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PINKoPANaTHER

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just wrote up a huge review of like 14 articles on Diffusion Tensor Imaging and its possible uses in the study of neuropharmacology only to have it eaten by my browser (autosave could not save it). Any way, it took an hour, now I'm pissed. Anyone want to look up diffusion tensor MRI or DTI, and share any papers that may be relevant I would appreciate it. DTI measures anisotropic diffusion across membranes, and theoretically can track neuronal pathways via - synaptic vesicle grabbed by SNAP/SNARE/Syntaxin proteins causing exocytosis of vesicle contents (water!, neurotransmitters) into synaptic cleft, followed by further diffusion of water across ion-channels - rinse and repeat. Could be great when looking at actual physiological mapping to go with current receptor mediated effects studies (this technique is like fMRI but with directionality (anisotropy), therefore each voxel contains more info, and better accuracy on activity)Here's some examples of application:

http://www.ncbi.nlm.nih.gov/pubmed/25877482

http://www.ncbi.nlm.nih.gov/pubmed/25879622
 

PINKoPANaTHER

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Got the idea while looking at diagnostic tests to incorporate into a clinical trial on multiple sclerosis treatment - the technique is still in its infancy, but appears to have huge potential. If people could send me/post other research on the subject and there "expert" opinions I would appreciate it
 

AromaticNitrogen

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Vigabatrin for Methamphetamine/Cocaine Dependence

Vigabatrin is an irreversible inhibitor of GABA-transamimase, the enzyme responsible for degrading GABA. Treatment with vigabatrin as standalone or adjunct therapy is indicated in infantile spasms (West Syndrome) in pediatric patients and in retractable complex partial seizures with or without secondary generalization in adult patients.

Use of vigabatrin is associated with progressive, typically permanent, visual field defect. Due to this effect with sustained use, it is not a first line treatment.

This study utilizes vigabatrin in a surprising off-label fashion to evaluate it's effect in patients with a long history of stimulant abuse and dependence. It is worth mentioning that visual field defect has not been shown to occur in less than twelve weeks of treatment.

Patients in this study were given a short course of vigabatrin treatment, and upon discontinuation, 16/18 remained drug free as suggested by toxicology screens.

It's a very interesting article, I just wanted to share.

http://archopht.jamanetwork.com/Mobile/article.aspx?articleid=418587
 

SteamboatBillJr

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A group of psychedelic users have observed music enhancing the therapeutic effects of psychedelics. The Beckley Foudnations research has recently confirmed LSD Enhances Emotional Responses to Music. The following shows music itself also has great therapeutic potential. This demonstrates music improving quality of life in schizophrenics.

Perhaps in the future researchers could compare the long term outcome of music guided psychedelic therapy vs only psychedelic therapy vs traditional therapy.

Asian Nursing Research said:
Effect of the Group Music Therapy on Brain Wave, Behavior, and Cognitive Function among Patients with Chronic Schizophrenia.
Kwon M, et al. Asian Nurs Res (Korean Soc Nurs Sci). 2013.

Abstract

PURPOSE: The purpose of the study was to examine the effect of group music therapy on brain waves, behavior, and cognitive function among patients with chronic schizophrenia.

METHODS: A quasi-experimental pretest-posttest design was used with nonequivalent control group. The potential participants were recruited from inpatients in a psychiatric facility in a metropolitan city, assigned either to the experimental group (n = 28) or to the control group (n = 27) according to their wards to avoid treatment contamination. The experimental group participated in the group music therapy for 13 sessions over 7 weeks while continuing their standard treatment. The control group only received a standard treatment provided in the hospitals. The outcome measures include brain wave by electroencephalography, behavior by Nurses' Observation Scale for Inpatient Evaluation, and cognitive function by Mini-Mental State Examination.

RESULTS: After participating in 13 sessions of the group music therapy, alpha waves measured from eight different sites were consistently present for the experimental group (p = .006-.045) than the control group, revealing that the participants in the music therapy may have experienced more joyful emotions throughout the sessions. The experimental group also showed improved cognitive function (F = 13.46, p = .001) and positive behavior (social competence, social interest & personal neatness) while their negative behaviors was significantly less than those of the control group (F = 24.04, p < .001).

CONCLUSION: The group music therapy used in this study was an effective intervention for improving emotional relaxation, cognitive processing abilities along with positive behavioral changes in patients with chronic schizophrenia. Our results can be useful for establishing intervention strategies toward psychiatric rehabilitation for those who suffer from chronic mental illnesses.

https://www.ncbi.nlm.nih.gov/pubmed/25030341/
 
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clubcard

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After the book (out of print) 'Opioids' by R. Lenz et al, the single most useful paper on the active sites (by moety) are shown. 20 mu, 20 delta & 20 kappa agonists were tried and if you put almost any opioid into it, you can see the overlay. Only 3 things are important:

-Aromatic
-positively ionizable function
-2 hydrogen bond acceptors

The paper is 'Insights into subtype selectivity of opioid agonists by ligand-based and structure-based methods' by Jianxin Cheng & Guixia Liu & Jing Zhang & Zhejun Xu & Yun Tang. Journal of Molecular Modeling, Accepted 4 May 2010

DOI 10.1007/s00894-010-0745-1

If you're researching opioids, the book and this single paper (plus plenty of your own ink & paper) is all you need to research ALL opioids. I know that digital versions of the book exist, but lack the interface an ACTUAL book is much better and you will soon find it with 20-30 bookmarks with labels in tiny lettering.

I'm pretty confident that is covers everything with just 1 or 2 minor misses due to the training models not having allylprodine & 14-cinnamoyloxycodeinone - Even without the aromatic, the latter is still very strong with a propene ester. Neither does it explain BDPC & Ciramadol where the amine is benzyl... but let's say it covers >99% of all the information you will need for this, the largest, most variable class of centrally acting agents.
 

sigmond

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The paradoxical psychological effects of lysergic acid diethylamide (LSD).

The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of 'loosened cognition' in the mid to long term that is conducive to improved psychological wellbeing.
http://www.ncbi.nlm.nih.gov/pubmed/26847689?dopt=Abstract

Death in a legal poppy field in Spain: http://www.ncbi.nlm.nih.gov/pubmed/26844398
 
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TheBlackPirate

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Exploring the therapeutic potential of Ayahuasca

Journal of Psychopharmacology said:
Psychopharmacology (Berl). 2015 Nov 27. [Epub ahead of print]

Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities.
Soler J1,2,3, Elices M1,3,4,5, Franquesa A4,6, Barker S7, Friedlander P8, Feilding A8, Pascual JC1,3,4, Riba J9,10,11,12.

Author information

1 Servei de Psiquiatria, Hospital de la Santa Creu i Sant Pau (Barcelona), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
2 Departamento de Psicologia Clínica i de la Salut, Universitat Autònoma de Barcelona, Barcelona, Spain.
3 Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain.
4 Departamento de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona, Barcelona, Spain.
5 Programa de Cognición, Instituto de Fundamentos y Métodos, Facultad de Psicología, Universidad de la República, Montevideo, Uruguay.
6 Les Corts Centre d'Higiene Mental, Barcelona, Spain.
7 Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive at River Road, Baton Rouge, LA, 70803, USA.
8 The Beckley Foundation, Beckley Park, Oxford, OX3 9SY, UK.
9 Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain. jriba[at]santpau.cat.
10 Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. jriba[at]santpau.cat.
11 Department of Pharmacology and Therapeutics, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. jriba[at]santpau.cat.
12 Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), C/ Sant Antoni María Claret, 167, 08025, Barcelona, Spain. jriba[at]santpau.cat.




Abstract

BACKGROUND:

Ayahuasca is a psychotropic plant tea used for ritual purposes by the indigenous populations of the Amazon. In the last two decades, its use has expanded worldwide. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties. Acute administration induces an introspective dream-like experience characterized by visions and autobiographic and emotional memories. Studies of long-term users have suggested its therapeutic potential, reporting that its use has helped individuals abandon the consumption of addictive drugs. Furthermore, recent open-label studies in patients with treatment-resistant depression found that a single ayahuasca dose induced a rapid antidepressant effect that was maintained weeks after administration. Here, we conducted an exploratory study of the psychological mechanisms that could underlie the beneficial effects of ayahuasca.


METHODS:

We assessed a group of 25 individuals before and 24 h after an ayahuasca session using two instruments designed to measure mindfulness capacities: The Five Facets Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ).


RESULTS:

Ayahuasca intake led to significant increases in two facets of the FFMQ indicating a reduction in judgmental processing of experiences and in inner reactivity. It also led to a significant increase in decentering ability as measured by the EQ. These changes are classic goals of conventional mindfulness training, and the scores obtained are in the range of those observed after extensive mindfulness practice.


CONCLUSIONS:

The present findings support the claim that ayahuasca has therapeutic potential and suggest that this potential is due to an increase in mindfulness capacities.



KEYWORDS:
Ayahuasca; Decentering; Human; Mindfulness; Therapeutic potential

PMID:
26612618
[PubMed - as supplied by publisher]
https://www.ncbi.nlm.nih.gov/pubmed/26612618/
 

Dresden

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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.
 

sigmond

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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.57Figure 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/
 

sigmond

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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
 

Dresden

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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.
 

sigmond

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benzos seem to be the first line treatment for both stiff person syndrome and a savagely stiff erection.
 

sigmond

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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
 
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