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Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat.

May 20, 2019 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

OBJECTIVE:
Psilocybin is a serotonin receptor agonist with a therapeutic potential for treatment-resistant depression and other psychiatric illnesses. We investigated whether the administration of psilocybin had an antidepressant-like effect in a rat model of depression.
METHODS:
Using the Flinders Sensitive Line (FSL) rat model of depression, we assessed the antidepressant-like effect of psilocin and psilocybin, measured as a reduction in immobility time in the forced swim test (FST). We measured locomotor activity in an open field test (OFT) to control for stimulant properties of the drugs. We performed a set of experiments to test different doses, treatment paradigms, and timing of the tests in relation to the drug administration.
RESULTS:
Psilocin and psilocybin showed no effect on immobility, struggling, or swimming behaviour in the FST and no effect on locomotor activity in the OFT. FSL rats did show significantly more immobility than their control strain, the Flinders Resistant Line, as expected.
CONCLUSION:
Psilocin and psilocybin showed no antidepressant-like effect in the FSL rats, despite a positive effect in humans. This suggests that other animal models of depression and other behavioural tests may be more appropriate for translational studies in the effects of psilocybin.
Jefsen, O., Højgaard, K., Christiansen, S. L., Elfving, B., Nutt, D. J., Wegener, G., & Müller, H. K. (2019). Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat. Acta neuropsychiatrica, 1-7., https://doi.org/10.1017/neu.2019.15
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N,N-dimethyltryptamine Prevents Renal Ischemia-Reperfusion Injury in a Rat Model

May 15, 2019 / DMT, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Abstract

BACKGROUND:

Ischemia reperfusion (I/R) injury remains one of the most challenging fields of organ transplantation. It is highly associated with the use of expanded criteria donors that might conclude to delayed graft function or early or late graft failure.

OBJECTIVE:

To investigate the metabolic, microcirculatory parameters, and histologic changes under the effect of N,N-dimethyltryptamine (DMT) in a renal I/R model in rats.

METHOD:

In 26 anesthetized rats both kidneys were exposed. In the control group (n = 6) no other intervention happened. In 20 other animals, the right renal vessels were ligated, and after 60 minutes the right kidney was removed. The left renal vessels were clamped for 60 minutes then released, followed by 120 minutes of reperfusion. In the I/R group (n = 10), there was no additive treatment, while in I/R + DMT group (n = 10) DMT was administered 15 minutes before ischemia. Blood samples were taken, laser Doppler measurement was performed, and both kidneys were evaluated histologically.

RESULTS:

Microcirculation (blood flux units [BFU]) diminished in all groups, but remarkably so in the I/R + DMT group. This group compensated better after the 30th minute of reperfusion. The control and I/R + DMT groups had similar BFUs after 120 minutes of reperfusion, but in the I/R group BFU was higher. Tubular necrosis developed in the I/R and I/R + DMT groups too; it was moderated under DMT effect, and severe without. Histologic injuries were less in I/R + DMT Group compared to non-treated animals.

CONCLUSION:

Histologic changes characteristic to I/R injuries were reversible and microcirculation recovered at the end of 120 minutes reperfusion under the administration of DMT. DMT can be used for renoprotection in kidney transplantation.

Nemes, B., Pető, K., Németh, N., Mester, A., Magyar, Z., Ghanem, S., … & Bidiga, L. (2019, May). N, N-dimethyltryptamine Prevents Renal Ischemia-Reperfusion Injury in a Rat Model. In Transplantation proceedings (Vol. 51, No. 4, pp. 1268-1275). Elsevier. 10.1016/j.transproceed.2019.04.005
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Cessation and reduction in alcohol consumption and misuse after psychedelic use

May 14, 2019 / LSD, Papers, Psychology, Publications / By / , , , , ,

Abstract

Background:

Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcohol use disorder (AUD) showed large, significant effects for LSD efficacy compared to control conditions. Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use disorders.

Aims:

To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use.

Methods:

An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non-clinical settings.

Results:

343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress.

Conclusions:

Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.
Garcia-Romeu, A., Davis, A. K., Erowid, F., Erowid, E., Griffiths, R. R., & Johnson, M. W. (2019). Cessation and reduction in alcohol consumption and misuse after psychedelic use. Journal of Psychopharmacology, 0269881119845793., https://doi.org/10.1177%2F0269881119845793
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MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials.

May 7, 2019 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:
Posttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Here we evaluate six phase 2 trials in a pooled analysis to determine the study design for phase 3 trials of MDMA-assisted psychotherapy for PTSD.
METHODS:
Six randomized, double-blind, controlled clinical trials at five study sites were conducted from April 2004 to February 2017. Active doses of MDMA (75-125 mg, n = 72) or placebo/control doses (0-40 mg, n = 31) were administered to individuals with PTSD during manualized psychotherapy sessions in two or three 8-h sessions spaced a month apart. Three non-drug 90-min therapy sessions preceded the first MDMA exposure, and three to four followed each experimental session.
RESULTS:
After two blinded experimental sessions, the active group had significantly greater reductions in CAPS-IV total scores from baseline than the control group [MMRM estimated mean difference (SE) between groups - 22.0 (5.17), P < 0.001]. The between-group Cohen’s d effect size was 0.8, indicating a large treatment effect. After two experimental sessions, more participants in the active group (54.2%) did not meet CAPS-IV PTSD diagnostic criteria than the control group (22.6%). Depression symptom improvement on the BDI-II was greatest for the active group compared to the control group, although only trended towards significant group differences [MMRM, estimated mean difference (SE) between groups - 6.0 (3.03), P = 0.053]. All doses of MDMA were well tolerated, with some expected reactions occurring at greater frequency for the active MDMA group during experimental sessions and the 7 days following.
CONCLUSIONS:
MDMA-assisted psychotherapy was efficacious and well tolerated in a large sample of adults with PTSD. These studies supported expansion into phase 3 trials and led to FDA granting Breakthrough Therapy designation for this promising treatment.
Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., … & Doblin, R. (2019). MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology, 1-11., https://doi.org/10.1007/s00213-019-05249-5
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Narrative identity, rationality, and microdosing classic psychedelics

May 6, 2019 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

BACKGROUND:

Microdosing involves ingesting a small dose of a classic psychedelic (e.g., LSD and psilocybin) at regular intervals for prolonged periods. The practice is said to reduce anxiety, improve mood, and offer several creative and practical benefits to users. Using the narrative identity theoretical framework, our aim was to explore the experiences of those who microdosed classic psychedelics. Specifically, we sought to understand how and why they began microdosing and how they made sense of their actions in the context of their conventional lives.

METHODS:

To understand the experiences of those who microdose classic psychedelics, we rely on data collected from semi-structured interviews with 30 people who had microdosed.

RESULTS:

Participants saw themselves as conventional citizens who microdosed for rational and instrumental purposes. They emphasized the rationality of microdosing by discussing (1) the practicality of their procurement and administration processes, (2) the connection between their microdosing practice and their general awareness in health and wellness, and (3) the benefits of the practice.

CONCLUSION:

Participants described their microdosing in the context of embracing traditional middle-class values. This created social distance between themselves and those who use drugs recreationally. While people who use drugs recreationally typically construct boundaries by distancing themselves from symbolic others (i.e., “crackheads,” “meth heads,” “junkies”), microdosers constructed boundaries by emphasizing connections to conventional citizens who embrace middle-class values. This connection to conventional citizens allows them to normalize their drug use and facilitates persistence.

Webb, M., Copes, H., & Hendricks, P. S. (2019). Narrative identity, rationality, and microdosing classic psychedelics. International Journal of Drug Policy, 70, 33-39., 10.1016/j.drugpo.2019.04.013
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Making psychedelics into medicines: The politics and paradoxes of medicalization

April 30, 2019 / Papers, Psychology, Publications / By /

Abstract

This commentary considers efforts to turn psychedelics into medications that can be administered through healthcare systems as examples of “medicalization.” I draw on ethnographic research both inside and outside of university-based clinical trials from 2014 to date, together with analogous examples from psychiatry and drug research and development. Rather than taking a normative stance on medicalization, I situate it in a wider political, economic, and cultural context to better understand its logics and effects. I begin by suggesting the resurgence of psychedelic science has been concerned with medicalization from the outset, recently prompting a crisis in the “psychedelics community” over its self-identity and values. Next, against the confident public messaging surrounding psychedelics, I consider how attempts to scale up and market psychedelic-assisted therapy could end up undermining the safety and efficacy of the therapy itself. I then outline the movements to decriminalize, legalize, and minimize the harms and risks of using psychedelics in their currently illicit therapeutic and recreational modalities. Finally, I explore how working toward psychedelic medicalization over the coming years may influence the movements toward decriminalizing and legalizing psychedelics use, focusing on the underarticulated ways in which medicalization may disregard or even hinder, rather than help, decriminalization and legalization efforts. I call attention to how the cost of gaining approval for therapies incentivizes the development of diluted-yet-profitable forms of psychedelic-assisted treatments, and how frameworks developed for “proper use” demarcate what counts as “abuse” and enable those with newly sanctioned access to psychedelics to condemn afresh their illicit use.

Noorani, T. (2019). Making psychedelics into medicines: The politics and paradoxes of medicalization. Journal of Psychedelic Studies, 1-6., https://doi.org/10.1556/2054.2019.018
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Effects of MDMA on attention to positive social cues and pleasantness of affective touch.

April 30, 2019 / MDMA, Papers, Psychology, Publications / By / , , , , ,

Abstract

The psychostimulant drug ±3,4-methylenedioxymethamphetamine (MDMA) reportedly produces distinctive feelings of empathy and closeness with others. MDMA increases social behavior in animal models and has shown promise in psychiatric disorders, such as autism spectrum disorder (ASD) and post-traumatic stress disorder (PTSD). How it produces these prosocial effects is not known. This behavioral and psychophysiological study examined the effects of MDMA, compared with the prototypical stimulant methamphetamine (MA), on two measures of social behavior in healthy young adults: (i) responses to socially relevant, “affective” touch, and (ii) visual attention to emotional faces. Men and women (N = 36) attended four sessions in which they received MDMA (0.75 or 1.5 mg/kg), MA (20 mg), or a placebo in randomized order under double-blind conditions. Responses to experienced and observed affective touch (i.e., being touched or watching others being touched) were assessed using facial electromyography (EMG), a proxy of affective state. Responses to emotional faces were assessed using electrooculography (EOG) in a measure of attentional bias. Subjective ratings were also included. We hypothesized that MDMA, but not MA, would enhance the ratings of pleasantness and psychophysiological responses to affective touch and increase attentional bias toward positive facial expressions. Consistent with this, we found that MDMA, but not MA, selectively enhanced ratings of pleasantness of experienced affective touch. Neither drug altered the ratings of pleasantness of observed touch. On the EOG measure of attentional bias, MDMA, but not MA, increased attention toward happy faces. These results provide new evidence that MDMA can enhance the experience of positive social interactions; in this case, pleasantness of physical touch and attentional bias toward positive facial expressions. The findings are consistent with evidence that the prosocial effects are unique to MDMA relative to another stimulant. Understanding the behavioral and neurobiological processes underlying the distinctive social effects of MDMA is a key step to developing the drug for psychiatric disorders.
Bershad, A. K., Mayo, L. M., Van Hedger, K., McGlone, F., Walker, S. C., & de Wit, H. (2019). Effects of MDMA on attention to positive social cues and pleasantness of affective touch. Neuropsychopharmacology, 1, https://doi.org/10.1038/s41386-019-0402-z
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100 years of mescaline

April 29, 2019 / Mescaline / Cacti, Papers, Psychology, Psychotic Disorders, Publications / By /

Abstract

In the hundred years since Ernst Späth’s synthesis of mescaline, it has been used in clinical research for many purposes, including the study of hallucinations, creativity, and schizophrenia. After Aldous Huxley described his experience with it in The Doors of Perception, it became a public sensation. During the 1960s it was largely replaced as a research compound by LSD. Today its scientific use is subject to strict controls, but the synthetic phenethylamines developed from it are widely used.

Jay, M. (2019). 100 years of mescaline. Monatshefte für Chemie-Chemical Monthly, 150(5), 957-959., https://doi.org/10.1007/s00706-019-02425-3
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Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects.

April 29, 2019 / LSD, Neuroscience, Papers, Pharmacology & Chemistry / By / , , , , ,

Abstract

AIMS:

The aim of the present study was to characterize the pharmacokinetics and exposure-subjective response relationship of a novel oral solution of lysergic acid diethylamide (LSD) that was developed for clinical use in research and patients.

METHOD:

LSD (100 μg) was administered in 27 healthy subjects using a placebo-controlled, double-blind, cross-over design. Plasma levels of LSD, nor-LSD, and 2-oxo-3-hydroxy-LSD (O-H-LSD) and subjective drug effects were assessed up to 11.5 hours.

RESULTS:

First-order elimination kinetics were observed for LSD. Geometric mean maximum concentration (Cmax ) values (range) of 1.7 (1.0-2.9) ng/mL were reached at a tmax (range) of 1.7 (1.0-3.4) hours after drug administration. The plasma half-life (t1/2 ) was 3.6 (2.4-7.3) hours. The AUC∞ was 13 (7.1-28) ng·h/mL. No differences in these pharmacokinetic parameters were found between male and female subjects. Plasma O-H-LSD but not nor-LSD (< 0.01 ng/mL) concentrations could be quantified in all subjects. Geometric mean O-H-LSD Cmax values (range) of 0.11 (0.07-0.19) ng/mL were reached at a tmax (range) of 5 (3.2-8) hours. The t1/2 and AUC∞ values of O-H-LSD were 5.2 (2.6-21) hours and 1.7 (0.85-4.3) ng·h/mL, respectively. The subjective effects of LSD lasted (mean ± SD) for 8.5 ± 2.0 hours (range: 5.3-12.8 h), and peak effects were reached 2.5 ± 0.6 hours (range 1.6-4.3 h) after drug administration. EC50 values were 1.0 ± 0.5 ng/mL and 1.9 ± 1.0 ng/mL for “good” and “bad” subjective drug effects, respectively.

CONCLUSION:

The present study characterized the pharmacokinetics of LSD and its main metabolite O-H-LSD. The subjective effects of LSD were closely associated with changes in plasma concentrations over time.

Holze, F., Duthaler, U., Vizeli, P., Müller, F., Borgwardt, S., & Liechti, M. E. (2019). Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects. British journal of clinical pharmacology., 10.1111/bcp.13918
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Serotonergic hallucinogens and recognition of facial emotion expressions: a systematic review of the literature.

April 26, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:
Recognition of emotions in facial expressions (REFE) is a key aspect of social cognition. Anxiety and mood disorders are associated with deficits in REFE, and anxiolytics and antidepressants reverse these deficits. Recent studies have shown that serotonergic hallucinogens (i.e. ayahuasca, dimethyltryptamine, psilocybin, lysergic acid diethylamide [LSD], and mescaline) have anxiolytic and antidepressant properties, but their effects on REFE are not well understood. The purpose of the study was to conduct a systematic review analyzing the effects of serotonergic hallucinogens on REFE in humans.
METHODS:
Studies published in the PubMed, PsycINFO, and Web of Science databases until 19 October 2018 which analyzed the effects of serotonergic hallucinogens on REFE in humans were included.
RESULTS:
Of the 62 studies identified, 8 studies were included. Included studies involved the administration of a single or a few doses of LSD or psilocybin, and most trials were randomized and controlled with placebo. LSD and psilocybin reduced the recognition of negative emotions in most studies and modulated amygdala activity to these stimuli, which was correlated with antidepressive effects in patients. Both drugs were well tolerated.
CONCLUSIONS:
Serotonergic hallucinogens reduced the recognition of negative emotions by modulating amygdala activity. Despite the small sample sizes, results suggest that serotonergic hallucinogens show promising beneficial effects on deficits in REFE.
Rocha, J. M., Osório, F. L., Crippa, J. A. S., Bouso, J. C., Rossi, G. N., Hallak, J. E., & dos Santos, R. G. (2019). Serotonergic hallucinogens and recognition of facial emotion expressions: a systematic review of the literature. Therapeutic advances in psychopharmacology, 9, 2045125319845774., https://doi.org/10.1177/2045125319845774
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