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Harmine is an inflammatory inhibitor through the suppression of NF-κB signaling

July 29, 2017 / Ayahuasca, Papers, Psychiatry & Medicine / By / , , , , ,

Abstract

Harmine is a major constituent in a hallucinogenic botanical mixture ayahuasca and medical plant Peganum harmala L. The plant is used for various illnesses and exhibits anti-inflammatory activity. However, the active constituents remain unclear. Here, we screened the seven alkaloids in P. harmala for their anti-inflammatory activity using an nuclear factor-κB (NF-κB) reporter assay. We found that harmine and harmol could inhibit NF-κB transactivity. As the most abundant compound, harmine inhibited tumor necrosis factor-α (TNF-α)- and lipopolysaccharides (LPS)-induced NF-κB transactivity and nuclear translocation in mouse macrophage RAW 264.7 cells. The mRNA and protein levels of NF-κB downstream inflammatory cytokines also reduced. In an LPS-challenged mouse model, harmine markedly averted inflammatory damage of the lung, and decreased serum TNF-α, interleukin-1β (IL-1β) and IL-6 levels. Our data indicate that harmine may exert the anti-inflammatory effect by inhibition of the NF-κB signaling pathway and harmine is probably responsible for the anti-inflammatory effects of P. harmala.

Liu, X., Li, M., Tan, S., Wang, C., Fan, S., & Huang, C. (2017). Harmine is an inflammatory inhibitor through the suppression of NF-κB signaling. Biochemical and Biophysical Research Communications. 10.1016/j.bbrc.2017.05.126
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Behavioral Changes Over Time Following Ayahuasca Exposure in Zebrafish

July 28, 2017 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Papers, Psychology / By / , , , , , ,

Abstract

The combined infusion of Banisteriopsis caapi stem and Psychotria viridis leaves, known as ayahuasca, has been used for centuries by indigenous tribes. The infusion is rich in N, N-dimethyltryptamine (DMT) and monoamine oxidase inhibitors, with properties similar to those of serotonin. Despite substantial progress in the development of new drugs to treat anxiety and depression, current treatments have several limitations. Alternative drugs, such as ayahuasca, may shed light on these disorders. Here, we present time-course behavioral changes induced by ayahuasca in zebrafish, as first step toward establishing an ideal concentration for pre-clinical evaluations. We exposed adult zebrafish to five concentrations of the ayahuasca infusion: 0 (control), 0.1, 0.5, 1, and 3 ml/L (n = 14 each group), and behavior was recorded for 60 min. We evaluated swimming speed, distance traveled, freezing and bottom dwelling every min for 60 min. Swimming speed and distance traveled decreased with an increase in ayahuasca concentration while freezing increased with 1 and 3 ml/L. Bottom dwelling increased with 1 and 3 ml/L, but declined with 0.1 ml/L. Our data suggest that small amounts of ayahuasca do not affect locomotion and reduce anxiety-like behavior in zebrafish, while increased doses of the drug lead to crescent anxiogenic effects. We conclude that the temporal analysis of zebrafish behavior is a sensitive method for the study of ayahuasca-induced functional changes in the vertebrate brain.
Savoldi, R., Polari, D., Pinheiro-da-Silva, J., Silva, P. F., Lobao-Soares, B., Yonamine, M., … & Luchiari, A. C. (2017). Behavioral changes over time following ayahuasca exposure in zebrafish. Frontiers in behavioral neuroscience, 11. 10.3389/fnbeh.2017.00139
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Side-effects associated with ketamine use in depression: a systematic review

July 27, 2017 / Depressive Disorders, Ketamine, Papers, Psychology / By / , , , ,

Abstract

This is the first systematic review of the safety of ketamine in the treatment of depression after single and repeated doses. We searched MEDLINE, PubMed, PsycINFO, and Cochrane Databases and identified 288 articles, 60 of which met the inclusion criteria. After acute dosing, psychiatric, psychotomimetic, cardiovascular, neurological, and other side-effects were more frequently reported after ketamine treatment than after placebo in patients with depression. Our findings suggest a selective reporting bias with limited assessment of long-term use and safety and after repeated dosing, despite these being reported in other patient groups exposed to ketamine (eg, those with chronic pain) and in recreational users. We recommend large-scale clinical trials that include multiple doses of ketamine and long-term follow up to assess the safety of long-term regular use.
Short, B., Fong, J., Galvez, V., Shelker, W., & Loo, C. K. (2017). Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry. 10.1016/S2215-0366(17)30272-9
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The 2017 Ayahuasca Technical Report

July 26, 2017 / Anthropology & Sociology, Anxiety Disorders / PTSD, Ayahuasca, Biology & Ethnobotany, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / By

ICEERS has just released the 2017 edition of the Ayahuasca Technical Report. Signed by ten of the world’s leading ayahuasca researchers, this report is an important document that summarizes the most relevant scientific findings from the past few decades, as well as key information about the history, legality, pharmacology, and potential therapeutic or adverse effects of ayahuasca. Our intention with this report is to provide objective and up-to-date information to policy makers, judges, lawyers and other officials in charge of developing policies, programs, legislation or involved in legal cases relating to ayahuasca.
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Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy

July 26, 2017 / Ayahuasca, DMT, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

The potential of psychedelic drugs in the treatment of mental health problems is increasingly being recognized. However, relatively little thrust has been given to the suggestion that individuals without any mental health problems may benefit from using psychedelic drugs, and that they may have a right to do so. This review considers contemporary research into the use of psychedelic drugs in healthy individuals, including neurobiological and subjective effects. In line with findings suggesting positive effects in the treatment of mental health problems, such research highlights the potential of psychedelic drugs for the enhancement of wellbeing even in healthy individuals. The relatively low risk associated with usage does not appear to align with stringent drug laws that impose heavy penalties for their use. Some policy implications, and suggestions for future research, are considered.
Elsey, J. W. (2017). Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy. Drug Science, Policy and Law, 3, 2050324517723232.
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Qualitative and Quantitative Features of Music Reported to Support Peak Mystical Experiences during Psychedelic Therapy Sessions

July 25, 2017 / Mushrooms / Psilocybin, Papers, Psychology / By / , , , ,

Abstract

Psilocybin is a classic (serotonergic) hallucinogen (“psychedelic” drug) that may occasion mystical experiences (characterized by a profound feeling of oneness or unity) during acute effects. Such experiences may have therapeutic value. Research and clinical applications of psychedelics usually include music listening during acute drug effects, based on the expectation that music will provide psychological support during the acute effects of psychedelic drugs, and may even facilitate the occurrence of mystical experiences. However, the features of music chosen to support the different phases of drug effects are not well-specified. As a result, there is currently neither real guidance for the selection of music nor standardization of the music used to support clinical trials with psychedelic drugs across various research groups or therapists. A description of the features of music found to be supportive of mystical experience will allow for the standardization and optimization of the delivery of psychedelic drugs in both research trials and therapeutic contexts. To this end, we conducted an anonymous survey of individuals with extensive experience administering psilocybin or psilocybin-containing mushrooms under research or therapeutic conditions, in order to identify the features of commonly used musical selections that have been found by therapists and research staff to be supportive of mystical experiences within a psilocybin session. Ten respondents yielded 24 unique recommendations of musical stimuli supportive of peak effects with psilocybin, and 24 unique recommendations of musical stimuli supportive of the period leading up to a peak experience. Qualitative analysis (expert rating of musical and music-theoretic features of the recommended stimuli) and quantitative analysis (using signal processing and music-information retrieval methods) of 22 of these stimuli yielded a description of peak period music that was characterized by regular, predictable, formulaic phrase structure and orchestration, a feeling of continuous movement and forward motion that slowly builds over time, and lower perceptual brightness when compared to pre peak music. These results provide a description of music that may be optimally supportive of peak psychedelic experiences. This description can be used to guide the selection and composition of music for future psychedelic research and therapy sessions.
Barrett, F. S., Robbins, H., Smooke, D., Brown, J. L., & Griffiths, R. R. (2017). Qualitative and quantitative features of music reported to support peak mystical experiences during psychedelic therapy sessions. Frontiers in psychology, 8. 10.3389/fpsyg.2017.01238
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Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

July 24, 2017 / Anxiety Disorders / PTSD, MDMA, Neuroscience, Papers, Psychology / By / , , , , , ,

Abstract

Rationale

3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA’s broad pharmacological profile, further investigation is warranted before moving to a complex clinical population.

Objectives

We aimed to inform clinical research by providing a translational model of MDMA’s effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction.

Methods

We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training.

Results

MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA’s effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA’s effect by 5-HTT inhibition also downregulated 5-HT2A-mediated behavior, and 5-HT2A antagonism disrupted MDMA’s effect on extinction.

Conclusions

We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

Young, M. B., Norrholm, S. D., Khoury, L. M., Jovanovic, T., Rauch, S. A., Reiff, C. M., … & Howell, L. L. (2017). Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3, 4-methylenedioxymethamphetamine (MDMA). Psychopharmacology, 234(19), 2883-2895. 10.1007/s00213-017-4684-8
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MDMA-induced indifference to negative sounds is mediated by the 5-HT2A receptor

July 22, 2017 / MDMA, Papers, Psychology / By / , , , ,

Abstract

BACKGROUND:
MDMA has been shown to induce feelings of sociability, a positive emotional bias and enhanced empathy. While previous research has used only visual emotional stimuli, communication entails more than that single dimension and it is known that auditory information is also crucial in this process. In addition, it is, however, unclear what the neurobiological mechanism underlying these MDMA effects on social behaviour is. Previously, studies have shown that MDMA-induced emotional excitability and positive mood are linked to the action on the serotonin (5-HT) 2A receptor.
AIM:
The present study aimed at investigating the effect of MDMA on processing of sounds (Processing of Affective Sounds Task (PAST)) and cognitive biases (Approach-Avoidance Task (AAT)) towards emotional and social stimuli and the role of 5-HT2A receptor in these effects.
METHODS:
Twenty healthy recreational users entered a 2 × 2, placebo-controlled, within-subject study with ketanserin (40 mg) as pre-treatment and MDMA (75 mg) as treatment. Behavioural (PAST, AAT) measures were conducted 90 min after treatment with MDMA, respectively, 120 min after ketanserin. Self-report mood measures and oxytocin concentrations were taken at baseline and before and after behavioural tests.
RESULTS:
Findings showed that MDMA reduced arousal elicited by negative sounds. This effect was counteracted by ketanserin pre-treatment, indicating involvement of the 5-HT2 receptor in this process. MDMA did not seem to induce a bias towards emotional and social stimuli. It increased positive and negative mood ratings and elevated oxytocin plasma concentrations. The reduction in arousal levels when listening to negative sounds was not related to the elevated subjective arousal.
CONCLUSION:
It is suggested that this decrease in arousal to negative stimuli reflects potentially a lowering of defences, a process that might play a role in the therapeutic process.
Kuypers, K. P. C., de la Torre, R., Pizarro, N., Xicota, L., & Ramaekers, J. G. MDMA-induced indifference to negative sounds is mediated by the 5-HT2A receptor. Psychopharmacology, 1-10. 10.1007/s00213-017-4699-1
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The hyperassociative mind: The psychedelic experience and Merleau-Ponty’s “wild being”

July 20, 2017 / Mescaline / Cacti, Papers, Philosophy & Religious Studies / By / , , , ,

Abstract

Purpose

In contemporary phenomenology, Dieter Lohmar has suggested that the new task of phenomenological research is to analyze the “alternative representational systems” of fantasy. In line with this program, we propose that psychedelic experience could also be suitable subject to this project subsumed under the wider category of fantasy activity. The aim of this paper is to show that psychedelic experiences offer a favorable situation to study the imagination.

Method

The paper applies the conceptual framework of the late Merleau-Ponty, developed in The Visible and the Invisible, using his mescaline analyses which have been elaborated in The Phenomenology of Perception.

Results

We demonstrate that psychedelic visions and emotional states can be discussed within the Merleau-Pontian framework of “wild world.” From the viewpoint of phenomenology, we suggest that psychedelic visions represent an ongoing sense-making and Gestalt-formation process in which the role of the elaborative activity of the subject is crucial. These – often unsettling – visions show the basic volatility and ambiguity of perception and fantasy, which also sheds light to the hidden schemes of perception, thinking, and emotion of normal consciousness.

Conclusions

Freud claimed that dreams are “the royal road” to the unconscious. In an analogous manner, while dreams were the primary psychoscope to the unconscious of psychoanalysis, in contemporary phenomenology psychedelic experiences may show a possible way to an another kind of unconscious, the phenomenological unconscious. This unconscious comprises the hidden schemes and basic affective emotional attitudes of the knowing subject.

Szummer, C., Horváth, L., SzabÓ, A., Frecska, E., & OrzÓi, K. (2017). The hyperassociative mind: The psychedelic experience and Merleau-Ponty’s “wild being”. Journal of Psychedelic Studies, (0), 1-10. 10.1556/2054.01.2017.006
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Screening of Hallucinogenic Compounds and Genomic Characterisation of 40 Anatolian Salvia Species

July 19, 2017 / Papers, Pharmacology & Chemistry, Salvia / Salvinorin A / By / , , , , ,

Abstract

Introduction
Salvia, an important and widely available member of Lamiaceae family. Although comparative analysis on secondary metabolites in several Salvia species from Turkey has been reported, their hallucinogenic chemicals have not been screened thoroughly.
Objective
This study provides LC–MS/MS analysis of 40 Salvia species for screening their psychoactive constituents of salvinorin A and salvinorin B. 5S–rRNA gene non-coding region of Salvia plants was sequenced, aligned and compared with that sequence of Salvia divinorum plant.
Methodology
Targeted molecules of salvinorin A and salvinorin B were quantified, using LC–MS/MS, from all aerial parts of 40 Salvia species, collected from different parts of Turkey. Regions of 5S–rRNA gene from different species were amplified by polymerase chain reaction and DNA sequences were aligned with Salvia divinorum DNA sequences.
Results
Very few of the Salvia species (S. recognita, S. cryptantha and S. glutinosa) contained relatively high levels of salvinorin A (212.86 ± 20.46 μg/g, 51.50 ± 4.95 μg/g and 38.92 ± 3.74 μg/g, respectively). Salvinorin B was also found in Salvia species of S. potentillifolia, S. adenocaulon and S. cryptantha as 2351.99 ± 232.22 μg/g, 768.78 ± 75.90 μg/g and 402.24 ± 39.71 μg/g, respectively. The sequences of 5S–rRNA gene of 40 different Salvia species were presented and it was found that none of the Salvia species in Turkey had similar DNA sequence to Salvia divinorum plant.
Conclusion
This is the first report of screening 40 Salvia species in Turkey according to their psychoactive constituents, salvinorin A and salvinorin B and their genomic structures. It is possible that some of these Salvia species may exhibit some psycho activity. Thus, they need to be screened further.
Hatipoglu, S. D., Yalcinkaya, B., Akgoz, M., Ozturk, T., Goren, A. C., & Topcu, G. (2017). Screening of Hallucinogenic Compounds and Genomic Characterisation of 40 Anatolian Salvia Species. Phytochemical Analysis. 10.1002/pca.2703
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