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Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study

/ Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / / , , , , , ,

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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Common neural signatures of psychedelics: Frequency-specific energy changes and repertoire expansion revealed using connectome-harmonic decomposition.

/ LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / / , , , ,

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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Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

/ LSD, Papers, Publications / / , , , , , ,

Abstract

BACKGROUND:

Lysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor contributions to its neurobiological effects remain unknown.

METHODS:

We therefore conducted a double-blind, randomized, counterbalanced, cross-over study (ClinicalTrials.gov, NCT02451072) during which 24 healthy human participants received either (i) placebo+placebo, (ii) placebo+LSD (100 µg po), or (iii) Ketanserin, a selective 5-HT2A receptor antagonist,+LSD. We quantified resting-state functional connectivity via a data-driven global brain connectivity method and compared it to cortical gene expression maps.

FINDINGS:

LSD reduced associative, but concurrently increased sensory-somatomotor brain-wide and thalamic connectivity. Ketanserin fully blocked the subjective and neural LSD effects. Whole-brain spatial patterns of LSD effects matched 5-HT2A receptor cortical gene expression in humans.

CONCLUSION:

Together, these results strongly implicate the 5-HT2A receptor in LSD’s neuropharmacology. This study therefore pinpoints the critical role of 5-HT2A in LSD’s mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics.

Preller, K. H., Burt, J. B., Ji, J. L., Schleifer, C. H., Adkinson, B. D., Stämpfli, P., … & Vollenweider, F. X. (2018). Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor. eLife, 7, e35082., 10.7554/eLife.35082

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Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting

/ Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / / , , , , ,

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.

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

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

/ Papers, Psychology, Publications / /

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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Research ethics aspects of experimentation with LSD on human subjects: a historical and ethical review.

/ LSD, Papers, Psychology, Publications / / ,

Abstract

In this paper our aim is to examine whether research conducted on human participants with LSD-25 (lysergic acid diethylamide) raises unique research ethical questions or demands particular concerns with regard to the design, conduct and follow-up of these studies, and should this be the case, explore and describe those issues. Our analysis is based on reviewing publications up to date which examine the clinical, research and other uses of LSD and those addressing ethical and methodological concerns of these applications, just as some historical examinations of this subject. The first chapters of the paper give an overview regarding the history of LSD-research with human participants, healthy volunteers and patients alike. The remaining chapters have a focus on questions regarding the potential ethical issues of such human trials in the contemporary research ethics framework. We also consider briefly political and regulatory issues regarding this substance that possibly affect its clinical and research applications.
Bodnár, K. J., & Kakuk, P. (2018). Research ethics aspects of experimentation with LSD on human subjects: a historical and ethical review. Medicine, Health Care and Philosophy, 1-11., 10.1007/s11019-018-9871-9
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More Realistic Forecasting of Future Life Events After Psilocybin for Treatment-Resistant Depression

/ Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / / ,

Abstract

Background: Evidence suggests that classical psychedelics can promote enduring changes in personality, attitudes and optimism, as well as improvements in mental health outcomes.
Aim: To investigate the effects of a composite intervention, involving psilocybin, on pessimism biases in patients with treatment-resistant depression (TRD).
Methods: Patients with TRD (n = 15) and matched, untreated non-depressed controls (n = 15) performed the Prediction Of Future Life Events (POFLE) task. The POFLE task requires participants to predict the likelihood of certain life events occurring within a 30-day period, after which the actual rate of event occurrence is reported; this gives an index of potential pessimism versus optimism bias. Psilocybin was administered in two oral dosing sessions (10 and 25 mg) one week apart. Main outcome measures were collected at baseline and one week after the second dosing session.
Results: Patients showed a significant pessimism bias at baseline [t(14) = -3.260, p = 0.006; 95% CI (-0.16, -0.03), g = 1.1] which was related to the severity of their depressive symptoms (rs = -0.55, p = 0.017). One week after psilocybin treatment, this bias was significantly decreased [t(14) = -2.714, p = 0.017; 95% CI (-0.21, -0.02), g = 0.7] and depressive symptoms were greatly improved [t(14) = 7.900, p < 0.001; 95% CI (16.17, 28.23), g = 1.9]; moreover, the magnitude of change in both variables was significantly correlated (r = -0.57, p = 0.014). Importantly, post treatment, patients became significantly more accurate at predicting the occurrence of future life events [t(14) = 1.857, p = 0.042; 95% CI (-0.01, 0.12), g = 0.6] whereas no such change was observed in the control subjects.
Conclusion: These findings suggest that psilocybin with psychological support might correct pessimism biases in TRD, enabling a more positive and accurate outlook.
Lyons, T., & Carhart-Harris, R. L. (2018). More realistic forecasting of future life events after psilocybin for treatment-resistant depression. Frontiers in psychology, 9. 10.3389/fpsyg.2018.01721
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Ibogaine as a treatment for substance misuse: Potential benefits and practical dangers.

/ Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / /

Abstract

Ibogaine is an indole alkaloid found in the root bark of the Iboga shrub native to west Africa possessing hallucinogenic properties. For centuries it has been used in religious ceremonies and to gain spiritual enlightenment. However, since the early 1960s, its apparent ability to reduce craving for psychoactive substances including alcohol, cocaine, methamphetamine, opiates, and nicotine has led to its use in detoxification treatments. In many instances, clients receive treatment in non-medical settings, with little by way of robust scientific clinical trials. This chapter provides an overview of the potential benefits that could arise from such research. This is balanced against the serious adverse effects that can occur due to undiagnosed health conditions and/or concomitant use of other drugs. A detailed update is provided of the 33 deaths known to have occurred, including 5 in the UK. Looking forward, there is a need to develop better opiate detoxification treatment against a background of increasing opioid-related fatalities. A congener of ibogaine, 18-MC, appears to be safer and is to undergo clinical trials. In the meantime, would-be consumers and treatment providers must make more careful, detailed risk-assessments before using ibogaine. Treatment outcomes, including deaths, need to be accurately recorded and published.
Corkery, J. M. (2018). Ibogaine as a treatment for substance misuse: Potential benefits and practical dangers. Progress in brain research, 242, 217-257., 10.1016/bs.pbr.2018.08.005
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Psychedelics and Acceptance and Commitment Therapy (ACT): A Process-Based Approach - September 15th

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