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Mushrooms / Psilocybin

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences

November 7, 2017 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , ,

Abstract

Rationale

Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared.

Objective

This study compared subjective, behavioral, and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects.

Methods

Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Instructions to participants and staff minimized expectancy effects. Various subjective, behavioral, and physiological effects were assessed after drug administration.

Results

High doses of both drugs produced similar increases in participant ratings of peak overall drug effect strength, with similar times to maximal effect and time-course. Psilocybin produced orderly dose-related increases on most participant-rated subjective measures previously shown sensitive to hallucinogens. DXM produced increases on most of these same measures. However, the high dose of psilocybin produced significantly greater and more diverse visual effects than DXM including greater movement and more frequent, brighter, distinctive, and complex (including textured and kaleidoscopic) images and visions. Compared to DXM, psilocybin also produced significantly greater mystical-type and psychologically insightful experiences and greater absorption in music. In contrast, DXM produced larger effects than psilocybin on measures of disembodiment, nausea/emesis, and light-headedness. Both drugs increased systolic blood pressure, heart rate, and pupil dilation and decreased psychomotor performance and balance.

Conclusions

Psilocybin and DXM produced similar profiles of subjective experiences, with psilocybin producing relatively greater visual, mystical-type, insightful, and musical experiences, and DXM producing greater disembodiment.

Carbonaro, T. M., Johnson, M. W., Hurwitz, E., & Griffiths, R. R. (2017). Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences. Psychopharmacology, 1-14. 10.1007/s00213-017-4769-4
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Multipotent and Poly-therapeutic Fungal Alkaloids of Claviceps purpurea

November 4, 2017 / LSD, Mushrooms / Psilocybin, Papers, Publications / By / , , , , , ,

Abstract

Claviceps are a group of phytopathogenic ascomycetes which includes around 50 known species. Claviceps purpurea, Claviceps fusiformis, Claviceps paspali, Claviceps africana, and Claviceps lutea are the most common and well-characterized fungi. Ergot alkaloids and other constituents derived from Claviceps are beneficial for various clinical applications in humans and animals. However, they also contain certain chemicals that are extremely addictive, abusive, and lethal. Ergot derivatives exhibit interesting pharmacokinetic and pharmacodynamic effects. Their pharmacodynamic actions are attributed to their agonistic, partial agonistic, and antagonistic effects on different receptors pertaining to the monoaminergic neurotransmitters. Due to their binding (with or without intrinsic effects) ability on the receptors, they induce numerous pharmacological effects which have potential medical values. Methysergide, ergotamine, dihydroergotamine, ergometrine (ergonovine), pergolide, ergoloid mesylates, and bromocriptine are the most popular ergot-based drugs used globally for treating numerous diseases. These drugs have been used to treat inflammatory-, infectious-, neurological-, cardiovascular-, gastrointestinal-, endocrinological-, sexual-, and urological-related pathologies. Hence, they are considered as a multipotent and poly-therapeutic fungus.

Majrashi, M., Ramesh, S., Deruiter, J., Mulabagal, V., Pondugula, S., Clark, R., & Dhanasekaran, M. (2017). Multipotent and Poly-therapeutic Fungal Alkaloids of Claviceps purpurea. In Medicinal Plants and Fungi: Recent Advances in Research and Development (pp. 229-252). Springer, Singapore. 10.1007/978-981-10-5978-0_8
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Dying to live: The power of transcendence in the treatment of existential anxiety

November 2, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

There is a notable lack of effective treatments and therapies available for the treatment of existential anxiety. There are, however, a number of avenues worthy of more attention, all experiential or using insights gained from experiences. Such experiences include near-death experiences (NDEs), out-of-body experiences (OBEs) and those yielded by classical psychedelics such as psilocybin. Of these, the psychedelics may have a particular utility when it comes to the treatment of existential anxiety. Psychedelics are currently undergoing a long-overdue scientific research renaissance, and there has been some highly promising research utilizing psilocybin in the treatment of existential anxiety and depression in terminally ill cancer patients, yielding compelling and robust findings. A single dose of psilocybin produced immediate and sustained decreases in anxiety and depression and improvements in outlook and life meaning in an overwhelming majority of study participants. At sufficient doses, psychedelics can occasion mystical-type experiences, and it appears this is intimately tied to their long-term psychotherapeutic efficacy. There is some intriguing overlap in aftereffects reported by those who have undergone mystical experiences via psychedelics, NDEs, and OBEs. An interesting property of the NDE is that the psychological changes appear to be mentally contagious, so that one may reap the benefits of the experience without incurring the risk of experiencing one. A common thread and apparently psychotherapeutic element linking these experiences is the experience of being disembodied and of transcending the limits of the body.
Gandy, S. (2017). Dying to live: The power of transcendence in the treatment of existential anxiety. Threshold: Journal of Interdisciplinary Consciousness Studies, 1(2), 25-36.
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Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression

October 30, 2017 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Rationale

Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome.

Objectives

The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients’ emotional processing biases.

Methods

Seventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin.

Results

We found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010).

Conclusions

Psilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.

Stroud, J. B., Freeman, T. P., Leech, R., Hindocha, C., Lawn, W., Nutt, D. J., … & Carhart-Harris, R. L. (2017). Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression. Psychopharmacology, 1-8. 10.1007/s00213-017-4754-y
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Perceptions of the medicinal value of hallucinogenic drugs among college students

October 17, 2017 / LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Publications / By / , ,

Abstract

Background

This survey examined perceptions among college students about the potential medicinal benefits of hallucinogenic drugs. Current research and potential benefits include an ability to help anxiety, post-traumatic stress disorder, and addiction with hallucinogen-assisted psychotherapy.

Methods

We devised and administered a survey on 124 students at two college campuses, one small private college in the mid-Atlantic and one medium-sized public university in the Midwest of the United States.

Results

Responses were similar across campuses, and in general, participants were reluctant to agree that hallucinogens can be therapeutic to the seven afflictions we questioned them about. However, the survey also revealed that a majority of participants believed there should be further research done exploring the medicinal benefits of such drugs.

Conclusion

These findings shed light on perceptions of hallucinogens as their use is being applied to a host of afflictions.

Wildberger, J. I., John, C. N., & Hallock, R. M. (2017). Perceptions of the medicinal value of hallucinogenic drugs among college students. Journal of Psychedelic Studies, (0), 1-5. 10.1556/2054.01.2017.008
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Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

October 13, 2017 / Depressive Disorders, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.
Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., … & Leech, R. (2017). Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific reports, 7(1), 13187. 10.1038/s41598-017-13282-7
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The relationships of classic psychedelic use with criminal behavior in the United States adult population

October 1, 2017 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Criminal behavior exacts a large toll on society and is resistant to intervention. Some evidence suggests classic psychedelics may inhibit criminal behavior, but the extent of these effects has not been comprehensively explored. In this study, we tested the relationships of classic psychedelic use and psilocybin use per se with criminal behavior among over 480,000 United States adult respondents pooled from the last 13 available years of the National Survey on Drug Use and Health (2002 through 2014) while controlling for numerous covariates. Lifetime classic psychedelic use was associated with a reduced odds of past year larceny/theft (aOR = 0.73 (0.65-0.83)), past year assault (aOR = 0.88 (0.80-0.97)), past year arrest for a property crime (aOR = 0.78 (0.65-0.95)), and past year arrest for a violent crime (aOR = 0.82 (0.70-0.97)). In contrast, lifetime illicit use of other drugs was, by and large, associated with an increased odds of these outcomes. Lifetime classic psychedelic use, like lifetime illicit use of almost all other substances, was associated with an increased odds of past year drug distribution. Results were consistent with a protective effect of psilocybin for antisocial criminal behavior. These findings contribute to a compelling rationale for the initiation of clinical research with classic psychedelics, including psilocybin, in forensic settings.
Hendricks, P. S., Crawford, M. S., Cropsey, K. L., Copes, H., Sweat, N. W., Walsh, Z., & Pavela, G. (2017). The relationships of classic psychedelic use with criminal behavior in the United States adult population. Journal of Psychopharmacology, 0269881117735685.
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Psychedelic Drugs in Biomedicine

September 22, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Substance Use Disorder / By / , , , ,

Abstract

Psychedelic drugs, such as lysergic acid diethylamide (LSD), mescaline, and psilocybin, exert profound effects on brain and behavior. After decades of difficulties in studying these compounds, psychedelics are again being tested as potential treatments for intractable biomedical disorders. Preclinical research of psychedelics complements human neuroimaging studies and pilot clinical trials, suggesting these compounds as promising treatments for addiction, depression, anxiety, and other conditions. However, many questions regarding the mechanisms of action, safety, and efficacy of psychedelics remain. Here, we summarize recent preclinical and clinical data in this field, discuss their pharmacological mechanisms of action, and outline critical areas for future studies of psychedelic drugs, with the goal of maximizing the potential benefits of translational psychedelic biomedicine to patients.
Kyzar, E. J., Nichols, C. D., Gainetdinov, R. R., Nichols, D. E., & Kalueff, A. V. (2017). Psychedelic Drugs in Biomedicine. Trends in Pharmacological Sciences. 10.1016/j.tips.2017.08.003
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Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review

September 22, 2017 / Anxiety Disorders / PTSD, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

Anxiety and depression are some of the most common psychiatric symptoms of patients suffering with life-threatening diseases, often associated with a low quality of life and a poor overall prognosis. 5-HT2A-receptor agonists (serotonergic hallucinogens, ‘psychedelics’) like lysergic acid diethylamide (LSD) and psilocybin were first investigated as therapeutic agents in the 1960s. Recently, after a long hiatus period of regulatory obstacles, interest in the clinical use of these substances has resumed. The current article provides a systematic review of studies investigating psychedelics in the treatment of symptoms of existential distress in life-threatening diseases across different periods of research, highlighting how underlying concepts have developed over time. A systematic search for clinical trials from 1960 to 2017 revealed 11 eligible clinical trials involving a total number of N=445 participants, of which 7 trials investigated the use of lysergic acid diethylamide (LSD) (N=323), 3 trials investigated the use of psilocybin (N=92), and one trial investigated the use of dipropyltryptamine (DPT) (N=30). The 4 more recent randomized controlled trials (RCTs) (N=104) showed a significantly higher methodological quality than studies carried out in the 1960s and 1970s. Evidence supports that patients with life threatening diseases associated with symptoms of depression and anxiety benefit from the anxiolytic and antidepressant properties of serotonergic hallucinogens. Some studies anecdotally reported improvements in patients´ quality of life and reduced fear of death. Moreover, low rates of side effects were reported in studies that adhered to safety guidelines. Further studies are needed to determine how these results can be transferred into clinical practice.
Reiche, S., Hermle, L., Gutwinski, S., Jungaberle, H., Gasser, P., & Majić, T. (2017). Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 10.1016/j.pnpbp.2017.09.012
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Identification of ω-N-Methyl-4-hydroxytryptamine (Norpsilocin) as a Psilocybe Natural Product

September 20, 2017 / Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Publications / By / , ,

Abstract

We report the identification of ω-N-methyl-4-hydroxytryptamine (norpsilocin, 1) from the carpophores of the hallucinogenic mushroom Psilocybe cubensis. The structure was elucidated by 1D and 2D NMR spectroscopy and high-resolution mass spectrometry. Norpsilocin has not previously been reported as a natural product. It likely represents the actual psychotropic agent liberated from its 4-phosphate ester derivative, the known natural product baeocystin. We further present a simple and artifact-free extraction method that prevents dephosphorylation and therefore helps reflect the naturally occurring metabolic profile of Psilocybe mushrooms in subsequent analyses.
Lenz, C., Wick, J., & Hoffmeister, D. (2017). Identification of ω-N-Methyl-4-hydroxytryptamine (Norpsilocin) as a Psilocybe Natural Product. Journal of Natural Products, 80(10), 2835-2838. 10.1021/acs.jnatprod.7b00407
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