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Psychology

Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity

January 13, 2020 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , , , , ,

Abstract

Background

The use of psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans.

Methods

We conducted a double-blind, randomized, counterbalanced, crossover study comprising 23 healthy human participants who received placebo and 0.2 mg/kg of psilocybin orally on 2 different test days. Participants underwent magnetic resonance imaging at 3 time points between administration and peak effects: 20 minutes, 40 minutes, and 70 minutes after administration. Resting-state functional connectivity was quantified via a data-driven global brain connectivity method and compared with cortical gene expression maps.

Results

Psilocybin reduced associative, but concurrently increased sensory, brain-wide connectivity. This pattern emerged over time from administration to peak effects. Furthermore, we showed that baseline connectivity is associated with the extent of psilocybin-induced changes in functional connectivity. Lastly, psilocybin-induced changes correlated in a time-dependent manner with spatial gene expression patterns of the 5-HT2A (5-hydroxytryptamine 2A) and 5-HT1A (5-hydroxytryptamine 1A) receptors.

Conclusions

These results suggest that the integration of functional connectivity in sensory regions and the disintegration in associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.

Preller, K. H., Duerler, P., Burt, J. B., Ji, J. L., Adkinson, B., Stämpfli, P., … & Anticevic, A. (2020). Psilocybin induces time-dependent changes in global functional connectivity: Psi-induced changes in brain connectivity. Biological Psychiatry., 10.1016/j.biopsych.2019.12.027
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A Dangerous Method? Psychedelic Therapy at Modum Bad, Norway, 1961-76

January 13, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

After many years of disregard, the use of psychedelic drugs in psychiatric treatment has re-emerged in recent years. The prospect that psychedelics may again be integrated into mainstream psychiatry has aroused interest in long-forgotten research and experience from the previous phase of psychedelic therapy, which lasted from the late 1940s to the 1970s. This article will discuss one large-scale psychedelic therapy programme at Modum Bad Nervesanatorium, a psychiatric clinic which treated 379 inpatients with psychedelic drugs during the years 1961-76. The psychiatrists there initially regarded the psychedelic treatment as efficacious and without serious negative reactions, but reports of long-term harm have since surfaced. This article discusses how insights from Modum Bad might benefit the new generation of psychedelic treatment efforts.
Johnstad, P. G. (2020). A dangerous method? Psychedelic therapy at Modum Bad, Norway, 1961–76. History of Psychiatry, 31(2), 217-226., https://doi.org/10.1177%2F0957154X19894537
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Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers.

January 11, 2020 / Ayahuasca, Papers, Psychology, Publications / By / ,

Abstract

RATIONALE:
There is a growing body of evidence demonstrating the therapeutic potential of ayahuasca for treating depression and anxiety. However, the mechanisms of action involved in ayahuasca’s therapeutic effects are unclear. Mindfulness and cognitive flexibility may be two possible psychological mechanisms. Like other classic psychedelics, ayahuasca also leads to an ‘afterglow’ effect of improved subjective well-being that persists after the acute effects have subsided. This period may offer a window of increased therapeutic potential.
OBJECTIVE:
To explore changes in mindfulness and cognitive flexibility before and within 24 h after ayahuasca use.METHODS:
Forty-eight participants (54% female) were assessed on measures of mindfulness (Five Facets Mindfulness Questionnaire (FFMQ)), decentering (Experiences Questionnaire (EQ)), and cognitive flexibility (Cognitive Flexibility Scale (CFS)), and completed the Stroop and Wisconsin Picture Card Sorting Task (WPCST) before drinking ayahuasca, and again within 24 h.
RESULTS:
Mindfulness (FFMQ total scores and four of the five mindfulness facets: observe, describe, act with awareness, and non-reactivity) and decentering (EQ) significantly increased in the 24 h after ayahuasca use. Cognitive flexibility (CFS and WPCST) significantly improved in the 24 h after ayahuasca use. Changes in both mindfulness and cognitive flexibility were not influenced by prior ayahuasca use.
CONCLUSIONS:
The present study supports ayahuasca’s ability to enhance mindfulness and further reports changes in cognitive flexibility in the ‘afterglow’ period occur, suggesting both could be possible psychological mechanisms concerning the psychotherapeutic effects of ayahuasca. Given psychological gains occurred regardless of prior ayahuasca use suggests potentially therapeutic effects for both naïve and experienced ayahuasca drinkers.
Murphy-Beiner, A., & Soar, K. (2020). Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers. Psychopharmacology, 1-9., https://doi.org/10.1007/s00213-019-05445-3
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Ayahuasca's 'afterglow': improved mindfulness and cognitive flexibility in ayahuasca drinkers.

January 11, 2020 / Ayahuasca, Papers, Psychology, Publications / By / ,

Abstract

RATIONALE:
There is a growing body of evidence demonstrating the therapeutic potential of ayahuasca for treating depression and anxiety. However, the mechanisms of action involved in ayahuasca’s therapeutic effects are unclear. Mindfulness and cognitive flexibility may be two possible psychological mechanisms. Like other classic psychedelics, ayahuasca also leads to an ‘afterglow’ effect of improved subjective well-being that persists after the acute effects have subsided. This period may offer a window of increased therapeutic potential.
OBJECTIVE:
To explore changes in mindfulness and cognitive flexibility before and within 24 h after ayahuasca use.METHODS:
Forty-eight participants (54% female) were assessed on measures of mindfulness (Five Facets Mindfulness Questionnaire (FFMQ)), decentering (Experiences Questionnaire (EQ)), and cognitive flexibility (Cognitive Flexibility Scale (CFS)), and completed the Stroop and Wisconsin Picture Card Sorting Task (WPCST) before drinking ayahuasca, and again within 24 h.
RESULTS:
Mindfulness (FFMQ total scores and four of the five mindfulness facets: observe, describe, act with awareness, and non-reactivity) and decentering (EQ) significantly increased in the 24 h after ayahuasca use. Cognitive flexibility (CFS and WPCST) significantly improved in the 24 h after ayahuasca use. Changes in both mindfulness and cognitive flexibility were not influenced by prior ayahuasca use.
CONCLUSIONS:
The present study supports ayahuasca’s ability to enhance mindfulness and further reports changes in cognitive flexibility in the ‘afterglow’ period occur, suggesting both could be possible psychological mechanisms concerning the psychotherapeutic effects of ayahuasca. Given psychological gains occurred regardless of prior ayahuasca use suggests potentially therapeutic effects for both naïve and experienced ayahuasca drinkers.
Murphy-Beiner, A., & Soar, K. (2020). Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers. Psychopharmacology, 1-9., https://doi.org/10.1007/s00213-019-05445-3
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Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer.

January 9, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:
A recently published randomized controlled trial compared single-dose psilocybin with single-dose niacin in conjunction with psychotherapy in participants with cancer-related psychiatric distress. Results suggested that psilocybin-assisted psychotherapy facilitated improvements in psychiatric and existential distress, quality of life, and spiritual well-being up to seven weeks prior to the crossover. At the 6.5-month follow-up, after the crossover, 60-80% of participants continued to meet criteria for clinically significant antidepressant or anxiolytic responses.
METHODS:
The present study is a long-term within-subjects follow-up analysis of self-reported symptomatology involving a subset of participants that completed the parent trial. All 16 participants who were still alive were contacted, and 15 participants agreed to participate at an average of 3.2 and 4.5 years following psilocybin administration.
RESULTS:
Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at the first and second follow-ups. Within-group effect sizes were large. At the second (4.5 year) follow-up approximately 60-80% of participants met criteria for clinically significant antidepressant or anxiolytic responses. Participants overwhelmingly (71-100%) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives.
CONCLUSION:
These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress. Limited conclusions, however, can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study. Nonetheless, the present study adds to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological, emotional, and spiritual well-being of patients with life-threatening cancer.
Agin-Liebes, G. I., Malone, T., Yalch, M. M., Mennenga, S. E., Ponté, K. L., Guss, J., … & Ross, S. (2020). Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Journal of Psychopharmacology, 0269881119897615., https://doi.org/10.1177%2F0269881119897615
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A qualitative descriptive analysis of effects of psychedelic phenethylamines and tryptamine

January 7, 2020 / DMT, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

OBJECTIVE:

The number of novel psychedelic phenethylamines and tryptamines has continued to increase, but little academic research has focused on the effects of these substances. We sought to determine and compare the subjective effects of various substances.

METHODS:

We conducted in-depth interviews with 39 adults (75.4% male and 87.2% White) who reported experience using psychedelic phenethylamines and/or tryptamines. Participants described the effects of compounds they have used. We examined the subjective drug effects in a qualitative descriptive manner.

RESULTS:

Participants reported on the use of 36 compounds. The majority (64.1%) reported the use of 2C series drugs, with 2C-B use being most prevalent; 38.5% reported the use of NBOMe, and 25.6% reported the use of DOx. With regard to tryptamines, 46.2% reported use, and 4-AcO-DMT was the most prevalent drug used in this class. 2C-B was often described as being more favorable than other 2C series compounds with the effects described as being comparable with MDMA and LSD. NBOMe effects were generally described in an unfavorable manner, and the effects of DOx were often described as lasting too long (12-36 hr). The effects of 4-AcO-DMT were often described as mimicking psilocybin.

CONCLUSION:

Knowing the effects of various compounds can inform education, prevention, and harm reduction efforts regarding the use of these drugs.

Palamar, J. J., & Acosta, P. (2020). A qualitative descriptive analysis of effects of psychedelic phenethylamines and tryptamines. Human Psychopharmacology: Clinical and Experimental, e2719., 10.1002/hup.2719
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Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species

January 7, 2020 / DMT, LSD, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

Serotonergic hallucinogens such as lysergic acid diethylamide (LSD) induce head twitches in rodents via 5-HT2A receptor activation. The goal of the present investigation was to determine whether a correlation exists between the potency of hallucinogens in the mouse head-twitch response (HTR) paradigm and their reported potencies in other species, specifically rats and humans. Dose-response experiments were conducted with phenylalkylamine and tryptamine hallucinogens in C57BL/6J mice, enlarging the available pool of HTR potency data to 41 total compounds. For agents where human data are available (n = 36), a strong positive correlation (r = 0.9448) was found between HTR potencies in mice and reported hallucinogenic potencies in humans. HTR potencies were also found to be correlated with published drug discrimination ED50 values for substitution in rats trained with either LSD (r = 0.9484, n = 16) or 2,5-dimethoxy-4-methylamphetamine (r = 0.9564, n = 21). All three of these behavioral effects (HTR in mice, hallucinogen discriminative stimulus effects in rats, and psychedelic effects in humans) have been linked to 5-HT2A receptor activation. We present evidence that hallucinogens induce these three effects with remarkably consistent potencies. In addition to having high construct validity, the HTR assay also appears to show significant predictive validity, confirming its translational relevance for predicting subjective potency of hallucinogens in humans. These findings support the use of the HTR paradigm as a preclinical model of hallucinogen psychopharmacology and in structure-activity relationship studies of hallucinogens. Future investigations with a larger number of test agents will evaluate whether the HTR assay can be used to predict the hallucinogenic potency of 5-HT2A agonists in humans.

Halberstadt, A. L., Chatha, M., Klein, A. K., Wallach, J., & Brandt, S. D. (2020). Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology, 107933., 10.1016/j.neuropharm.2019.107933
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The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis.

January 2, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

The current meta-analysis examined the effects of psilocybin in combination with behavioral interventions on anxiety and depression in samples with elevated symptoms. Across four studies (one uncontrolled; three randomized, placebo-controlled; N = 117), within-group pre-post and pre-follow-up effects on anxiety and depression were large (Hedges’ gs=1.16 to 1.47) and statistically significant. Across three placebo-controlled studies, pre-post placebo-controlled effects were also large (gs = 0.82 to 0.83) and statistically significant. No serious adverse events were reported. Limitations include the small number of studies and risk for bias within studies. Results tentatively support future research on psilocybin for the treatment of anxiety and depression.

Goldberg, S. B., Pace, B. T., Nicholas, C. R., Raison, C. L., & Hutson, P. R. (2020). The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis. Psychiatry Research, 112749., https://doi.org/10.1016/j.psychres.2020.112749
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[Neuroscientific and psychological explanations for the therapeutic effects of psychedelics]

January 1, 2020 / Papers, Psychology, Publications / By /

Abstract

Psychedelics have a strong therapeutic potential for the treatment of biomedical disorders, but the working mechanisms underlying psychedelics are only poorly understood.<br/> AIM: To discuss different mechanisms underlying the therapeutic effects of classic psychedelics.<br/> METHOD: To make a distinction between different levels of explanation: the pharmacological, the neurocognitive and the psychological level.<br/> RESULTS: At the pharmacological level, classic psychedelics affect via the serotonin-receptor, the production of glutamate and brain-derived neurotrophic factor (bdnf), which stimulate neurogenesis. Psychedelics also have anti-flammatory properties and thereby have a protective effect on the brain. At the neurocognitive level, psychedelics have been associated with a reduced activation of the default mode network, which has been implicated in self-referential processing and rumination. At the same time, the brain’s entropy increases, reflected in an increased connectivity between different brain areas. At the psychological level, the therapeutic efficacy of psychedelics has been attributed to the mystical experience, as well as to its awe-inducing potential, the feelings of connectedness and an enhanced awareness of emotions.<br/> CONCLUSION: Psycholytic and psychedelic therapy act at different levels, but ultimately the combination of different mechanisms will help us to understand how psychedelics – in the right set and setting – can be used successfully in therapeutic practice.
van Elk, M. (2020). Neuroscientific and psychological explanations for the therapeutic effects of psychedelics. Tijdschrift Voor Psychiatrie, 62(8), 677-683., https://pubmed.ncbi.nlm.nih.gov/32816296/
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Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity.

December 20, 2019 / Anxiety Disorders / PTSD, LSD, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , , ,

Abstract

BACKGROUND:
The practice of “microdosing,” or the use of repeated, very low doses of lysergic acid diethylamide (LSD) to improve mood or cognition, has received considerable public attention, but empirical studies are lacking. Controlled studies are needed to investigate both the therapeutic potential and the neurobiological underpinnings of this pharmacologic treatment.
METHODS:
The present study was designed to examine the effects of a single low dose of LSD (13 μg) versus placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, 18 to 35 years old, participated in 2 functional magnetic resonance imaging scanning sessions in which they received placebo or LSD under double-blind conditions. During each session, the participants completed drug effect and mood questionnaires, and physiological measures were recorded. During expected peak drug effect, they underwent resting-state blood oxygen level-dependent and arterial spin labeling scans. Cerebral blood flow as well as amygdala and thalamic connectivity were analyzed.
RESULTS:
LSD increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum, and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. This low dose of LSD had weak and variable effects on mood, but its effects on positive mood were positively correlated with the increase in amygdala-middle frontal gyrus connectivity strength.
CONCLUSIONS:
These preliminary findings show that a very low dose of LSD, which produces negligible subjective changes, alters brain connectivity in limbic circuits. Additional studies, especially with repeated dosing, will reveal whether these neural changes are related to the drug’s purported antidepressant effect.

Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Bershad, A. K., Preller, K. H., Lee, R., Keedy, S., Wren-Jarvis, J., Bremmer, M. P., & de Wit, H. (2019). Preliminary report on the effects of a low dose of LSD on resting state amygdalar functional connectivity. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging., https://doi.org/10.1016/j.bpsc.2019.12.007
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