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Systematic Review on the Mechanisms of Action of Psilocybin in the Treatment of Depression
- M. C. Q. Lin, H. Lee, V. W. L. Tsang, B. Chai, A. Howard, C. Uy, J. O. Elefante
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S416-S417
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Introduction
Despite emerging evidence suggesting the efficacy of psilocybin in the treatment of mood disorders such as depression, the exact mechanisms by which psilocybin is able to elicit these antidepressant effects remains unknown.
ObjectivesAs the use of psilocybin as a treatment modality for depression has garnered increasing interest, this study aims to summarize the existing evidence of the mechanism of action with which psilocybin alleviates depressive symptoms, focusing specifically on the neurobiological effects of psilocybin in human subjects.
MethodsFour databases (Ovid MEDLINE, EMBASE, psychINFO, and Web of Science) were searched using a combination of MeSH terms and free text keywords in September 2021. The original search included both human and animal studies and must have included testing of the mechanism of action of psilocybin. Only antidepressant effects were considered, with no other mood disorders or psychiatric diagnoses included. Two independent researchers screened at every stage of the review, with a third researcher resolving any conflicts. Though a full systematic review outlining the current literature on the complete mechanisms of action of psilocybin on depression was conducted, this abstract will focus specifically on the nine papers that included human subjects, disregarding the five animal models. PROSPERO registration number: 282710.
ResultsAfter removing duplicates, the search identified 2193 papers and forty-nine were selected for full text review. Out of nine papers outlining the mechanisms of action of psilocybin use in human subjects, three papers investigated psilocybin’s effect on serotonin or glutamate receptor activity, two found an increase in synaptogenesis in regions such as the medial frontal cortex and hippocampus. Four found variation in blood flow to the amygdala, two found altered blood flow to the prefrontal cortex, and one found a reduction in delta power during sleep. Four papers found changes in functional connectivity or neurotransmission, most commonly in the hippocampus or prefrontal cortex.
ConclusionsOverall, the exact mechanism of psilocybin’s potential antidepressant effect remains unclear. Multiple pathways may be involved, including alterations in serotonin and glutamate receptor activity, as well as shifts in amygdala activity, neurogenesis, and functional connectivity in various brain regions. The relative lack of studies, and the variety of neurobiological modalities and endpoints used challenged the consolidation of data into consensus findings. Further studies are needed to better characterize psilocybin’s mechanism of action and to better understand the clinical effects of the use of psilocybin in the treatment of depression.
Disclosure of InterestNone Declared
Safety and Tolerability of Intramuscular and Sublingual Ketamine for Psychiatric Treatment in the Roots to Thrive Ketamine Assisted Therapy Program
- V. W. L. Tsang, B. Tao, S. Dames, Z. Walsh, P. Kryskow
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S605-S606
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Introduction
Ketamine has been increasingly used to treat mental health conditions yet there is a lack of safety data on intramuscular (IM) and sublingual (SL) dosing in a community setting. The Roots to Thrive Ketamine assisted Therapy (RTT-KaT) program is a 12-week program with 12 Community of Practice (CoP) group therapy sessions and three ketamine sessions.
ObjectivesTo provide preliminary data on RTT-KAT adverse events to subsequently inform safe use of IM and SL ketamine for the treatment of psychiatric disorders.
MethodsRetrospective chart review of the RTT-KaT Program on four cohorts (n=128) between September 2020 to December 2021. Eligible patients include those with post-traumatic stress disorder, depression, generalized anxiety, burnout/adjustment disorder, substance use disorder, obsessive compulsive disorder, disordered eating, and disordered sleep. Baseline characteristics and adverse events were captured including medication administration before, during, and after RTT-KaT sessions. Chi-squared test with Yates’ continuity correction was used to assess side effects in subgroups from ketamine administration.
ResultsRTT-KaT was well tolerated with no loss to follow up. There were 351 IM (mean dose = 102.553mg) and 96 SL (mean dose = 276.667mg) sessions of ketamine. Of the 448 sessions, the prevalence of elevated blood pressure increased by 12.31% from baseline (36.85%), with all post-treatment elevations being transient. The prevalence of elevated blood pressure post-KaT session was also similar between IM (+11.69% from 37.71% baseline) and SL (+15.12% from 32.98% baseline) administration. Regarding adverse effects, 12.05% of sessions experienced nausea , 2.52% had an episode of vomiting , 3.35% had a headache , and seven sessions experienced dizziness. The incidence of adverse events was not significantly associated with past psychedelic experiences (X2 = 0.0543, p-value = 0.8157), nor past psychiatric diagnosis (X2 = 0.0109, p-value = 0.917). . There was no significant association between administration route and incidence of nausea, which was the most common side effect(X2 = 1.112, p-value = 0.2916). Male gender was also significantly associated with lower incidence of nausea (X2 = 4.2841, p-value = 0.03847).
ConclusionsThe group therapy model described provides a comprehensive approach and presents a promising model for operating a KaT program outside of a clinical trial setting.These findings suggest good safety and acceptability for RTT-KaT among individuals seeking treatment for mental health issues. Majority of participants did not experience adverse reactions and the adverse events that were recorded involved transient symptoms that were resolved with rest and/or medications.
Disclosure of InterestNone Declared
A systematic review to assess the use of psilocybin in the treatment of headaches
- S. Bhanot, M. C. Q. Lin, S. Bains, A. Monroe, V. W. L. Tsang
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S617-S618
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Introduction
Psilocybin is a naturally occurring psychedelic compound whose effects have been seen in studies for treatment of depression, anxiety and pain management. Given its structural similarities to 5-hydroxytryptamine, a monoamine controlling brain modulation of pain input, preliminary studies sought to test serotonergic interactions of psilocybin with headaches.
ObjectivesExplore efficacy of psilocybin as treatment for individuals with headaches, including migraines, essential headaches, cluster headaches and unclassified head pains.
MethodsStudies were found from six major databases, with inclusion criteria consisting of participants with any type of headache using psilocybin as a treatment. Each study was independently screened by two reviewers at two stages, with inconsistencies reviewed by a third, senior reviewer.
ResultsThe systematic review evaluated eight articles. Benefits of macrodosing were explored in one study which reported higher levels of pain relief in comparison to microdosing and conventional pain medications. Top benefits of microdosing as reported by participants included convenience, perceived safety and reduced side effects when compared to hallucinogenic doses of psilocybin. Participants across five studies reported improvements to their headaches as characterized by changes in frequency, intensity, duration and remission period. Reported improvements were clinically significant in the six studies and statistically significant in three papers. With psilocybin intervention, two studies reported a decrease in headache attack frequency, three studies reported a decrease in intensity, and one study indicated a decrease in duration. The greatest benefit reported was for psilocybin taken during a remission period, with the average length of that remission period between headaches extending for 91% of participants. One study focused on the dosages of psilocybin in relation to its efficacy, indicating that there was more headache pain relief amongst macrodosers, with a difference of 12.3% of participants experiencing pain reduction 3 days after dosage in comparison to microdosers. 18% of participants who experienced essential headaches also experienced hallucinations as a result of ingested psilocybin. Others showed a temporary increase in symptoms of anxiety and pain - 5.3% with microdosing and 14.1% macrodosing. One study observed an increase in average arterial pressure after ingestion.
ConclusionsSix of eight screened papers showed that psilocybin was clinically significant in the treatment of headaches as captured through self-reports. While the first controlled study for psilocybin use for headaches was detailed in this study, psilocybin remains illegal in many countries, presenting a need for further regulated research.
Disclosure of InterestNone Declared
Dispositional Optimism in Christian Populations Compared to other Religious Groups: a Scoping Review
- W. W. L. Cheung, C. Liu, V. W. L. Tsang
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S991-S992
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Introduction
There are various ways people cope with life events. One can expect generalized positive or negative outcomes across various life domains, called dispositional optimism. This can be explained by attribution theory: how people explain past events, their causations, and outcomes. Understanding attribution styles is important to help people reframe current circumstances and improve mental wellbeing. Our hypothesis is that people of different religious groups may exhibit various levels of optimism and pessimism based on their values, teachings, and practices. Previous research has found that people of Christian faith, or those with a religious faith in general, look to their religion as a way of coping during life adversities. Certain religious practices such as prayers and Church gatherings have been found to improve mental health through increasing dispositional optimism. While the relationship between religiosity and mental health has been previously examined in different religious populations, there are few studies that focused on comparing this relationship across religions.
ObjectivesThe objective of this scoping review is to understand the link between religiosity and mental health, focusing primarily on how people of the Christian religion demonstrate dispositional optimism or pessimism when coping with adverse life events, compared to other religious groups or atheists.
MethodsThis scoping review included original peer reviewed study articles that studied mental health in terms of dispositional optimism or pessimism in people of Christian religion compared to other religious groups. This review used online databases, Ovid MEDLINE and PsycInfo, and used extraction tables to analyze the results of past research.
ResultsThe results of this scoping review revealed that people of Christian religion, especially those high in religiosity, use their religion as a method of coping. This population also showed higher dispositional optimism compared to atheists or those that believe in other religions. However, when compared to other religions such as Buddhism and Muslim, Christian populations showed lower dispositional optimism.
ConclusionsIt is evident that religious involvement is linked to aspects of mental health, but comparing the effects of different religions is still a topic of exploration that can be investigated further to allow deeper understanding of their similarities and differences, as well as the mechanisms by which religion can affect mental health. In this review, a gap in the body of knowledge regarding the relationship between religion and pessimism was revealed. Future research directions could include examining whether dispositional pessimism varies across religious groups, as it does not necessarily have a perfectly inverse relationship with optimism.
Disclosure of InterestNone Declared
Explanatory Style in Asian Populations: A Scoping Review
- C. Siu, E. Gacayan, V. W. L. Tsang
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S156
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Introduction
Cultural upbringing is an important factor that affects how one perceives the world and determines how blame is assigned when facing unfavorable outcomes. Governed by explanatory style, which refers to one’s pattern of causal explanations towards positive and negative situations, pessimism is defined as classifying bad events as internal, stable, and global within the personalization, permanence, and pervasiveness dimensions respectively (Peterson, 1992). This indicates that a pessimistic person would attribute a bad event as their own fault, as lasting, and as having great impact across all domains of their lives (Peterson, 1992).
ObjectivesPrevious research has shown that when comparing the levels of pessimism between Mainland Chinese individuals, Chinese American individuals, and White American individuals, the Mainland Chinese group is found to be the most pessimistic (Lee & Seligman, 1997). However, much of the existing research to date assessing pessimism and optimism in Asian samples do not define these concepts within the realms of the explanatory style. Instead, a broader and more generalized understanding is usually used. This review therefore seeks to investigate whether Asians are more pessimistic compared to people of other races as defined by the explanatory style (Peterson, 1992).
MethodsA search was conducted in two bibliographic databases (Medline OVID and PsycINFO) to identify articles for inclusion. Two reviewers screened the search independently through Covidence and performed a result analysis.
ResultsA total of 20 peer-reviewed articles published between 1972 and 2022 are included that broadly compare the explanatory styles of Asians to other racial groups. Of the 20 studies, 3 papers specifically compare optimism versus pessimism in Asian groups, 4 papers mention coping strategies for “bad events”, 2 papers mention self-esteem, and 2 papers each mention causal attributions for success and failure respectively. When compared to other races, Asians were found to be more pessimistic, turn to faith and religion as a coping mechanism, have lower self-esteem, attribute success to external factors and internalize failure.
ConclusionsIt is concluded that Asian groups internalize bad events, and view good events as external, which aligns with Asian groups being more pessimistic on the personalization dimension as defined by the explanatory style (Spencer-Rodgers et al., 2004; Anderson, 1999; Park & Kim, 1998). By understanding the cultural implications of the explanatory style, one can recognize why and in what way people behave and cope differently across cultures when facing adversity.
Disclosure of InterestNone Declared
Varenicline induced auditory hallucinations in a young female with bipolar disorder: a case report
- S. Bhanot, V. W. L. Tsang, L. Jia
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S764
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Introduction
Creating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be one of the most effective medications for smoking cessation and abstinence, caution is needed when starting patients on this medication. In this case, a young female provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance abuse and medical noncompliance. She also endorsed a long history of smoking, alcohol, cocaine, cannabis and ketamine use. In addition to being stabilized for bipolar disorder, the patient was started on varenicline for smoking cessation on Day 14 of admission.
ObjectivesThis case report highlights the potential risk of de-stabilization in a vulnerable youth with newly diagnosed bipolar I disorder and precarious social circumstances, in attempts to further concurrent approaches to psychiatric care.
MethodsIn addition to qualitative observations, the main objective exam used to track patient progress through the duration of her hospitalization was the mental status exam (MSE). This is standard practice for psychiatric care and qualitatively assessed factors related to a patient’s behavioral and cognitive functioning. Important factors assessed for this patient include appearance and behavior, speech, affect and mood, thought form, thought content, perceptual abnormalities, insight and cognition.
ResultsPerceptual abnormalities, including auditory hallucinations, were not recorded at admission and the patient’s symptoms of mania were resolving clinically on Day 18. Two days after starting varenicline, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought-form disorganization. The patient also reported hearing auditory hallucinations of a derogatory nature, with her mood appearing more distressed during varenicline use. Symptoms were found to be resolved shortly after the discontinuation of varenicline on Day 18 and the patient appeared to be less distressed on following days. In this case, these symptoms were not in keeping with her bipolar diagnosis and thought to be secondary to varenicline after the consideration of potential alternative contributors.
ConclusionsThe occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder.
Disclosure of InterestNone Declared
A Pilot Study Comparing a Community of Practice Group Therapy Program with and without Concurrent Ketamine-assisted Therapy
- V. W. L. Tsang, R. Moyer, P. Kryskow, Z. Walsh, S. Dames
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S89
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Introduction
Healthcare practitioners (HCPs) are facing a mental health crisis. Group therapies have long been used to treat symptoms associated with PTSD, anxiety and/or depression, however no studies have investigated the role of implementing group therapy with and without ketamine-assisted therapies (KaT).
ObjectivesThe current study investigated the effects of the Roots to Thrive (RTT) group therapy intervention both with and without adjunctive KaT.
MethodsIn the present study we conduct a secondary analysis of data derived from the 12-week group psychotherapy program to that of the same program with adjunct KaT. Participants were administered a series of validated psychiatric assessment tools before and after the 12-weeks. Inclusion criteria included a diagnosis of treatment resistant mental health condition (depression, PTSD and/or generalized anxiety disorder) and a score of 15 or greater on the PTSD Checklist for DSM-5 (PCL-5). To assess the effects of time x group interaction and calculate differences between the RTT only and RTT-KaT subgroups, a repeated measures ANOVA was conducted. Effect sizes were calculated through partial eta-squared.
ResultsForty-nine HCPs with treatment-resistant PTSD, anxiety and/or depression were treated with the RTT group therapy model to target their symptoms. A total of 49 individuals (34 female, 10 male, 3 other) with a median age of 47 years old (SD 14.19) participated in the study. There were no statistically significant differences between RTT only (n=14) and RTT KaT (n=35) subgroups across gender [X2 (1, N=44) = 2.84, ns] or age [F (1, 36) = .257, p = .615]. From pre- to post-treatment, all patients showed significant reductions in scores of PTSD (from 39.3 to 20.99), depression (from 15.5 to 7.7) and anxiety (from 15.5 to 6.2). Two-way repeated measures ANOVA did not reveal any significant between-group differences between the RTT and RTT-KaT subgroups.
ConclusionsThis observational study provides preliminary support for the potential of the RTT community of care model of group therapy and adds to a small but growing body of knowledge on the integration of group therapy and the broad category of psychedelic psychotherapies. Given the rapid proliferation and expansion of KaT clinics throughout North America, the finding that KaT did not appear to impact changes related to the RTT intervention suggests the need for further research to better explain the potential impacts of relational transference between the two groups, and the distinct contributions of ketamine administration in a group therapy context.
Disclosure of InterestNone Declared