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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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Increased thalamic resting-state connectivity as a core driver of LSD-induced hallucinations

September 21, 2017 / LSD, Neuroscience, Papers, Publications / By / , , , , , ,

Abstract

OBJECTIVE:
It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system.
METHOD:
100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects.
RESULTS:
LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects.
CONCLUSION:
Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT2A -receptor in altered states of consciousness.
Mueller, F., Lenz, C., Dolder, P., Lang, U., Schmidt, A., Liechti, M., & Borgwardt, S. (2017). Increased thalamic resting‐state connectivity as a core driver of LSD‐induced hallucinations. Acta Psychiatrica Scandinavica. 10.1111/acps.12818
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Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting

September 21, 2017 / Anthropology & Sociology, Depressive Disorders, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

OBJECTIVE:
This study aimed to longitudinally investigate whether ever having used a psychedelic drug can have a protective effect on incidence of suicidality among marginalised women.
DESIGN:
Longitudinal community-based cohort study.
SETTING:
Data were drawn from a prospective, community-based cohort of marginalised women in Metro Vancouver, Canada.
PARTICIPANTS:
766 women completed the baseline questionnaire between January 2010 and August 2014. Participants who did not report suicidality at baseline and who completed at least one follow-up visit were included.
MAIN OUTCOME MEASURE:
Extended Cox regression was used to model predictors of new suicidality (suicide ideation or attempts) over 54-month follow-up.
RESULTS:
Nearly half (46%; n=355) of participants reported prior suicidality and were thus excluded from the present analyses. Of 290 women eligible at baseline, 11% (n=31) reported recent suicidality during follow-up, with an incidence density of 4.42 per 100 person-years (95% CI 3.10 to 6.30). In multivariable analysis, reported lifetime psychedelic drug use was associated with a 60% reduced hazard for suicidality (adjusted HR (AHR) 0.40; 95% CI 0.17 to 0.94). Crystal methamphetamine use (AHR 3.25; 95% CI 1.47 to 7.21) and childhood abuse (AHR 3.54; 95% CI 1.49 to 8.40) remained independent predictors of suicidality.
CONCLUSION:
The high rate of suicidality identified in this study is of major concern. Alongside emerging evidence on the potential of psychedelic-assisted therapy to treat some mental illness and addiction issues, our findings demonstrate that naturalistic psychedelic drug use is independently associated with reduced suicidality, while other illicit drug use and childhood trauma predispose women to suicidality. While observational, this study supports calls for further investigation of the therapeutic utility of psychedelic drugs in treating poor mental health and promoting mental wellness.
Argento, E., Strathdee, S. A., Tupper, K., Braschel, M., Wood, E., & Shannon, K. (2017). Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting. BMJ open, 7(9), e016025. 10.1136/bmjopen-2017-016025
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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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Long-lasting subjective effects of LSD in normal subjects

September 16, 2017 / LSD, Papers, Psychology / By / ,

Abstract

Rationale

Lysergic acid diethylamide (LSD) and other serotonergic hallucinogens can induce profound alterations of consciousness and mystical-type experiences, with reportedly long-lasting effects on subjective well-being and personality.

Methods

We investigated the lasting effects of a single dose of LSD (200 μg) that was administered in a laboratory setting in 16 healthy participants. The following outcome measures were assessed before and 1 and 12 months after LSD administration: Persisting Effects Questionnaire (PEQ), Mysticism Scale (MS), Death Transcendence Scale (DTS), NEO-Five Factor Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI).

Results

On the PEQ, positive attitudes about life and/or self, positive mood changes, altruistic/positive social effects, positive behavioral changes, and well-being/life satisfaction significantly increased at 1 and 12 months and were subjectively attributed by the subjects to the LSD experience. Five-Dimensions of Altered States of Consciousness (5D-ASC) total scores, reflecting acutely induced alterations in consciousness, and Mystical Experience Questionnaire (MEQ30) total scores correlated with changes in well-being/life satisfaction 12 months after LSD administration. No changes in negative attitudes, negative mood, antisocial/negative social effects, or negative behavior were attributed to the LSD experience. After 12 months, 10 of 14 participants rated their LSD experience as among the top 10 most meaningful experiences in their lives. Five participants rated the LSD experience among the five most spiritually meaningful experiences in their lives. On the MS and DTS, ratings of mystical experiences significantly increased 1 and 12 months after LSD administration compared with the pre-LSD screening. No relevant changes in personality measures were found.

Conclusions

In healthy research subjects, the administration of a single dose of LSD (200 μg) in a safe setting was subjectively considered a personally meaningful experience that had long-lasting subjective positive effects.

Schmid, Y., & Liechti, M. E. (2017). Long-lasting subjective effects of LSD in normal subjects. Psychopharmacology, 1-11. 10.1007/s00213-017-4733-3
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Mystical mobilities and entheogenic Latin America

September 10, 2024 / Anthropology & Sociology, Ayahuasca, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Publications, Scienitific Discipline / By /

Abstract

In this paper, I seek to explore the concept of mystical mobility as a way of addressing travelling and thus using mobility resources that go beyond the transport agenda. I propose to address innovative paths and research questions by discussing alternative cultural geographies in order to seriously reconsider the concept of mobility in a broad sense. The work aims to introduce the notion of ‘mystical mobility’ and its relationship with entheogens (i.e. psychoactive substances) as a new component of mobility studies, also considering how physical and mystical trips are (or are not) combined.
Giucci, G. (2017). Mystical mobilities and entheogenic Latin America. The Journal of Transport History, 0022526617731482.
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Harmine suppresses the proliferation and migration of human ovarian cancer cells through inhibiting ERK/CREB pathway

September 13, 2017 / Ayahuasca, Papers, Psychiatry & Medicine, Publications / By / , , , , ,

Abstract

Ovarian cancer is the most lethal gynaecological cancer and the sixth most common cause of cancer related death among Western women. Recent studies show that harmine, a small-molecular β-carboline alkaloid present in medicinal plants, displayed obvious anticancer effects in several cancer cells. However, the effect of harmine on ovarian cancer is not well understood. In the present study, the effect of harmine on the cell proliferation and migration of ovarian cancer SKOV-3 cells and the underlying mechanism were investigated. Our results indicated that harmine significantly suppressed the proliferation of SKOV-3 cells in a dose-dependent manner. Interestingly, it also inhibited the epidermal growth factor (EGF)-induced proliferation of SKOV-3 cells. Moreover, the migration of SKOV-3 cells was markedly inhibited by harmine treatment. Further study showed that harmine inhibited not only the basal phosphorylation level of extra­cellular signal-regulated kinase 1/2 (ERK1/2) and cyclic adenosine monophosphate response element-binding protein (CREB) but also EGF-induced ERK1/2 and CREB phosphorylation. Finally, harmine significantly suppressed the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) family MMP-2, and MMP-9. In conclusion, our data revealed that harmine inhibited the proliferation and migration of SKOV-3 cells, which might be mediated by ERK/CREB pathway. These findings elucidate that harmine may act as a potential therapeutic drug for ovarian cancer treatment.

Gao, J., Zhu, H., Wan, H., Zou, X., Ma, X., & Gao, G. (2017). Harmine suppresses the proliferation and migration of human ovarian cancer cells through inhibiting ERK/CREB pathway. Oncology Reports, 38(5), 2927-2934. 10.3892/or.2017.5952
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Psychedelic pleasures: An affective understanding of the joys of tripping

September 13, 2017 / LSD, Mushrooms / Psilocybin, Papers, Philosophy & Religious Studies, Psychology, Publications / By /

Abstract

BACKGROUND:
This paper considers the pleasures of psychedelic drugs and proposes a Deleuzian understanding of drugged pleasures as affects. In spite of a large body of work on psychedelics, not least on their therapeutic potentials, the literature is almost completely devoid of discussions of the recreational practices and pleasures of entheogenic drugs. Yet, most people do not use psychedelics because of their curative powers, but because they are fun and enjoyable ways to alter the experience of reality.
METHODS:
In the analytical part of the paper, I examine 100 trip reports from an internet forum in order to explore the pleasures of tripping.
RESULTS:
The analyses map out how drugs such as LSD and mushrooms – in combination with contextual factors such as other people, music and nature – give rise to a set of affective modifications of the drug user’s capacities to feel, sense and act.
CONCLUSION:
In conclusion it is argued that taking seriously the large group of recreational users of hallucinogens is important not only because it broadens our understanding of how entheogenic drugs work in different bodies and settings, but also because it may enable a more productive and harm reductive transmission of knowledge between the scientific and recreational psychedelic communities.
Bøhling, F. (2017). Psychedelic pleasures: An affective understanding of the joys of tripping. International Journal of Drug Policy, 49, 133-143. 10.1016/j.drugpo.2017.07.017
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