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Psychology

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety

Abstract

BACKGROUND:

A recent epidemiological study suggested that 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used for spiritual and recreational reasons is associated with subjective improvement in depression and anxiety. Further exploration of the potential psychotherapeutic effects of 5-MeO-DMT could inform future clinical trials.

OBJECTIVES:

We examined self-reported improvement in depression and anxiety among people who use 5-MeO-DMT in a group setting with structured procedures guiding dose and administration of 5-MeO-DMT. Such procedures also include activities for the preparation of, and support during/following sessions, which are similar to procedures used in clinical trials of hallucinogen administration. Next, we examined whether depression or anxiety were improved following use, and whether the acute subjective effects (mystical/challenging) or beliefs about the 5-MeO-DMT experience were associated with improvements in these conditions.

METHODS:

Respondents (n = 362; Mage = 47.7; Male = 55%; White/Caucasian = 84%) completed an anonymous web-based survey.

RESULTS:

Of those reporting having been diagnosed with depression (41%) or anxiety (48%), most reported these conditions were improved (depression = 80%; anxiety = 79%) following 5-MeO-DMT use, and fewer reported they were unchanged (depression = 17%; anxiety = 19%) or worsened (depression = 3%; anxiety = 2%). Improvement in depression/anxiety conditions were associated with greater intensity of mystical experiences and higher ratings of the spiritual significance and personal meaning of the 5-MeO-DMT experience. There were no associations between depression or anxiety improvement and the intensity of acute challenging physical/psychological effects during the 5-MeO-DMT experience.

CONCLUSIONS:

Future prospective controlled clinical pharmacology studies should examine the safety and efficacy of 5-MeO-DMT administration for relieving depression and anxiety.

Davis, A. K., So, S., Lancelotta, R., Barsuglia, J. P., & Griffiths, R. R. (2018). 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. The American journal of drug and alcohol abuse, 1-9., 10.1080/00952990.2018.1545024
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Psychedelics and Dying Care: A Historical Look at the Relationship between Psychedelics and Palliative Care.

Abstract

This article examines the historical relationship between psychedelics and palliative care. Historians have contributed to a growing field of studies about how psychedelics have been used in the past, but much of that scholarship focused on interrogating questions of legitimacy or proving that psychedelics had therapeutic potential. Palliative care had not yet developed as medical sub-specialty, more often leaving dying care on the margins of modern, pharmaceutical-based treatments. As psychedelic researchers in the 1950s began exploring different applications for psychoactive substances such as LSD and mescaline, however, dying care came into clearer focus as a potential avenue for psychedelics. Before that application gained momentum in clinical or philosophical discussions, psychedelics were criminalized and some of those early discussions were lost. This article looks back at historical discussions about LSD’s potential for easing the anxiety associated with dying, and considers how those early conversations might offer insights into today’s more articulated discussions about psychedelics in palliative care.
Dyck, E. (2019). Psychedelics and Dying Care: A Historical Look at the Relationship between Psychedelics and Palliative Care. Journal of psychoactive drugs, 1-6., 10.1080/02791072.2019.1581308
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Recreational use of psychedelics is associated with elevated personality trait openness: Exploration of associations with brain serotonin markers

Abstract

BACKGROUND:

Recent studies have suggested therapeutic benefits of psychedelics for a variety of mental health conditions. The understanding of how single psychedelic administrations can induce long-lasting effects are, in large, still lacking. However, recent studies in both healthy and clinical populations suggest a role for personality changes.

AIM:

To test support for some of these plausible mechanisms we evaluated (cross-sectional) associations between recreational use of psychedelics and 3,4-methylene-dioxymethamphetamine (MDMA) and (a) personality measures and (b) key markers of cerebral serotonergic signalling (serotonin transporter and serotonin-2A-receptor binding).

METHODS:

In 10 psychedelic-preferring recreational users, 14 MDMA-preferring users and 21 non-using controls, personality was assessed using the ‘big five’ instrument Revised NEO Personality Inventory (NEO-PI-R). Frontal serotonin transporter and serotonin-2A-receptor binding potentials were quantified using [11C]DASB and [18F]altanserin positron emission tomography, respectively.

RESULTS:

Of the five NEO-PI-R traits, only openness to experience scores differed between the three groups; psychedelic-preferring recreational users showing higher openness to experience scores when compared with both MDMA-preferring users and controls. Openness to experience scores were positively associated with lifetime number of psychedelic exposures, and among all MDMA-preferring user/psychedelic-preferring recreational user individuals, frontal serotonin transporter binding – but not frontal serotonin-2A-receptor binding – was positively associated with openness to experience.

CONCLUSION:

Our findings from this cross-sectional study support increasing evidence of a positive association between psychedelic experiences and openness to experience, and (a) expands this to the context of ‘recreational’ psychedelics use, and (b) links serotonergic neurotransmission to openness to experience. A modulation of personality induced by psychedelic experiences may have important therapeutic implications via its impact on peoples’ value systems, cognitive flexibility, and individual and social behaviour.

Erritzoe, D., Smith, J., Fisher, P. M., Carhart-Harris, R., Frokjaer, V. G., & Knudsen, G. M. (2019). Recreational use of psychedelics is associated with elevated personality trait openness: Exploration of associations with brain serotonin markers. Journal of Psychopharmacology., 10.1177/0269881119827891
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Sub-Acute Effects of Psilocybin on Empathy, Creative Thinking, and Subjective Well-Being

Abstract

Creative thinking and empathy are crucial for everyday interactions and subjective well-being. This is emphasized by studies showing a reduction in these skills in populations where social interaction and subjective well-being are significantly compromised (e.g., depression). Anecdotal reports and recent studies suggest that a single administration of psilocybin can enhance such processes and could therefore be a potential treatment. However, it has yet to be assessed whether effects outlast acute intoxication. The present study aimed to assess the sub-acute effects of psilocybin on creative thinking, empathy, and well-being. Participants attending a psilocybin retreat completed tests of creative (convergent and divergent) thinking and empathy, and the satisfaction with life scale on three occasions: before ingesting psilocybin (N = 55), the morning after (N = 50), and seven days after (N = 22). Results indicated that psilocybin enhanced divergent thinking and emotional empathy the morning after use. Enhancements in convergent thinking, valence-specific emotional empathy, and well-being persisted seven days after use. Sub-acute changes in empathy correlated with changes in well-being. The study demonstrates that a single administration of psilocybin in a social setting may be associated with sub-acute enhancement of creative thinking, empathy, and subjective well-being. Future research should test whether these effects contribute to the therapeutic effects in clinical populations.

Mason, N. L., Mischler, E., Uthaug, M. V., & Kuypers, K. P. (2019). Sub-Acute Effects of Psilocybin on Empathy, Creative Thinking, and Subjective Well-Being. Journal of psychoactive drugs, 1-12., 10.1080/02791072.2019.1580804
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Effective connectivity changes in LSD-induced altered states of consciousness in humans

Abstract

Psychedelics exert unique effects on human consciousness. The thalamic filter model suggests that core effects of psychedelics may result from gating deficits, based on a disintegration of information processing within cortico–striato–thalamo-cortical (CSTC) feedback loops. To test this hypothesis, we characterized changes in directed (effective) connectivity between selected CTSC regions after acute administration of lysergic acid diethylamide (LSD), and after pretreatment with Ketanserin (a selective serotonin 2A receptor antagonist) plus LSD in a double-blind, randomized, placebo-controlled, cross-over study in 25 healthy participants. We used spectral dynamic causal modeling (DCM) for resting-state fMRI data. Fully connected DCM models were specified for each treatment condition to investigate the connectivity between the following areas: thalamus, ventral striatum, posterior cingulate cortex, and temporal cortex. Our results confirm major predictions proposed in the CSTC model and provide evidence that LSD alters effective connectivity within CSTC pathways that have been implicated in the gating of sensory and sensorimotor information to the cortex. In particular, LSD increased effective connectivity from the thalamus to the posterior cingulate cortex in a way that depended on serotonin 2A receptor activation, and decreased effective connectivity from the ventral striatum to the thalamus independently of serotonin 2A receptor activation. Together, these results advance our mechanistic understanding of the action of psychedelics in health and disease. This is important for the development of new pharmacological therapeutics and also increases our understanding of the mechanisms underlying the potential clinical efficacy of psychedelics.

Preller, K. H., Razi, A., Zeidman, P., Stämpfli, P., Friston, K. J., & Vollenweider, F. X. (2019). Effective connectivity changes in LSD-induced altered states of consciousness in humans. Proceedings of the National Academy of Sciences, 201815129., 10.1073/pnas.1815129116
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Psychedelic medicine: The biology underlying the persisting psychedelic effects.

Abstract

Psychedelic substances have regained interest as therapeutic agents in the treatment of stress-related disorders. The effects seem to be of persisting nature even after a single dose. Also in lower than ‘regular’ recreational doses, so-called micro-doses, without the typical effects on consciousness, users report beneficial effects on cognitive processes and well-being. The exact neurobiological mechanism underlying these persisting effects is not clear. While previous research has mainly focused on the central nervous system including the immune system and the neuroendocrine system, I propose a central role for sleep and the microbiome in the effects of regular and low doses of psychedelics respectively. It will be explained why this is hypothesized and studies to test this idea proposed. It is concluded that while these studies are needed to understand the biology underlying psychedelic medicine, it is also important to approach it in a holistic way, including all the above mentioned biological processes psychedelics are known to affect, and explore the role of other substance-related factors like route of administration and form, and factors like diet and lifestyle which are part of the psychedelic experience.

Kuypers, K. P. C. (2019). Psychedelic medicine: The biology underlying the persisting psychedelic effects. Medical hypotheses125, 21-24., https://doi.org/10.1016/j.mehy.2019.02.029
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The tripping point: The potential role of psychedelic-assisted therapy in the response to the opioid crisis

Abstract

The increasing contamination of the drug supply with illicitly manufactured fentanyl and related analogs in North America has resulted in the most severe drug-overdose crisis in history. Available pharmacotherapy options for the treatment of opioid use disorder have had limited success in curbing the current crisis, and a growing body of evidence highlights the need for innovative interventions that target underlying social-structural drivers of opioid use disorder. Re-emerging clinical research suggests that psychedelic-assisted therapy has potential as an alternative treatment for refractory substance use disorders and related comorbidities. Based on the available evidence, our viewpoint supports advancing research on the potential role of psychedelic-assisted therapy within a multifaceted response to the opioid crisis.

Argento, E., Tupper, K. W., & Socias, M. E. (2019). The tripping point: The potential role of psychedelic-assisted therapy in the response to the opioid crisis. International Journal of Drug Policy66, 80-81., 10.1016/j.drugpo.2018.11.006
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Ayahuasca and Public Health: Health Status, Psychosocial Well-Being, Lifestyle, and Coping Strategies in a Large Sample of Ritual Ayahuasca Users

Assessing the health status of ayahuasca users has been challenging due to the limitations involved in randomized clinical trials and psychometric approaches. The main objective of this study is the implementation of an approach based on public health indicators. We developed a self-administered questionnaire that was administered to long-term ayahuasca users around Spain. The questionnaire was administrated face-to-face to participants (n = 380) in places where ayahuasca ceremonies were occurring. Public health indicators were compared with Spanish normative data, and intergroup analyses were conducted. Long-term ayahuasca use was associated with higher positive perception of health or with a healthy lifestyle, among other outcomes. Fifty-six percent of the sample reported reducing their use of prescription drugs due to ayahuasca use. Participants who used ayahuasca more than 100 times scored higher in personal values measures. The main conclusion of this study is that a respectful and controlled use of hallucinogenic/psychedelic drugs taken in communitarian settings can be incorporated into modern society with benefits for public health. This new approach, based on the use of health indicators that were not used in previous ayahuasca studies, offers relevant information about the impact of long-term exposure to ayahuasca on public health.

Ona, G., Kohek, M., Massaguer, T., Gomariz, A., Jiménez, D. F., Dos Santos, R. G., … & Bouso, J. C. (2019). Ayahuasca and Public Health: Health Status, Psychosocial Well-Being, Lifestyle, and Coping Strategies in a Large Sample of Ritual Ayahuasca Users. Journal of psychoactive drugs, 1-11., 10.1080/02791072.2019.1567961
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A systematic study of microdosing psychedelics

Abstract

The phenomenon of ‘microdosing’, that is, regular ingestion of very small quantities of psychedelic substances, has seen a rapid explosion of popularity in recent years. Individuals who microdose report minimal acute effects from these substances yet claim a range of long-term general health and wellbeing benefits. There have been no published empirical studies of microdosing and the current legal and bureaucratic climate makes direct empirical investigation of the effects of psychedelics difficult. In Study One we conducted a systematic, observational investigation of individuals who microdose. We tracked the experiences of 98 microdosing participants, who provided daily ratings of psychological functioning over a six week period. 63 of these additionally completed a battery of psychometric measures tapping mood, attention, wellbeing, mystical experiences, personality, creativity, and sense of agency, at baseline and at completion of the study. Analyses of daily ratings revealed a general increase in reported psychological functioning across all measures on dosing days but limited evidence of residual effects on following days. Analyses of pre and post study measures revealed reductions in reported levels of depression and stress; lower levels of distractibility; increased absorption; and increased neuroticism. To better understand these findings, in Study Two we investigated pre-existing beliefs and expectations about the effects of microdosing in a sample of 263 naïve and experienced microdosers, so as to gauge expectancy bias. All participants believed that microdosing would have large and wide-ranging benefits in contrast to the limited outcomes reported by actual microdosers. Notably, the effects believed most likely to change were unrelated to the observed pattern of reported outcomes. The current results suggest that dose controlled empirical research on the impacts of microdosing on mental health and attentional capabilities are needed.

Polito, V., & Stevenson, R. J. (2019). A systematic study of microdosing psychedelics. PloS one14(2), e0211023., 10.1371/journal.pone.0211023.
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Greater empathy in MDMA users

3,4-Methylenedioxymethamphetamine (MDMA) is widely known for its positive acute effects on social behaviour, such as increasing empathy, whilst also attenuating the negative impact of social exclusion. However there is a scarcity of research that investigates the long-term impact of recreational MDMA use on these fundamental social processes.

Sixty-seven individuals were split into three groups based on their drug-use history: poly-drug MDMA users (n = 25), poly-drug users who do not use MDMA (n = 19), alcohol-only users (n = 23), and were tested in an independent groups design. Participants completed both a self-report measure of emotional and cognitive empathy, along with the Multifaceted Empathy Task – a computerised assessment of empathy – and the Cyberball Game – a social exclusion paradigm.

MDMA users had significantly greater subjective emotional empathy, and greater cognitive empathy on the computer task compared with the poly-drug users who do not use MDMA. There were no significant differences in subjective responses to social exclusion between the groups. Indices of MDMA use did not correlate with empathy.

Long-term MDMA users in this sample exhibited normal psychosocial functioning in regard to empathy and social pain and had higher subjective emotional empathy. This conflicts with previous suggestions that moderate, long-term MDMA use may cause heightened social distress, and is further evidence of the safety of the drug, which is relevant to considerations of its therapeutic use.
Carlyle, M., Stevens, T., Fawaz, L., Marsh, B., Kosmider, S., & Morgan, C. J. (2019). Greater empathy in MDMA users. Journal of Psychopharmacology, 0269881119826594., 10.1177/0269881119826594
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Online Event - Psychedelic Care in Recreational Settings - 3 October 2024

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