OPEN Foundation

Search
Close this search box.

Psychology

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
Link to full text

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
Link to full text

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
Link to full text

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
Link to full text

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
Link to full text

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.
Link to full text

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
Link to full text

Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports.

Abstract

The real or perceived proximity to death often results in a non-ordinary state of consciousness characterized by phenomenological features such as the perception of leaving the body boundaries, feelings of peace, bliss and timelessness, life review, the sensation of traveling through a tunnel and an irreversible threshold. Near-death experiences (NDEs) are comparable among individuals of different cultures, suggesting an underlying neurobiological mechanism. Anecdotal accounts of the similarity between NDEs and certain drug-induced altered states of consciousness prompted us to perform a large-scale comparative analysis of these experiences. After assessing the semantic similarity between ≈15,000 reports linked to the use of 165 psychoactive substances and 625 NDE narratives, we determined that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine consistently resulted in reports most similar to those associated with NDEs. Ketamine was followed by Salvia divinorum (a plant containing a potent and selective κ receptor agonist) and a series of serotonergic psychedelics, including the endogenous serotonin 2A receptor agonist N,N-Dimethyltryptamine (DMT). This similarity was driven by semantic concepts related to consciousness of the self and the environment, but also by those associated with the therapeutic, ceremonial and religious aspects of drug use. Our analysis sheds light on the long-standing link between certain drugs and the experience of “dying”, suggests that ketamine could be used as a safe and reversible experimental model for NDE phenomenology, and supports the speculation that endogenous NMDA antagonists with neuroprotective properties may be released in the proximity of death.
Martial, C., Cassol, H., Charland-Verville, V., Pallavicini, C., Sanz, C., Zamberlan, F., … & Tagliazucchi, E. (2019). Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports. Consciousness and cognition69, 52-69., 10.1016/j.concog.2019.01.011
Link to full text

How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review.

Abstract

We conducted a review of systematic reviews (SRs) and randomized-controlled trials (RCTs) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders. Five data bases were systematically searched (2006-August 2018); 4 SRs (of 11 RCTs) and 14 RCTs (1629 participants) were included. Diagnoses were: dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette`s disorder. Outcome variables were too heterogeneous to conduct a  meta-analysis. A narrative synthesis method was applied. The study quality was assessed using the risk-of-bias tool and SIGN-checklists. THC- and CBD-based medicines, given as adjunct to pharmaco- and psychotherapy, were associated with improvements of several symptoms of mental disorders, but not with remission. Side effects occurred, but severe adverse effects were mentioned in single cases only. In order to provide reliable treatment recommendations, more and larger RCTs with follow-up assessments, consistent outcome measures and active comparisons are needed.
Hoch, E., Niemann, D., von Keller, R., Schneider, M., Friemel, C. M., Preuss, U. W., … & Pogarell, O. (2019). How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review. European archives of psychiatry and clinical neuroscience269(1), 87-105., https://doi.org/10.1007/s00406-019-00984-4
Link to full text

Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels.

Abstract

The main psychedelic component of magic mushrooms is psilocybin, which shows promise as a treatment for depression and other mental disorders. Psychedelic effects are believed to emerge through stimulation of serotonin 2A receptors (5-HT2ARs) by psilocybin’s active metabolite, psilocin. We here report for the first time the relationship between intensity of psychedelic effects, cerebral 5-HT2AR occupancy and plasma levels of psilocin in humans. Eight healthy volunteers underwent positron emission tomography (PET) scans with the 5-HT2AR agonist radioligand [11C]Cimbi-36: one at baseline and one or two additional scans on the same day after a single oral intake of psilocybin (3-30 mg). 5-HT2AR occupancy was calculated as the percent change in cerebral 5-HT2AR binding relative to baseline. Subjective psychedelic intensity and plasma psilocin levels were measured during the scans. Relations between subjective intensity, 5-HT2AR occupancy, and plasma psilocin levels were modeled using non-linear regression. Psilocybin intake resulted in dose-related 5-HT2AR occupancies up to 72%; plasma psilocin levels and 5-HT2AR occupancy conformed to a single-site binding model. Subjective intensity was correlated with both 5-HT2AR occupancy and psilocin levels as well as questionnaire scores. We report for the first time that intake of psilocybin leads to significant 5-HT2AR occupancy in the human brain, and that both psilocin plasma levels and 5-HT2AR occupancy are closely associated with subjective intensity ratings, strongly supporting that stimulation of 5-HT2AR is a key determinant for the psychedelic experience. Important for clinical studies, psilocin time-concentration curves varied but psilocin levels were closely associated with psychedelic experience.
Madsen, M. K., Fisher, P. M., Burmester, D., Dyssegaard, A., Stenbæk, D. S., Kristiansen, S., … & Erritzoe, D. (2019). Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology, 1., 10.1038/s41386-019-0324-9
Link to full text