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dabei seit 2012
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  Geschrieben: 22.10.17 18:06
Sehr interessante und leicht verständliche Powerpoint zur Struktur-Wirkungsbeziehung von Opioiden. Geht nicht besonders tief ins Detail, gut für den Einstieg

The opiate receptor: A model explaining structure-activity relationships of opiate agonists and antagonist

On pethidine and methadone derivatives
"Kleinbürgerlich biegen die Rechten,
das bürgerliche Recht zum eigenen Besten,
Spielen die Opfer, in weissen Westen,
geschneidert aus tiefbraunen Uniformresten."

Arbeitstitel Tortenschlacht - Ernst der Lage
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dabei seit 2012
4.607 Forenbeiträge
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  Geschrieben: 24.10.17 13:19
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial


"Kleinbürgerlich biegen die Rechten,
das bürgerliche Recht zum eigenen Besten,
Spielen die Opfer, in weissen Westen,
geschneidert aus tiefbraunen Uniformresten."

Arbeitstitel Tortenschlacht - Ernst der Lage
Traumländer



dabei seit 2012
2.460 Forenbeiträge
5 Tripberichte
1 Galerie-Bilder

  Geschrieben: 24.10.17 14:36
Damit du nicht immer der einzigste biste:

Auswirkungen von Katadolon R © auf die funktionelle Organisation des primären somatosensorischen Kortex bei Fibromyalgie

Habs selbst noch nicht gelesen, aber das erschien, als ich nach "Katadolon Neuroprotektiv" gesucht habe.
"Immer wieder, wenn ich aus dem Leib aufwache in mich selbst, lasse ich das andere hinter mir und trete ein in mein Selbst; ich sehe eine wunderbar gewaltige Schönheit und [...] bin in eins mit dem Göttlichen" (Plot. IV.8.6)
Abwesender Träumer



dabei seit 2012
138 Forenbeiträge
1 Tripberichte

  Geschrieben: 24.10.17 20:42
Kratom Withdrawal Symptoms
http://mentalhealthdaily.com/2017/01/16/kratom-withdrawal-symptoms/
 
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dabei seit 2012
4.607 Forenbeiträge
1 Tripberichte
9 Galerie-Bilder

  Geschrieben: 02.11.17 16:36
Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy

Literature review: Considerations for Psychedelic Research

The Renewal of Psychedelic Research: Implications for Humanistic and Transpersonal Psychology
"Kleinbürgerlich biegen die Rechten,
das bürgerliche Recht zum eigenen Besten,
Spielen die Opfer, in weissen Westen,
geschneidert aus tiefbraunen Uniformresten."

Arbeitstitel Tortenschlacht - Ernst der Lage
Moderator



dabei seit 2012
4.607 Forenbeiträge
1 Tripberichte
9 Galerie-Bilder

  Geschrieben: 14.11.17 14:46
Mechanism of 6-hydroxydopamine neurotoxicity: the role of NADPH oxidase and microglial activation in 6-hydroxydopamine induced degeneration of dopaminergic neurons
"Kleinbürgerlich biegen die Rechten,
das bürgerliche Recht zum eigenen Besten,
Spielen die Opfer, in weissen Westen,
geschneidert aus tiefbraunen Uniformresten."

Arbeitstitel Tortenschlacht - Ernst der Lage
Moderator



dabei seit 2012
4.607 Forenbeiträge
1 Tripberichte
9 Galerie-Bilder

  Geschrieben: 22.11.17 21:48
zuletzt geändert: 22.11.17 22:02 durch Neopunk (insgesamt 1 mal geändert)
The bioavailability and pharmacokinetics of morphine after intravenous, oral and buccal administration in healthy volunteers
"Kleinbürgerlich biegen die Rechten,
das bürgerliche Recht zum eigenen Besten,
Spielen die Opfer, in weissen Westen,
geschneidert aus tiefbraunen Uniformresten."

Arbeitstitel Tortenschlacht - Ernst der Lage
Moderator



dabei seit 2010
2.326 Forenbeiträge
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3 Langzeit-TB
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  Geschrieben: 23.11.17 17:30
The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis

Studie schrieb:
Ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressed patients with suicidal ideation. Ketamine’s effects on suicidal ideation were partially independent of its effects on mood, although subsequent trials in transdiagnostic samples are required to confirm that ketamine exerts a specific effect on suicidal ideation. Additional research on ketamine’s long-term safety and its efficacy in reducing suicide risk is needed before clinical implementation.

"The only way to write honestly about the scene is to be part of it. If there is one quick truism about psychedelic drugs, it is that anyone who tries to write about them without first-experience is a fool and a fraud." ― Hunter S. Thompson (1967)
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dabei seit 2012
4.607 Forenbeiträge
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  Geschrieben: 24.11.17 15:42
zuletzt geändert: 25.11.17 14:18 durch Neopunk (insgesamt 1 mal geändert)
Heute mal was zu Analytik, v.a. Urintests:

False-Positive Interferences of Common Urine Drug Screen Immunoassays: A Review

Seitman et al. schrieb:
Abstract:

Urine drug screen (UDS) immunoassays are a quick and inexpensive method for determining the presence of drugs of abuse. Many cross-reactivities exist with other analytes, potentially causing a false-positive result in an initial drug screen. Knowledge of these potential interferents is important in determining a course of action for patient care. We present an inclusive review of analytes causing false-positive interferences with drugs-of-abuse UDS immunoassays, which covers the literature from the year 2000 to present. English language articles were searched via the SciFinder platform with the strings ‘false positive [drug] urine’ yielding 173 articles. These articles were then carefully analyzed and condensed to 62 that included data on causes of false-positive results. The discussion is separated into six sections by drug class with a corresponding table of cross-reacting compounds for quick reference. False-positive results were described for amphetamines, opiates, benzodiazepines, cannabinoids, tricyclic antidepressants, phencyclidine, lysergic acid diethylamide and barbiturates. These false-positive results support the generally accepted practice that immunoassay positive results are considered presumptive until confirmed by a second independent chemical technique.


Objective Testing – Urine and other Drug Tests

Hadland & Levy schrieb:
Abstract:

Drug testing, when carefully collected and thoughtfully interpreted, offers a critical adjunct to clinical care and substance use treatment. However, because test results can be misleading if not interpreted in the correct clinical context, clinicians should always conduct a careful interview with adolescent patients to understand what testing is likely to show and then use testing to validate or refute their expectations. Due to the ease with which samples can be tampered, providers should also carefully reflect on their own collection protocols and sample validation procedures to ensure optimal accuracy.


How often do false-positive phencyclidine urine screens occur with use of common medications?

Renagaran & Mullins schrieb:
Abstract:
  • Background: Previous reports describe false-positive urine immunoassay screens for phencyclidine (PCP) associated with use of tramadol, dextromethorphan, or diphenhydramine. The likelihood of these false positives is unknown.
  • Objective: We sought to find the relative frequency of false-positive PCP screens associated with these medications and to look for any other medications with similar associations.
  • Methods: In an IRB-approved study, we retrospectively reviewed charts of all ED encounters with positive urine screens for PCP in our hospital from 2007 through 2011, inclusive. Urine samples were tested for drugs of abuse using the Siemens Syva EMIT II Immunoassay. Our laboratory routinely confirmed all positive screens using GC-MS with results classified as either "confirmed" (true positive) or "failed to confirm" (false positive). We recorded all medications mentioned in the chart as current medications or medications given before the urine sample. We used Fisher's exact test to compare frequencies of tramadol, dextromethorphan, diphenhydramine, and other medications between the two groups.
  • Results: Tramadol, dextromethorphan, alprazolam, clonazepam, and carvedilol were significantly more frequent among the false-positive group, but the latter three were also associated with polysubstance abuse. Diphenhydramine was more frequently recorded among the false-positive group, but this was not statistically significant.
  • Conclusion: False-positive urine screens for PCP are associated with tramadol and dextromethorphan and may also occur with diphenhydramine. Positive PCP screens associated with alprazolam, clonazepam, and carvedilol were also associated with polysubstance abuse.


False positive ketamine urine immunoassay screen result induced by quetiapine: A case report

Liu et al. schrieb:
Abstract:

Ketamine immunoassay urine drug screen (UDS) is commonly used in Taiwan. However, there was limited report about possible drug which may cause false positive results in ketamine screen test. We report two cases who used quetiapine showed positive in ketamine urine immunoassay screen initially, and found to be false positive in confirmation test. Clinicians should be aware of the false positive result of ketamine UDS caused by currently used medication.


Laboratory Testing for Prescription Opioids

Milone schrieb:
Abstract:

Opioid analgesic misuse has risen significantly over the past two decades, and these drugs now represent the most commonly abused class of prescription medications. They are a major cause of poisoning deaths in the USA exceeding heroin and cocaine. Laboratory testing plays a role in the detection of opioid misuse and the evaluation of patients with opioid intoxication. Laboratories use both immunoassay and chromatographic methods (e.g., liquid chromatography with mass spectrometry detection), often in combination, to yield high detection sensitivity and drug specificity. Testing methods for opioids originated in the workplace-testing arena and focused on detection of illicit heroin use. Analysis for a wide range of opioids is now required in the context of the prescription opioid epidemic. Testing methods have also been primarily based upon urine screening; however, methods for analyzing alternative samples such as saliva, sweat, and hair are available. Application of testing to monitor prescription opioid drug therapy is an increasingly important use of drug testing, and this area of testing introduces new interpretative challenges. In particular, drug metabolism may transform one clinically available opioid into another. The sensitivity of testing methods also varies considerably across the spectrum of opioid drugs. An understanding of opioid metabolism and method sensitivity towards different opioid drugs is therefore essential to effective use of these tests. Improved testing algorithms and more research into the effective use of drug testing in the clinical setting, particularly in pain medicine and substance abuse, are needed.


False-Positive Phencyclidine Immunoassay Results Caused by Venlafaxine and O-Desmethylvenlafaxine

Urine Drug Testing in Clinical Practice - The Art ad Science of Patient Care (Edition 4)

Urine drug screens

Edit: Link gefixt.
"Kleinbürgerlich biegen die Rechten,
das bürgerliche Recht zum eigenen Besten,
Spielen die Opfer, in weissen Westen,
geschneidert aus tiefbraunen Uniformresten."

Arbeitstitel Tortenschlacht - Ernst der Lage
Traumländer



dabei seit 2015
59 Forenbeiträge

  Geschrieben: 25.11.17 13:45
Wow, du bist echt 'n bisschen sowas wie der Grandmaster der "wissenschaftliche-Artikel-Recherche" - kann man das so sagen? :D

Vorweg noch eben: Der erste Link funktioniert leider nicht, die anderen aber schon.
Beim Draufklicken steht dort nur auf 'ner ansonsten leeren, weißen Seite "Your session has timed out. Please go back to the article page and click the PDF link again."

Vielleicht kannste da noch mal schauen, ob du das beheben kannst auf sie Schnelle!


Mir ist aufgefallen, dass das (logischerweise) echt viel überzeugender und standfester auf mich wirkt beim Lesen, wenn der Verfasser eines Beitrags sich auf wissenschaftliche Artikel bezieht. Da fühl ich mich voll wie ein kleiner Lowbob, wenn ich - wie gestern, wo es ja in dem anderen Thread auch um falsch-positive Ergebnisse von DXM/Keta/etc. ging - lediglich aus anderen Foren rezitiere!
Die eigene Erfahrung ist natürlich auch immer ein wichtiger Faktor, aber es verleitet oft dazu, die Erkenntnis dann als allgemeingültig darzustellen.
Bsp.: "Ich habe DXM genommen und am nächsten Tag hatte ich kein positives Ergebnis bei einem Drogentest." Folgerung: "Ey Leute. DXM verursacht kein positives Ergebnis bei drogentests im Nachhinein. Ich kann es bestätigen!"
Auch wenn es wahrscheinlich auf die meisten anderen User zutrifft, ist es eben keine wissenschaftliche Erkenntnis, auf die sich jeder verlassen kann oder sollte.

Statistiken, die die Erfahrungen einer großen Anzahl von Menschen bündeln und dokumentieren sind folglich dadurch total erstaunlich und wertvoll, weil dort dann auch Abweichungen, wie z.B. selten auftauchende falsch-positive Ergebnissse für Quetiapin/Seroquel, erfasst werden können (hätte ich nie im Leben gedacht, dass das bei Seroquel vorkommt!).

Auf der anderen Seite, finde ich, ist es wiederum viel schwieriger derartige Statistiken zum Beispiel hinsichtlich der Frage "Kann ich DXM nehmen, obwohl ich übermorgen einen Drogenschnelltest machen muss?" zu interpretieren. Weißt du / wisst ihr, was ich meine?
Wenn jemand dazu in einem Forum schreibt "Ich hab schon dreimal DXM genommen und danach einen Drogentest bestanden" ist für die meisten ihre Frage mit gutem Gewissen beantwortet.
Wenn aus einer Statistik jedoch so etwas herauskommt wie (ist jetzt nur ausgedacht um es zu verdeutlichen) "Nach dem Konsum von DXM tritt bei 0,2% der Menschen danach ein falsch-positives Ergebnis für PCP auf", kann ich mir vorstellen, dass Leute danach verwirrter sind als vorher, weil sie einerseits wissen, dass mit sehr hoher Wahrscheinlichkeit alles gut gehen wird.
Andererseits liegt nun das Wissen vor, dass definitiv die Möglichkeit besteht, das Screening wegen DXM zu verkacken.

Aber naja, ich denke mal, das ist dann ein Risiko, das dann jeder für sich selbst abwägen muss. Und ich denke auch, dass in meinem Beispiel Leute, die mit Vernuft vorgehen, im Zweifelsfall eher auf den Konsum verzichten würden, um auf der sicheren Seite zu sein.

Wie dem auch sei. Ich bin auf jeden Fall voll beeindruckt von deiner wissenschaftlichen Vorgehensweise und finde das richtig gut, dass du - wie einige wenige andere User ja auch - so ziemlich jede deiner Thesen in Antworten auf Userfragen mit seriösen Quellen untermauerst!

Ich stell mir jetzt selbst mal den Vorsatz auf, mir daran ein Beispiel zu nehmen und zukünftig, wenn es sinnvoll und von Wichtigkeit ist, auch so wie du vorzugehen!

Neopunk, du schriebst in 'nem älteren Beitrag, dass du die Artikel von http://sci-hub.cc/ beziehst. Ist es das einzige Archiv für eben solche Artikel, oder beziehste die Dokumente auch noch von anderen Seiten? Falls ja, fänd ich's richtig gut, wenn du die mal hier auflisten würdest! Mindestens ich würde davon profitieren und es gerne nutzen, um meine Beiträge dadurch seriöser zu gestalten.

Danke im Voraus und schönes Wochenende an alle LdT-People!

 
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dabei seit 2012
4.607 Forenbeiträge
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  Geschrieben: 26.11.17 13:09
Psychedelika und MDMA in der Psychotherapie:

The Therapeutic Potential of Psychedelic Drugs: Past, Present and Future

Carhart-Harris & Goodwin schrieb:
Abstract:

Plant-based psychedelics such as psilocybin have an ancient history of medicinal use. After the first English-language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aides to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programmes. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and 3 separate clinical trials of psilocybin for depressive symptoms. In this Circumspective piece, Robin Carhart-Harris and Guy Goodwin share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.


Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study

Mithoefer et al. schrieb:
Abstract:

We report follow-up data evaluating the long-term outcomes for the first completed trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for chronic, treatment-resistant post-traumatic stress disorder (PTSD) (Mithoefer et al., 2011). All of the 19 subjects who received MDMA-assisted treatment in the original trial participated in the long-term follow-up (LTFU), with 16 out of 19 completing all of the long-term outcome measures, which were administered from 17 to 74 months after the original study’s final MDMA session (mean = 45.4; SD = 17.3). Our primary outcome measure used was the Clinician-Administered PTSD Scale (CAPS). Secondary outcome measures were the Impact of Events Scale-Revised (IES-R) and the Neuroticism Extroversion Oppenness Personality Inventory-Revised (NEO PI-R) Personality Inventory. We also collected a long-term follow-up questionnaire. Results for the 16 CAPS completers showed there were no statistical differences between mean CAPS score at LTFU (mean = 23.7; SD = 22.8) (tmatched = 0.1; df = 15, p = 0.91) and the mean CAPS score previously obtained at Study Exit (mean = 24.6, SD = 18.6). On average, subjects maintained statistically and clinically-significant gains in symptom relief, although two of these subjects did relapse. It was promising that we found the majority of these subjects with previously severe PTSD who were unresponsive to existing treatments had symptomatic relief provided by MDMA-assisted psychotherapy that persisted over time, with no subjects reporting harm from participation in the study.


A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)

Oehen et al. schrieb:
Abstract:

Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988-1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).


Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

Griffiths et al. schrieb:
Abstract:

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.


Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

et al. schrieb:
Abstract:
  • Background:
    Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression.
  • Methods:
    In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks.
  • Results:
    Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60–80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression.
  • Conclusions:
    In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress.


Psychedelika

von Heyden & Jungaberle schrieb:
Abstract:
Psychedelika (klassische bzw. serotonerge Halluzinogene) sind psychoaktive Substanzen, welche Wahrnehmung, Affekte sowie eine Reihe kognitiver Prozesse intensiv verändern können. Die Mehrheit ihrer Vertreter gilt als physiologisch sicher und nicht addiktiv. Ihre Geschichte reicht bis in prähistorische Zeit zurück. Mit der Entdeckung der Wirkstoffe Meskalin, Lysergsäurediethylamid (LSD), Dimethyltryptamin (DMT) und Psilocybin begann sowohl ihre wissenschaftliche Erforschung als auch die Verbreitung ihres nicht medizinischen Gebrauchs. Psychedelika stellen eine pharmakologisch, psychometrisch und tierexperimentell abgrenzbare Substanzklasse dar, die zunehmend im Interesse der medizinischen Grundlagen- und Therapieforschung steht. Dieses Kapitel strebt hinsichtlich der relevanten Wissensgebiete einen ausgewogenen Kurzüberblick über die Substanzklasse und ihre wichtigsten Vertreter an, wobei dem historisch komplexen Wirkgefüge zwischen Medizin- und Sozialgeschichte der Substanzklasse ein Schwerpunkt gewidmet ist.


The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

Vollenweider & Kometer schrieb:
Abstract:

After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.


Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Carhart-Harris et al. schrieb:
Abstract:
  • Background:
    Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.
  • Methods:
    In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.
  • Findings:
    Psilocybin's acute psychedelic effects typically became detectable 30–60 min after dosing, peaked 2–3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0–1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference −11·8, 95% CI −9·15 to −14·35, p=0·002, Hedges' g=3·1) and 3 months (−9·2, 95% CI −5·69 to −12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.
  • Interpretation:
    This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.


Psilocybin with psychological support for treatment-resistant depression: six-month follow-up

Carhart-Harris et al. schrieb:
Abstract:
  • Rationale:
    Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy.
  • Objectives:
    Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression.
  • Methods:
    Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure.
  • Results:
    Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen’s d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen’s d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience.
  • Conclusions:
    Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.


@Kreisverkehr:

Neben sci-hub.cc (was bei mir jetzt down ist, .bz geht aber noch) nutze ich (vor allem für diesen Thread) das Plug-in unpaywall , welches für Mozilla Firefox und Chrome erhältlich ist. Darauf habe ich schon mal in diesem Thread hingewiesen. Es nutzt die Datenbank der Suchmaschine BASE (Bielefeld Academic Search Engine). Leider sind dort nicht alle Open-Access Artikel, die es so gibt, gelistet, weshalb ich auch hin und wieder über kostenlose Artikel stolpere, die ich mit Google Scholar finde, die aber nicht per unpaywall als kostenlos angezeigt werden. Daher lohnt sich immer ein aufmerksamer Blick auf den Seiten der jeweiligen Journale. Meist findet sich dort ein Button mit der Aufschrift "Purchase PDF", welcher bei kostenlosen Volltexten als "Download PDF" angezeigt wird. Auf manchen Seiten, wie beispielsweise der des Sage Verlag ist das ungünstig umgesetzt, da dort immer "Download PDF" angezeigt wird. In diesen Fällen kann man sich meist an geöffneten/geschlossenen Vorhängeschloss-Symbolen orientieren.
Es lohnt sich außerdem immer ein Blick auf die Seite Researchgate. Viele der dort zu findenden Artikel sind bereits über die Seite erworben und hochgeladen. Andere Artikel kann man nach erfolger Registrierung anfragen und erhält diese dann in den meisten Fällen innerhalb von ein paar Tagen.
Die Zeitschrift Spektrum verlinkt in ihre Artikeln meist die zitierten Studien, die sogar erstaunlich oft Open-Access sind.
"Kleinbürgerlich biegen die Rechten,
das bürgerliche Recht zum eigenen Besten,
Spielen die Opfer, in weissen Westen,
geschneidert aus tiefbraunen Uniformresten."

Arbeitstitel Tortenschlacht - Ernst der Lage
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  Geschrieben: 28.11.17 19:42
Oxycodone to Oxymorphone Metabolism
"Kleinbürgerlich biegen die Rechten,
das bürgerliche Recht zum eigenen Besten,
Spielen die Opfer, in weissen Westen,
geschneidert aus tiefbraunen Uniformresten."

Arbeitstitel Tortenschlacht - Ernst der Lage
Ex-Träumer
  Geschrieben: 29.11.17 20:49
Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

Zitat:
This emerging field offers very promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer.

 
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  Geschrieben: 30.11.17 13:43
Grapefruit Juice Enhances the Exposure to Oral Oxycodone

Nieminen et al. schrieb:
Grapefruit juice alters the concentrations of many CYP3A substrates. The objective of this study was to examine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral oxycodone in a randomized cross-over study with two phases at an interval of 4 weeks. Twelve healthy volunteers ingested 200 ml of grapefruit juice or water t.i.d. for 5 days. An oral dose of oxycodone hydrochloride 10 mg was administered on day 4. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed from the plasma samples for 48 hr and behavioural and analgesic effects were recorded for 12 hr. Grapefruit juice increased the mean area under the oxycodone concentration-time curve (AUC(0-∞) ) by 1.7-fold (p<0.001), the peak plasma concentration by 1.5-fold (p<0.001) and the half-life of oxycodone by 1.2-fold (p<0.001) as compared to the water. The metabolite-to-parent AUC(0-∞) ratios (AUC(m)/AUC(p) ) of noroxycodone and noroxymorphone decreased by 44% (p<0.001) and 45% (p<0.001), respectively. Oxymorphone AUC(0-∞) increased by 1.6-fold (p<0.01) after grapefruit juice, but the AUC(m)/AUC(p) remained unchanged. Pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice. Analgesic effects were not influenced. Grapefruit juice inhibited the CYP3A4-mediated first-pass metabolism of oxycodone, decreased the formation of noroxycodone and noroxymorphone and increased that of oxymorphone. We conclude that dietary consumption of grapefruit products may increase the concentrations and effects of oxycodone in clinical use.

"Kleinbürgerlich biegen die Rechten,
das bürgerliche Recht zum eigenen Besten,
Spielen die Opfer, in weissen Westen,
geschneidert aus tiefbraunen Uniformresten."

Arbeitstitel Tortenschlacht - Ernst der Lage
Moderator



dabei seit 2012
4.607 Forenbeiträge
1 Tripberichte
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  Geschrieben: 06.12.17 22:30
Methoxetamine: From drug of abuse to rapid-acting antidepressant

Coppola & Mondola schrieb:
Methoxetamine is a dissociative anaesthetic showing pharmacodynamic similarities with its analogue ketamine, a medication with demonstrated rapid-acting antidepressant effects. Like ketamine and other arylcyclohexylamine compounds, methoxetamine is thought to be both a noncompetitive NMDA receptor antagonist and a dopamine reuptake inhibitor. Furthermore, it acts as an agonist at dopamine D2, serotonin 5HT2, muscarinic cholinergic, sigma-1, opioid mu and k receptors. The hypothesis is that methoxetamine can produce rapid antidepressant effects in patients with resistant and non-resistant unipolar and bipolar depression.


Structure–activity relationships of serotonin 5-HT2A agonists

David Nichols schrieb:
Of the 14 known types of serotonin receptors one of the most extensively studied is the 5-HT2A (5-hydroxytryptamine) receptor. In the brain, this receptor plays a key role in regulation of cortical function and cognition, appears to be the principal target for the hallucinogenic/psychedelic drugs such as lysergic acid diethylamide (LSD), and also is a target for the newest atypical antipsychotic agents, which are antagonists or inverse agonists at this site. Among the structure–activity relationships that are known for this receptor type, there are three chemical classes of agonists: tryptamines, ergolines, and phenethylamines. Important structural features are identified for agonist activity and some of these agonists have features in common. In addition to effects at the receptor will be the focus, these drugs are also hallucinogenic (psychedelic) agents, and much of the SAR was developed on the basis of effects in humans, before modern pharmacological techniques were available. A certain amount of our knowledge therefore relies on those human studies.

"Kleinbürgerlich biegen die Rechten,
das bürgerliche Recht zum eigenen Besten,
Spielen die Opfer, in weissen Westen,
geschneidert aus tiefbraunen Uniformresten."

Arbeitstitel Tortenschlacht - Ernst der Lage

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