEA, a number of them proved capable of inhibiting the stimulation of the pure agonist, thereby demonstrating cannabinoid receptor antagonist properties.

I have been sick lately and found that Echinacea helped me recover far faster than I imagined. I decided to read a bit about it, besides what you can find in wikipedia, to see what science had to say about it. I was also particularly interested in finding an article that dealt with how echinacea interacts with the endocannabinoid system. I find it relavant to today's politics as certain, most likely uneducated, folk have called for bans on all chemicals that interact with the endocannabinoid system (as a means of banning various synthetic thc esque chemicals); this would (unintentionally?) include the likes of many OTC things such as echinacea tea or echinacea couch drops... etc.

Particuarly I think the article, if indirectly, does a good job of describing the daunting-ness of the task of explaining how echinacea can function as an immunomodulator. A major trouble has been determining which chemicals found in echinacea are actually responsible for the physiological effects.

-I have access to the full text via my university VPN.
 
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I tried VPN'n into my uni network; they don't have access to that journal.
I would also be interested in getting a copy of that paper.
I can request a copy but it could take 2-3 days. Surely someone else out there can help us out..
 
Anyone have access to this?

Clinical toxicology of newer recreational drugs.
Hill SL, Thomas SH.
Source

National Poisons Information Service (Newcastle Unit), Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne , UK.
Abstract

Introduction. Novel synthetic 'designer' drugs with stimulant, ecstasy-like (entactogenic) and/or hallucinogenic properties have become increasingly popular among recreational drug users in recent years. The substances used change frequently in response to market trends and legislative controls and it is an important challenge for poisons centres and clinical toxicologists to remain updated on the pharmacological and toxicological effects of these emerging agents. Aims. To review the available information on newer synthetic stimulant, entactogenic and hallucinogenic drugs, provide a framework for classification of these drugs based on chemical structure and describe their pharmacology and clinical toxicology. Methods. A comprehensive review of the published literature was performed using PUBMED and Medline databases, together with additional non-peer reviewed information sources, including books, media reports, government publications and internet resources, including drug user web forums. Epidemiology. Novel synthetic stimulant, entactogenic or hallucinogenic designer drugs are increasingly available to users as demonstrated by user surveys, poisons centre calls, activity on internet drug forums, hospital attendance data and mortality data. Some population sub groups such as younger adults who attend dance music clubs are more likely to use these substances. The internet plays an important role in determining the awareness of and availability of these newer drugs of abuse. Classification. Most novel synthetic stimulant, entactogenic or hallucinogenic drugs of abuse can be classified according to chemical structure as piperazines (e.g. benzylpiperazine (BZP), trifluoromethylphenylpiperazine), phenethylamines (e.g. 2C or D-series of ring-substituted amfetamines, benzodifurans, cathinones, aminoindans), tryptamines (e.g. dimethyltryptamine, alpha-methyltryptamine, ethyltryptamine, 5-methoxy-alphamethyltryptamine) or piperidines and related substances (e.g. desoxypipradrol, diphenylprolinol). Alternatively classification may be based on clinical effects as either primarily stimulant, entactogenic or hallucinogenic, although most drugs have a combination of such effects. Clinical toxicology. Piperazines, phenethylamines, tryptamines and piperidines have actions at multiple central nervous system (CNS) receptor sites, with patterns of effects varying between agents. Predominantly stimulant drugs (e.g. benzylpiperazine, mephedrone, naphyrone, diphenylprolinol) inhibit monoamine (especially dopamine) reuptake and are characteristically associated with a sympathomimetic toxidrome. Entactogenic drugs (e.g. phenylpiperazines, methylone) provoke central serotonin release, while newer hallucinogens (e.g. 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT), 2,5-dimethoxy-4-bromoamfetamine (DOB)) are serotonin receptor agonists. As a result, serotoninergic effects predominate in toxicity. Conclusions. There are limited reliable data to guide clinicians managing patients with toxicity due to these substances. The harms associated with emerging recreational drugs are not fully documented, although it is clear that they are not without risk. Management of users with acute toxic effects is pragmatic and primarily extrapolated from experience with longer established stimulant or hallucinogenic drugs such as amfetamines, 3,4-methylenedioxymethamfetamine (MDMA) and lysergic acid diethylamide (LSD).
 
^^ I would also be interested in getting a copy of this paper;
as above the offer stand that I can request a copy thru my uni but it'd take a day or two for them to get around to sending it to me.
So hopefully someone can help us out before hand
 
thanks guys for posting it!!!
heres my short review / thoughts on the article

Title: 'Ward, J.; Rhyee, S.; Plansky, J. (2011). "Methoxetamine: A novel ketamine analog and growing health-care concern". Clinical Toxicology: 1'
DOI: http://dx.doi.org/10.3109%2F15563650.2011.617310

Not really what i expected. It was about guy who presented in emergency care due to overdose of MXE. It was the first time the person used MXE and he ordered it online.

the article states that MXE is NMDA receptor blocker and works as dopamine reuptaker aswell, although formal pharmacology has not yet been determined. GC-MS was ran and substance identified as MXE, nothing was said about impurities so we can assume it was quite pure. Substance came from UK. They assume MXE abuse will rise in future as its easy to order online and prices are cheap

I guess we can conclude that overdosing from MXE alone is pretty hard
 
Clinical toxicology of newer recreational drugs:

http://www.filesonic.com/file/2857293425

From the MXE article:

Although Internet vendors state that methoxetamine is not for human consumption, the drug is clearly used for illicit purposes

There are currently no legal restrictions within the United States (U.S) prohibiting the purchase or use of methoxetamine

Can you really call it illicit use if it's not illegal?

^ They do say, "mechanism of action likely involves... formal pharmacology has not yet been determined." And it sounds more like he just freaked out and called an ambulance rather than really overdosed, heart rate and blood pressure weren't that high.
 
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Clinical toxicology of newer recreational drugs:

Can you really call it illicit use if it's not illegal?

I guess they mean "illicit" as in contrary to the stated "not for human consumption" instuctions.

Incidentally, why use filesonic - have to wait to download, enter a captcha... I don't understand why everyone doesn't use sendspace, so much less hassle. %)
 
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