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Journal of Psychoactive Drugs 2023Renewed interest in psychedelic substances in the 21 century has seen the exploration of psychedelic treatments for various psychiatric disorders including substance use... (Review)
Review
Renewed interest in psychedelic substances in the 21 century has seen the exploration of psychedelic treatments for various psychiatric disorders including substance use disorder (SUD). This review aimed to assess the effectiveness of psychedelic treatments for people with SUD and those falling below diagnostic thresholds (i.e. substance misuse). We systematically searched 11 databases, trial registries, and psychedelic organization websites for empirical studies examining adults undergoing psychedelic treatment for SUD or substance misuse, published in the English language, between 2000 and 2021. Seven studies investigating treatment using psilocybin, ibogaine, and ayahuasca, alone or adjunct with psychotherapy reported across 10 papers were included. Measures of abstinence, substance use, psychological and psychosocial outcomes, craving, and withdrawal reported positive results, however, this data was scarce among studies examining a wide range of addictions including opioid, nicotine, alcohol, cocaine and unspecified substance. The qualitative synthesis from three studies described subjective experience of psychedelic-assisted treatments enhanced self-awareness, insight, and confidence. At present, there is no sufficient research evidence to suggest effectiveness of any of the psychedelics on any specific substance use disorder or substance misuse. Further research using rigorous effectiveness evaluation methods with larger sample sizes and longer-term follow-up is required.
Topics: Adult; Humans; Hallucinogens; Psilocybin; Substance-Related Disorders; Psychotherapy; Ibogaine; Lysergic Acid Diethylamide
PubMed: 36933948
DOI: 10.1080/02791072.2023.2190319 -
Toxics Feb 2023Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause... (Review)
Review
Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause at what doses. This review aimed to collect information on the health-hazardous doses of psychedelic substances, to be aware of the risks to which patients may be subjected. We focused on ergolamines, simple tryptamines, and phenylethylamines. We reviewed articles published in major medical and scientific databases. Studies reporting toxic or lethal doses in humans and animals were included. We followed PRISMA criteria for revisions. We identified 3032 manuscripts for inclusion. Of these, 33 were ultimately useful and gave relevant information about effects associated with high psychedelics doses. Despite having different molecular structures and different mechanisms of action, psychedelics are effective at very low doses, are not addictive, and are harmful at extremely high doses. For LSD and psilocybin, no dose has been established above which the lives of users are endangered. In contrast, MDMA appears to be the most dangerous substance, although reports are biased by recreational missuses. It seems that it is not only the dose that makes the poison. In the case of psychedelics, the set and setting make the poison.
PubMed: 36851023
DOI: 10.3390/toxics11020148 -
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 -
Health Psychology Review Mar 2024The detrimental effects of Post-Traumatic Stress Symptoms (PTSS) and Post-Traumatic Stress Disorder (PTSD) and the benefits of Post-Traumatic Growth (PTG) are well...
The detrimental effects of Post-Traumatic Stress Symptoms (PTSS) and Post-Traumatic Stress Disorder (PTSD) and the benefits of Post-Traumatic Growth (PTG) are well established for cancer survivors. Increased cancer survival rates necessitate an understanding of how these two paradoxical outcomes, PTSS/PTSD and PTG, are targeted through interventions. This systematic scoping review aims to (a) examine existing evidence on interventions targeting PTSS/PTSD and/or PTG among cancer survivors and (b) identify knowledge gaps to inform future research. Following the six steps of a scoping review, 76 articles met the inclusion criteria. Quantitative articles were examined using descriptive analysis. Frequency counts of the collated data were tabulated into summary tables. Qualitative articles were reviewed using meta-synthesis. Most articles were quantitative (n = 52) and targeted PTG (n = 68) through promising intervention approaches such as psychotherapy, mindfulness, physical activity, and psilocybin-assisted therapy. Three key implications for future research and practice were synthesized: (1) mechanistic considerations for intervention design that provide a roadmap for rigorous and theoretically-grounded research; (2) the need for improved representation of cancer survivors in trials; and (3) potential facilitators of intervention efficacy. Together, these findings can direct future research to optimize interventions to reduce PTSS/PTSD and promote PTG achievement among cancer survivors.
Topics: Humans; Stress Disorders, Post-Traumatic; Posttraumatic Growth, Psychological; Cancer Survivors; Adaptation, Psychological; Mindfulness; Neoplasms
PubMed: 36632776
DOI: 10.1080/17437199.2022.2162947 -
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 -
Neuroscience and Biobehavioral Reviews Jan 2023Major depressive disorders are prevalent conditions with limited treatment response and remission. Pharmacogenomics tests including CYP2D6 and CYP2C19 genomic variants... (Meta-Analysis)
Meta-Analysis Review
Effectiveness of pharmacogenomic tests including CYP2D6 and CYP2C19 genomic variants for guiding the treatment of depressive disorders: Systematic review and meta-analysis of randomised controlled trials.
Major depressive disorders are prevalent conditions with limited treatment response and remission. Pharmacogenomics tests including CYP2D6 and CYP2C19 genomic variants provide the most reliable actionable approach to guide choice and dosing of antidepressants in major depression to improve outcomes. We carried out a meta-analysis and meta-regression analyses of randomised controlled trials evaluating pharmacogenomic tests with CYP2D6 and CYP2C19 polymorphisms in major depression. A systematic review was conducted according to PRISMA and Cochrane guidelines to search several electronic databases. Logarithmically transformed odds ratios (OR) and confidence intervals (CI) for improvement, response and remission were calculated. A random-effects meta-analysis and meta-regression analyses were subsequently carried out. Twelve randomised controlled trials were included. Pharmacogenomic tests in the treatment of depression were more effective than treatment as usual for improvement (OR:1.63, CI: 1.19-2.24), response (OR: 1.46; CI: 1.16-1.85) and remission (OR: 1.85; CI: 1.23-2.76) with no evidence of publication bias. Remission was less favourable in recent studies. The results are promising but cautious use of pharmacogenomics in major depression is advisable. PROSPERO registration ID: CRD42021261143.
Topics: Humans; Depressive Disorder, Major; Cytochrome P-450 CYP2D6; Pharmacogenetics; Cytochrome P-450 CYP2C19; Genomics; Randomized Controlled Trials as Topic
PubMed: 36463971
DOI: 10.1016/j.neubiorev.2022.104965 -
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