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The ethics of psychedelic research in disorders of consciousness.

October 9, 2019 / Ayahuasca, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

This article provides an ethical analysis of psychedelic research involving disorders of consciousness patients. We apply two internationally accepted approaches for analyzing the ethics of human research, the Value-Validity Framework and Component Analysis, to a research program recently proposed by Scott and Carhart-Harris. We focus on Scott and Carhart-Harris’s proposal, but the ethical frameworks outlined are applicable to other novel research protocols in the science of consciousness.
Peterson, A., Tagliazucchi, E., & Weijer, C. (2019). The ethics of psychedelic research in disorders of consciousness. Neuroscience of Consciousness, 2019(1), niz013., https://doi.org/10.1093/nc/niz013
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Acute effects of lysergic acid diethylamide (LSD) on resting brain function.

September 30, 2019 / LSD, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

Lysergic acid diethylamide (LSD) is a potent hallucinogenic substance that was extensively investigated by psychiatrists during the 1950s and 1960s. Researchers were interested in the unique effects induced by this substance, some of which resemble symptoms seen in schizophrenia. Moreover, during that period LSD was studied and used for the treatment of several mental disorders such as depression, anxiety, addiction and personality disorders. Despite this long history of research, how LSD induces its specific effects on a neuronal level has been relatively unclear. In recent years there has been a revival of research in hallucinogenic drugs and their possible clinical applications. These contemporary studies in the UK and Switzerland include neuroimaging studies using functional magnetic resonance imaging (fMRI). In this review, we collect and interpret these recent neuroimaging findings. Overall, previous results across studies indicate that LSD administration is associated with extensive alterations in functional brain connectivity, measuring the correlated activities between different brain regions. The studies mostly reported increases in connectivity between regions and, more specifically, consistently found increased connectivity within the thalamocortical system. These latter observations are in agreement with models proposing that hallucinogenic drugs exert their effects by inhibiting cerebral filtering of external and internal data. However, studies also face several limitations, including potential biases of neuroimaging measurements.
Müller, F., & Borgwardt, S. (2019). Acute effects of lysergic acid diethylamide (LSD) on resting brain function. Swiss Medical Weekly, 149(3940)., https://doi.org/10.4414/smw.2019.20124
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The Psilocybin-Telomere Hypothesis: An Empirically Falsifiable Prediction Concerning the Beneficial Neuropsychopharmacological Effects of Psilocybin on Genetic Aging

September 24, 2019 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By /

Abstract

We introduce a novel hypothesis which states that the therapeutic utilisation of psilocybin has beneficial effects on genetic aging. Ex hypothesi, we predict a priori that controlled psilocybin interventions exert quantifiable positive impact on leucocyte telomere length (telomeres are a robust predictor of mortality and multifarious aging-related diseases). Our hypothesising follows the Popperian logic of scientific discovery, viz., bold (and refutable) conjectures form the very foundation of scientific progress. The ‘psilocybin-telomere hypothesis’ is formalised as a logically valid deductive (syllogistic) argument and we provide substantial evidence to support the underlying premises. Impetus for our theorising derives from a plurality of converging empirical sources indicating that psilocybin has persistent beneficial effects on various aspects of mental health (e.g., in the context of depression, anxiety, PTSD, OCD, addiction, etc.). Additional support is based on a large corpus of studies that establish reliable correlations between mental health and telomere attrition (improved mental health is generally correlated with longer telomeres). Another pertinent component of our argument is based on recent studies which demonstrate that “meditative states of consciousness” provide beneficial effects on genetic aging. Similarly, psilocybin can induce states of consciousness that are neurophysiologically and phenomenologically significantly congruent with meditative states. Furthermore, prior research has demonstrated that a single dose of psilocybin can occasion life-changing transformative experiences (≈ 70% of healthy volunteers rate their experience with psilocybin amongst the five personally most meaningful lifetime events, viz., ranked next to giving birth to a child or losing a loved one). We postulate that these profound psychological events leave quantifiable marks at the molecular genetic/epigenetic level. Given the ubiquitous availability and cost effectiveness of telomere length assays, we suggest that quantitative telomere analysis should be regularly included in future psilocybin studies as an adjunctive biological marker (i.e., to facilitate scientific consilience via methodological triangulation). In order to substantiate the ‘psilocybin-telomere hypothesis’ potential neuropsychopharmacological, endocrinological, and genetic mechanisms of action are discussed (e.g., HPA-axis reactivity, hippocampal neurogenesis, neurotropic growth factors such as BDNF, 5-HT2A receptor agonism, neuroplasticity/synaptoplasticity, brain-wide alterations in neuronal functional connectivity density, involvement of the SLC6A4 serotonin transporter gene, inter alia). The proposed research agenda is thus intrinsically highly interdisciplinary, and it has deep ramifications from a philosophy of science perspective as it connects the epistemic level (qualitative experiential phenomenology) with the ontic level (quantitative molecular genetics) of analysis. In the long term, multidisciplinary and innovative investigations of the ‘psilocybin-telomere hypothesis’ could contribute to the improvement of senotherapeutic psychological interventions and the identification of novel geroprotective and neuroprotective/restorative pharmaceutical targets to decelerate genetic aging and improve well-being and quality of life during the aging process.
Germann, C. B. (2020). The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging. Medical hypotheses, 134, 109406., https://doi.org/10.1016/j.mehy.2019.109406
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The psychedelic renaissance: the next trip for psychiatry?

September 23, 2019 / Depressive Disorders, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By

Abstract

The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
Kelly, J. R., Baker, A., Babiker, M., Burke, L., Brennan, C., & O’Keane, V. (2019). The psychedelic renaissance: the next trip for psychiatry?. Irish journal of psychological medicine, 1-5., https://doi.org/10.1017/ipm.2019.39
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Self-Rated Effectiveness of Microdosing With Psychedelics for Mental and Physical Health Problems Among Microdosers

September 13, 2019 / Anthropology & Sociology, Anxiety Disorders / PTSD, Papers, Psychology, Publications / By / , , ,

Abstract

Background: There is a growing interest in the use of psychedelic substances for health related purposes, including symptom relief for disorders like anxiety, depression, and pain. Although the focus of recent clinical trials has been on high doses of these substances, anecdotal evidence suggests that low (micro) doses are also effective, and may be more suitable for certain conditions. Nonetheless, empirical evidence regarding the efficacy of microdosing with psychedelics for symptomatic relief is lacking. The present study aimed to investigate, by means of an online questionnaire, the self-rated effectiveness (SRE) of microdosing with psychedelics (MDP) for mental and physiological disorders compared to the conventional prescribed treatment and to regular doses of psychedelics. Methods: An online questionnaire was launched on several websites and fora between March and July 2018. Respondents who had consented, were 18 years of age or older, had experience with microdosing and were diagnosed with at least one mental or physiological disorder by a medical doctor or therapist (N = 410; 7.2%) were included in the analyses. Odds ratio were calculated to compare the SRE of MDP with conventional treatment, and regular psychedelic doses for mental and physiological diagnoses for each of the three effectiveness questions (“Did it work,” “Symptom disappear,” “Quality of life improved”). Results: Odds ratio showed that SRE of MDP was significantly higher compared to that of conventional treatments for both mental and physiological diagnoses; and that these effects were specific for ADHD/ADD and anxiety disorders. In contrast, SRE of MDP was lower compared to that of higher, regular psychedelic doses for mental disorders such as anxiety and depression, while for physiological disorders no difference was shown. Conclusion: This study demonstrates that SRE of MDP to alleviate symptoms of a range of mental or physiological diagnoses is higher compared to conventionally offered treatment options, and lower than regular (‘full’) psychedelic doses. Future RCTs in patient populations should objectively assess the effectivity claims of psychedelics, and whether these are dose related, disorder specific, and superior to conventional treatments.

Hutten, N. R., Mason, N. L., Dolder, P. C., & Kuypers, K. P. (2019). Self-rated effectiveness of microdosing with psychedelics for mental and physical health problems amongst microdosers. Frontiers in psychiatry, 10, 672. 10.3389/fpsyt.2019.00672

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The Impact of Childhood Maltreatment on Intravenous Ketamine Outcomes for Adult Patients with Treatment-Resistant Depression

September 11, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , ,

Abstract

Childhood maltreatment is associated with a poor treatment response to conventional antidepressants and increased risk for treatment-resistant depression (TRD). The N-methyl-D-aspartate receptor (NDMAR) antagonist ketamine has been shown to rapidly improve symptoms of depression in patients with TRD. It is unknown if childhood maltreatment could influence ketamine’s treatment response. We examined the relationship between childhood maltreatment using the Childhood Trauma Questionnaire (CTQ) and treatment response using the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) in TRD patients receiving intravenous ketamine at a community outpatient clinic. We evaluated treatment response after a single infusion (n = 115) and a course of repeated infusions (n = 63). Repeated measures general linear models and Bayes factor (BF) showed significant decreases in QIDS-SR after the first and second infusions, which plateaued after the third infusion. Clinically significant childhood sexual abuse, physical abuse, and cumulative clinically significant maltreatment on multiple domains (maltreatment load) were associated with better treatment response to a single and repeated infusions. After repeated infusions, higher load was also associated with a higher remission rate. In contrast to conventional antidepressants, ketamine could be more effective in TRD patients with more childhood trauma burden, perhaps due to ketamine’s proposed ability to block trauma-associated behavioral sensitization.

O’Brien, B., Lijffijt, M., Wells, A., Swann, A. C., & Mathew, S. J. (2019). The impact of childhood maltreatment on intravenous ketamine outcomes for adult patients with treatment-resistant depression. Pharmaceuticals, 12(3), 133., 10.3390/ph12030133
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Exploring ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada

September 5, 2019 / Ayahuasca, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Introduction and Aims

A previous observational study of ayahuasca‐assisted therapy demonstrated statistically significant reductions in self‐reported problematic cocaine use among members of an Indigenous community in Canada. This paper aims to qualitatively explore the impact of ayahuasca‐assisted therapy on addiction and other substance use‐related outcomes and elucidate the lived experiences of participants.

Design and Methods

Qualitative interviews were conducted with 11 adult Indigenous participants of the ayahuasca‐assisted ‘Working with Addiction and Stress’ ceremonial retreats (June–September 2011). Semi‐structured interviews assessed experiences of participants following the retreats at 6‐month follow up. Thematic analysis of interview transcripts was conducted.

Results

Narratives revealed that the retreats helped participants identify negative thought patterns and barriers related to their addiction in ways that differed from conventional therapies. All participants reported reductions in substance use and cravings; eight participants reported complete cessation of at least one substance at follow up. Increased connectedness with self, others and nature/spirit was described as a key element associated with reduced substance use and cravings.

Discussion and Conclusions

This analysis expands upon prior quantitative results highlighting the therapeutic potential of ayahuasca‐assisted therapy and provides important contextual insights into why ayahuasca‐assisted therapy may have been beneficial for members of an Indigenous community seeking to address their problematic use of substances. Given limited efficacy of conventional treatments for resolving addiction issues, further research should investigate the role of ayahuasca and other psychedelic‐assisted therapies in enhancing connectedness and other key factors that may improve well‐being and reduce harmful substance use

Argento, E., Capler, R., Thomas, G., Lucas, P., & Tupper, K. W. (2019). Exploring ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada. Drug and alcohol review.

Hallucinogens and Their Therapeutic Use: A Literature Review

September 1, 2019 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, DMT, Iboga / Ibogaine, Ketamine, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

The exploration of possible therapeutic benefits of hallucinogenic substances has undergone a revitalization in the past decade. This literature review investigated the published literature regarding the psychotherapeutic uses of hallucinogens in psychiatric disorders. The results showed that a variety of substances have been evaluated in the treatment of psychiatric disorders, including ayahuasca, ibogaine, ketamine, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, and psilocybin. The conditions treated ranged from depression to autism, with the largest volume of research dedicated to substance use disorders. The majority of studies that were reviewed demonstrated significant associations with improvement in the conditions investigated. However, it was difficult to draw definitive conclusions as most studies suffered from small sample sizes, inconsistent measures, and poor study design. To properly assess the risks and potential benefits of hallucinogens in psychiatric treatment, there is a need for well designed, standardized studies that demonstrate the impact of hallucinogenic substances on psychiatric conditions.

BEGOLA, M. J., & SCHILLERSTROM, J. E. (2019). Hallucinogens and Their Therapeutic Use: A Literature Review. Journal of Psychiatric Practice®, 25(5), 334-346., 10.1097/PRA.0000000000000409
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Repeated ketamine injections in synergy with antidepressants for treating refractory depression: A case showing 6-month improvement.

August 30, 2019 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

WHAT IS KNOWN AND OBJECTIVE:
Some patients with refractory depression who fail to respond to rapid injection of standard-dose ketamine are injected with high doses, but the safety and efficacy of this practice are unclear.
CASE DESCRIPTION:
A 57-year-old woman with refractory depression whose symptoms did not improve after 20-seconds intravenous injection of 0.5 mg/kg ketamine went into remission following eight, 1-minute intravenous injections of 1 mg/kg ketamine delivered over a 4-week period. By 6-month follow-up, no significant adverse events had occurred and cognitive function had improved.
WHAT IS NEW AND CONCLUSION:
High-dose intravenous injections of ketamine may stably improve depressive symptoms and cognitive function in patients with refractory depression who do not respond to rapid intravenous injection of standard-dose ketamine. The high-dose treatment appears to be associated with only mild side effects.
Wang, M., Xiong, Z., Su, B., Wang, L., Li, Z., Yang, Y., & Fang, J. (2019). Repeated ketamine injections in synergy with antidepressants for treating refractory depression: A case showing 6-month improvement. Journal of clinical pharmacy and therapeutics., https://doi.org/10.1111/jcpt.13041
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Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism.

August 29, 2019 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

We recently reported that naltrexone blocks antidepressant effects of ketamine in humans, indicating that antidepressant effects of ketamine require opioid receptor activation. However, it is unknown if opioid receptors are also involved in ketamine’s antisuicidality effects. Here, in a secondary analysis of our recent clinical trial, we test whether naltrexone attenuates antisuicidality effects of ketamine. Participants were pretreated with naltrexone or placebo prior to intravenous ketamine in a double-blinded crossover design. Suicidality was measured with the Hamilton Depression Rating Scale item 3, Montgomery-Åsberg Depression Rating Scale item 10, and Columbia Suicide Severity Rating Scale. In the 12 participants who completed naltrexone and placebo conditions, naltrexone attenuated the antisuicidality effects of ketamine on all three suicidality scales/subscales (linear mixed model, fixed pretreatment effect, p < 0.01). Results indicate that opioid receptor activation plays a significant role in the antisuicidality effects of ketamine.
Williams, N. R., Heifets, B. D., Bentzley, B. S., Blasey, C., Sudheimer, K. D., Hawkins, J., … & Schatzberg, A. F. (2019). Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism. Molecular psychiatry, 1-8., https://doi.org/10.1038/s41380-019-0503-4
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