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Modulation of Social Cognition via Hallucinogens and "Entactogens".

December 3, 2019 / Ayahuasca, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

Social cognition is a fundamental ability in human everyday lives. Deficits in social functioning also represent a core aspect of many psychiatric disorders. Yet, despite its significance, deficits in social cognition skills are insufficiently targeted by current treatments. Hallucinogens and entactogens have been shown to have the potential to modulate social processing. This article reviews the literature on the influence of hallucinogens and entactogens on social processing in controlled experimental studies in humans and elucidates the underlying neurobiological and neuropharmacological mechanisms. Furthermore, it identifies current knowledge gaps and derives implications for hallucinogen-assisted treatment approaches as well as the development of novel medication for trans-diagnostic impairments in social cognition.

Preller, K. H., & Vollenweider, F. X. (2019). Modulation of Social Cognition via Hallucinogens and “Entactogens”. Frontiers in Psychiatry, 10., https://doi.org/10.3389/fpsyt.2019.00881
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Therapeutic use of serotoninergic hallucinogens: A review of the evidence and of the biological and psychological mechanisms.

December 3, 2019 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, DMT, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Serotoninergic hallucinogens include drugs such as lysergic acid diethylamide (LSD), dimethyltryptamine (DMT) and psilocybin. Recent trials with single/few doses of these compounds show that they induce rapid and sustained antidepressive, anxiolytic, and antiaddictive effects. These effects are also observed in religious groups using the DMT-containing brew ayahuasca. The agonist action of these substances on 5-HT2A receptors expressed in frontal and limbic areas increase glutamatergic transmission and neuroplasticity. These neurochemical effects are associated with acute alterations on self-perception and increases in introspection and positive mood, and with subacute and long-term decreases in psychiatric symptoms, increases in some personality traits such as openness, improvements in emotional processing, and increases in empathy. These are preliminary but promising results that should be further explored in controlled trials with larger sample sizes, especially considering that these compounds could be beneficial in the treatment of treatment-resistant psychiatric disorders.
dos Santos, R. G., & Hallak, J. E. C. (2019). Therapeutic use of serotoninergic hallucinogens: a review of the evidence and of the biological and psychological mechanisms. Neuroscience & Biobehavioral Reviews., https://doi.org/10.1016/j.neubiorev.2019.12.001
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Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics.

November 29, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , ,

Abstract

Psychedelic therapies can engender enduring improvements in psychological well-being. However, relatively little is known about the psychological mechanisms through which the salutary effects of psychedelics emerge. Through integrating extant research on psychedelics with contemporary existential psychology, we present a novel hypothesis that reduced death anxiety may be a key mechanism underpinning the therapeutic effects of psychedelics. In developing this hypothesis, we also provide a complementary review of mechanisms through which psychedelics may reduce death anxiety. We conclude that an awareness of the role of death anxiety in psychopathology has the potential to guide future research into psychedelic therapies.

Moreton, S. G., Szalla, L., Menzies, R. E., & Arena, A. F. (2019). Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics. 29, 1-12., https://doi.org/10.1007/s00213-019-05391-0
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Twenty percent better with 20 micrograms? A qualitative study of psychedelic microdosing self-rapports and discussions on YouTube.

November 28, 2019 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

Background

Psychedelic microdosing is the trending practice of using tiny repeated doses of psychedelic substances to facilitate a range of supposed benefits. With only a few published studies to date, the subject is still under-researched, and more knowledge is warranted. Social media and internet discussion forums have played a vital role in the growing visibility of the microdosing phenomenon, and the present study utilized YouTube contents to improve comprehension of the microdosing practice as well as the social interactions and discussions around microdosing.

Methods

Microdosing self-disclosure in YouTube videos and their following comments were qualitatively analyzed by inductive thematic analysis. Various software was utilized to enable gathering and sorting relevant data.

Results

Microdosing of psychedelic substances, primarily LSD and psilocybin, was used for therapeutic and enhancement purposes, and predominantly beneficial effects were reported. Many different applications and outcomes were discussed, and therapeutic effects for depression appeared especially noteworthy. Intentions for use were recognized as an influencing factor for the progression and outcomes of microdosing. The function of social interactions was mainly to discuss views on the microdosing phenomenon, strategies for optimal results, minimize risks, and share emotional support.

Conclusions

Potentially, microdosing could provide some of the same benefits (for certain conditions) as full-dose interventions with less risk of adverse reactions related to the sometimes intense experiences of higher doses. Microdosing may well also mean additional benefits, as well as risks, through the repeated exposure over extended periods.
Andersson, M., & Kjellgren, A. (2019). Twenty percent better with 20 micrograms? A qualitative study of psychedelic microdosing self-rapports and discussions on YouTube. Harm reduction journal, 16(1), 1-12., https://doi.org/10.1186/s12954-019-0333-3
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Microdosing psychedelics: Motivations, subjective effects and harm reduction

November 30, 2021 / LSD, Microdosing, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By / , , , ,

Abstract

Background: In recent years there has been growing media attention on microdosing psychedelics (e.g., LSD, psilocybin). This refers to people routinely taking small doses of psychedelic substances to improve mental health and wellbeing, or to enhance cognitive performance. Research evidence is currently limited. This paper examines microdosing motivations, dosing practices, perceived short-term benefits, unwanted effects, and harm reduction practices.

Methods: An international online survey was conducted in 2018 examining people’s experiences of using psychedelics. Eligible participants were aged 16 years or older, had used psychedelics and could comprehend written English. This paper focuses on 525 participants who were microdosing psychedelics at the time of the survey.

Results: Participants were primarily motivated to microdose to improve mental health (40%), for personal development (31%) and cognitive enhancement (18%). Most were microdosing with psilocybin (55%) or LSD/1P-LSD (48%). Principal components analysis generated three factors examining perceived short-term benefits of microdosing: improved mood and anxiety, enhanced connection to others and environment, and cognitive enhancement; and three factors examining negative and potentially unwanted effects: stronger-than-expected psychedelic effects, anxiety-related effects, and physical adverse effects. Most participants (78%) reported at least one harm reduction practice they routinely performed while microdosing.

Conclusion: Our findings suggest that people microdosing are commonly doing so as a self-managed therapy for mental health, either as an alternative or adjunct to conventional treatments. This is despite psychedelics remaining prohibited substances in most jurisdictions. Recent findings from clinical trials with standard psychedelic doses for depression and anxiety suggest that a neurobiological effect beyond placebo is not unreasonable. Randomised controlled trials are needed, complemented by mixed methods social science research and the development of novel resources on microdosing harm reduction.

Lea, T., Amada, N., Jungaberle, H., Schecke, H., & Klein, M. (2020). Microdosing psychedelics: Motivations, subjective effects and harm reduction. The International journal on drug policy, 75, 102600. https://doi.org/10.1016/j.drugpo.2019.11.008

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Microdosing psychedelics: Motivations, subjective effects and harm reduction.

November 25, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

BACKGROUND:
In recent years there has been growing media attention on microdosing psychedelics (e.g., LSD, psilocybin). This refers to people routinely taking small doses of psychedelic substances to improve mental health and wellbeing, or to enhance cognitive performance. Research evidence is currently limited. This paper examines microdosing motivations, dosing practices, perceived short-term benefits, unwanted effects, and harm reduction practices.
METHODS:
An international online survey was conducted in 2018 examining people’s experiences of using psychedelics. Eligible participants were aged 16 years or older, had used psychedelics and could comprehend written English. This paper focuses on 525 participants who were microdosing psychedelics at the time of the survey.
RESULTS:
Participants were primarily motivated to microdose to improve mental health (40%), for personal development (31%) and cognitive enhancement (18%). Most were microdosing with psilocybin (55%) or LSD/1P-LSD (48%). Principal components analysis generated three factors examining perceived short-term benefits of microdosing: improved mood and anxiety, enhanced connection to others and environment, and cognitive enhancement; and three factors examining negative and potentially unwanted effects: stronger-than-expected psychedelic effects, anxiety-related effects, and physical adverse effects. Most participants (78%) reported at least one harm reduction practice they routinely performed while microdosing.
CONCLUSION:
Our findings suggest that people microdosing are commonly doing so as a self-managed therapy for mental health, either as an alternative or adjunct to conventional treatments. This is despite psychedelics remaining prohibited substances in most jurisdictions. Recent findings from clinical trials with standard psychedelic doses for depression and anxiety suggest that a neurobiological effect beyond placebo is not unreasonable. Randomised controlled trials are needed, complemented by mixed methods social science research and the development of novel resources on microdosing harm reduction.

Lea, T., Amada, N., Jungaberle, H., Schecke, H., & Klein, M. (2020). Microdosing psychedelics: Motivations, subjective effects and harm reduction. International Journal of Drug Policy, 75, 102600., https://doi.org/10.1016/j.drugpo.2019.11.008
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Psilocybin-assisted therapy for depression: How do we advance the field?

November 22, 2019 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

In the quest for new treatment options for depression, attention is being paid to the potential role of psychedelic drugs. Psilocybin is of particular interest given its mechanism of action, its benefits in early trials and its relatively low side effects burden. This viewpoint outlines a number of key issues that remain to be elucidated about its potential use in the clinical environment, including clarification of the profile of people most likely to benefit and those who might experience adverse effects, longer-term outcomes and the role of psychotherapeutic input alongside the drug itself. There are also opportunities to understand better, the neurobiology underpinning its effects.

Meikle, S. E., Liknaitzky, P., Rossell, S. L., Ross, M., Strauss, N., Thomas, N., … & Castle, D. J. (2019). Psilocybin-assisted therapy for depression: How do we advance the field?. Australian & New Zealand Journal of Psychiatry, 0004867419888575., https://doi.org/10.1177/0004867419888575
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The Impact of Ayahuasca on Suicidality: Results From a Randomized Controlled Trial.

November 19, 2019 / Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / By / , , , , ,

Abstract

Suicide is a major public health problem. Given increasing suicide rates and limitations surrounding current interventions, there is an urgent need for innovative interventions for suicidality. Although ayahuasca has been shown to target mental health concerns associated with suicidality (i.e., depression and hopelessness), research has not yet explored the impact of ayahuasca on suicidality. Therefore, we conducted secondary analyses of a randomized placebo-controlled trial in which individuals with treatment-resistant depression were administered one dose of ayahuasca (n = 14) or placebo (n = 15). Suicidality was assessed by a trained psychiatrist at baseline, as well as 1 day, 2 days, and 7 days after the intervention. A fixed-effects linear mixed model, as well as between and within-groups Cohen’s d effect sizes were used to examine changes in suicidality. Controlling for baseline suicidality, we found a significant effect for time (p < .05). The effect of the intervention (i.e., ayahuasca vs. placebo) trended toward significance (p = .088). At all time points, we found medium between-group effect sizes (i.e., ayahuasca vs. placebo; day 1 Cohen’s d = 0.58; day 2 d = 0.56; day 7 d = 0.67), as well as large within-group (ayahuasca; day 1 Cohen’s d = 1.33; day 2 d = 1.42; day 7 d = 1.19) effect sizes, for decreases in suicidality. Conclusions: This research is the first to explore the impact of ayahuasca on suicidality. The findings suggest that ayahuasca may show potential as an intervention for suicidality. We highlight important limitations of the study, potential mechanisms, and future directions for research on ayahuasca as an intervention for suicidality. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02914769.

Zeifman, R., Palhano-Fontes, F., Hallak, J., Nunes, E. A., Maia-de-Oliveira, J. P., & de Araujo, D. B. (2019). The Impact of Ayahuasca on Suicidality: Results From a Randomized Controlled Trial. Frontiers in Pharmacology, 10, 1325.
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Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects.

November 16, 2019 / Anxiety Disorders / PTSD, LSD, MDMA, Papers, Psychology, Publications / By / , , , , ,

Abstract

Lysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and D-amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and D-amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three substances induce distinct acute subjective effects. However, differences in acute responses to these prototypical psychoactive substances have not been characterized in a controlled study. We investigated the acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), D-amphetamine (40 mg), and placebo in a randomized, double-blind, cross-over study in 28 healthy subjects. All of the substances produced comparable increases in hemodynamic effects, body temperature, and pupil size, indicating equivalent autonomic responses at the doses used. LSD and MDMA increased heart rate more than D-amphetamine, and D-amphetamine increased blood pressure more than LSD and MDMA. LSD induced significantly higher ratings on the 5 Dimensions of Altered States of Consciousness scale and Mystical Experience Questionnaire than MDMA and D-amphetamine. LSD also produced greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity than MDMA and D-amphetamine. LSD also induced greater impairments in subjective ratings of concentration, sense of time, and speed of thinking compared with MDMA and D-amphetamine. MDMA produced greater ratings of good drug effects, liking, high, and ego dissolution compared with D-amphetamine. D-Amphetamine increased ratings of activity and concentration compared with LSD. MDMA but not LSD or D-amphetamine increased plasma concentrations of oxytocin. None of the substances altered plasma concentrations of brain-derived neurotrophic factor. These results indicate clearly distinct acute effects of LSD, MDMA, and D-amphetamine and may assist the dose-finding in substance-assisted psychotherapy research.
Holze, F., Vizeli, P., Müller, F., Ley, L., Duerig, R., Varghese, N., … & Liechti, M. E. (2019). Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects. Neuropsychopharmacology, 1-11., https://doi.org/10.1038/s41386-019-0569-3
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Locomotor effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in mice: psychostimulant effects, stereotypy, and sensitization

November 15, 2019 / MDMA, Neuroscience, Papers, Pharmacology & Chemistry, Publications / By / , , ,

Abstract

Rationale

There is a renewed interest in the use of 3,4-methylenedioxymethamphetamine (MDMA) for treating psychiatric conditions. Although MDMA has entered phase II clinical trials and shows promise as an adjunct treatment, there is an extensive literature detailing the potential neurotoxicity and adverse neurobehavioral effects associated with MDMA use. Previous research indicates that the adverse effects of MDMA may be due to its metabolism into reactive catechols that can enter the brain and serve directly as neurotoxicants. One approach to mitigate MDMA’s potential for adverse effects is to reduce O-demethylation by deuterating the methylenedioxy ring of MDMA. There are no studies that have evaluated the effects of deuterating MDMA on behavioral outcomes.

Objectives

The purpose of the present study was to assess the motor-stimulant effects of deuterated MDMA (d2-MDMA) and compare them to MDMA in male mice.

Methods

Two experiments were performed to quantify mouse locomotor activity and to vary the drug administration regimen (single bolus administration or cumulative administration).

Results

The results of Experiments 1 and 2 indicate that d2-MDMA is less effective at eliciting horizontal locomotion than MDMA; however, the differences between the compounds diminish as the number of cumulative administrations increase. Both d2-MDMA and MDMA can elicit sensitized responses, and these effects cross-sensitize to the prototypical drug of abuse methamphetamine. Thus, d2-MDMA functions as a locomotor stimulant similar to MDMA, but, depending on the dosing regimen, may be less susceptible to inducing sensitization to stereotyped movements.

Conclusions

These findings indicate that d2-MDMA is behaviorally active and produces locomotor effects that are similar to MDMA, which warrant additional assessments of d2-MDMA’s behavioral and physiological effects to determine the conditions under which this compound may serve as a relatively safer alternative to MDMA for clinical use.
Berquist, M. D., Leth-Petersen, S., Kristensen, J. L., & Fantegrossi, W. E. (2020). Locomotor effects of 3, 4-methylenedioxymethamphetamine (MDMA) and its deuterated form in mice: psychostimulant effects, stereotypy, and sensitization. Psychopharmacology, 237(2), 431-442; https://doi.org/10.1007/s00213-019-05380-3

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