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INTRODUCTION: Psychedelic-assisted therapy with psilocybin has shown promise in Phase 2 trials for alcohol use disorder (AUD). Set and setting, particularly factors facilitating a connection with nature, may positively influence the psychedelic experience and therapeutic outcomes. But to date, randomized controlled trials of interventions to enhance set and setting for psychedelic-assisted therapy are lacking. METHODS: This was a pilot randomized, controlled trial of Visual Healing, a nature-themed video intervention to optimize set and setting, versus Standard set and setting procedures with two open-label psilocybin 25 mg dosing sessions among 20 participants with AUD. For the first session, participants randomized to Visual Healing viewed nature-themed videos during the preparation session and the ascent and descent phases of the psilocybin dosing session while participants randomized to the Standard condition completed a meditation during the preparatory session and wore eyeshades and listened to a music playlist throughout the dosing session. For the second session 4 weeks later, participants chose either Visual Healing or Standard procedures. Primary outcomes were feasibility, safety, and tolerability of Visual Healing. Secondary and exploratory outcomes were changes in alcohol use, psychedelic effects, anxiety and stress. RESULTS: Nineteen of 20 (95%) randomized participants (mean age 49 ± 11 years, 60% female) completed the 14-week study. During the first psilocybin session, participants viewed an average of 37.9 min of the 42-min video and there were no video-related adverse events. Peak increase in post-psilocybin blood pressure was significantly less for participants randomly assigned to Visual Healing compared to Standard procedures. Alcohol use decreased significantly in both Visual Healing and Standard groups and psychedelic effects, stress, and anxiety were similar between groups. DISCUSSION: In this open-label pilot study, viewing Visual Healing vide

Wickzell, Arvid. Magic mushrooms or a miracle drug? The Swedish media coverage of psilocybin. Bachelor’s thesis, Umeå University, 2023. Abstract. This bachelor’s thesis presents a study on how Swedish mass media is covering the subject of psilocybin. With a social constructionist, critical discourse, framing and agenda setting perspective, the thesis aim is to analyze the media discourse around the subject and to answer the main research question; how does Swedish mass media report about psilocybin? The main question is followed by sub questions; (a) how is psilocybin being framed, (b) whose opinion is voiced in the media, (c) has the way mass media reports on the subject changed over time? The research questions are answered by using quantitative research method, and critical media discourse analysis, on material from four Swedish publications, both web and print based. The material spans from the year 1995 to 2022. Results show a change over time. A higher interest in the subject, and a change in types of texts being produced. A new way to frame the subject, changing from articles mainly about psilocybin in a crime context, to articles about psilocybin in a medical context. The opinions that are being voiced in the media are mainly by scientists, medical professionals, and law enforcement. Key words: agenda setting, drugs, debate, discourse analysis, framing, media, press, psilocybin, newspapers, Sweden.

The Governor's Monthly News Conference, an unedited exchange between reporters and Governor Spencer Cox. Gov. In his monthly news conference, Governor Cox addressed many topics hitting the legislature, including abortion, LGBTQ youth, agriculture, the psilocybin bill, social media, and the shrinking Great Salt Lake. Cox also said he is supporting governor candidates in the 2024 Presidential Election. He also spoke highly of Utah hosting the NBA All-Star event, and possibly the Olympics in the future.

Background: Major depressive disorder (MDD) is a leading cause of global disability with associated cognitive deficits increasing the risk of relapse and impaired psychosocial disability. Effective therapeutic interventions that target both the affective and cognitive aspects of the disorder are imperative. Psilocybin, a classic serotonergic compound, has recently remerged as a promising treatment option for MDD, but a comprehensive analysis of the existing literature on its effects on cognitive deficits is lacking. This systematic review aims to explore the effects of psilocybin on cognitive flexibility and emotional processing in individuals with MDD. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic search was conducted in PubMed and PsychInfo to identify relevant studies. Inclusion criteria, based on the PICO-model, encompassed empirical studies examining the effects of psilocybin and other classical psychedelics on cognitive and emotional processes in individuals diagnosed with MDD or healthy controls. The risk of bias was assessed presenting a table summarizing the methodological strengths and weaknesses of each study. Results: A total of 37 studies met the inclusion criteria and were included in the systematic review. Findings indicate that psilocybin administration in individuals with MDD leads to improvements in cognitive flexibility and emotional processing that may be long-term. Specifically, an improvement in cognitive flexibility measured by set-shift tasks, a reduction in rumination levels, and an increase in psychological flexibility were observed post-psilocybin treatment, as well as decreased recognition of negative expressions and increased emotional empathy. The neurobiological mechanisms underlying these effects were explored, with evidence suggesting decreased global segregation of networks, enhanced engagement of key brain regions involved in cognitive control pro

Background: Major depressive disorder (MDD) is a leading cause of global disability with associated cognitive deficits increasing the risk of relapse and impaired psychosocial disability. Effective therapeutic interventions that target both the affective and cognitive aspects of the disorder are imperative. Psilocybin, a classic serotonergic compound, has recently remerged as a promising treatment option for MDD, but a comprehensive analysis of the existing literature on its effects on cognitive deficits is lacking. This systematic review aims to explore the effects of psilocybin on cognitive flexibility and emotional processing in individuals with MDD. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic search was conducted in PubMed and PsychInfo to identify relevant studies. Inclusion criteria, based on the PICO-model, encompassed empirical studies examining the effects of psilocybin and other classical psychedelics on cognitive and emotional processes in individuals diagnosed with MDD or healthy controls. The risk of bias was assessed presenting a table summarizing the methodological strengths and weaknesses of each study. Results: A total of 37 studies met the inclusion criteria and were included in the systematic review. Findings indicate that psilocybin administration in individuals with MDD leads to improvements in cognitive flexibility and emotional processing that may be long-term. Specifically, an improvement in cognitive flexibility measured by set-shift tasks, a reduction in rumination levels, and an increase in psychological flexibility were observed post-psilocybin treatment, as well as decreased recognition of negative expressions and increased emotional empathy. The neurobiological mechanisms underlying these effects were explored, with evidence suggesting decreased global segregation of networks, enhanced engagement of key brain regions involved in cognitive control pro

BackgroundPsilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes.MethodData were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis.ResultsResults support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater 'dread of ego dissolution' in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not.ConclusionsThese findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.

BackgroundPast research reports a positive relationship between experience with classic serotonergic psychedelics and nature relatedness (NR). However, these studies typically do not distinguish between different psychedelic compounds, which have a unique psychopharmacology and may be used in specific contexts and with different intentions. Likewise, it is not clear whether these findings can be attributed to substance use per se or unrelated variables that differentiate psychedelic users from nonusers.AimsThe present study was designed to determine the relative degree to which lifetime experience with different psychedelic substances is predictive of self-reported NR among psychedelic-experienced users.MethodsWe conducted a combined reanalysis of five independent datasets (N = 3817). Using standard and regularized regression analyses, we tested the relationship between degree of experience with various psychedelic substances (binary and continuous) and NR, both within a subsample of psychedelic-experienced participants as well as the complete sample including psychedelic-naïve participants.Results/outcomesAmong people experienced with psychedelics, only past use of psilocybin (versus LSD, mescaline, Salvia divinorum, ketamine, and ibogaine) was a reliable predictor of NR and its subdimensions. Weaker, less reliable results were obtained for the pharmacologically similar N,N-dimethyltryptamine (DMT). Results replicate when including psychedelic-naïve participants. In addition, among people exclusively experience with psilocybin, use frequency positively predicted NR.Conclusions/interpretationResults suggest that experience with psilocybin is the only reliable (and strongest) predictor of NR. Future research should focus on psilocybin when investigating effects of psychedelic on NR and determine whether pharmacological attributes or differences in user expectations/use settings are responsible for this observation.

BackgroundMusic listening is a staple and valued component of psychedelic therapy, and previous work has shown that psychedelics can acutely enhance music-evoked emotion.AimsThe present study sought to examine subjective responses to music before and after psilocybin therapy for treatment-resistant depression, while functional magnetic resonance imaging (fMRI) data was acquired.MethodsNineteen patients with treatment-resistant depression received a low oral dose (10 mg) of psilocybin, and a high dose (25 mg) 1 week later. fMRI was performed 1 week prior to the first dosing session and 1 day after the second. Two scans were conducted on each day: one with music and one without. Visual analogue scale ratings of music-evoked 'pleasure' plus ratings of other evoked emotions (21-item Geneva Emotional Music Scale) were completed after each scan. Given its role in musical reward, the nucleus accumbens (NAc) was chosen as region of interest for functional connectivity (FC) analyses. Effects of drug (vs placebo) and music (vs no music) on subjective and FC outcomes were assessed. Anhedonia symptoms were assessed pre- and post-treatment (Snaith-Hamilton Pleasure Scale).ResultsResults revealed a significant increase in music-evoked emotion following treatment with psilocybin that correlated with post-treatment reductions in anhedonia. A post-treatment reduction in NAc FC with areas resembling the default mode network was observed during music listening (vs no music).ConclusionThese results are consistent with current thinking on the role of psychedelics in enhancing music-evoked pleasure and provide some new insight into correlative brain mechanisms.

Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m-2; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement. ClinicalTrials.gov identifier NCT04661514 .

BACKGROUND: In a recent clinical trial examining the comparative efficacy of psilocybin therapy (PT) versus escitalopram treatment (ET) for major depressive disorder, 14 of 16 major efficacy outcome measures yielded results that favored PT, but the Quick Inventory of Depressive Symptomatology, Self-Report, 16 items (QIDS-SR16) did not. AIMS: The present study aims to (1) rationally and psychometrically account for discrepant results between outcome measures and (2) to overcome psychometric problems particular to individual measures by re-examining between-condition differences in depressive response using all outcome measures at item-, facet-, and factor-levels of analysis. METHOD: Four depression measures were compared on the basis of their validity for examining differences in depressive response between PT and ET conditions. RESULTS/OUTCOMES: Possible reasons for discrepant findings on the QIDS-SR16 include its higher variance, imprecision due to compound items and whole-scale and unidimensional sum-scoring, vagueness in the phrasing of scoring options for items, and its lack of focus on a core depression factor. Reanalyzing the trial data at item-, facet-, and factor-levels yielded results suggestive of PTs superior efficacy in reducing depressed mood, anhedonia, and a core depression factor, along with specific symptoms such as sexual dysfunction. CONCLUSION/INTERPRETATION: Our results raise concerns about the adequacy of the QIDS-SR16 for measuring depression, as well as the practice of relying on individual scales that tend not to capture the multidimensional structure or core of depression. Using an alternative approach that captures depression more granularly and comprehensively yielded specific insight into areas where PT therapy may be particularly useful to patients and clinicians.

Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium-high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose-response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personal

Wickzell, Arvid. Magic mushrooms or a miracle drug? The Swedish media coverage of psilocybin. Bachelor’s thesis, Umeå University, 2023. Abstract. This bachelor’s thesis presents a study on how Swedish mass media is covering the subject of psilocybin. With a social constructionist, critical discourse, framing and agenda setting perspective, the thesis aim is to analyze the media discourse around the subject and to answer the main research question; how does Swedish mass media report about psilocybin? The main question is followed by sub questions; (a) how is psilocybin being framed, (b) whose opinion is voiced in the media, (c) has the way mass media reports on the subject changed over time? The research questions are answered by using quantitative research method, and critical media discourse analysis, on material from four Swedish publications, both web and print based. The material spans from the year 1995 to 2022. Results show a change over time. A higher interest in the subject, and a change in types of texts being produced. A new way to frame the subject, changing from articles mainly about psilocybin in a crime context, to articles about psilocybin in a medical context. The opinions that are being voiced in the media are mainly by scientists, medical professionals, and law enforcement. Key words: agenda setting, drugs, debate, discourse analysis, framing, media, press, psilocybin, newspapers, Sweden.

The aim of this systematic review is to present the current literature on the therapeutic potential of the classic psychedelic compound psilocybin for depressive disorders and the neurocognitive mechanisms involved recorded with functional magnetic resonance imaging (fMRI). A comprehensive literature search was conducted in the electronic databases Web of Science, Scopus and Medline EBSCO using a Boolean search string containing the keywords psilocybin, depression, fMRI, MRI and PET. Our inclusion criteria require original neuroimaging research articles published in scientific peer-reviewed journals involving participants diagnosed with depression receiving psilocybin in conjunction with psychological support. Five articles were identified including a total of 104 participants with depression and 75 who received treatment, resulting in significant reduction of depressive symptoms associated with observable changes in neural activity. Specifically reduced cerebral blood flow (CBF) in amygdala, decreased brain modularity along with functional changes in default mode network (DMN), executive network (EN), salience network (SN), decrease in functional connectivity (FC) between ventromedial prefrontal cortex (vmPFC) to amygdala and increased amygdala reactivity to fearful faces. Limitations of our systematic review include a currently limited amount of articles published and thus lack of control groups in most studies. The current evidence indicates that the therapeutic potential of psilocybin-assisted therapy may provide fast acting and efficient amelioration of depressive symptoms and the effects may be mediated by neurocognitive changes acute and post-treatment. The preliminary results warrants further research in order to optimize treatment and establish safety and efficacy long term.

Depression is a mental illness that is characterized by a depressed mood, reduced energy levels, loss of interest in activities, and decreased concentration. It is the biggest cause behind the approximately 800 000 suicides committed every year, and one of the largest contributors to global disability. Between 12-55% of all patients suffering from depression do not experience improvement of symtoms after two or more pharmaceutical treatments. Even when the treatments do work, it often takes several weeks for them to acheive full effect.In recent years, research on the antidepressant effects of the controlled substance psilocybin has resumed after a long hiatus. Psilocybin is a psychedelic substance with hallucinogenic, mind-altering properties. It occurs naturally in several species of mushrooms, and has a long history of usage in spiritual rituals by native populations of South America. After ingestion, psilocybin is converted to its active form, psilocin, by enzymes found in the body. Psilocin has a structure similar to serotonin, and the hallucionogenic effects are mediated by psilocin binding to serotonin receptors. The mechanism behind the potential antidepressant effects is not yet fully known, but believed to involve several pathways.This bachelor´s thesis aimed to, through reviewing literature, examine whether psilocybin can constitute a safe and effective treatment for depression. Six scientific studies on the topic were chosen from the databases PubMed and ScienceDirect to be presented in this thesis. All of the chosen studies used established rating scales to evaluate the degree of depressive symtoms before and after one to two doses of psilocybin.The results from the analysed studies indicate that psilocybin, when combined with psychological support, has the potential to constitute a safe and effective treatment for depression. This presupposes that 20-30 mg is administrated in a safe environment with professionally trained indivuduals present. The effec

We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N = 102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants in the waitlist condition (63.6%). Using data from the two trials with control arms, the psilocybin arm showed a lower likelihood of symptom worsening versus waitlist, and no difference in the likelihood of symptom worsening versus escitalopram. The limitation of a relatively small sample size should be addressed in future studies.

BackgroundPrevious research suggests that mindfulness meditation and psychedelic substances show promise as mental health interventions, but relatively little remains known about their potential impact on leadership outcomes. AimsThis study aimed to investigate if and how mindfulness meditation and psychedelic use may impact leadership among respondents with a management position as their primary role at work. MethodsUsing samples representative of the US and UK adult populations with regard to sex, age, and ethnicity, this study used quantitative and qualitative methods to examine if and how mindfulness meditation and psychedelic use may impact leadership. ResultsAmong respondents with a management position as their primary role at work (n = 3,150), 1,373 reported having tried mindfulness meditation and 559 reported having tried psychedelics. In covariate-adjusted regression analyses, both lifetime number of hours of mindfulness meditation practice and greater psychological insight during respondents' most intense psychedelic experience were associated with describing a positive impact on leadership (ORs = 2.33, 3.49; ps < 0.001), while qualitative analyses revealed nuances in the type of impacts mindfulness meditation and psychedelic use had on leadership. There were several subthemes (e.g., focus, creativity, patience, empathy, compassion) that were frequently reported with both mindfulness meditation and psychedelic use. There were also unique subthemes that were more commonly reported with mindfulness meditation (e.g., improved sleep, stress reduction, calming effects) and psychedelic use (e.g., greater self-understanding, less hierarchical attitudes toward colleagues, positive changes in interpersonal attitudes and behaviors), respectively. ConclusionAlthough causality cannot be inferred due to the research design, the findings in this study suggest potential complementary effects of mindfulness meditation and psychedelic use on leadership, which could insp

Rationale Psilocybin is a serotonergic psychedelic that has gained prominent attention recently as a potential therapeutic for neuropsychiatric disorders including Major Depressive Disorder. Pre-clinical and initial studies in humans suggest that serotonin 2A receptor agonists, including serotonergic psychedelics, have anti-inflammatory effects. This may contribute to its therapeutic effects as previous studies indicate a link between neuropsychiatric disorders and inflammatory processes. However, the effect of psilocybin on biomarkers of inflammation has not been evaluated in humans. Objectives Investigate the effect of a single dose of psilocybin on peripheral biomarkers of inflammation in healthy humans. Methods Blood samples were collected from 16 healthy participants before and one day after the administration of a single oral dose of psilocybin (mean dose: 0.22 mg/kg) and subsequently analyzed for concentrations of high-sensitivity C-reactive protein (hsCRP), tumor-necrosis-factor (TNF) and soluble urokinase plasminogen activator receptor (suPAR). Change in inflammatory markers was evaluated using a paired t-test where p < 0.05 was considered statistically significant. Results We did not observe statistically significant changes in any of the above biomarkers of inflammation (all Cohen's d ≤ 0.31; all p ≥ 0.23). Conclusions Our data do not support that a single dose of psilocybin reduces biomarkers of inflammation in healthy individuals one day after administration. Nevertheless, we suggest that future studies consider additional markers of inflammation, including markers of neuroinflammation, and evaluate potential anti-inflammatory effects of psilocybin therapy in clinical cohorts where more prominent effects may be observable., Rationale: Psilocybin is a serotonergic psychedelic that has gained prominent attention recently as a potential therapeutic for neuropsychiatric disorders including Major Depressive Disorder. Pre-clinical and initial studies in humans suggest that serotonin 2A receptor agonists, including serotonergic psychedelics, have anti-inflammatory effects. This may contribute to its therapeutic effects as previous studies indicate a link between neuropsychiatric disorders and inflammatory processes. However, the effect of psilocybin on biomarkers of inflammation has not been evaluated in humans. Objectives: Investigate the effect of a single dose of psilocybin on peripheral biomarkers of inflammation in healthy humans. Methods: Blood samples were collected from 16 healthy participants before and one day after the administration of a single oral dose of psilocybin (mean dose: 0.22 mg/kg) and subsequently analyzed for concentrations of high-sensitivity C-reactive protein (hsCRP), tumor-necrosis-factor (TNF) and soluble urokinase plasminogen activator receptor (suPAR). Change in inflammatory markers was evaluated using a paired t-test where p < 0.05 was considered statistically significant. Results: We did not observe statistically significant changes in any of the above biomarkers of inflammation (all Cohen's d ≤ 0.31; all p ≥ 0.23). Conclusions: Our data do not support that a single dose of psilocybin reduces biomarkers of inflammation in healthy individuals one day after administration. Nevertheless, we suggest that future studies consider additional markers of inflammation, including markers of neuroinflammation, and evaluate potential anti-inflammatory effects of psilocybin therapy in clinical cohorts where more prominent effects may be observable.

Background: The classical psychedelics, psilocybin, peyote, ayahuasca/N,N-dimethyltryptamine, and lysergic acid diethylamide are considered promising new treatments for psychiatric illnesses, such as depression, anxiety, addiction, and obsessive-compulsive disorders. However, their profound and characteristic subjective effects raise concern for distinctive biases in randomized clinical trials. Methods: We performed a systematic literature search to identify all clinical trials on classical psychedelics with patient populations to examine descriptive data and determine the risk of bias. Two independent reviewers searched three databases (PubMed, Embase, and APA PsycNet) and extracted information on study design, study population, use of active or inactive placebo, dropouts, evaluation of blinding of intervention, and reporting of expectancy and therapeutic alliance. Results: We included 10 papers reporting on 10 unique trials. The trials generally included populations that were predominantly white and highly educated. The trials had small samples and considerable dropout. Blinding was either unsuccessful or not reported regardless of type of placebo. Few trials published protocols, statistical analysis plans (SAPs), and outcomes relating to psychotherapy fidelity. All trials but one were rated as high risk of bias. Conclusion: Successful blinding of intervention is a significant challenge in this field. To better accommodate this, we suggest that future trials use a parallel-group design and utilize an active placebo on a psychedelic-naïve population. Future trials should publish trial protocol and SAPs, use clinician-rated outcomes accessed by a blinded rater, evaluate blinding of intervention, and consider measuring expectancy and therapeutic fidelity.

The Governor's Monthly News Conference, an unedited exchange between reporters and Governor Spencer Cox. Gov. In his monthly news conference, Governor Cox addressed many topics hitting the legislature, including abortion, LGBTQ youth, agriculture, the psilocybin bill, social media, and the shrinking Great Salt Lake. Cox also said he is supporting governor candidates in the 2024 Presidential Election. He also spoke highly of Utah hosting the NBA All-Star event, and possibly the Olympics in the future.

The aim of this systematic review is to present the current literature on the therapeutic potential of the classic psychedelic compound psilocybin for depressive disorders and the neurocognitive mechanisms involved recorded with functional magnetic resonance imaging (fMRI). A comprehensive literature search was conducted in the electronic databases Web of Science, Scopus and Medline EBSCO using a Boolean search string containing the keywords psilocybin, depression, fMRI, MRI and PET. Our inclusion criteria require original neuroimaging research articles published in scientific peer-reviewed journals involving participants diagnosed with depression receiving psilocybin in conjunction with psychological support. Five articles were identified including a total of 104 participants with depression and 75 who received treatment, resulting in significant reduction of depressive symptoms associated with observable changes in neural activity. Specifically reduced cerebral blood flow (CBF) in amygdala, decreased brain modularity along with functional changes in default mode network (DMN), executive network (EN), salience network (SN), decrease in functional connectivity (FC) between ventromedial prefrontal cortex (vmPFC) to amygdala and increased amygdala reactivity to fearful faces. Limitations of our systematic review include a currently limited amount of articles published and thus lack of control groups in most studies. The current evidence indicates that the therapeutic potential of psilocybin-assisted therapy may provide fast acting and efficient amelioration of depressive symptoms and the effects may be mediated by neurocognitive changes acute and post-treatment. The preliminary results warrants further research in order to optimize treatment and establish safety and efficacy long term.

Depression is a mental illness that is characterized by a depressed mood, reduced energy levels, loss of interest in activities, and decreased concentration. It is the biggest cause behind the approximately 800 000 suicides committed every year, and one of the largest contributors to global disability. Between 12-55% of all patients suffering from depression do not experience improvement of symtoms after two or more pharmaceutical treatments. Even when the treatments do work, it often takes several weeks for them to acheive full effect.In recent years, research on the antidepressant effects of the controlled substance psilocybin has resumed after a long hiatus. Psilocybin is a psychedelic substance with hallucinogenic, mind-altering properties. It occurs naturally in several species of mushrooms, and has a long history of usage in spiritual rituals by native populations of South America. After ingestion, psilocybin is converted to its active form, psilocin, by enzymes found in the body. Psilocin has a structure similar to serotonin, and the hallucionogenic effects are mediated by psilocin binding to serotonin receptors. The mechanism behind the potential antidepressant effects is not yet fully known, but believed to involve several pathways.This bachelor´s thesis aimed to, through reviewing literature, examine whether psilocybin can constitute a safe and effective treatment for depression. Six scientific studies on the topic were chosen from the databases PubMed and ScienceDirect to be presented in this thesis. All of the chosen studies used established rating scales to evaluate the degree of depressive symtoms before and after one to two doses of psilocybin.The results from the analysed studies indicate that psilocybin, when combined with psychological support, has the potential to constitute a safe and effective treatment for depression. This presupposes that 20-30 mg is administrated in a safe environment with professionally trained indivuduals present. The effec

A U.S. Special Operations Command (SOCOM) funded study completed in 2017 found that U.S. special operations forces (SOF) have a 30% higher suicide rate than the U.S. military average. Nearly half of the twenty-nine suicide cases explored in the psychological autopsy study had a diagnosed mental health disorder. These findings underscore how suicide, and its contributing factors, are a growing threat to the health of the force and combat readiness across SOCOM. This thesis examined psychedelic-assisted therapy as a component of an overall holistic approach to addressing mental health conditions and combatting suicide across SOCOM. We reviewed two emerging psychedelic treatments for ameliorating mood and trauma-based mental health disorders, comparing them to two in-use novel therapies. Notwithstanding limits to existing data, our review found that psychedelic-assisted therapies show potential in three critical ways. There is a rapid and sustained decrease in disorder-related symptoms, exhibited efficacy in treatment-resistant cases, and minimal adverse events when administered in a controlled environment. Alone, no single weapon or piece of technology has ever won a war, and in a similar fashion, successful mental health treatment models for suicide prevention strategies require a multi-faceted approach. While psychedelic therapies are not a panacea for the mental health crisis within the military, they carry emended potential to be another tool for treatment and recovery., Major, United States Army, Major, United States Army, Major, United States Army, Approved for public release. Distribution is unlimited.

This dissertation has taken an interdisciplinary approach to investigate and give insights into psilocybin’s neurobiological underpinnings. Psilocybin is a naturally occurring serotonergic psychedelic and is the main ingredient in hallucinogenic mushrooms. Research has demonstrated that psilocybin profoundly activates the serotonin (5-hydroxytryptamine) 2A (5-HT2A) receptors. Upon activation of these receptors in the brain, psilocybin induces profound perceptual changes such as hallucinations and illusions, altering one’s self-perception, bodily image and mood. There is a growing interest in psilocybin’s therapeutic utility, focusing on psychiatric disorders, such as treatment-resistant depression. Despite psilocybin’s therapeutic potential, the underlying neurobiological mechanisms of psilocybin remain elusive. Therefore, this dissertation aimed to understand and delineate the acute dose-dependent effects of psilocybin on an epigenetic, neurobiological and cognitive level.

This dissertation examines how psychedelic substances become drawn into particular sociohistorical and political arrangements, and how psychedelic experiences with psilocybin ‘magic mushrooms’ are used as tools of subjectivation. Guided by literatures in philosophy, critical theory, and the social sciences that focus on subjectivity, assemblage theory, and critical posthumanism, I argue that psychedelics are drawn into variegated assemblages, each of which conceptualizes the nature of psychedelics in highly specific ways that reflect implicit conceptions of the world and the self. In developing the concept of psychedelic assemblages, this research provides a window onto the politics of the self in the Anthropocene. Drawing on mixed and netnographic methods, I conducted 30 semi-structured interviews and acquired 100 experience reports from online forums, using this data to demonstrate how psychedelic mushroom experiences are used as technologies of the self, or practices that individuals engage as a means of changing their subjectivity. Among the changes in subjectivity provoked by psychedelic mushroom experiences, there are sometimes reports of changes in human-environment relations based on an enhanced connection or relationship with nature.

Survey-based studies suggest naturalistic psychedelic use provides mental health benefits similar to those observed in clinical trials. The current study sought to confirm these findings in a large group of psychedelic users and to conduct a novel examination of associations between amount of psychedelic use and behavioral outcomes, as well as frequency of harms ascribed to psychedelic use. A cross-sectional, online survey was completed by 2,510 adults reporting at least one lifetime psychedelic experience. Participants retrospectively completed a battery of instruments assessing depression, anxiety, and emotional well-being prior to and following psychedelic exposure. Participants also reported preferred psychedelic agent, number of uses, and harms attributed to psychedelic use. Psychedelic use was associated with significant improvements in depressive and anxious symptoms and with increased emotional well-being. These improvements increased in magnitude with increasing psychedelic exposure, with a ceiling effect. However, improvements were noted following a single lifetime use. Strong evidence for benefit of one preferred psychedelic agent over another was not observed, but enduring increases in factors related to mystical-experience and prosocial perspective taking associated with enhanced mental health. Thirteen percent of the survey sample (n = 330) endorsed at least one harm from psychedelic use, and these participants reported less mental health benefit. Results from the current study add to a growing database indicating that psychedelic use-even outside the context of clinical trials-may provide a wide range of mental health benefits, while also posing some risk for harm in a minority of individuals.

The research and use of psychedelic medicines to treat common mental health disorders has increased substantially in the past 2 decades. At the same time, knowledge is relatively uncommon among midwives regarding (1) the relative benefits of psychedelic-assisted therapy, (2) best practices associated with the delivery of psychedelic-assisted therapy, and (3) responsible integration of this potentially useful intervention into mental health treatment plans. The purpose of this review is to describe current applications of psychedelic medicines to treat common mental health disorders, to describe the current legal status of these medicines used in this context, and to explore the potential for midwifery practice in this area with further training. This article also addresses the disparities regarding LGBTQIA+ and BIPOC populations in relation to this topic and their historical exclusion from research and treatment access in this field.

RationaleA general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of 'connectedness' as 'a state of feeling connected to self, others and the wider world'. Existing tools for measuring connectedness have focused on particular aspects of connectedness, such as 'social connectedness' or 'nature connectedness', which we hypothesise to be different expressions of a common factor of connectedness. Here, we sought to develop a new scale to measure connectedness as a construct with these multiple domains. We hypothesised that (1) our scale would measure three separable subscale factors pertaining to a felt connection to 'self', 'others' and 'world' and (2) improvements in total and subscale WCS scores would correlate with improved mental health outcomes post psychedelic use.ObjectivesTo validate and test the 'Watts Connectedness Scale' (WCS).MethodsPsychometric validation of the WCS was carried out using data from three independent studies. Firstly, we pooled data from two prospective observational online survey studies. The WCS was completed before and after a planned psychedelic experience. The total sample of completers from the online surveys was N = 1226. Exploratory and confirmatory factor analysis were performed, and construct and criterion validity were tested. A third dataset was derived from a double-blind randomised controlled trial (RCT) comparing psilocybin-assisted therapy (n = 27) with 6 weeks of daily escitalopram (n = 25) for major depressive disorder (MDD), where the WCS was completed at baseline and at a 6-week primary endpoint.ResultsAs hypothesised, factor analysis of all WCS items revealed three main factors with good internal consistency. WCS showed good construct validity. Significant p

Although early therapeutic research on psychedelics dates back to the 1940s, this field of investigation was met with many cultural and legal challenges in the 1970s. Over the past two decades, clinical trials using psychedelics have resumed. Therefore, the goal of this study was to (1) better characterize the recent uptrend in psychedelics in clinical trials and (2) identify areas where potentially new clinical trials could be initiated to help in the treatment of widely prevalent medical disorders. A systematic search was conducted on the clinicaltrials.gov database for all registered clinical trials examining the use of psychedelic drugs and was both qualitatively and quantitatively assessed. Analysis of recent studies registered in clinicaltrials.gov was performed using Pearson's correlation coefficient testing. Statistical analysis and visualization were performed using R software. In totality, 105 clinical trials met this study's inclusion criteria. The recent uptrend in registered clinical trials studying psychedelics (p = 0.002) was similar to the uptrend in total registered clinical trials in the registry (p < 0.001). All trials took place from 2007 to 2020, with 77.1% of studies starting in 2017 or later. A majority of clinical trials were in phase 1 (53.3%) or phase 2 (25.7%). Common disorders treated include substance addiction, post-traumatic stress disorder, and major depressive disorder. Potential research gaps include studying psychedelics as a potential option for symptomatic treatment during opioid tapering. There appears to be a recent uptrend in registered clinical trials studying psychedelics, which is similar to the recent increase in overall trials registered. Potentially, more studies could be performed to evaluate the potential of psychedelics for symptomatic treatment during opioid tapering and depression refractory to selective serotonin reuptake inhibitors.

Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain's control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states. Using brain states derived from existing functional magnetic resonance imaging (fMRI) datasets, we show that LSD and psilocybin reduce control energy required for brain state transitions compared to placebo. Furthermore, across individuals, reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors (obtained from publicly available positron emission tomography (PET) data under non-drug conditions), we demonstrate an association between the 5-HT2a receptor and reduced control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, we demonstrate that receptor-informed network control theory can model the impact of neuropharmacological manipulation on brain activity dynamics.

Psychedelics are increasingly being recognized for their potential to treat a wide range of brain disorders including depression, post-traumatic stress disorder (PTSD), and substance use disorder. Their broad therapeutic potential might result from an ability to rescue cortical atrophy common to many neuropsychiatric and neurodegenerative diseases by impacting neurotrophic factor gene expression, activating neuronal growth and survival mechanisms, and modulating the immune system. While the therapeutic potential of psychedelics has not yet been extended to neurodegenerative disorders, we provide evidence suggesting that approaches based on psychedelic science might prove useful for treating these diseases. The primary target of psychedelics, the 5-HT2A receptor, plays key roles in cortical neuron health and is dysregulated in Alzheimer's disease. Moreover, evidence suggests that psychedelics and related compounds could prove useful for treating the behavioral and psychological symptoms of dementia (BPSD). While more research is needed to probe the effects of psychedelics in models of neurodegenerative diseases, the robust effects of these compounds on structural and functional neuroplasticity and inflammation clearly warrant further investigation.

After a long hiatus, psychiatry is undergoing a resurgence of interest in psychedelic drugs as therapy for a wide range of mental health disorders Accumulating clinical evidence suggests substantial potential for psychedelics used in a therapeutic context, as treatment for, among other disorders, depression, post-traumatic stress disorder (PTSD), and addictions to tobacco, opioids and alcohol. As soon as 2024, powerful new therapeutic modalities could become available for individuals with mental health problems refractory to traditional therapies. Yet research has lagged on economic considerations, such as costs and cost-effectiveness, the economic effects of widespread implementation, pricing, and economic appraisal's methodological considerations relevant to psychedelic therapies. These issues are critical if psychedelic therapies are to become widely accessible. We describe six types of economic analyses and their rationale for decisions and planning including the needs of health care payers. We also outline desirable features of this research, including scientific rigor, long horizons, equity, and a global view.

BackgroundOver the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap.AimHere, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes.MethodIndividuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were N = 302, N = 182, N = 155 and N = 109, respectively.ResultsRelative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16.ConclusionThese results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.

Healthful behaviours such as maintaining a balanced diet, being physically active and refraining from smoking have major impacts on the risk of developing cancer, diabetes, cardiovascular diseases and other serious conditions. The burden of the so-called 'lifestyle diseases'-in personal suffering, premature mortality and public health costs-is considerable. Consequently, interventions designed to promote healthy behaviours are increasingly being studied, e.g., using psychobiological models of behavioural regulation and change. In this article, we explore the notion that psychedelic substances such as psilocybin could be used to assist in promoting positive lifestyle change conducive to good overall health. Psilocybin has a low toxicity, is non-addictive and has been shown to predict favourable changes in patients with depression, anxiety and other conditions marked by rigid behavioural patterns, including substance (mis)use. While it is still early days for modern psychedelic science, research is advancing fast and results are promising. Here we describe psychedelics' proposed mechanisms of action and research findings pertinent to health behaviour change science, hoping to generate discussion and new research hypotheses linking the two areas. Therapeutic models including psychedelic experiences and common behaviour change methods (e.g., Cognitive Behaviour Therapy, Motivational Interviewing) are already being tested for addiction and eating disorders. We believe this research may soon be extended to help promote improved diet, exercise, nature exposure and also mindfulness or stress reduction practices, all of which can contribute to physical and psychological health and well-being.

BackgroundPsilocybin-induced mystical-type experiences are associated with lasting positive psychological outcomes. Recent studies indicate that trait mindfulness is increased 3 months after psilocybin intake, preceded by decreases in neocortical serotonin 2A receptor (5-HT2AR) binding. However, the association between psilocybin-induced mystical-type experiences and subsequent changes in trait mindfulness remains unexplored, as does the association between pre-drug trait mindfulness and 5-HT2AR binding in the healthy brain. AimWe evaluated whether psilocybin induced lasting increases in trait mindfulness in healthy volunteers, and whether the mystical-type experience was associated with this increase. We further examined the association between pre-drug trait mindfulness and 5-HT2AR binding in neocortex and selected frontolimbic regions. Materials and methodsForty-six medium-high dose psilocybin sessions were conducted in 39 healthy individuals. The mystical-type experience was measured with the Mystical Experience Questionnaire (MEQ) at the end of the session. Trait mindfulness was measured using the Mindful Attention and Awareness Scale (MAAS) at baseline and 3 months after the psilocybin session. Thirty-two of the participants completed pre-drug [C-11]-Cimbi-36 positron emission tomography (PET) to assess 5-HT2AR binding in neocortex and, post-hoc, in the frontolimbic regions amygdala, frontal cortex, and anterior cingulate cortex. ResultsThe MAAS score was significantly increased at 3-month follow-up (p = 3.24 x 10(-6)), a change positively associated with the MEQ score (p = 0.035). Although the association between pre-drug MAAS score and neocortex 5-HT2AR binding was not significant (p = 0.24), post-hoc analyses revealed a significant negative association between MAAS and right amygdala 5-HT2AR binding (p(FWER) = 0.008). ConclusionWe here show that lasting changes in trait mindfulness following psilocybin administration are positively associated with intens

Background: Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap. Aim: Here, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes. Method: Individuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were N = 302, N = 182, N = 155 and N = 109, respectively. Results: Relative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16. Conclusion: These results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.

Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging researchers, review the 42 research articles published to date, based on the 17 unique studies evaluating psychedelic effects on rs-fMRI, focusing on methodological variation. Prominently, we observe that nearly all studies vary in data processing and analysis methodology, two datasets are the foundation of over half of the published literature, and there is lexical ambiguity in common outcome metric terminology. We offer guidelines for future studies that encourage coherence in the field. Psychedelic rs-fMRI will benefit from the development of novel methods that expand our understanding of the brain mechanisms mediating its intriguing effects; yet, this field is at a crossroads where we must also consider the critical importance of consistency and replicability to effectively converge on stable representations of the neural effects of psychedelics.

Objectives: Absenteeism from work due to illness, and related costs, has increased steadily during the past decades. In recent years, there has been a reemergence of research on the therapeutic effects of classic psychedelics showing associations with both physical and mental health. However, the association between classic psychedelics and sick leave remains unknown. The aim of this study is to investigate the association between lifetime classic psychedelic use and sick leave in the past 30 days among adults in the United States (N = 407,717), using data from the National Survey on Drug Use and Health (2005-2019), weighted to be representative of the US adult population. Methods: The primary analysis was conducted using multiple linear regression, controlling for sociodemographic characteristics, risky behavior, and use of other substances. Results: There was a significant and negative association between lifetime classic psychedelic use and sick leave in the past 30 days (B = -0.09, p < 0.01) when adjusting for all control variables. Conclusion: These findings suggest that classic psychedelics could potentially lead to reduced sick leave and associated costs in the general population, but more research is needed to investigate potential causal pathways of classic psychedelics on sick leave and evaluate possible mechanisms.

BackgroundPsilocybin-induced mystical-type experiences are associated with lasting positive psychological outcomes. Recent studies indicate that trait mindfulness is increased 3 months after psilocybin intake, preceded by decreases in neocortical serotonin 2A receptor (5-HT2AR) binding. However, the association between psilocybin-induced mystical-type experiences and subsequent changes in trait mindfulness remains unexplored, as does the association between pre-drug trait mindfulness and 5-HT2AR binding in the healthy brain. AimWe evaluated whether psilocybin induced lasting increases in trait mindfulness in healthy volunteers, and whether the mystical-type experience was associated with this increase. We further examined the association between pre-drug trait mindfulness and 5-HT2AR binding in neocortex and selected frontolimbic regions. Materials and methodsForty-six medium-high dose psilocybin sessions were conducted in 39 healthy individuals. The mystical-type experience was measured with the Mystical Experience Questionnaire (MEQ) at the end of the session. Trait mindfulness was measured using the Mindful Attention and Awareness Scale (MAAS) at baseline and 3 months after the psilocybin session. Thirty-two of the participants completed pre-drug [C-11]-Cimbi-36 positron emission tomography (PET) to assess 5-HT2AR binding in neocortex and, post-hoc, in the frontolimbic regions amygdala, frontal cortex, and anterior cingulate cortex. ResultsThe MAAS score was significantly increased at 3-month follow-up (p = 3.24 x 10(-6)), a change positively associated with the MEQ score (p = 0.035). Although the association between pre-drug MAAS score and neocortex 5-HT2AR binding was not significant (p = 0.24), post-hoc analyses revealed a significant negative association between MAAS and right amygdala 5-HT2AR binding (p(FWER) = 0.008). ConclusionWe here show that lasting changes in trait mindfulness following psilocybin administration are positively associated with intens

Background: Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap. Aim: Here, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes. Method: Individuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were N = 302, N = 182, N = 155 and N = 109, respectively. Results: Relative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16. Conclusion: These results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.

Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging researchers, review the 42 research articles published to date, based on the 17 unique studies evaluating psychedelic effects on rs-fMRI, focusing on methodological variation. Prominently, we observe that nearly all studies vary in data processing and analysis methodology, two datasets are the foundation of over half of the published literature, and there is lexical ambiguity in common outcome metric terminology. We offer guidelines for future studies that encourage coherence in the field. Psychedelic rs-fMRI will benefit from the development of novel methods that expand our understanding of the brain mechanisms mediating its intriguing effects; yet, this field is at a crossroads where we must also consider the critical importance of consistency and replicability to effectively converge on stable representations of the neural effects of psychedelics.

The psychedelic 5-HT2A receptor (5HT2AR) agonist psilocybin (or the active metabolite psilocin) has emerged as potential useful drug for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. However, the mechanisms responsible for such effects remain incompletely characterized. We aimed to study in vitro pharmacological profile and in vivo acute mechanism of psilocin/psilocybin. Competition binding studies with psilocin were performed in brain and cell cultures. The role of 5HT2AR, 5-HT2C receptors (5HT2CR) and 5-HT1A receptors (5HT1AR) on the psychosis-like head-twitch response (HTR) and on body temperature in mice after psilocybin administration were evaluated. Psilocin showed similar affinities for 5HT2AR (Ki: 120-173 nM), 5HT2CR (Ki: 79-311 nM) and 5-HT1AR (Ki: 152-146 nM) in human and mice brain. Psilocybin induced a dosedependent HTR (maximal effect 17.07 +/- 1.31 at 1 mg/kg i.p.) that was completely suppressed by the 5HT2AR antagonist MDL11939 (1 mg/kg). Higher doses of psilocybin (3 mg/kg) induced lower HTR (9.00 +/- 0.53). The 5HT2CR antagonist SB242084 (0.1 mg/kg) increased HTR exerted by psilocybin (3 mg/kg). Psilocybin significantly raised core body temperature at low dose (0.125 mg/kg) (Emax=0.67 +/- 0.15 degrees C), whereas a significant decrease was induced by doses over 1 mg/kg (Emax = -1.31 +/- 0.16 degrees C). Pre-treatment with the 5HT1AR antagonist WAY100635 reversed the decrease of body temperature after psilocybin (1 mg/kg), causing hyperthermia (Emax = 0.94 +/- 0.26 degrees C). The present work provides key findings on the 5HT2AR, 5-HT2CR and 5HT1AR involvement in the acute central effects of psilocybin. The results may be relevant for understanding the mechanism of action underlying the therapeutic effects and side effects of this psychedelic drug.

Although several studies and reports have shown the potential analgesic use of serotonergic psychedelics in cancer pain, phantom limb pain and cluster headache, evidence supporting their use for chronic pain is still limited. The past years have seen a considerable renewal of interest toward the therapeutic use of these compounds for mood disorders, resulting in a marked increase in the number of people turning to psychedelics in an attempt to self-medicate a health condition or improve their wellbeing. In western countries particularly, this population of users overlaps substantially with chronic pain sufferers, representing a unique opportunity to evaluate the effects these compounds have on pain and wellbeing. Here, we report results from an online survey conducted between August 2020 and July 2021 in a population of 250 chronic pain sufferers who had experience with psychedelics, either in microdoses (small sub-hallucinogenic doses), macrodoses (hallucinogenic doses), or both. Macrodoses, while less often used for analgesic purposes than microdoses, were reported to induce a higher level of pain relief than both microdoses and conventional pain medications (including opioids and cannabis). Although the effects were weaker and potentially more prone to expectation bias than with macrodoses, our results also suggested some benefits of psychedelics in microdoses for pain management. The reported analgesic effect appeared unrelated to mood improvements associated with psychedelic use, or the advocacy of psychedelic use. Taken together, our findings indicate interesting potential analgesic applications for psychedelics that warrant further clinical research.

Psychedelic drugs such as psilocybin have shown substantial promise for the treatment of several psychiatric conditions including mood and addictive disorders. They also have the remarkable property of producing persisting positive psychological changes in healthy volunteers for at least several months. In this study (NCT03289949), 35 medium-high doses of psilocybin were administered to 28 healthy volunteers (12 females). By the end of the dosing day, participants reported the intensity of their acute experience using the 30-item Mystical Experience Questionnaire (MEQ) and an open-form qualitative report from home. Persisting psychological effects attributed to the psilocybin experience were measured using the Persisting Effects Questionnaire (PEQ) 3-months after administration. Using a linear latent-variable model we show that the MEQ total score is positively associated with the later emergence of positive PEQ effects (p = 3 x 10(-5)). Moreover, the MEQ subscales "Positive Mood" (p(corr) = 4.1 x 10(-4)) and "Mysticality" (p(corr) = 2.0 x 10(-4)) are associated with positive PEQ whereas the subscales "Transcendence of Time and Space" (p(corr) = 0.38) and "Ineffability" (p(corr) = 0.45) are not. Using natural language pre-processing, we provide the first qualitative descriptions of the "Complete Mystical Experience" induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the Universe, familial love, and the experience of profound beauty. Combining qualitative and quantitative methods, this paper expands understanding of the acute psilocybin induced experience in healthy volunteers and suggests an importance of the type of experience in predicting lasting positive effects.

Background: Psilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans. Aim: Evaluate changes in resting-state functional connectivity (RSFC) at 1 week and 3 months after one psilocybin dose in 10 healthy psychedelic-naive volunteers and explore associations between change in RSFC and related measures. Methods: Participants received 0.2-0.3 mg/kg psilocybin in a controlled setting. Participants completed resting-state functional magnetic resonance imaging (fMRI) scans at baseline, 1-week and 3-month post-administration and [11C]Cimbi-36 PET scans at baseline and 1 week. We examined changes in within-network, between-network and region-to-region RSFC. We explored associations between changes in RSFC and psilocybin-induced phenomenology as well as changes in psychological measures and neocortex serotonin 2A receptor binding. Results: Psilocybin was well tolerated and produced positive changes in well-being. At 1 week only, executive control network (ECN) RSFC was significantly decreased (Cohen's d = -1.73, pFWE = 0.010). We observed no other significant changes in RSFC at 1 week or 3 months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at 1 week predicted increased mindfulness at 3 months (r = -0.65). Conclusions: These findings in a small cohort indicate that psilocybin affects ECN function within the psychedelic 'afterglow' period. Our findings implicate ECN modulation as mediating psilocybin-induced, long-lasting increases in mindfulness. Although our findings implicate a neural pathway mediating lasting psilocybin effects, it is notable that changes in neuroimaging measures at 3 months, when personality changes are observed, remain to be identified.

Major depression disorder is increasing globally, causing great personal suffering and economic burdens to society. Current antidepressant medications are not sufficiently able to treat all cases of depression and are often associated with troubling side effects. There is a great need for the development of novel treatments, and classic psychedelic drugs are currently being investigated with new interest. The legal status has hindered research, but promising results from pioneering studies on the antidepressant effect of psilocybin have recently given psilocybin breakthrough therapy status, allowing further research to occur more freely. This systematic review aims to investigate the literature available on psilocybin’s effect on major depressive disorder. Five studies were selected according to set inclusion and exclusion criteria. Results are suggesting that psilocybin combined with psychological support is a fast-acting antidepressant agent, able to produce a sustained decrease in symptoms of depression with minimal side effects. However, current studies come with several limitations and further research is needed before the antidepressant effect of psilocybin can be stated as a fact.

Major depression disorder is increasing globally, causing great personal suffering and economic burdens to society. Current antidepressant medications are not sufficiently able to treat all cases of depression and are often associated with troubling side effects. There is a great need for the development of novel treatments, and classic psychedelic drugs are currently being investigated with new interest. The legal status has hindered research, but promising results from pioneering studies on the antidepressant effect of psilocybin have recently given psilocybin breakthrough therapy status, allowing further research to occur more freely. This systematic review aims to investigate the literature available on psilocybin’s effect on major depressive disorder. Five studies were selected according to set inclusion and exclusion criteria. Results are suggesting that psilocybin combined with psychological support is a fast-acting antidepressant agent, able to produce a sustained decrease in symptoms of depression with minimal side effects. However, current studies come with several limitations and further research is needed before the antidepressant effect of psilocybin can be stated as a fact.

Recent evidence shows significant potential for therapies involving psychedelic substances such as psilocybin and MDMA to improve clinical outcomes for patients experiencing various mental disorders. However, research to date focuses almost exclusively on adults. I argue that adolescents should be included in research into psychedelic therapies. First, I demonstrate the pressing need for novel interventions to address the growing mental health burden of adolescents, and I draw on empirical evidence to show that research into psychedelic therapies presents an opportunity to address this shortfall. Secondly, I argue that psychedelics pose low risk to young patients, particularly relative to existing psychiatric medications. I then address two major concerns specific to adolescent contexts. First, I address the risks of using psychedelic substances at earlier stages of physiological and cognitive development. I note that the lack of understanding of the risks underscores the need for including adolescents in research. I then address the added complexity of consent in the adolescent context. I highlight some additional concerns that should be addressed in an “enhanced” informed consent process for adolescents and defend the view that capable adolescents should be able to consent to psychedelic interventions. I ultimately hold that including adolescents in emerging psychedelic research has the potential to substantiate innovative treatments that could improve their clinical outcomes, long-term mental health and quality of life., Des données récentes montrent que les thérapies faisant appel à des substances psychédéliques telles que la psilocybine et la MDMA ont un potentiel important pour améliorer les résultats cliniques des patients souffrant de divers troubles mentaux. Cependant, les recherches menées à ce jour se concentrent presque exclusivement sur les adultes. Je soutiens que les adolescents devraient être inclus dans la recherche sur les thérapies psychédéliques. Tout d’abord, je démontre le besoin urgent de nouvelles interventions pour répondre au fardeau croissant de la santé mentale des adolescents, et je m’appuie sur des preuves empiriques pour montrer que la recherche sur les thérapies psychédéliques offre une opportunité de répondre à ce manque. Deuxièmement, je soutiens que les psychédéliques présentent un faible risque pour les jeunes patients, en particulier par rapport aux médicaments psychiatriques existants. J’aborde ensuite deux préoccupations majeures spécifiques aux contextes adolescents. Premièrement, j’aborde les risques liés à l’utilisation de substances psychédéliques à des stades précoces du développement physiologique et cognitif. Je note que le manque de compréhension de ces risques souligne la nécessité d’inclure les adolescents dans la recherche. J’aborde ensuite la complexité supplémentaire du consentement dans le contexte des adolescents. Je souligne certaines préoccupations supplémentaires qui devraient être abordées dans un processus de consentement éclairé “amélioré” pour les adolescents, et je défends l’idée que les adolescents capables devraient être en mesure de consentir à des interventions psychédéliques. Je soutiens finalement que l’inclusion des adolescents dans la recherche émergente sur les psychédéliques a le potentiel de justifier des traitements innovants qui pourraient améliorer leurs résultats cliniques, leur santé mentale à long terme et leur qualité de vie.

Psychedelic drugs such as psilocybin have shown substantial promise for the treatment of several psychiatric conditions including mood and addictive disorders. They also have the remarkable property of producing persisting positive psychological changes in healthy volunteers for at least several months. In this study (NCT03289949), 35 medium-high doses of psilocybin were administered to 28 healthy volunteers (12 females). By the end of the dosing day, participants reported the intensity of their acute experience using the 30-item Mystical Experience Questionnaire (MEQ) and an open-form qualitative report from home. Persisting psychological effects attributed to the psilocybin experience were measured using the Persisting Effects Questionnaire (PEQ) 3-months after administration. Using a linear latent-variable model we show that the MEQ total score is positively associated with the later emergence of positive PEQ effects (p = 3 x 10(-5)). Moreover, the MEQ subscales "Positive Mood" (p(corr) = 4.1 x 10(-4)) and "Mysticality" (p(corr) = 2.0 x 10(-4)) are associated with positive PEQ whereas the subscales "Transcendence of Time and Space" (p(corr) = 0.38) and "Ineffability" (p(corr) = 0.45) are not. Using natural language pre-processing, we provide the first qualitative descriptions of the "Complete Mystical Experience" induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the Universe, familial love, and the experience of profound beauty. Combining qualitative and quantitative methods, this paper expands understanding of the acute psilocybin induced experience in healthy volunteers and suggests an importance of the type of experience in predicting lasting positive effects.

Background: Psilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans. Aim: Evaluate changes in resting-state functional connectivity (RSFC) at 1 week and 3 months after one psilocybin dose in 10 healthy psychedelic-naive volunteers and explore associations between change in RSFC and related measures. Methods: Participants received 0.2-0.3 mg/kg psilocybin in a controlled setting. Participants completed resting-state functional magnetic resonance imaging (fMRI) scans at baseline, 1-week and 3-month post-administration and [11C]Cimbi-36 PET scans at baseline and 1 week. We examined changes in within-network, between-network and region-to-region RSFC. We explored associations between changes in RSFC and psilocybin-induced phenomenology as well as changes in psychological measures and neocortex serotonin 2A receptor binding. Results: Psilocybin was well tolerated and produced positive changes in well-being. At 1 week only, executive control network (ECN) RSFC was significantly decreased (Cohen's d = -1.73, pFWE = 0.010). We observed no other significant changes in RSFC at 1 week or 3 months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at 1 week predicted increased mindfulness at 3 months (r = -0.65). Conclusions: These findings in a small cohort indicate that psilocybin affects ECN function within the psychedelic 'afterglow' period. Our findings implicate ECN modulation as mediating psilocybin-induced, long-lasting increases in mindfulness. Although our findings implicate a neural pathway mediating lasting psilocybin effects, it is notable that changes in neuroimaging measures at 3 months, when personality changes are observed, remain to be identified.