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Psilocybin-assisted therapy for anxiety and depression: implications for euthanasia

/ Anxiety Disorders / PTSD, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Psychology, Publications / /

Abstract

Despite their stigmatisation, psychedelic drugs are once again being clinically researched in Europe and North America. This long-awaited renaissance is showing very promising results and, unlike the pioneering research that occurred before these drugs were outlawed over 30 years ago, the current methodology is rigorous and of a very high standard.
Strauss, N. (2017). Psilocybin-assisted therapy for anxiety and depression: implications for euthanasia. The Medical Journal of Australia, 206(11), 468-469. 10.5694/mja17.00081
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Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression

/ Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , , ,

Abstract

Objective:

To identify patients’ perceptions of the value of psilocybin as a treatment for depression.

Method:

Twenty patients enrolled in an open-label trial of psilocybin for treatment-resistant depression participated in a semistructured interview at 6-month follow-up. Thematic analysis was used to identify patients’ experiences of the treatment and how it compared with previous treatments.

Results:

Two main change processes were identified in relation to the treatment. The first concerned change from disconnection (from self, others, and world) to connection, and the second concerned change from avoidance (of emotion) to acceptance. A third theme concerned comparison between psilocybin and conventional treatments. Patients reported that medications and some short-term talking therapies tended to reinforce their sense of disconnection and avoidance, whereas treatment with psilocybin encouraged connection and acceptance.

Conclusion:

These results suggest that psilocybin treatment for depression may work via paradigmatically novel means, antithetical to antidepressant medications, and some short-term talking therapies.
Watts, R., Day, C., Krzanowski, J., Nutt, D., & Carhart-Harris, R. (2017). Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression. Journal of Humanistic Psychology, 0022167817709585.

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Dreams and psychedelics: neurophenomenological comparison and therapeutic implications

/ Ayahuasca, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / /

Abstract

A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. However, the mechanisms of therapeutic action are still not fully explained. Given that an altered state of consciousness is a common denominator that characterizes all classical psychedelics and given that both rapid eye movement sleep (REMS) and psychedelics modulate perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body, in the present article, these two states of consciousness are systematically compared, and therapeutically relevant conclusions are drawn based on available evidence.
Kraehenmann, R. (2017). Dreams and psychedelics: neurophenomenological comparison and therapeutic implications. Current neuropharmacology. 10.2174/1573413713666170619092629
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In vitro antiviral effects of Peganum harmala seed extract and its total alkaloids against Influenza virus

/ Papers, Psychiatry & Medicine, Publications / / , , ,

Abstract

This research was aimed to evaluate the in vitro antiviral effect and the mechanism of the effect of Peganum. harmala seeds extract against influenza A virus infection using Madin-Darby canine kidney (MDCK) cells. In this research, ethyl alcohol extract of P. harmala seeds and its total alkaloids was prepared. The potential antiviral activity of the extract and its total alkaloids against influenza A/Puerto Rico/8/34 (H1N1; PR8) virus was assessed. The mode of action of the extract to inhibit influenza replication was investigated using virucidal activity, hemagglutination inhibition assay, time of addition assays, RNA replication, western blot analysis and RNA polymerase blocking assay. The crud extract of P. harmala seed and its total alkaloids showed the best inhibitory effect against influenza A virus replication in MDCK cells using MTT assay, TCID50 method and hemagglutination assay. Our results indicated that the extract inhibits viral RNA replication and viral polymerase activity but did not effect on hemagglutination inhibition and virucidal activity. This study showed that, in vitro antiviral activity of P. harmala seed extract against influenza virus is most probably associated with inhibiting viral RNA transcription. Therefore, this extract and its total alkaloid should be further characterized to be developed as anti-influenza A virus agent.

Moradi, M. T., Karimi, A., Rafieian-Kopaei, M., & Fotouhi, F. (2017). In vitro antiviral effects of Peganum harmala seed extract and its total alkaloids against Influenza virus. Microbial Pathogenesis. 10.1016/j.micpath.2017.06.014
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Harmine produces antidepressant-like effects via restoration of astrocytic functions

/ Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / / , , , , , ,

Abstract

Depression is a world-wide disease with no effective therapeutic methods. Increasing evidence indicates that astrocytic pathology contributes to the formation of depression. In this study, we investigated the effects of harmine, a natural β-carboline alkaloid and potent hallucinogen, known to modulate astrocytic glutamate transporters, on chronic unpredictable stress (CUS)-induced depressive-like behaviors and astrocytic dysfunctions. Results showed that harmine treatment (10, 20 mg/kg) protected the mice against the CUS-induced increases in the immobile time in the tail suspension test (TST) and forced swimming test (FST), and also reversed the reduction in sucrose intake in the sucrose preference experiment. Harmine treatment (20 mg/kg) prevented the reductions in brain-derived neurotrophic factor (BDNF) protein levels and hippocampal neurogenesis induced by CUS. In addition, harmine treatment (20 mg/kg) increased the protein expression levels of glutamate transporter 1 (GLT-1) and prevented the CUS-induced decreases in glial fibrillary acidic protein (GFAP) protein expressions in the prefrontal cortex and hippocampus, suggesting that restoration of astrocytic functions may be a potential mechanism underlying the antidepressant-like effects of harmine. This opinion was proved by the results that administration of mice with l-Alpha-Aminoadipic Acid (L-AAA), a gliotoxin specific for astrocytes, attenuated the antidepressant-like effects of harmine, and prevented the improvement effects of harmine on BDNF protein levels and hippocampal neurogenesis. These results provide further evidence to confirm that astrocytic dysfunction contributes critically to the development of depression and that harmine exerts antidepressant-like effects likely through restoration of astrocytic functions.

Liu, F., Wu, J., Gong, Y., Wang, P., Zhu, L., Tong, L. J., … & Huang, C. (2017). Harmine produces antidepressant-like effects via restoration of astrocytic functions. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 10.1016/j.pnpbp.2017.06.012
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Neuroticism is associated with challenging experiences with psilocybin mushrooms

/ Mushrooms / Psilocybin, Papers, Psychology / / , ,

Abstract

Objectives

Classic hallucinogens (e.g. psilocybin and LSD) have substantial effects on perception, cognition, and emotion that can often be psychologically challenging, however we know very little regarding the source of significant individual variability that has been observed in the frequency and intensity of challenging experiences (i.e. “bad trips”) with psychedelics. Previous clinical and observational literature suggests that there may be an association between neuroticism and challenging psychedelic experiences.

Methods

Data from two online surveys of challenging experiences with psilocybin were analyzed. Multivariate analysis was used to estimate the associations between total score and scores from seven sub-factors (fear, grief, physical distress, insanity, isolation, death, and paranoia) of the Challenging Experience Questionnaire (CEQ), and scale scores from the Ten Item Personality Inventory (TIPI) in Study 1 (N = 1993) and the Big Five Inventory (BFI) in Study 2 (N = 981).

Results

CEQ scores were negatively associated with emotional stability scores (the inverse of neuroticism) in Study 1 and positively associated with neuroticism scores in Study 2.

Conclusions

Neuroticism may contribute to the strength of challenging experiences with psychedelics in uncontrolled settings.

Barrett, F. S., Johnson, M. W., & Griffiths, R. R. (2017). Neuroticism is associated with challenging experiences with psilocybin mushrooms. Personality and Individual Differences, 117, 155-160. 10.1016/j.paid.2017.06.004
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Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775)

/ LSD, Neuroscience, Papers, Psychology, Publications / / , , , , , ,

Abstract

Lysergic acid diethylamide (LSD) is perhaps one of the best-known psychoactive substances and many structural modifications of this prototypical lysergamide have been investigated. Several lysergamides were recently encountered as “research chemicals” or new psychoactive substances (NPS). Although lysergic acid morpholide (LSM-775) appeared on the NPS market in 2013, there is disagreement in the literature regarding the potency and psychoactive properties of LSM-775 in humans. The present investigation attempts to address the gap of information that exists regarding the analytical profile and pharmacological effects of LSM-775. A powdered sample of LSM-775 was characterized by X-ray crystallography, nuclear magnetic resonance stereoscopy (NMR), gas chromatography mass spectrometry (GC-MS), high mass accuracy electrospray MS/MS, HPLC diode array detection, HPLC quadrupole MS, and GC solid-state infrared analysis. Screening for receptor affinity and functional efficacy revealed that LSM-775 acts as a nonselective agonist at 5-HT1A and 5-HT2A receptors. Head twitch studies were conducted in C57BL/6J mice to determine whether LSM-775 activates 5-HT2A receptors and produces hallucinogen-like effects in vivo. LSM-775 did not induce the head twitch response unless 5-HT1A receptors were blocked by pretreatment with the antagonist WAY-100,635 (1 mg/kg, subcutaneous). These findings suggest that 5-HT1A activation by LSM-775 masks its ability to induce the head twitch response, which is potentially consistent with reports in the literature indicating that LSM-775 is only capable of producing weak LSD-like effects in humans.
Brandt, S. D., Kavanagh, P. V., Twamley, B., Westphal, F., Elliott, S. P., Wallach, J., … & Halberstadt, A. L. (2017). Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM‐775). Drug Testing and Analysis. 10.1002/dta.2222
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Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice

/ Ayahuasca, Neuroscience, Papers, Psychology / / , , , , , ,

Abstract

The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old) received ayahuasca or water (1.5 mL/kg, orally) twice a week for 12 months and were tested in the Morris water maze (MWM), open field and elevated plus maze (EPM) tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition) of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.
Correa-Netto, N. F., Coelho, L. S., Galfano, G. S., Nishide, F., Tamura, F., Shimizu, M. K., … & Linardi, A. (2017). Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice. Brazilian Journal of Medical and Biological Research, 50(7). 10.1590/1414-431×20176037
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Potential Therapeutic Effects of Psilocybin

/ Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / / ,

Abstract

Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.
Johnson, M. W., & Griffiths, R. R. (2017). Potential Therapeutic Effects of Psilocybin. Neurotherapeutics, 1-7. 10.1007/s13311-017-0542-y
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Healing culture and its somewhat humorous discontents - July 22

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