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Frontiers in Psychiatry 2023Psychedelic-assisted therapy [e.g., with lysergic acid diethylamide (LSD)] has shown promising results as treatment for substance use disorders (SUDs). Previous...
BACKGROUND
Psychedelic-assisted therapy [e.g., with lysergic acid diethylamide (LSD)] has shown promising results as treatment for substance use disorders (SUDs). Previous systematic reviews assessing the efficacy of psilocybin in SUDs only included clinical trials conducted in the last 25 years, but they may have missed clinical trials assessing the efficacy of psilocybin that were conducted before the 1980s, given much research has been done with psychedelics in the mid-20th century. In this systematic review, we specifically assessed the efficacy of psilocybin in patients with a SUD or non-substance-related disorder with no publication date restrictions in our search strategy.
METHODS
A systematic literature search was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from the earliest published manuscript up to September 2, 2022, in seven electronic databases, including clinical trials in patients with a SUD or non-substance-related disorder evaluating the efficacy of psilocybin.
RESULTS
A total of four studies (six articles, of which two articles were long-term follow-up results from the same trial) were included in this systematic review. Psilocybin-assisted therapy was administered to = 151 patients in a dose ranging from 6 to 40 mg. Three studies focused on alcohol use disorder, and one study on tobacco use disorder. In a pilot study ( = 10), the percentage of heavy drinking days decreased significantly between baseline and weeks 5-12 (mean difference of 26.0, 95% CI = 8.7-43.2, = 0.008). In another single-arm study ( = 31), 32% (10/31) became completely abstinent from alcohol (mean duration of follow-up 6 years). In a double-blind, placebo-controlled randomized controlled trial (RCT, = 95), the percentage of heavy drinking days during the 32-week double-blind period was significantly lower for psilocybin compared to placebo (mean difference of 13.9, 95% CI = 3.0-24.7, = 0.01). In a pilot study ( = 15), the 7-day point prevalence of smoking abstinence at 26 weeks was 80% (12/15), and at 52 weeks 67% (10/15).
CONCLUSION
Only one RCT and three small clinical trials were identified assessing the efficacy of psilocybin combined with some form of psychotherapy in patients with alcohol and tobacco use disorder. All four clinical trials indicated a beneficial effect of psilocybin-assisted therapy on SUD symptoms. Larger RCTs in patients with SUDs need to evaluate whether psilocybin-assisted therapy is effective in patients with SUD.
PubMed: 36846225
DOI: 10.3389/fpsyt.2023.1134454 -
Journal of Affective Disorders Apr 2023Cognitive impairment experienced by people with bipolar disorders (BD) or major depressive disorder (MDD) is associated with impaired psychosocial function and poorer... (Review)
Review
BACKGROUND
Cognitive impairment experienced by people with bipolar disorders (BD) or major depressive disorder (MDD) is associated with impaired psychosocial function and poorer quality of life. Sleep disturbance is another core symptom of mood disorders which may be associated with, and perhaps worsen, cognitive impairments. The aim of this systematic review was to critically assess the relationship between sleep disturbance and cognitive impairment in mood disorders.
METHODS
In this systematic review, relevant studies were identified using electronic database searches of PsychINFO, MEDLINE, Embase and Web of Science.
FINDINGS
Fourteen studies were included; eight investigated people with BD, five investigated people with MDD, and one included both people with MDD and people with BD. One study was an intervention for sleep disturbance and the remaining thirteen studies used either a longitudinal or cross-sectional observational design. Ten studies reported a significant association between subjectively measured sleep disturbance and cognitive impairment in people with MDD or BD after adjusting for demographic and clinical covariates, whereas no such association was found in healthy participants. Two studies reported a significant association between objectively measured (actigraphy or polysomnography) sleep abnormalities and cognitive impairment in mood disorders. One study of cognitive behavioural therapy for insomnia modified for BD (CBTI-BD) found an association between improvements in sleep and cognitive performance in BD.
INTERPRETATION
There is preliminary evidence to suggest a significant association between sleep disturbance and cognitive impairment in mood disorders. These findings highlight the need for further research of sleep disturbances and cognitive impairment in people with mood disorders.
Topics: Humans; Mood Disorders; Depressive Disorder, Major; Cross-Sectional Studies; Quality of Life; Cognitive Dysfunction; Sleep; Sleep Wake Disorders
PubMed: 36739007
DOI: 10.1016/j.jad.2023.01.114 -
International Journal of Bipolar... Jan 2023Given the likelihood of progressive illness in bipolar disorder (BD), it is important to understand the benefits and risks of interventions administered early in illness... (Review)
Review
A systematic review of interventions in the early course of bipolar disorder I or II: a report of the International Society for Bipolar Disorders Taskforce on early intervention.
BACKGROUND
Given the likelihood of progressive illness in bipolar disorder (BD), it is important to understand the benefits and risks of interventions administered early in illness course. We conducted a systematic review of the effectiveness of interventions in the early course of BD I or II.
METHODS
We completed a systematic search on MEDLINE, PsycINFO, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL and Google Scholar from 1/1/1979 till 14/9/2022. We included controlled trials examining intervention effects on symptomatic, course, functional and tolerability outcomes of patients in the 'early course' of BD I or II. We classified patients to be in early course if they (a) were seeking help for the first time for a manic episode, (b) had a lifetime history of up to 3 manic episodes, or (c) had up to 6 lifetime mood episodes. Evidence quality was assessed using the GRADE approach.
RESULTS
From 4135 unique publications we included 25 reports representing 2212 participants in 16 randomized studies, and 17,714 participants from nine non-randomized studies. Available evidence suggested that in early illness course, lithium use was associated with lower recurrence risk compared with other mood stabilizers. Mood stabilizers were also associated with better global functioning, compared with the use of antipsychotics in the medium term. While summative findings regarding psychological therapies were limited by heterogeneity, family-focused and cognitive-behavioral interventions were associated with reduced recurrence risk or improved symptomatic outcomes. There was some evidence that the same pharmacological interventions were more efficacious in preventing recurrences when utilized in earlier rather than later illness course.
CONCLUSIONS AND RECOMMENDATIONS
While there are promising initial findings, there is a need for more adequately powered trials to examine the efficacy and tolerability of interventions in youth and adults in early illness course. Specifically, there is a compelling need to compare the relative benefits of lithium with other pharmacological agents in preventing recurrences. In addition to symptomatic outcomes, there should be a greater focus on functional impact and tolerability. Effective pharmacological and psychological interventions should be offered to those in early course of BD, balancing potential risks using shared decision-making approaches.
PubMed: 36595095
DOI: 10.1186/s40345-022-00275-3 -
Frontiers in Psychiatry 2022Obsessive-compulsive disorder (OCD) is a highly prevalent chronic disorder, often refractory to treatment. While remaining elusive, a full understanding of the...
INTRODUCTION
Obsessive-compulsive disorder (OCD) is a highly prevalent chronic disorder, often refractory to treatment. While remaining elusive, a full understanding of the pathophysiology of OCD is crucial to optimize treatment. Transcranial magnetic stimulation (TMS) is a non-invasive technique that, paired with other neurophysiological techniques, such as electromyography, allows for assessment of human corticospinal neurophysiology. It has been used in clinical populations, including comparisons of patients with OCD and control volunteers. Results are often contradictory, and it is unclear if such measures change after treatment. Here we summarize research comparing corticospinal excitability between patients with OCD and control volunteers, and explore the effects of treatment with repetitive TMS (rTMS) on these excitability measures.
METHODS
We conducted a systematic review and meta-analysis of case-control studies comparing various motor cortical excitability measures in patients with OCD and control volunteers. Whenever possible, we meta-analyzed motor cortical excitability changes after rTMS treatment.
RESULTS
From 1,282 articles, 17 reporting motor cortex excitability measures were included in quantitative analyses. Meta-analysis regarding cortical silent period shows inhibitory deficits in patients with OCD, when compared to control volunteers. We found no statistically significant differences in the remaining meta-analyses, and no evidence, in patients with OCD, of pre- to post-rTMS changes in resting motor threshold, the only excitability measure for which longitudinal data were reported.
DISCUSSION
Our work suggests an inhibitory deficit of motor cortex excitability in patients with OCD when compared to control volunteers. Cortical silent period is believed to reflect activity of GABA receptors, which is in line with neuroimaging research, showing GABAergic deficits in patients with OCD. Regardless of its effect on OCD symptoms, rTMS apparently does not modify Resting Motor Threshold, possibly because this measure reflects glutamatergic synaptic transmission, while rTMS is believed to mainly influence GABAergic function. Our meta-analyses are limited by the small number of studies included, and their methodological heterogeneity. Nonetheless, cortical silent period is a reliable and easily implementable measurement to assess neurophysiology in humans, . The present review illustrates the importance of pursuing the study of OCD pathophysiology using cortical silent period and other easily accessible, non-invasive measures of cortical excitability.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201764], identifier [CRD42020201764].
PubMed: 36569621
DOI: 10.3389/fpsyt.2022.1050480 -
Cureus Oct 2022Psilocybin is a plant alkaloid that is derived from precursors of tryptamine and is present in many different types of mushrooms. It has been utilized by indigenous... (Review)
Review
Psilocybin is a plant alkaloid that is derived from precursors of tryptamine and is present in many different types of mushrooms. It has been utilized by indigenous peoples of Central and South America for centuries in a ceremonial setting to promote spiritual experiences. Indigenous societies have long employed psilocybin and other 5-HT 2A agonist classic psychedelics in their rites. They were a focus in psychiatry in the middle of the 20th century as both experimental medicines and tools for studying brain function. Due to the fact that traditional psychedelics were being used for purposes other than medical research and in connection with the burgeoning counterculture by the late 1960s and early 1970s, these scientific investigations fell out of favor. However, thanks to a number of encouraging studies that validated the earlier research, interest in traditional psychedelics has surged among scientists in the 21st century. In this review, we examine therapeutic studies on psilocybin, the traditional psychedelic that has received the lion's share of recent attention. According to three controlled studies, psilocybin may reduce symptoms of depression and anxiety in the context of cancer-related psychological discomfort for at least six months after a single acute treatment for mood and anxiety disorders. Three months after two acute doses, individuals in a small, open-label study with treatment-resistant depression reported fewer depressive and anxiety symptoms. Small, open-label pilot studies on addiction have demonstrated encouraging success rates for alcohol and cigarette addiction. The review also briefly discusses the synthesis, mechanism of action, effects, molecular pharmacology, adverse effects, and contraindications of psilocybin.
PubMed: 36381758
DOI: 10.7759/cureus.30214 -
Addiction Biology Nov 2022Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by...
Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5-HT receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group or difficulty in determining the effect of classic psychedelics in isolation. On the other hand, preclinical studies (n = 7) investigating the effect of these compounds on voluntary alcohol consumption are scarce and show some conflicting data. Among these compounds, psilocybin seems to show the most consistent data indicating that this compound could be a potential candidate to treat alcohol use disorders. In the absence of understanding the biological and/or psychological mechanisms, more studies including methodological quality parameters are needed to finally determine the effects of classic psychedelics on alcohol consumption.
Topics: Animals; Humans; Hallucinogens; Psilocybin; Alcoholism; Lysergic Acid Diethylamide; Mescaline
PubMed: 36301215
DOI: 10.1111/adb.13229 -
The International Journal of... Mar 2023Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of...
Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering, and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents-lysergic acid diethylamide, psilocybin, and ayahuasca-modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics, and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research in such a way as to elucidate the neurocognitive mechanisms of psychedelics.
Topics: Hallucinogens; Default Mode Network; Psilocybin; Lysergic Acid Diethylamide; Brain; Magnetic Resonance Imaging
PubMed: 36272145
DOI: 10.1093/ijnp/pyac074 -
Chronic Stress (Thousand Oaks, Calif.) 2022A stressor-related disorder wherein traumatic experience precipitates protracted disruptions to mood and cognition, post-traumatic stress disorder (PTSD) is associated... (Review)
Review
A stressor-related disorder wherein traumatic experience precipitates protracted disruptions to mood and cognition, post-traumatic stress disorder (PTSD) is associated with wide-ranging abnormalities across the body. While various methods have investigated these deviations, only proton magnetic resonance spectroscopy (H MRS) enables noninvasive measurement of small-molecule metabolites in the living human. H MRS has correspondingly been employed to test hypotheses about the composition and function of multiple brain regions putatively involved in PTSD. Here we systematically review methodological considerations and reported findings, both positive and negative, of the current H-MRS literature in PTSD (N = 32 studies) to communicate the brain regional metabolite alterations heretofore observed, providing random-effects model meta-analyses for those most extensively studied. Our review suggests significant PTSD-associated decreases in N-acetyl aspartate in bilateral hippocampus and anterior cingulate cortex with less evident effect in other metabolites and regions. Model heterogeneities diverged widely by analysis (I < 0.01% to 90.1%) and suggested regional dependence on quantification reference (creatine or otherwise). While observed variabilities in methods and reported findings suggest that H-MRS explorations of PTSD could benefit from methodological standardization, informing this standardization by quantitative assessment of the existing literature is currently hampered by its small size and limited scope.
PubMed: 36237981
DOI: 10.1177/24705470221128004 -
International Journal of Molecular... Sep 2022This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment-psilocybin and... (Review)
Review
This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment-psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances were controversial in the past, recent studies indicate the potential of those substances as novel antidepressant agents. The PubMed/MEDLINE database was used to identify articles for systematic review, using the following search terms: (depression) AND (psilocybin) OR (ketamine). From 617 items, only 12 articles were obtained in the final analyses. Three articles were devoted to psilocybin in depression treatment and nine to esketamine. In most studies, esketamine showed a significant reduction in both depressive symptoms and suicidal ideation shortly after intake and after a month of treatment compared to baseline and to standard-of-care antidepressant agents. Psilocybin's antidepressive effects occurred one day after intake and after 6-7 weeks of treatment and were maintained for up to 6 or 8 months of follow-up. One study indicated that psilocybin's effects are comparable with and may be superior to escitalopram treatment. Both esketamine and psilocybin demonstrated rapid and long-term effects in reducing depression symptoms and, after overcoming some limitations, may be considered as novel antidepressant agents in future.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Treatment-Resistant; Hallucinogens; Humans; Ketamine; Psilocybin
PubMed: 36232748
DOI: 10.3390/ijms231911450 -
CNS Drugs Oct 2022Preliminary results from randomized controlled studies as well as identified molecular, cellular, and circuit targets of select psychedelics (e.g., psilocybin) suggest...
BACKGROUND
Preliminary results from randomized controlled studies as well as identified molecular, cellular, and circuit targets of select psychedelics (e.g., psilocybin) suggest that their effects are transdiagnostic. In this review, we exploit the Research Domain Criteria (RDoC) transdiagnostic framework, to synthesize extant literature on psilocybin.
OBJECTIVE
We aimed to identify RDoC-based effects of psilocybin and vistas for future mechanistic and interventional research.
METHODS
A systematic search in electronic databases (i.e., PubMed, Scopus, PsycINFO, and Web of Science) performed in January and February 2021 identified English articles published between 1990 and 2020 reporting the effects of psilocybin on mental health measures. Data from included articles were retrieved and organized according to the RDoC bio-behavioral matrix and its constituent six main domains, namely: positive valence systems, negative valence systems, cognitive systems, social processes, sensorimotor systems, and arousal and regulatory systems.
RESULTS
The preponderance of research with psilocybin has differentially reported beneficial effects on positive valence systems, negative valence system, and social process domains. The data from the included studies support both short-term (23 assessments) and long-term (15 assessments) beneficial effects of psilocybin on the positive valence systems. While 12 of the extracted outcome measures suggest that psilocybin use is associated with increases in the "fear" construct of the negative valence systems domain, 19 findings show no significant effects on this construct, and seven parameters show lowered levels of the "sustained threat" construct in the long term. Thirty-four outcome measures revealed short-term alterations in the social systems' construct namely, "perception and understanding of self," and "social communications" as well as enhancements in "perception and understanding of others" and "affiliation and attachment". The majority of findings related to the cognitive systems' domain reported dyscognitive effects. There have been relatively few studies reporting outcomes of psilocybin on the remaining RDoC domains. Moreover, seven of the included studies suggest the transdiagnostic effects of psilocybin. The dashboard characterization of RDoC outcomes with psilocybin suggests beneficial effects in the measures of reward, threat, and arousal, as well as general social systems.
CONCLUSIONS
Psilocybin possesses a multi-domain effectiveness. The field would benefit from highly rigorous proof-of-mechanism research to assess the effects of psilocybin using the RDoC framework. The combined effect of psilocybin with psychosocial interventions with RDoC-based outcomes is a priority therapeutic vista.
Topics: Hallucinogens; Humans; Psilocybin
PubMed: 36097251
DOI: 10.1007/s40263-022-00944-y