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Psychology

MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials.

May 7, 2019 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , , ,

Abstract

BACKGROUND:
Posttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Here we evaluate six phase 2 trials in a pooled analysis to determine the study design for phase 3 trials of MDMA-assisted psychotherapy for PTSD.
METHODS:
Six randomized, double-blind, controlled clinical trials at five study sites were conducted from April 2004 to February 2017. Active doses of MDMA (75-125 mg, n = 72) or placebo/control doses (0-40 mg, n = 31) were administered to individuals with PTSD during manualized psychotherapy sessions in two or three 8-h sessions spaced a month apart. Three non-drug 90-min therapy sessions preceded the first MDMA exposure, and three to four followed each experimental session.
RESULTS:
After two blinded experimental sessions, the active group had significantly greater reductions in CAPS-IV total scores from baseline than the control group [MMRM estimated mean difference (SE) between groups - 22.0 (5.17), P < 0.001]. The between-group Cohen’s d effect size was 0.8, indicating a large treatment effect. After two experimental sessions, more participants in the active group (54.2%) did not meet CAPS-IV PTSD diagnostic criteria than the control group (22.6%). Depression symptom improvement on the BDI-II was greatest for the active group compared to the control group, although only trended towards significant group differences [MMRM, estimated mean difference (SE) between groups - 6.0 (3.03), P = 0.053]. All doses of MDMA were well tolerated, with some expected reactions occurring at greater frequency for the active MDMA group during experimental sessions and the 7 days following.
CONCLUSIONS:
MDMA-assisted psychotherapy was efficacious and well tolerated in a large sample of adults with PTSD. These studies supported expansion into phase 3 trials and led to FDA granting Breakthrough Therapy designation for this promising treatment.
Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., … & Doblin, R. (2019). MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology, 1-11., https://doi.org/10.1007/s00213-019-05249-5
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Narrative identity, rationality, and microdosing classic psychedelics

May 6, 2019 / LSD, Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Personality, Psychiatry, Psychology, Psychopharmacology, Publications / By / , ,

Abstract

BACKGROUND:

Microdosing involves ingesting a small dose of a classic psychedelic (e.g., LSD and psilocybin) at regular intervals for prolonged periods. The practice is said to reduce anxiety, improve mood, and offer several creative and practical benefits to users. Using the narrative identity theoretical framework, our aim was to explore the experiences of those who microdosed classic psychedelics. Specifically, we sought to understand how and why they began microdosing and how they made sense of their actions in the context of their conventional lives.

METHODS:

To understand the experiences of those who microdose classic psychedelics, we rely on data collected from semi-structured interviews with 30 people who had microdosed.

RESULTS:

Participants saw themselves as conventional citizens who microdosed for rational and instrumental purposes. They emphasized the rationality of microdosing by discussing (1) the practicality of their procurement and administration processes, (2) the connection between their microdosing practice and their general awareness in health and wellness, and (3) the benefits of the practice.

CONCLUSION:

Participants described their microdosing in the context of embracing traditional middle-class values. This created social distance between themselves and those who use drugs recreationally. While people who use drugs recreationally typically construct boundaries by distancing themselves from symbolic others (i.e., “crackheads,” “meth heads,” “junkies”), microdosers constructed boundaries by emphasizing connections to conventional citizens who embrace middle-class values. This connection to conventional citizens allows them to normalize their drug use and facilitates persistence.

Webb, M., Copes, H., & Hendricks, P. S. (2019). Narrative identity, rationality, and microdosing classic psychedelics. International Journal of Drug Policy, 70, 33-39., 10.1016/j.drugpo.2019.04.013
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Making psychedelics into medicines: The politics and paradoxes of medicalization

April 30, 2019 / Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By /

Abstract

This commentary considers efforts to turn psychedelics into medications that can be administered through healthcare systems as examples of “medicalization.” I draw on ethnographic research both inside and outside of university-based clinical trials from 2014 to date, together with analogous examples from psychiatry and drug research and development. Rather than taking a normative stance on medicalization, I situate it in a wider political, economic, and cultural context to better understand its logics and effects. I begin by suggesting the resurgence of psychedelic science has been concerned with medicalization from the outset, recently prompting a crisis in the “psychedelics community” over its self-identity and values. Next, against the confident public messaging surrounding psychedelics, I consider how attempts to scale up and market psychedelic-assisted therapy could end up undermining the safety and efficacy of the therapy itself. I then outline the movements to decriminalize, legalize, and minimize the harms and risks of using psychedelics in their currently illicit therapeutic and recreational modalities. Finally, I explore how working toward psychedelic medicalization over the coming years may influence the movements toward decriminalizing and legalizing psychedelics use, focusing on the underarticulated ways in which medicalization may disregard or even hinder, rather than help, decriminalization and legalization efforts. I call attention to how the cost of gaining approval for therapies incentivizes the development of diluted-yet-profitable forms of psychedelic-assisted treatments, and how frameworks developed for “proper use” demarcate what counts as “abuse” and enable those with newly sanctioned access to psychedelics to condemn afresh their illicit use.

Noorani, T. (2019). Making psychedelics into medicines: The politics and paradoxes of medicalization. Journal of Psychedelic Studies, 1-6., https://doi.org/10.1556/2054.2019.018
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Effects of MDMA on attention to positive social cues and pleasantness of affective touch.

April 30, 2019 / MDMA, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , ,

Abstract

The psychostimulant drug ±3,4-methylenedioxymethamphetamine (MDMA) reportedly produces distinctive feelings of empathy and closeness with others. MDMA increases social behavior in animal models and has shown promise in psychiatric disorders, such as autism spectrum disorder (ASD) and post-traumatic stress disorder (PTSD). How it produces these prosocial effects is not known. This behavioral and psychophysiological study examined the effects of MDMA, compared with the prototypical stimulant methamphetamine (MA), on two measures of social behavior in healthy young adults: (i) responses to socially relevant, “affective” touch, and (ii) visual attention to emotional faces. Men and women (N = 36) attended four sessions in which they received MDMA (0.75 or 1.5 mg/kg), MA (20 mg), or a placebo in randomized order under double-blind conditions. Responses to experienced and observed affective touch (i.e., being touched or watching others being touched) were assessed using facial electromyography (EMG), a proxy of affective state. Responses to emotional faces were assessed using electrooculography (EOG) in a measure of attentional bias. Subjective ratings were also included. We hypothesized that MDMA, but not MA, would enhance the ratings of pleasantness and psychophysiological responses to affective touch and increase attentional bias toward positive facial expressions. Consistent with this, we found that MDMA, but not MA, selectively enhanced ratings of pleasantness of experienced affective touch. Neither drug altered the ratings of pleasantness of observed touch. On the EOG measure of attentional bias, MDMA, but not MA, increased attention toward happy faces. These results provide new evidence that MDMA can enhance the experience of positive social interactions; in this case, pleasantness of physical touch and attentional bias toward positive facial expressions. The findings are consistent with evidence that the prosocial effects are unique to MDMA relative to another stimulant. Understanding the behavioral and neurobiological processes underlying the distinctive social effects of MDMA is a key step to developing the drug for psychiatric disorders.
Bershad, A. K., Mayo, L. M., Van Hedger, K., McGlone, F., Walker, S. C., & de Wit, H. (2019). Effects of MDMA on attention to positive social cues and pleasantness of affective touch. Neuropsychopharmacology, 1, https://doi.org/10.1038/s41386-019-0402-z
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100 years of mescaline

April 29, 2019 / Cacti / Mescaline, Creativity, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Publications / By /

Abstract

In the hundred years since Ernst Späth’s synthesis of mescaline, it has been used in clinical research for many purposes, including the study of hallucinations, creativity, and schizophrenia. After Aldous Huxley described his experience with it in The Doors of Perception, it became a public sensation. During the 1960s it was largely replaced as a research compound by LSD. Today its scientific use is subject to strict controls, but the synthetic phenethylamines developed from it are widely used.

Jay, M. (2019). 100 years of mescaline. Monatshefte für Chemie-Chemical Monthly, 150(5), 957-959., https://doi.org/10.1007/s00706-019-02425-3
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Serotonergic hallucinogens and recognition of facial emotion expressions: a systematic review of the literature.

April 26, 2019 / Anxiety disorders / PTSD, Depression, LSD, Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , , ,

Abstract

BACKGROUND:
Recognition of emotions in facial expressions (REFE) is a key aspect of social cognition. Anxiety and mood disorders are associated with deficits in REFE, and anxiolytics and antidepressants reverse these deficits. Recent studies have shown that serotonergic hallucinogens (i.e. ayahuasca, dimethyltryptamine, psilocybin, lysergic acid diethylamide [LSD], and mescaline) have anxiolytic and antidepressant properties, but their effects on REFE are not well understood. The purpose of the study was to conduct a systematic review analyzing the effects of serotonergic hallucinogens on REFE in humans.
METHODS:
Studies published in the PubMed, PsycINFO, and Web of Science databases until 19 October 2018 which analyzed the effects of serotonergic hallucinogens on REFE in humans were included.
RESULTS:
Of the 62 studies identified, 8 studies were included. Included studies involved the administration of a single or a few doses of LSD or psilocybin, and most trials were randomized and controlled with placebo. LSD and psilocybin reduced the recognition of negative emotions in most studies and modulated amygdala activity to these stimuli, which was correlated with antidepressive effects in patients. Both drugs were well tolerated.
CONCLUSIONS:
Serotonergic hallucinogens reduced the recognition of negative emotions by modulating amygdala activity. Despite the small sample sizes, results suggest that serotonergic hallucinogens show promising beneficial effects on deficits in REFE.
Rocha, J. M., Osório, F. L., Crippa, J. A. S., Bouso, J. C., Rossi, G. N., Hallak, J. E., & dos Santos, R. G. (2019). Serotonergic hallucinogens and recognition of facial emotion expressions: a systematic review of the literature. Therapeutic advances in psychopharmacology, 9, 2045125319845774., https://doi.org/10.1177/2045125319845774
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Dimethyltryptamine: Endogenous Role and Therapeutic Potential.

April 25, 2019 / Anxiety disorders / PTSD, Depression, DMT, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Safety, Substance Use Disorder / By / , ,

Abstract

N, N-dimethyltryptamine (DMT) is an indole alkaloid produced by a number of plants and animals, including humans. Its psychoactive effects were first described in 1956 by Stephen Szára, but have been exploited for centuries by South American indigenous populations in the form of ayahuasca. In the present review, we assess the state of the art regarding a putative role for endogenous DMT and potential clinical applications of ayahuasca and DMT. A review assessing the pharmacological profile of DMT and its clinical effects in humans was performed using the PubMed data base until 5 August 2018 with the words: ayahuasca and N,N-dimethyltryptamine. While the role of endogenous DMT remains unclear, ayahuasca has promising results in anxiety, depression and substance dependence. Since ayahuasca has a good safety profile, it is crucial to conduct further research aimed at developing new treatments for psychiatric disorders.
Rodrigues, A. V., Almeida, F. J., & Vieira-Coelho, M. A. (2019). Dimethyltryptamine: endogenous role and therapeutic potential. Journal of psychoactive drugs, 1-12., https://doi.org/10.1080/02791072.2019.1602291
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Survey of subjective “God encounter experiences”: Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT.

April 23, 2019 / Ayahuasca, Consciousness, DMT, LSD, Mushrooms / Psilocybin, Mystical experiences, Papers, Personal development, Phenomenology, Psychology, Psychopharmacology, Publications, Spirituality / By / , , , ,

Abstract

Naturally occurring and psychedelic drug-occasioned experiences interpreted as personal encounters with God are well described but have not been systematically compared. In this study, five groups of individuals participated in an online survey with detailed questions characterizing the subjective phenomena, interpretation, and persisting changes attributed to their single most memorable God encounter experience (n = 809 Non-Drug, 1184 psilocybin, 1251 lysergic acid diethylamide (LSD), 435 ayahuasca, and 606 N,N-dimethyltryptamine (DMT)). Analyses of differences in experiences were adjusted statistically for demographic differences between groups. The Non-Drug Group was most likely to choose “God” as the best descriptor of that which was encountered while the psychedelic groups were most likely to choose “Ultimate Reality.” Although there were some other differences between non-drug and the combined psychedelic group, as well as between the four psychedelic groups, the similarities among these groups were most striking. Most participants reported vivid memories of the encounter experience, which frequently involved communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing. The encounter experience fulfilled a priori criteria for being a complete mystical experience in approximately half of the participants. More than two-thirds of those who identified as atheist before the experience no longer identified as atheist afterwards. These experiences were rated as among the most personally meaningful and spiritually significant lifetime experiences, with moderate to strong persisting positive changes in life satisfaction, purpose, and meaning attributed to these experiences. Among the four groups of psychedelic users, the psilocybin and LSD groups were most similar and the ayahuasca group tended to have the highest rates of endorsing positive features and enduring consequences of the experience. Future exploration of predisposing factors and phenomenological and neural correlates of such experiences may provide new insights into religious and spiritual beliefs that have been integral to shaping human culture since time immemorial.
Griffiths, R. R., Hurwitz, E. S., Davis, A. K., Johnson, M. W., & Jesse, R. (2019). Survey of subjective” God encounter experiences”: Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT. PloS one, 14(4), e0214377., https://doi.org/10.1371/journal.pone.0214377
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Survey of subjective "God encounter experiences": Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT.

April 23, 2019 / Ayahuasca, Consciousness, DMT, LSD, Mushrooms / Psilocybin, Mystical experiences, Papers, Personal development, Phenomenology, Psychology, Psychopharmacology, Publications, Spirituality / By / , , , ,

Abstract

Naturally occurring and psychedelic drug-occasioned experiences interpreted as personal encounters with God are well described but have not been systematically compared. In this study, five groups of individuals participated in an online survey with detailed questions characterizing the subjective phenomena, interpretation, and persisting changes attributed to their single most memorable God encounter experience (n = 809 Non-Drug, 1184 psilocybin, 1251 lysergic acid diethylamide (LSD), 435 ayahuasca, and 606 N,N-dimethyltryptamine (DMT)). Analyses of differences in experiences were adjusted statistically for demographic differences between groups. The Non-Drug Group was most likely to choose “God” as the best descriptor of that which was encountered while the psychedelic groups were most likely to choose “Ultimate Reality.” Although there were some other differences between non-drug and the combined psychedelic group, as well as between the four psychedelic groups, the similarities among these groups were most striking. Most participants reported vivid memories of the encounter experience, which frequently involved communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing. The encounter experience fulfilled a priori criteria for being a complete mystical experience in approximately half of the participants. More than two-thirds of those who identified as atheist before the experience no longer identified as atheist afterwards. These experiences were rated as among the most personally meaningful and spiritually significant lifetime experiences, with moderate to strong persisting positive changes in life satisfaction, purpose, and meaning attributed to these experiences. Among the four groups of psychedelic users, the psilocybin and LSD groups were most similar and the ayahuasca group tended to have the highest rates of endorsing positive features and enduring consequences of the experience. Future exploration of predisposing factors and phenomenological and neural correlates of such experiences may provide new insights into religious and spiritual beliefs that have been integral to shaping human culture since time immemorial.
Griffiths, R. R., Hurwitz, E. S., Davis, A. K., Johnson, M. W., & Jesse, R. (2019). Survey of subjective” God encounter experiences”: Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT. PloS one, 14(4), e0214377., https://doi.org/10.1371/journal.pone.0214377
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Psychedelics as a treatment for disorders of consciousness

April 21, 2019 / Anthropology, Consciousness, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Publications / By / ,

Abstract

Based on its ability to increase brain complexity, a seemingly reliable index of conscious level, we propose testing the capacity of the classic psychedelic, psilocybin, to increase conscious awareness in patients with disorders of consciousness. We also confront the considerable ethical and practical challenges this proposal must address, if this hypothesis is to be directly assessed.

Scott, G., & Carhart-Harris, R. L. (2019). Psychedelics as a treatment for disorders of consciousness. Neuroscience of consciousness, 2019(1), niz003. 10.1093/nc/niz003
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