-
Journal of Affective Disorders Jun 2024Electrophysiologic measures provide an opportunity to inform mechanistic models and possibly biomarker prediction of response. Serotonergic psychedelics (SPs) (i.e.,... (Review)
Review
Spectral signatures of psilocybin, lysergic acid diethylamide (LSD) and ketamine in healthy volunteers and persons with major depressive disorder and treatment-resistant depression: A systematic review.
BACKGROUND
Electrophysiologic measures provide an opportunity to inform mechanistic models and possibly biomarker prediction of response. Serotonergic psychedelics (SPs) (i.e., psilocybin, lysergic acid diethylamide (LSD)) and ketamine represent new investigational and established treatments in mood disorders respectively. There is a need to better characterize the mechanism of action of these agents.
METHODS
We conducted a systematic review investigating the spectral signatures of psilocybin, LSD, and ketamine in persons with major depressive disorder (MDD), treatment-resistant depression (TRD), and healthy controls.
RESULTS
Ketamine and SPs are associated with increased theta power in persons with depression. Ketamine and SPs are also associated with decreased spectral power in the alpha, beta and delta bands in healthy controls and persons with depression. When administered with SPs, theta power was increased in persons with MDD when administered with SPs. Ketamine is associated with increased gamma band power in both healthy controls and persons with MDD.
LIMITATIONS
The studies included in our review were heterogeneous in their patient population, exposure, dosing of treatment and devices used to evaluate EEG and MEG signatures. Our results were extracted entirely from persons who were either healthy volunteers or persons with MDD or TRD.
CONCLUSIONS
Extant literature evaluating EEG and MEG spectral signatures indicate that ketamine and SPs have reproducible effects in keeping with disease models of network connectivity. Future research vistas should evaluate whether observed spectral signatures can guide further discovery of therapeutics within the psychedelic and dissociative classes of agents, and its prediction capability in persons treated for depression.
Topics: Humans; Psilocybin; Ketamine; Lysergic Acid Diethylamide; Depressive Disorder, Major; Depression; Healthy Volunteers; Hallucinogens
PubMed: 38570038
DOI: 10.1016/j.jad.2024.03.165 -
Brain Sciences Mar 2024This study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with... (Review)
Review
OBJECTIVE
This study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD).
METHODS
The Preferred Reporting Items for Systematic Reviews (PRISMA) was used as a guide to structure and report the findings for this review. A literature search included the MEDLINE database up until December 2022. We included randomized or open-label human studies of MDMA, psilocybin, mescaline, LSD, DMT, or cannabis reporting non-emotionally charged neurocognitive outcomes ("cold cognition") measured through validated neuropsychological tests.
RESULTS
A total of 43 full-text papers on MDMA (15), cannabis (12), LSD (6), psilocybin (9), DMT/ayahuasca (1), and mescaline (0) were included, mostly on healthy subjects. A single article on MDMA's effects on cognition in subjects with PTSD was included; there were no studies on psychedelics and neurocognition in MDD. Most of the studies on healthy subjects reported detrimental or neutral effects on cognition during the peak effect of psychedelics with a few exceptions (e.g., MDMA improved psychomotor function). Performance on the type of neurocognitive dimension (e.g., attention, memory, executive function, psychomotor) varies by type of psychedelic, dosage, and cognitive testing.
CONCLUSIONS
Small samples and a lack of uniformed methods across studies preclude unequivocal conclusions on whether psychedelics enhance, decrease, or have no significant effect on cognitive performance. It is foreseen that psychedelics will soon become an available treatment for various psychiatric disorders. The acute and long-term effects on cognition caused by psychedelics should be assessed in future studies.
PubMed: 38539636
DOI: 10.3390/brainsci14030248 -
Frontiers in Psychiatry 2024Psilocybin is a classic psychedelics, which has been shown to have antidepressant effects by many studies in recent years. In this study, we aim to evaluate the...
INTRODUCTION
Psilocybin is a classic psychedelics, which has been shown to have antidepressant effects by many studies in recent years. In this study, we aim to evaluate the efficacy, acceptability and tolerability of psilocybin in the treatment of primary (major depressive disorder) or secondary (experiencing distress related to life-threatening diagnoses and terminal illness) depression.
METHODS
We searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov for clinical trials of psilocybin for depression (updated to 4 October, 2023). Effect size Hedges' g was used as an indicator of efficacy, and other outcomes included response rate, drop-out rate, and adverse events.
RESULTS
A total of 10 studies were finally included in systematic review. 8 studies were included in the meta-analysis, involving a total of 524 adult patients, and produced a large effect size in favor of psilocybin (Hedge's g =-0.89, 95% CI -1.25~-0.53, I² = 70.19%, P<0.01). The therapeutic effects of psilocybin increase with increasing doses. Adverse events caused by psilocybin are generally transient and reversible, but serious adverse events also may occur.
DISCUSSION
Our study shows that psilocybin has both short-term and long-term antidepressant effects and holds promise as a potential complementary or alternative therapy for depression, probably. Further research may reveal more about its therapeutic potential.
PubMed: 38426002
DOI: 10.3389/fpsyt.2024.1359088 -
Journal of Psychopharmacology (Oxford,... May 2024Recent interest in the potential therapeutic effects of psychedelics has led to investigations into their influence on molecular signaling pathways within the brain. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent interest in the potential therapeutic effects of psychedelics has led to investigations into their influence on molecular signaling pathways within the brain.
AIMS
Integrated review and analysis of different studies in this field.
METHODS
A systematic search was conducted across international databases including Embase, Scopus, Web of Science, and PubMed from inception to 9 July 2023. Eligibility criteria encompassed published and peer-reviewed studies evaluating changes in brain-derived neurotrophic factor (BDNF) levels after psychedelic consumption.
OUTCOMES
A total of nine studies were included in our study. The meta-analysis demonstrated significantly higher BDNF levels in psychedelic consumers compared to healthy controls, with a pooled standardized mean difference of 0.26 (95% CI: 0.10-0.42, = 38.51%, < 0.001). Leave-one-out analysis indicated robustness in results upon removal of individual psychedelics. No significant publication bias was observed. The results highlight the potential influence of psychedelics on neuroplasticity by altering BDNF levels.
CONCLUSIONS
More precisely, the documented rise in BDNF levels indicates a neurobiological mechanism by which psychedelics could enhance synaptic plasticity and foster the growth of neurons. Given the limited data available on this topic, the conclusions remain uncertain. Consequently, we highly recommend additional research with more extensive sample sizes to yield more reliable evidence in this field.
Topics: Brain-Derived Neurotrophic Factor; Humans; Hallucinogens; Neuronal Plasticity; Brain
PubMed: 38385351
DOI: 10.1177/02698811241234247 -
Frontiers in Psychiatry 2024The practice of taking small, sub-hallucinogenic doses of psychedelics, known as microdosing, has exploded in popularity over the last decade. Users claim benefits...
INTRODUCTION
The practice of taking small, sub-hallucinogenic doses of psychedelics, known as microdosing, has exploded in popularity over the last decade. Users claim benefits ranging from improved mood and enhanced creativity to an increased sense of meaning and connectedness in life. While research on microdosing is still lagging behind the shift in public opinion, several papers have been published in the last five years which attempted to assess the effects of microdosing.
METHODS
This review paper aimed to critically analyze the research practices used in the recent wave of microdosing research: We reviewed 15 papers published before the closing date of this review in March 2022.
RESULTS
Our review concludes that it is premature to draw any conclusions about the efficacy or safety of microdosing since the research quality cannot be considered confirmatory.
DISCUSSION
We propose some potential causes for the current state of the literature and some suggestions for how these causes may be ameliorated.
PubMed: 38374976
DOI: 10.3389/fpsyt.2024.1217102 -
International Journal of Behavioral... Feb 2024Demoralization, a significant mental health concern in patients with chronic diseases, can have a large impact on physical symptom burden and quality of life. The... (Review)
Review
BACKGROUND
Demoralization, a significant mental health concern in patients with chronic diseases, can have a large impact on physical symptom burden and quality of life. The present review aimed to evaluate the effectiveness of interventions for demoralization among patients with chronic diseases.
METHOD
PubMed, Scopus, Embase, and Web of Science were systematically searched. Research on providing interventions to patients with chronic diseases that included quantitative data on demoralization was then systematically reviewed.
RESULTS
Fourteen studies were included, most of which considered demoralization as a secondary outcome. Interventions included evidence-based meaning-centered psychotherapy, dignity therapy, psilocybin-assisted psychotherapy, and others. Ten studies used randomized controlled designs. Six of these investigated evidence-based meaning-centered therapy, and four investigated dignity therapy, showing the best empirical support for these intervention types. Most studies showed significant impacts on demoralization in patients with chronic diseases.
CONCLUSION
This systematic review provides insights into potential psychological interventions for reducing demoralization in patients with chronic diseases. Randomized controlled designs and adequately powered samples, with demoralization as the primary outcome, are needed to more clearly evaluate its effectiveness.
PubMed: 38316668
DOI: 10.1007/s12529-024-10262-w -
Clinical Psychopharmacology and... Feb 2024Psilocybin is a classical psychedelic which has been utilised for healing purposes for millenia. However, with its classification as a Schedule I substance, research... (Review)
Review
Psilocybin is a classical psychedelic which has been utilised for healing purposes for millenia. However, with its classification as a Schedule I substance, research into this compound is scarce with few FDA-approved clinical studies. Despite this, profound findings into its antidepressant effects (largely through its action on 5-HT1a receptors) in mental illnesses such as major depressive disorder have rapidly increased interest back into their potential therapeutic benefits. This systematic review provides an analysis of the studies examining the clinical use of psilocybin for major depressive disorder. In total 6 studies were selected, including 319 participants, with half being randomised controlled trials and half open label trials. In every study psychological support was included as an integral part of the treatment. It was found that every study significantly favoured the use of psilocybin in reducing depressive symptoms, with few side effects. This gives psilocybin an advantage over commonly prescribed selective serotonin reuptake inhibitors (SSRIs), which carry more risk and cause more adverse effects. This drug therefore shows promise for being used as a clinical treatment for major depressive disorder, however future research should develop a paradigm for its use, with the timing of sessions and type of psychological support specified to allow for more precise analysis of the clinical effects of the drug. Additionally, more studies into its clinical efficacy are needed for appropriate detection of any publication bias. With this, psilocybin could prove to be revolutionary in treating depression and become an alternative medication to SSRIs.
PubMed: 38247407
DOI: 10.9758/cpn.23.1120 -
Journal of Affective Disorders Apr 2024Inadequate outcomes with monoamine-based treatments in depressive disorders are common and provide the impetus for mechanistically-novel treatments. Esketamine is a... (Review)
Review
BACKGROUND
Inadequate outcomes with monoamine-based treatments in depressive disorders are common and provide the impetus for mechanistically-novel treatments. Esketamine is a proven treatment recently approved for adults with Treatment-Resistant Depression (TRD) while psilocybin is an investigational treatment. Translation of the clinical meaningfulness for these foregoing agents in adults with TRD is required. Herein we evaluate the Number Needed to Treat (NNT) and Harm (NNH) of esketamine and psilocybin in adults with TRD.
METHODS
We conducted a systematic review of randomized controlled trials, comparing the clinical efficacy of oral psilocybin to the co-commencement of intranasal esketamine with an oral antidepressant in adults with TRD.
RESULTS
25 mg psilocybin had a significant reduction in depressive symptoms at 21-days post-dose, the NNT was 5 [95 % CI = 3.1, 18.5]. Psilocybin-induced nausea had a significant NNH = 5. Fixed-dosed esketamine at 56 mg and 84 mg had a significant effect at 28-days post-dose, (NNT of 7 [95 % CI = 3.5, 46.7], [95 % CI = 3.6, 142.2]). Esketamine-induced headache, nausea, dizziness, and dissociation had NNHs <10.
LIMITATIONS
The preliminary results may only reflect a small portion of the patient population. These results require replication and longer term studies investigating maintenance therapy.
CONCLUSION
Relatively few pharmacologic agents are proven safe and effective in adults with TRD. NNT estimates for investigational psilocybin and esketamine in TRD indicate clinical meaningfulness. The NNH profile for both aforementioned agents is clinically acceptable. Our results underscore the clinical relevance of these treatment options in adults with TRD.
Topics: Adult; Humans; Psilocybin; Depression; Drug Therapy, Combination; Depressive Disorder, Treatment-Resistant; Nausea; Ketamine
PubMed: 38244804
DOI: 10.1016/j.jad.2024.01.142 -
Journal of Psychopharmacology (Oxford,... Jan 2024Growing clinical interest in psychedelic-assisted therapies has led to a second wave of research involving psilocybin, lysergic acid diethylamide (LSD),... (Review)
Review
BACKGROUND
Growing clinical interest in psychedelic-assisted therapies has led to a second wave of research involving psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA) and other substances. Data suggests that these compounds have the potential to treat mental health conditions that are especially prevalent in older adults such as depression, anxiety, existential distress, and posttraumatic stress disorder.
AIMS
The goal of this study was to quantify the prevalence of older adults enrolled in psychedelic clinical trials and explore safety data in this population.
METHODS
A systematic review was conducted following the 2020 PRISMA guidelines. Search criteria included all trials published in English using psychedelic substances to treat psychiatric conditions, including addiction as well as existential distress related to serious illness. Articles were identified from literature searches on PubMed, EBSCO, and EMBASE.
RESULTS
4376 manuscripts were identified, of which 505 qualified for further review, with 36 eventually meeting eligibility criteria. Of the 1400 patients enrolled in the 36 studies, only 19 were identified as 65 or older, representing less than 1.4% of all trial participants. For 10 of these 19 older adults, detailed safety data was obtained. No serious adverse events (AEs) occurred in any older adults and only transient mild-to-moderate AEs related to anxiety, gastrointestinal upset, and hypertension were reported during the psychedelic dosing sessions.
CONCLUSIONS
While existing data in older adults is limited, it suggests that psychedelic-assisted psychotherapy can be safe and well tolerated in older adults. Therefore, psychedelic-assisted psychotherapy should be more rigorously investigated for the treatment of psychiatric conditions in this population.
Topics: Humans; Aged; Hallucinogens; Lysergic Acid Diethylamide; Psilocybin; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy
PubMed: 38240068
DOI: 10.1177/02698811231215420 -
The Primary Care Companion For CNS... Jan 2024To investigate the relationship between psychedelic microdosing and its effects on mental health, aiming to understand if microdosing can improve mental well-being....
To investigate the relationship between psychedelic microdosing and its effects on mental health, aiming to understand if microdosing can improve mental well-being. PubMed and Scopus were searched on December 25, 2022, using search terms related to psychedelics, microdosing, and mental health. The inclusion criteria focused on studies published between January 1, 2012, and November 30, 2022. There were no language restrictions for the initial search; however, for the study selection, only articles in English were considered. A total of 45 articles were initially identified. After removing duplicates, 27 unique articles were screened based on their titles and abstracts, resulting in 19 articles included in the final review. The studies were selected based on their relevance to the relationship between mental health and psychedelic microdosing. The extracted data from the selected studies included sample sizes, demographics, survey designs, and qualitative and quantitative analyses related to the outcomes of individuals with mental health issues who also engaged in psychedelic microdosing. The QualSyst Quality Assessment Checklist was used to assess the methodological rigor and quality of each study. The data extraction process involved systematically reviewing each article and summarizing key findings related to the impact of microdosing on mental health. The review revealed that microdosing psychedelics, such as lysergic acid diethylamide and psilocybin, showed potential benefits on mental health. Users reported positive effects, including improved mood, increased focus, and better daily function. However, there were also challenges reported, such as physiologic discomfort and increased anxiety. Some studies observed that positive expectations about microdosing led to positive outcomes. The studies varied in design, with some being observational, others placebo-controlled, and some relying on self-reported data. There is a growing body of evidence suggesting a positive correlation between psychedelic microdosing and improved mental well-being. However, due to the limited number of controlled studies and the small sample sizes in some of the studies, the causal relationship between microdosing and mental health improvement remains uncertain. The review calls for further research with double-blind experiments, control groups, and larger sample sizes that represent the general population to better understand the potential benefits and risks of psychedelic microdosing on mental health. . .
Topics: Humans; Hallucinogens; Mental Health; Psilocybin; Lysergic Acid Diethylamide; Anxiety; Randomized Controlled Trials as Topic
PubMed: 38228068
DOI: 10.4088/PCC.23r03581