⫸STICKY⫷ The N&PD Recent Journal ARTICLE Club

[Gaius]

Apparently it's a relatively potent N-acylethanolamine acid amide hydrolase and anadamide uptake inhibitor fwiw.

CBD was the only compound to inhibit FAAH, whereas the BDS of CBC > CBG > CBGV inhibited NAAA. CBC = CBG > CBD inhibited ACU, as did the BDS of THCVA, CBGV, CBDA and THCA, but the latter extracts were more potent inhibitors.

 

[AlphaMethylPhenyl]

There is probably an undiscovered mechanism against depression. I know, it may be due to trpa receptors, but I don't think so. Just read the abstracts please/concluding sentence of each. I'm trying to find out why it has antidepressant effects. I could do more research but I already typed this twice and I'm sick as a dog. Thanks.

http://www.biomedsearch.com/nih/Antidepressant-like-effect-Delta9-tetrahydrocannabinol/20332000.html

http://www.biomedsearch.com/nih/Inhibitory-effect-cannabichromene-major-non/22300105.html

http://www.biomedsearch.com/nih/cannabinoid-TRPA1-agonist-cannabichromene-inhibits/23373571.html

http://www.biomedsearch.com/nih/Non-psychoactive-cannabinoids-modulate-descending/20942863.html

http://www.biomedsearch.com/nih/Pha...on-natural-constituent-Cannabis/20619971.html

 

[jaurk]

Every 25i study to date, with free links to paid papers

 

[ebola?]

^^^^^
very nice.

I think that we should establish a norm in here that each post should contain at least a little description and commentary (even just a couple sentences) in addition to the link. I think that this would pique more vigorous discussion.

ebola

 

[sekio]

L-Methylphenidate Is Stereoselectively Hydrolyzed by Human Carboxylesterase CES1A1
Zejin Sun, Daryl J. Murry, Sonal P. Sanghani, Wilhelmina I. Davis, Natalia Y. Kedishvili, Qin Zou, Thomas D. Hurley and William F. Bosron
http://jpet.aspetjournals.org/content/310/2/469.long

Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo.
Hannestad J, Gallezot JD, Planeta-Wilson B, Lin SF, Williams WA, van Dyck CH, Malison RT, Carson RE, Ding YS.
http://www.ncbi.nlm.nih.gov/pubmed/20691429


Medical Marijuana: Clearing Away the Smoke
Igor Grant, J. Hampton Atkinson, Ben Gouaux, and Barth Wilsey
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358713

As with all medications, benefits and risks need to be weighed in recommending cannabis to patients. We present an algorithm that may be useful to physicians in determining whether cannabis might be recommended as a treatment in jurisdictions where such use is permitted.

Cannabis is suggested as a treatment option for neuropathic pain, where standard Rx treatments fail, and the risk of substance abuse and mood disorders is judged to be acceptably low. I like that patient preference for oral versus smoked versus vapourised marijuana is part of the treatment too.

Concerns have long been voiced that rapid tolerance to adverse effects might portend tolerance to beneficial effects. Data from studies using oral sprays of cannabinoids or dronabinol in multiple sclerosis report that individuals can reduce the incidence and severity of adverse effects by downward self-titration without loss of analgesia. Other studies in this population note that overall the incidence and severity of adverse effects diminishes over time without evidence of tolerance to analgesic effects. Yet it is rare that clinical trials of cannabinoids extend follow-up beyond 12 weeks, leaving questions on maintenance of gains or need for dose escalation unanswered. One study with 12-month follow-up concluded there may be sustained analgesia for pain associated with multiple sclerosis, where about 30% of cannabinoid-treated participants report continued “improvement” at 12 months compared to about 15% on placebo on doses conservatively limited to a maximum of 25mg THC daily. This suggests that pain relief may be sustained without dose increases. But the study design was not intended to determine the proportion of patients who experienced diminution of effect, or whether dose escalation, even within the set boundary, was needed for maintenance of efficacy.

This is pretty suprising. I don't think one can say the same about the other "habit forming" drugs, esp. opioids and benzodiazepines.

Also:

The classification of marijuana as a Schedule I drug as well as the continuing controversy as to whether or not cannabis is of medical value are obstacles to medical progress in this area. Based on evidence currently available the Schedule I classification is not tenable; it is not accurate that cannabis has no medical value, or that information on safety is lacking. It is true cannabis has some abuse potential, but its profile more closely resembles drugs in Schedule III (where codeine and dronabinol are listed). The continuing conflict between scientific evidence and political ideology will hopefully be reconciled in a judicious manner [...]

Sick burn, guys.

 

[endotropic]

Spatiotemporal Brain Dynamics of Emotional Face Processing Modulations Induced by the Serotonin 1A/2A Receptor Agonist Psilocybin.

Abstract
Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control.

Nice to see human psychedelic research chugging along, even if the conclusions you can draw from an EEG study are less than stellar. I found this really interesting as well:

Participants were excluded, if they had history of drug dependence, as assessed by a self-made consumption questionnaire, or if they were currently using drugs as assessed by a urine drug test. Nevertheless, seven participants were occasional smokers (<6 cigarettes/day), 7 participants reported a sporadic or rare cannabis use in the past (<2 joints/month), one participant reported previous experience with MDMA (one pill lifetime), and one reported previous experience with psilocybin (one administration lifetime).

All but one of the subjects were totally psychedelic naive! And yet no significant increase in anxiety scores.

 

[Vieno]

I'm trying to track down a certain article, it's not really the purpose of this thread to ask questions like this but I figured someone here could help. Sorry if this is inappropriate.

In this thread (http://www.bluelight.ru/vb/threads/427070-Bupe-SHOULD-block-the-effects-of-Pot-but-doesnt-why): it is said:

researchers have even found it possible to largely recreate the effects of opioid agonists using nothing more than serotonin modulation systems (closed loop) on mU knockout mice.

Does anyone know what is this experiment - a link to the article?

Thanks!

E: Oh and feel free to give me better ideas regarding how to track down the article/experiment in question, I don't think this is very effective

 

[sekio]

Repeated S-ketamine Infusions in Therapy Resistant Depression: A Case Series
J. Clin. Pharmacol., Sept. 2013 http://onlinelibrary.wiley.com/doi/10.1002/jcph.122/abstract

All six of the evaluated unipolar patients (demographic and clinical characteristics see Table 1) suffered from a major depressive episode according to DSM IV criteriaand had proven to be pharmacoresistant despite stepwise treatment with at least two antidepressants from different biochemical classes given in sufficient dosages for an appropriate duration. No psychiatric and no significant somatic comorbidity could be evaluated. In two patients ECT had been performed before treatment with ketamine infusions. In the other four patients, ECT had been also discussed as a treatment option but was refused by the patients. All patients were informed about the off label therapeutic use and possible side effects of ketamine infusions and gave their written informed consent before initiation of ketamine therapy. Treatment was started with a 40 minute administration of 0.25 mg S ketamine/kg body weight i.v. in the presenceof the psychiatrist and an anesthesiologist. [...] Three patients showed an improvement in depressive symptoms in both the short and the longer term in two patients (one male, one female), the HAMD score indicated remission (see Figure 1 and Table1); in one male patient treatment was discontinued
because a severe dissociative condition was reported after the first administration. One of the female patients also reported pronounced dissociative symptoms.

5/6 is pretty good, I think.

 

[endotropic]

Repeated S-ketamine Infusions in Therapy Resistant Depression: A Case Series
J. Clin. Pharmacol., Sept. 2013 http://onlinelibrary.wiley.com/doi/10.1002/jcph.122/abstract


5/6 is pretty good, I think.

On first glance, this looked less promising than I had hoped. A typical result for an SSRI trial is 1/3 no response, 1/3 partial response, 1/3 total remission, and these results match that pattern pretty closely.

On the other hand, the fact that these 6 were all refractory to standard treatment gives enough reason to move ahead to larger trials, I think.

 

[ebola?]

40 minute administration of 0.25 mg S ketamine/kg body weight i.v.

Okay...so for a person of average weight, this is like 17.5 mg pushed over 40 minutes, presumably of the more active enantiomer. I would expect pretty moderate effects. What does this suggest about dosing regimens people should take at home for personal, 'clandestine' treatment of depression?

in one male patient treatment was discontinued because a severe dissociative condition was reported after the first administration. One of the female patients also reported pronounced dissociative symptoms.

Okay...so getting high as hell on site is enough to warrant discontinuation of treatment? That doesn't seem fair.

ebola

 

[sekio]

I think it's only discontinued if you find it unpleasant.

What does this suggest about dosing regimens people should take at home for personal, 'clandestine' treatment of depression?

200 mg nasally is probably not a good dose.

 

[ebola?]

lol, does it suggest anything a bit less obvious?

ebola

 

[sekio]

Mimic the study. Threshold doses, repeated application weekly in a controlled setting, until depression remits.

Journal bites with sekio!


Psychedelics and Mental Health: A Population Study
Teri S. Krebs, Pål-Ørjan Johansen

Objective - To evaluate the association between the lifetime use of psychedelics and current mental health in the adult population.

Method - Data drawn from years 2001 to 2004 of the National Survey on Drug Use and Health consisted of 130,152 respondents, randomly selected to be representative of the adult population in the United States. Standardized screening measures for past year mental health included serious psychological distress (K6 scale), mental health treatment (inpatient, outpatient, medication, needed but did not receive), symptoms of eight psychiatric disorders (panic disorder, major depressive episode, mania, social phobia, general anxiety disorder, agoraphobia, posttraumatic stress disorder, and non-affective psychosis), and seven specific symptoms of non-affective psychosis. We calculated weighted odds ratios by multivariate logistic regression controlling for a range of sociodemographic variables, use of illicit drugs, risk taking behavior, and exposure to traumatic events.
Results - 21,967 respondents (13.4% weighted) reported lifetime psychedelic use. There were no significant associations between lifetime use of any psychedelics, lifetime use of specific psychedelics (LSD, psilocybin, mescaline, peyote), or past year use of LSD and increased rate of any of the mental health outcomes. Rather, in several cases psychedelic use was associated with lower rate of mental health problems.

Interestingly enough, psychedelics might not actually make you any more insane than the rest of us.

---

Exercise increases plasma THC concentrations in regular cannabis users
Alexander Wong, Mark E. Montebello, Melissa M. Norberg, Kieron Rooney, Nicholas Lintzeris, Raimondo Bruno, Jessica Booth, Jonathon C. Arnold, Iain S. McGregor

Results - Exercise induced a small, statistically significant increase in plasma THC levels accompanied by a statistically significant increase in plasma FFA and glycerol levels. Exercise-induced increases in plasma THC concentrations were positively correlated with body mass index. Fasting induced a significant increase in plasma FFA levels, and a lowering of blood glucose, but did not significantly alter plasma cannabinoid levels.

Exercising makes you higher, yo!

 

[atara]

http://arxiv.org/abs/1206.0312

Quantitative Analysis of Narrative Reports of Psychedelic Drugs

The first, in my reading, rigorous statistical work on the subjective effects of psychedelic drugs outside of a clinical setting. The interesting thing is that it is all stuff that we on bluelight could very well do ourselves, using the data available to us both on Erowid and in the Trip Reports forum. Also interesting is that the most famously spiritual compound, DPT, turns out to be the most unpredictable.

"You have finished three cups of the finest wine in China, and still you say you have not yet moistened your lips!"

 

[endotropic]

http://arxiv.org/abs/1206.0312
The interesting thing is that it is all stuff that we on bluelight could very well do ourselves, using the data available to us both on Erowid and in the Trip Reports forum.

I'm not so sure about that, their software doesn't exactly sound "off the shelf". Maybe we could do without some of it by crowdsourcing some of the analysis?

Anyways nice find, thanks for the post.

edit: I like this line, "Differences between drug narratives likely also reflect author demographics and the varying context of drug use. Such potential limitations could be addressed by collecting a new corpus in which author demographic information is also obtained."

I think the authors overestimate drug users' general willingness to disclose personal information 8)

 

[sekio]

Occurrence of the Synthetic Analgesic Tramadol in an African Medicinal Plant
Angewandte Chemie 2013
Ahcène Boumendjel, Germain Sotoing Taïwe, Elisabeth Ngo Bum, Tanguy Chabrol, Chantal Beney, Valérie Sinniger, Romain Haudecoeur, Laurence Marcourt, Soura Challal, Emerson Ferreira Queiroz, Florence Souard, Marc Le Borgne, Thierry Lomberget, Antoine Depaulis, Catherine Lavaud, Richard Robins, Jean-Luc Wolfender, Bruno Bonaz, Michel De Waard

The root of the matter: The analgesic tramadol has been isolated from the root bark of N. latifolia, an African medical plant. This finding is a rare example of a common synthetic drug that occurs at considerable concentrations in nature.

Mother nature beat us to the punch!

 

[ebola?]

Loving how they bent over backward performing verification necessary to preclude another Acacia-study scandal...

ebola

 

[AlphaMethylPhenyl]

That one was hilarious. What was it - amphetamine, nicotine, mescaline, and others in one plant?! haha

 

[endotropic]

That one was hilarious. What was it - amphetamine, nicotine, mescaline, and others in one plant?! haha

I remember that one, did they ever discover the source of contamination?

 

[Cortexiphan]

More 25B-NBOME PET studies

Only recently the first successful serotonin 2A (5-HT2A) receptor agonist PET radioligands have been described, with [11C]Cimbi-36 reported as the most promising in the pig brain so far. Agonist radioligands may target specifically the G protein-coupled state of the receptors and thereby provide a more meaningful assessment of available receptors than antagonist radioligands. In the current study we characterized [11C]Cimbi-36 receptor binding in the primate brain.

On five experimental days, a total of 14 PET measurements were conducted in three female rhesus monkeys. On each day, PET measurements were conducted after intravenous injection of [11C]Cimbi-36 during baseline conditions and after intravenous infusion of the 5-HT2 receptor antagonist ketanserin (n = 3) or the 5-HT2C receptor antagonist SB 242084 (n = 2). On four of the experimental days an additional baseline PET measurement was conducted after injection of [11C]MDL 100907. All PET measurements were performed for 2 h in a HRRT PET system and arterial blood was obtained for measurement of the [11C]Cimbi-36 input function. Quantification of [11C]Cimbi-36 receptor binding was performed using kinetic and graphical analysis.

After injection of [11C]Cimbi-36 the regional distribution of radioactivity in brain was in accordance with the known 5-HT2 receptor distribution. The two-tissue compartment model was superior for the description of the time–radioactivity curves of all examined brain regions. BPND values obtained with reference tissue models correlated with corresponding values obtained with kinetic modeling. Administration of ketanserin decreased the binding in all brain regions but did not affect the cerebellar distribution volume. The BPND of [11C]Cimbi-36 was 56 ± 8% of [11C]MDL 100907 across cortical regions, but higher in other brain regions including choroid plexus. After administration of SB 242084, [11C]Cimbi-36 binding was nearly completely inhibited in the choroid plexus, partly reduced in several subcortical regions (e.g. hippocampus), but not affected in the cortical regions.

The receptor binding of [11C]Cimbi-36 can be quantified using kinetic modeling and the cerebellum was found to be a suitable reference region. The difference between [11C]Cimbi-36 and [11C]MDL 100907 binding in the choroid plexus is related to 5-HT2C receptor binding of [11C]Cimbi-36. [11C]Cimbi-36 is the first agonist radioligand suitable for examination of 5-HT2A receptors in the cortical regions and of 5-HT2C receptors in the choroid plexus of the primate brain.

Keywords
5-HT2A; 5-HT2C; [11C]Cimbi-36; Agonist; Monkey; Serotonin receptors

http://www.sciencedirect.com/science/article/pii/S1053811913008975