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Psychology

Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions

November 13, 2018 / History, LSD, Mushrooms / Psilocybin, Neuroscience, Other subjects, Other substances, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Safety / By / ,

Abstract

Humans have used serotonergic hallucinogens (i.e. psychedelics) for spiritual, ceremonial, and recreational purposes for thousands of years, but their administration as part of a structured therapeutic intervention is still a relatively novel practice within Western medical and psychological frameworks. In the mid-20th century, considerable advances were made in developing therapeutic approaches integrating administration of low (psycholytic) and high (psychedelic) doses of serotonergic hallucinogens for treatment of a variety of conditions, often incorporating psychoanalytic concepts prevalent at that time. This work contributed seminal insights regarding how these substances may be employed with efficacy and safety in targeted therapeutic interventions, including the importance of optimizing set (frame of mind) and setting (therapeutic environment). More recently, clinical and pharmacological research has revisited the effects and therapeutic potential of psychedelics utilizing a variety of approaches. The current article provides an overview of past and present models of psychedelic therapy, and discusses important considerations for future interventions incorporating the use of psychedelics in research and clinical practice.

Garcia-Romeu, A., & Richards, W. A. (2018). Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions. International Review of Psychiatry, 30(4), 291-316., 10.1080/09540261.2018.1486289.
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Acute effects of ayahuasca in a juvenile non-human primate model of depression

November 8, 2018 / Ayahuasca, Depression, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , , , , ,

Abstract

OBJECTIVE:
The incidence rate of major depression in adolescents reaches approximately 14%. This disorder is usually recurrent, without remission of symptoms even after pharmacological treatment, and persists throughout adult life. Since the effects of antidepressants take approximately 2 weeks to begin, new pharmacological therapies are under continuous exploration. Recent evidence suggests that psychedelics could produce rapid antidepressant effects. In this study, we evaluated the potential antidepressant effects of ayahuasca in a juvenile non-human primate model of depression.
METHODS:
While living with their families, juvenile marmosets (8 males; 7 females) were observed on alternate days for four weeks during a baseline phase. This was followed by 8 weeks of an induced depressive state protocol, the social isolated context (IC), in which the animals were monitored in the first and last weeks. Subsequently, five males and four females were randomly selected for treatment, first with a single administration of saline vehicle (1.67 mL/300 g of body weight, via gavage), followed by a single dose of ayahuasca (1.67 mL/300 g of body weight, via gavage). Both phases lasted 1 week and the animals were monitored daily. A third week of sampling was called the tardive-pharmacological effects phase. In all phases the marmosets were assessed for behavior, fecal cortisol levels, and body weight.
RESULTS:
After IC, the animals presented typical hypocortisolemia, but cortisol recovered to baseline levels 24 h after an acute dose of ayahuasca; this recovery was not observed in vehicle-treated animals. Additionally, in males, ayahuasca, but not the vehicle, reduced scratching, a stereotypic behavior, and increased feeding. Ayahuasca treatment also improved body weight to baseline levels in both sexes. The ayahuasca-induced behavioral response had long-term effects (14 days). Thus, in this translational juvenile animal model of depression, ayahuasca presented beneficial effects.
CONCLUSIONS:
These results can contribute to the validation of ayahuasca as an antidepressant drug and encourage new studies on psychedelic drugs as a tool for treating mood disorders, including for adolescents with early-onset depression.
da Silva, F. S., Silva, E. A., Sousa Jr, G. M. D., Maia-de-Oliveira, J. P., Soares-Rachetti, V. D. P., de Araujo, D. B., … & Galvão-Coelho, N. L. (2018). Acute effects of ayahuasca in a juvenile non-human primate model of depression. Brazilian Journal of Psychiatry, (AHEAD), 0-0. 10.1590/1516-4446-2018-0140
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Predicting Responses to Psychedelics: A Prospective Study

November 2, 2018 / Ayahuasca, Cacti / Mescaline, DMT, Iboga / Ibogaine, LSD, Mushrooms / Psilocybin, Mystical experiences, Neuroscience, Other subjects, Papers, Personality, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Salvia / Salvinorin A / By / , , , , , ,

Abstract

Responses to psychedelics are notoriously difficult to predict, yet significant work is currently underway to assess their therapeutic potential and the level of interest in psychedelics among the general public appears to be increasing. We aimed to collect prospective data in order to improve our ability to predict acute- and longer-term responses to psychedelics. Individuals who planned to take a psychedelic through their own initiative participated in an online survey (www.psychedelicsurvey.com). Traits and variables relating to set, setting and the acute psychedelic experience were measured at five different time points before and after the experience. Principle component and regression methods were used to analyse the data. Sample sizes for the five time points were N = 654, N = 535, N = 379, N = 315, and N = 212 respectively. Psychological well-being was increased 2 weeks after a psychedelic experience and remained at this level after 4 weeks. Higher ratings of a “mystical-type experience” had a positive effect on the change in well-being after a psychedelic experience, whereas the other acute psychedelic experience measures, i.e., “challenging experience” and “visual effects”, did not influence the change in well-being after the psychedelic experience. Having “clear intentions” for the experience was conducive to mystical-type experiences. Having a positive “set” as well as having the experience with intentions related to “recreation” were both found to decrease the likelihood of having a challenging experience. The baseline trait “absorption” and higher drug doses promoted all aspects of the acute experience, i.e., mystical-type and challenging experiences, as well as visual effects. When comparing the relative contribution of different types of variables in explaining the variance in the change in well-being, it seemed that baseline trait variables had the strongest effect on the change in well-being after a psychedelic experience. These results confirm the importance of extra-pharmacological factors in determining responses to a psychedelic. We view this study as an early step towards the development of empirical guidelines that can evolve and improve iteratively with the ultimate purpose of guiding crucial clinical decisions about whether, when, where and how to dose with a psychedelic, thus helping to mitigate risks while maximizing potential benefits in an evidence-based manner.

Haijen, E. C. H. M., Kaelen, M., Roseman, L., Timmermann, C., Russ, S., Nutt, D., & Carhart-Harris, R. L. (2018). Predicting responses to psychedelics: a prospective study. Frontiers in pharmacology, 9, 897., 10.3389/fphar.2018.00897
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Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study

November 1, 2018 / Depression, Ketamine, Medicine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , , ,

Abstract

BACKGROUND:

Novel interventions for treatment-resistant depression (TRD) in adolescents are urgently needed. Ketamine has been studied in adults with TRD, but little information is available for adolescents. This study investigated efficacy and tolerability of intravenous ketamine in adolescents with TRD, and explored clinical response predictors.

METHODS:

Adolescents, 12-18 years of age, with TRD (failure to respond to two previous antidepressant trials) were administered six ketamine (0.5 mg/kg) infusions over 2 weeks. Clinical response was defined as a 50% decrease in Children’s Depression Rating Scale-Revised (CDRS-R); remission was CDRS-R score ≤28. Tolerability assessment included monitoring vital signs and dissociative symptoms using the Clinician-Administered Dissociative States Scale (CADSS).

RESULTS:

Thirteen participants (mean age 16.9 years, range 14.5-18.8 years, eight biologically male) completed the protocol. Average decrease in CDRS-R was 42.5% (p = 0.0004). Five (38%) adolescents met criteria for clinical response. Three responders showed sustained remission at 6-week follow-up; relapse occurred within 2 weeks for the other two responders. Ketamine infusions were generally well tolerated; dissociative symptoms and hemodynamic symptoms were transient. Higher dose was a significant predictor of treatment response.

CONCLUSIONS:

These results demonstrate the potential role for ketamine in treating adolescents with TRD. Limitations include the open-label design and small sample; future research addressing these issues are needed to confirm these results. Additionally, evidence suggested a dose-response relationship; future studies are needed to optimize dose. Finally, questions remain regarding the long-term safety of ketamine as a depression treatment; more information is needed before broader clinical use.

Cullen, K. R., Amatya, P., Roback, M. G., Albott, C. S., Westlund Schreiner, M., Ren, Y., … & Reigstad, K. (2018). Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study. Journal of child and adolescent psychopharmacology, 28(7), 437-444., 10.1089/cap.2018.0030

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3,4-Methylenedioxymethamphetamineassisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial

October 29, 2018 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , , ,

Abstract

Background:

Posttraumatic stress disorder often does not resolve after conventional psychotherapies or pharmacotherapies. Pilot studies have reported that 3,4-methylenedioxymethamphetamine (MDMA) combined with psychotherapy reduces posttraumatic stress disorder symptoms.

Aims:

This pilot dose response trial assessed efficacy and safety of MDMA-assisted psychotherapy across multiple therapy teams.

Methods:

Twenty-eight people with chronic posttraumatic stress disorder were randomized in a double-blind dose response comparison of two active doses (100 and 125 mg) with a low dose (40 mg) of MDMA administered during eight-hour psychotherapy sessions. Change in the Clinician-Administered PTSD Scale total scores one month after two sessions of MDMA served as the primary outcome. Active dose groups had one additional open-label session; the low dose group crossed over for three open-label active dose sessions. A 12-month follow-up assessment occurred after the final MDMA session.

Results:

In the intent-to-treat set, the active groups had the largest reduction in Clinician-Administered PTSD Scale total scores at the primary endpoint, with mean (standard deviation) changes of −26.3 (29.5) for 125 mg, −24.4 (24.2) for 100 mg, and −11.5 (21.2) for 40 mg, though statistical significance was reached only in the per protocol set (p=0.03). Posttraumatic stress disorder symptoms remained lower than baseline at 12-month follow-up (p<0.001) with 76% (n=25) not meeting posttraumatic stress disorder criteria. There were no drug-related serious adverse events, and the treatment was well-tolerated.

Conclusions:

Our findings support previous investigations of MDMA-assisted psychotherapy as an innovative, efficacious treatment for posttraumatic stress disorder.
Ot’alora G, M., Grigsby, J., Poulter, B., Van Derveer III, J. W., Giron, S. G., Jerome, L., … & Mithoefer, M. C. (2018). 3, 4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial. Journal of Psychopharmacology, 32(12), 1295-1307, https://doi.org/10.1177%2F0269881118806297
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Common neural signatures of psychedelics: Frequency-specific energy changes and repertoire expansion revealed using connectome-harmonic decomposition.

October 25, 2018 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Psychopharmacology, Publications / By / , , , ,

Abstract

The search for the universal laws of human brain function is still on-going but progress is being made. Here we describe the novel concepts of connectome harmonics and connectome-harmonic decomposition, which can be used to characterize the brain activity associated with any mental state. We use this new frequency-specific language to describe the brain activity elicited by psilocybin and LSD and find remarkably similar effects in terms of increases in total energy and power, as well as frequency-specific energy changes and repertoire expansion. In addition, we find enhanced signatures of criticality suggesting that the brain dynamics tune toward criticality in both psychedelic elicited states. Overall, our findings provide new evidence for the remarkable ability of psychedelics to change the spatiotemporal dynamics of the human brain.
Atasoy, S., Vohryzek, J., Deco, G., Carhart-Harris, R. L., & Kringelbach, M. L. (2018). Common neural signatures of psychedelics: Frequency-specific energy changes and repertoire expansion revealed using connectome-harmonic decomposition. Progress in brain research, 242, 97-120., 10.1016/bs.pbr.2018.08.009
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Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting

October 25, 2018 / Consciousness, Creativity, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , ,

Abstract

INTRODUCTION:

Taking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including creativity and problem-solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics, it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults.

METHODS:

During a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were expected to be manifested.

RESULTS:

We found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected.

CONCLUSION:

While this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.

Prochazkova, L., Lippelt, D. P., Colzato, L. S., Kuchar, M., Sjoerds, Z., & Hommel, B. (2018). Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting. Psychopharmacology, 235(12), 3401-3413., 10.1007/s00213-018-5049-7
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Psychedelics and Personality.

October 17, 2018 / Anxiety disorders / PTSD, Ayahuasca, Depression, DMT, LSD, Mushrooms / Psilocybin, Papers, Personality, Psychiatry, Psychology, Psychopharmacology, Publications, Substance Use Disorder / By / , , ,

Abstract

In the past decade, an increasing number of clinical trials are reporting evidence that psychedelics or serotonergic hallucinogens (such as lysergic acid diethylamide, psilocybin, and ayahuasca/dimethyltryptamine) could be effective in the treatment of mood, anxiety, and substance use disorders. The mechanisms responsible for these effects are not fully understood but seem to involve changes in bran dynamics in areas rich in serotonergic 5-HT2A receptors and in personality. In the present text, we present a brief and critical overview of the current research in this field, pointing out both promises and limitations of these studies.
Aixalà, M., dos Santos, R. G., Hallak, J. E., & Bouso, J. C. (2018). Psychedelics and Personality., https://doi.org/10.1021/acschemneuro.8b00237
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Psychedelic Moral Enhancement

October 16, 2018 / Other subjects, Other substances, Papers, Psychology, Psychopharmacology, Publications / By /

Abstract

The moral enhancement (or bioenhancement) debate seems stuck in a dilemma. On the one hand, the more radical proposals, while certainly novel and interesting, seem unlikely to be feasible in practice, or if technically feasible then most likely imprudent. But on the other hand, the more sensible proposals – sensible in the sense of being both practically achievable and more plausibly ethically justifiable – can be rather hard to distinguish from both traditional forms of moral enhancement, such as non-drug-mediated social or moral education, and non-moral forms of bioenhancement, such as smart-drug style cognitive enhancement. In this essay, I argue that bioethicists have paid insufficient attention to an alternative form of moral bioenhancement – or at least a likely candidate – that falls somewhere between these two extremes, namely the (appropriately qualified) use of certain psychedelic drugs.
Earp, B. D. (2018). Psychedelic moral enhancement. Royal Institute of Philosophy Supplements, 83, 415-439., 10.1017/S1358246118000474
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