The use of ketamine and ketamine-assisted psychotherapy (KAP) for treatment of depression has grown dramatically, though much of these data are short term. The clinical profile of maintenance treatment remains poorly characterized. We assessed maintenance KAP for efficacy, tolerability, and reasons for dropout. This observational study retrospectively analyzed electronic health records from an addiction psychiatry practice offering intramuscular ketamine with contemporaneous psychotherapy for the treatment of depression. All patients receiving treatment between January 2016 and September 2022 were included, yielding 1,114 sessions from 70 patients. The response was quantified via the clinical global impression-severity scale. Side effects and reasons for dropout were extracted from charts. Comorbidities include an anxiety disorder (79%) or substance use disorder (49%). The induction yielded 82% response, maintained above 80% after six months (sessions q21 days, 1.13 mg/kg mean dose). Many (38%) remained in treatment for at least one year. Nausea management accounted for nearly all as-needed medication use. Antihypertensives were seldom utilized. Chronic side effects were notable for one case of ketamine use disorder, resulting in residential treatment. Dropouts cited logistical reasons half the time and side effects only 9.7% of the time. KAP yielded robust improvements in mood, anxiety, and substance use. Maintenance sessions effectively extended benefit and were largely well tolerated.

This prospective, randomized, placebo-controlled study assessed the effects of Ashwagandha root extract (ARE) on cognition, energy, and mood in adults with self-reported cognitive and energy problems. Healthy subjects aged 30-75 years were randomized to receive ashwagandha () root extract (ARE) 600 mg/day ( = 60)/identical placebo ( = 60) orally for 8 weeks. Cognitive function was assessed at baseline and week 8 using a Computerized Mental Performance Assessment System (COMPASS). Secondary outcomes were Profile of Mood States Abbreviated Version (POMS-A), Mental Fatigue Scale (MFS) and Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) for effects on mood, mental fatigue and executive function, respectively, assessed at baseline, week 4 and 8. Greater improvement ( < .05) from baseline scores were seen with ARE as against placebo for COMPASS items episodic memory, working memory and accuracy of attention. ARE also improved the POMS-A, MFS and BRIEF-A scores from baseline suggesting an improvement in mood, vigor, and an increase in the executive functioning respectively with ARE. The herb was well tolerated and had a good patient compliance with no serious adverse events reported in either of the groups. This study suggests that a dose of 600 mg a day can improve cognition, energy, and mood in adults with self-reported cognitive and energy problems.

The aim of this study was to explore the perception of psychedelics within the medical population. Participants were asked by questionnaire about the potential of abuse, the somatic and psychiatric complications, and the risks of self-harm and aggression associated with the use of psychedelics using Likert Scales. A total of 407 participants were included. In our sample, the following means were found: 3.05 for general risk (<.001), 2.68 for self-harm risk (<.001), 2.47 for aggression (<.001), 2.71 for addictive risk (< .001), 2.76 for psychiatric disorder risk (<.001), and 2.11 for somatic disorder(< .001). Physicians from the lower mean of age were significantly more supportive of therapeutic potential, while general practitioners were significantly less likely to consider psychedelics as a treatment than specialists (<.001). By the term therapeutic potential, we meant the therapeutic value attributable to psychedelics and the risks expressed the possibility of damage caused by the use of the drug. Clinicians who considered psychedelics as a potential treatment were less likely to associate these with risks than their counterparts (<.001). The results of this study show that the perception of the danger of psychedelic use was important in the medical community in France.

Despite psychedelic microdosing being a growing practice, the research on the topic is still in its infancy. While several studies have described the characteristics, motivations and practices of microdosers, the differences between individuals that only microdose and those that use both micro and macrodoses of psychedelics remain unexplored. In an online survey, we collected data of 6193 psychedelic consumers of which 2488 were microdosers of up to 11 different classical and atypical psychedelics. In comparison to respondents that use both microdoses and macrodoses, exclusive microdosers were older in age (46.4 vs. 42.0 years), had a larger proportion of females (68.4% vs. 44.7%), were non-Caucasian (25.4% vs. 14.7%), urban residents (43.9% vs. 38.5%), and had a lower average lifetime use of non-psychedelic substances (3.8 vs. 4.7 substances). Most consumers (52.5%) microdosed psychedelics multiple times a month, commonly using psilocybin (74.5%), LSD (34.4%), and ketamine (15.8%), with most users (64.6%) not testing their substances. The most common reason for microdosing was improving general wellbeing (73.0%), and psychedelics were used for treating several physical and mental health conditions. Additional analyses examined spending habits of consumers. This study adds to the growing literature on the naturalistic use of psychedelic microdosers.

Psychedelic-assisted therapy is becoming increasingly acknowledged as an effective therapeutic intervention for various psychiatric illnesses. However, the evaluation of masking success is rarely reported in trials. The objective of the present systematic review was to evaluate placebo-control and masking in studies exploring psychedelic-assisted therapy. Nine (k = 9) studies dating between January 2010 and March 2023 were retrieved using six databases, following strict inclusion and exclusion criteria. The results show that almost 78% of the studies had, at best, "poor" masking success. At the same time, 60% of active placebo and 75% of inactive placebo studies showed large effect sizes. In other words, masking influences, including benign unmasking, cannot be excluded. We therefore conclude that efficacy of psilocybin, Ayahuasca, or LSD is only one of the possible interpretations of large, positive changes in symptomatology for patients suffering from, for example, alcohol use disorder, anxiety with or without life-threatening disease, anxiety and/or depression with life-threatening cancer, treatment-resistant depression or major depressive disorder. We recommend care be taken to increase successful masking procedures and discuss alternative treatment designs to better control for potential masking influences.

Psychedelic use has been increasingly accepted socially and legally. However, there is a gap in understanding how religion can influence the relationship between psychedelics and mental health. This study aims to explore this relationship by examining the impact of lifetime classic psychedelic use (LCPU), religious attendance, and religious salience on monthly psychological distress, using the K6 scale. The data for this project is sourced from the National Survey of Drug Use and Health (NSDUH) from 2008 to 2019, with a sample size of 458,372. The analysis utilizes several Ordinary Least Square regression models conducted in Stata 17. The results indicate that both religion and psychedelic use are associated with lower levels of psychological distress. While increased religious salience is linked to reduced distress, this effect is weakened by psychedelic use, as higher salience is associated with higher levels of distress among individuals who have used psychedelics. However, a three-way interaction analysis reveals that individuals with high religious salience and attendance experience the lowest levels of distress.

Methamphetamine (METH) consumption is associated with aggression. Decoction derived from the kratom ( Korth.) leaf has been used as a METH substitute in Southeast Asia. Given its perceived benefit, we investigated the relationship between kratom use and aggression in a treatment sample of METH users and kratom use history. Four hundred and three male METH users participated in this cross-sectional study. A semi-structured questionnaire and several objective clinical measures were administered. Results indicate that there were no significant differences in aggression and its dimensions between METH users and kratom use history. However, two distinct Clusters (1 and 2) of METH users kratom use history were studied. Users in Cluster 1 were characterized by a higher quantity and frequency of daily kratom use, longer duration of kratom use, and use of kratom at a younger age. Users in Cluster 2 exhibited the opposite characteristics. Kratom dependence and the first age of kratom use were identified as risk factors for aggression in Cluster 1. The frequency of daily kratom use appeared as a protective factor against aggression in Cluster 2. The results offer partial support to the instrumental kratom use concept; lower frequency (1 to 3 times) of kratom use may potentially minimize aggression in METH users presenting with mild to moderate kratom dependence.

Many methadone maintenance treatment (MMT) participants experienced a tapering phase. The benefit of tapering is based on a balance between meeting the desire to reduce methadone dose and reduction in relapse. We aimed to develop and validate a nomogram to assess relapse risk after dose tapering. We developed and internally validated a nomogram for risk assessment before dose tapering in 432 participants with dose tapering in the non-Guangzhou region of Guangdong, China, and externally validated it in 117 participants with dose tapering in Guangzhou. Cox regression analysis showed that the taper start week ( = 0.14, [0.08-0.22]) was an independent risk predictor of the relapse risk after tapering. The C-index of the nomogram was 0.76 (95%: 0.73-0.79) in the training cohort, 0.76 (95%: 0.72-0.80) in the testing cohort, and 0.84 (95%: 0.80-0.88) in the validation cohort. Decision curve analysis showed that the nomogram had better discriminative ability than other predictors. The nomogram was developed to assess the risk of relapse for MMT participants who volunteer a tapering phase and may help participants better make decisions about whether and how to reduce the dose to minimize the harm of relapse.

Esketamine, the isolated S-enantiomer of ketamine, has been a recent breakthrough as a non-monoaminergic treatment for treatment-resistant depression (TRD). This case report explores a rare adverse event in a 41-year-old female with TRD, who, despite experiencing significant depressive improvement with esketamine, encountered a severe dissociative episode accompanied by hallucinogenic-like phenomena. While esketamine's efficacy in TRD is well-documented, this pronounced dissociation should be taken into consideration by researchers and clinicians before prescribing. As esketamine continues to aid TRD treatment, comprehension of its safety profile becomes essential for informed decision-making, ensuring optimized patient care in the vast development of antidepressant therapies.

Psilocybin-containing mushrooms, commonly known as magic mushrooms, drastically affect mental processing, cognitive functioning, and the mood state. In the present study, we investigated the effect of the extract on spatial memory and the brain-derived neurotrophic factor (BDNF) in rats exposed to chronic unpredictable mild stress (CUMS). The duration of CUMS was 4 weeks. Spatial learning and memory were measured using the Morris water maze apparatus. The extract was intraperitoneally injected (20 mg/kg) in different time periods: 5 min before training, 24 h before training, 48 h before training, 5 min after training, and 5 min before the probe test. Results showed that CUMS impaired spatial learning and memory, and decreased BDNF in the hippocampus. (24 and 48 h before training) restored spatial learning, while (48 h before training) restored spatial memory impairment in CUMS rats. (24 and 48 h before training) increased BDNF in CUMS rats. administrations (expect 48 h before training) impaired spatial learning and memory and decreased BDNF levels in controls. In conclusion, we suggested that may be beneficial for the improvement of memory deficits induced by CUMS, while the time of injection seems to be an important factor in its final effect.

Alcohol misuse is common in persons on opioid agonist maintenance treatment (OAMT). We tested the efficacy of screening and brief intervention (SBI) for harmful/hazardous alcohol use in buprenorphine/naloxone (BNX)-assisted OAMT. It was a double-blind, parallel-group, randomized trial, where 150 participants with alcohol misuse (Alcohol Use Disorder Identification Test - AUDIT 8-19) on BNX were allocated equally to receive either a single session SBI or screening and brief advice (control). Participants were followed up at three months. The primary outcome was the change in AUDIT; other outcomes were risk transition, change in the frequency of heavy drinking, days of abstinence from alcohol, Gamma-glutamyl transferase (GGT) levels, non-prescription opioid use, and adherence to BNX. Follow-up data was gathered from 138 participants. SBI participants had a higher reduction in AUDIT scores at the follow-up (F = 129. 173, df = 1,  < .001, η =.469). A higher proportion of participants transitioned to a low-risk category in the SBI group. The SBI group showed a higher reduction in heavy drinking and days of alcohol abstinence. Although the proportion of persons with normal serum GGT increased in both groups, the difference was not significant at the follow-up. The SBI group performed better in non-prescription opioid use and BNX adherence.

Buprenorphine is an effective treatment for opioid use disorder but can be slow when using a standard low-dose titration protocol to avoid precipitated withdrawal. This presents a substantial practical barrier in clinical practice. Recent low-dose induction strategies have attempted to simplify and shorten the process required for successful induction, including our own transdermal buprenorphine method, which achieves induction to sublingual buprenorphine/naloxone after 48 h. Here, we present two inpatients with active unregulated fentanyl use that were successfully initiated on buprenorphine extended-release with a novel 24-h transdermal buprenorphine protocol without precipitating withdrawal. This protocol may represent a substantial improvement in the practical feasibility of initiating buprenorphine for patients and providers, although further study is required to confirm efficacy and tolerability.

Presently, 24 states have legalized adult use (recreational) cannabis, each following medical-only access. Although states that pass adult use laws report substantial declines in the number of registered medical patients, these laws expand the market, potentially enhancing patient benefits. However, research on federal adult use cannabis legislation in Canada suggests that adult use laws negatively impact medical patients. The purpose of this mixed-methods study was to examine medical cannabis patients' perceptions of the impact of adult use cannabis laws in the US. We conducted an online survey with forced choice and open-ended questions in a convenience sample of 505 medical cannabis patients. Quantitative analysis indicated that adult use laws decreased stress and legal concerns, and that patient perceptions of cannabis product quality and availability were higher, but prices were also higher. Qualitative analysis largely aligned with quantitative findings, however data were somewhat divergent on price and product availability (with some patients reporting lower prices and accessibility issues). Mixed-methods analysis revealed that legalization also reduced patients' experience of social stigma. Addressing the patient concerns revealed by these data may help to restore or maintain patient access to affordable, medically relevant cannabis products as additional states merge medical cannabis programs into adult use paradigms.

Evidence suggests that individuals who use methamphetamine are at a significantly higher risk of developing psychosis compared to non-users. This study aims to examine the rate of psychosis among methamphetamine users and to investigate factors related to methamphetamine-associated psychosis (MAP). Two thousand ninety-eight (2,098) individuals with methamphetamine use were admitted to outpatient care. Available admissions data included clinical interviews, the Addiction Profile Index (API), and API-clinical forms. MAP was identified in 267 (12.7%) participants. Our data analysis found significant sociodemographic, clinical, and personality differences between MAP and non-MAP cohorts on admission. Multivariate regression analysis revealed that older age (OR = 1.049), younger age of substance use onset (OR = 0.960), more frequent MA use (OR = 1.622), being single (OR = 1.974), lower education (OR = 0.46), increased number of withdrawal symptoms (OR = 1.100), higher lack of anger control scores (OR = 1.422), higher lack of assertiveness scores (OR = 1.396), and higher anxiety scores (OR = 1.715) were significantly associated with MAP. Although factors identified in this study represent state (on admission) rather than stable characterological traits, these results may nonetheless help us better characterize contextual factors associated with MAP in an outpatient population.

International consensus has emerged, which proposes that the measurement and standardization of the quantity of THC potency, or dose (mgTHC), is a requisite for identifying consistent relationships between patterns of cannabis use and the risk for negative health outcomes, especially critical given the increasing number of U.S. states and European countries considering legalizing cannabis for recreational use. Despite the lack of measurement approaches that provide accurate, real-time data on THC dosage, the number of states that have implemented legal adult use cannabis markets has coincided with the use of regulatory seed-to-sale or track-and-trace systems. Seed-to-sale tracking systems are designed to track the amount of cannabis cultivated, and typically leverage biochemical testing contractors to label the THC potencies and amounts on a diverse array of cannabis products. We propose leveraging seed-to-sale tracking systems to facilitate a more objective measure of THC potency. In the current review, we will: 1) summarize the complexities of accurately measuring the multidimensional aspects of cannabis use patterns; 2) review recent advancements in quantifying THC and the importance of standardizing THC dose in measuring cannabis use; and 3) discuss the potential value of future research efforts examining how state-level seed-to-sale tracking data can inform the standard THC dose.

The rising prevalence of kratom use in the United States has led to increased encounters with individuals who consume kratom and those who develop Kratom Use Disorder (KUD) among healthcare professionals. This case series highlights the need for diverse treatment approaches tailored to the individual motivations for kratom consumption. Three cases are presented: one involving the progression from kratom use for energy to opioid-driven use with subsequent challenges in detoxification and transition to naltrexone necessitating buprenorphine low-dose induction for maintenance; another detailing successful inpatient detoxification using methadone and symptom-driven clonidine, followed by successful maintenance treatment with naltrexone; and a final case involving kratom consumption for pain and anxiety self-management by an individual without a history of addictive disorders, without meeting KUD criteria. These cases underscore the complexity of managing individuals who consume kratom as well as those who develop dependence, emphasizing the need for individualized treatment approaches considering various factors such as motivation for use, psychiatric comorbidities, and response to interventions.

Emerging evidence indicates that ayahuasca consumption may have beneficial mental health effects. This study undertakes the largest analysis to date of associations between naturalistic ayahuasca use and current mental health status via an online cross-sectional survey. The sample included 7,576 participants (average age 41, 47% female) who had consumed ayahuasca in religious, traditional, or non-traditional settings in over 50 countries. Bivariate analysis, multivariate linear regressions and generalized structural equation modeling were used to explore associations between ayahuasca use variables, current mental health (K10, SF-12 MCS), and psychological well-being change (PWG). The number of ayahuasca uses was found to be positively associated with current mental health status (all measures), and this remained highly significant in multivariate models, with little evidence of associations diminishing over time. Variables such as the strength of the mystical experience, self-insights, and community/social variables were also positively associated with current mental health and PWG, while acute extreme fear and integration difficulties were negatively associated. Findings suggest that naturalistic ayahuasca use is associated with better current mental health status and enhanced psychological wellbeing for individuals with and without a history of mental illness, independent of community effects, with certain variables contributing positively or negatively to these effects.

Despite increasing interest in psychedelics and their potential therapeutic effects, research on inhaled -Dimethyltryptamine (DMT) remains limited. Inhaled DMT has a reputation for rapid, dramatic onset and a brief duration, but correlates of use frequency remain poorly understood. A sample recruited from relevant internet sites, including nearly 400 people who had inhaled DMT, reported substance use histories, motivations for use, DMT sources, risk perceptions, and other variables. Generally, participants reported initiation motivated by curiosity about DMT's effects, interest in psychedelics more broadly, and potential spiritual benefits. Those who had used other psychoactive substances (especially ayahuasca) and who had extracted DMT themselves reported inhaled DMT more frequently. Most (>60%) reported obtaining DMT from a friend and claimed it was "slightly difficult" to procure. Participants most commonly inhaled DMT from a glass pipe, in private homes, frequently alone or in small groups. Salient positives associated with inhaling DMT included psychologically cleansing or cathartic experiences. Associated challenges concerned difficult integration, aversive experiences, or "bad trips." Participants rated DMT as very or slightly safe. These data underscore the need for continued work on this topic to inform education and harm reduction efforts, particularly as the molecule's reputation for ameliorative effects receives media coverage.

Credibility and expectancy are important aspects of therapy/treatment processes. We aimed to perform cross-cultural validation and examine the psychometric properties of the Credibility/Expectancy Questionnaire (CEQ). Ninety-one patients with opioid use disorder from Tobacco, Alcohol, and Drug Addiction Treatment Program were included in the study. Sociodemographic data form, CEQ, Beck Depression Inventory (BDI), State and Trait Anxiety Inventory (STAI), and Attitudes Toward Seeking Psychological Professional Help Scale-Short Form (ATSPPHS-SF) were filled out by participants. Confirmatory factor analyses showed that CEQ has two factors in our sample, similar to the original version. Reliability analyses showed that CEQ has a high internal consistency and test-retest reliability. Regarding convergent validity results, CEQ was correlated with ATSPPHS-SF. No significant correlation was found between CEQ and BDI and STAI regarding discriminant validity results. In conclusion, the Turkish version of CEQ is a valid, reliable scale and could be used in patients with opioid use disorder. In patients with opioid use disorder, we contributed to the addiction literature by adapting a short and effective survey that measures trust and expectation.

3,4-methylenedioxymethamphetamine (MDMA) assisted therapy has been shown to be a safe and effective treatment for PTSD and emerging research suggests a change in personality traits may be a factor in treatment response. Most prior research on MDMA and personality has focused on cross-sectional comparisons of MDMA users and non-users; as such, well-controlled research assessing personality and affective states following MDMA vs placebo administration is needed. In the current pre-registered study, we investigated the impact of MDMA administration on five-factor model (FFM) traits and affective states before and 48 h after drug administration in a randomized, placebo-controlled study of healthy adults ( = 34). Statistical significance was not observed for the four a priori hypotheses; however, medium effect sizes were found between MDMA administration and trait Openness and Positive Affect 48 h following drug administration, compared to placebo ( = .79 and .51, respectively). This study provides initial results to help guide future well-powered studies with large samples and longer follow-up timepoints to continue to investigate how MDMA impacts personality and emotional experience, which may inform optimization of MDMA treatment approaches.

Cannabis, often criticized, has active compounds that indicate multiple medical benefits. However, before the potential decriminalization and legalization of medical cannabis, pharmacists play a crucial role in the decision-making for personalized therapy and evidence-based medicine. This study investigates pharmacists' perspectives on medical cannabis, covering medical use, societal impact, research, legality, and regulation. This study was conducted through semi-structured interviews with pharmacists from different sectors. Interviews were conducted with 16 pharmacists, with 4 from each sector: industry, academia, community, and hospital. There was a consensus on the need for streamlined research before potential decriminalization and legalization of cannabis, highlighting concerns about abuse and misuse despite its benefits. With that in mind, all participants agree that there is a need to update the current legislation and regulations to better control the use and distribution of medical cannabis. Several participants also called to attention that education plays an important role in the potential decriminalization of medical cannabis, with cannabis-related stigma being a potential deterrent for not only the public but also healthcare professionals. As medical cannabis is a new subject in Malaysia, this study could ignite further multidisciplinary human-related research with strict regulations which will ultimately result in evidence-based medicine.

Given the scarcity of literature regarding COVID-19 impacts on cannabis consumers with chronic illnesses who widely use cannabis to manage their health conditions, we aim to assess the effect of COVID-19 on cannabis use patterns among adults living with chronic diseases. Cannabis consumers with a chronic disease ( = 1,466) from COVID-19 Cannabis Health Study were included in this analysis. The primary outcomes were change in cannabis dosage, past 30-day cannabis usage, and change in route of cannabis administration, with the main exposure being self-reported fear of COVID-19 diagnosis. Significant differences were found between changes in cannabis dose by fear of COVID-19 diagnosis ( = .03) where 41.5% of adults fearing diagnosis reported an increase in their cannabis dosage since the pandemic. Multinomial logistic regression showed that individuals who feared COVID-19 diagnosis had 50% greater odds [aOR = 1.50, 95% CI: 1.02-2.24 of decreasing their cannabis in reference to their dose staying the same, than those without fear of COVID-19, adjusting for socio-demographics. Our findings highlight the significant association between fear of COVID-19 diagnosis and changes in cannabis usage patterns among adults with chronic diseases. This underscores the pandemic's impact on health-related behaviors and the role of cannabis as a coping mechanism during uncertain times.

Ayahuasca is a brew traditionally prepared with a mixture of leaves and vine and has demonstrated therapeutic properties for depression. Knowledge of the brew composition is important to improve the therapeutic potential and decrease side effects if ayahuasca becomes an option for refractory depression treatment. Ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) was applied to analyze 126 ayahuasca samples collected from different groups and geographic origins. We were able to observe a differentiation in the metabolite composition of ayahuasca samples prepared by diverse groups. These samples presented different antioxidant effects based on FRAP and ORAC assays. Exploratory statistical analysis demonstrated a trend of separating the samples according to the religious group. The most important identified compounds for differentiation of the brew prepared by distinct religious groups are glycosylated and/or phenolic compounds. The comparison based on the mode of ayahuasca preparation presented more variability than the comparison based on the botanical variety of used. We conclude that ayahuasca samples prepared with "caupuri" or "tucunacá" separately exhibited differences in the analysis of L-glutamate and the metabolism of arginine and proline. This suggests that a possible variation in this pathway could explain the occurrence of swollen stem nodes in "caupuri," one of the varieties.

Despite the high prevalence of cannabis consumption, there is limited information about cannabis based on scientific evidence available and targeted toward young adults, especially considering accessible language and ease of access. The present study aimed to develop the proof of concept of a chatbot for the dissemination of evidence and scientific information about cannabis, focused on a young adult audience. The proof of concept involved stages of literature review, conversation flow development, content evaluation through a panel of experts ( = 10) and usability analysis using a sample of potential users (young adults,  = 10). The chatbot developed presents information on epidemiology, toxicology, acute and chronic effects of cannabis use, information on cannabis use disorder, and the use of cannabinoids for medicinal purposes. The content evaluation through the Health Education Content Validation Instrument concluded that the tool was considered to have a good structure and content (Content Validity Index > 0,78; overall score = 9.0/10.0). The tool also proved to be functional and highly usable according to the analysis with the . Digital strategies such as chatbots can help in health education and scientific communication within stigmatized areas, such as the consumption of psychoactive substances.

Dysfunctional attitudes - a cornerstone to cognitive psychotherapy - vary with both psychological and pharmacological interventions. Post-acute changes in these cognitions appear to covary with the acute reactions to psychedelics that often precede improved outcomes. An examination of post-acute changes in dysfunctional attitudes could support targeting them in psychedelic-assisted therapy. Screened participants ( = 400+) reported the acute, subjective experiences associated with their most significant psychedelic response as well as post-acute changes in dysfunctional attitudes and subsequent alterations in wellbeing. Dysfunctional attitudes, emotional breakthroughs, and challenging experiences accounted for significant, unique variance in wellbeing. The effects of dysfunctional attitudes generally exceeded those of acute reactions. Comparisons among those acute responses revealed that the effect of emotional breakthroughs exceeded challenging experiences, which exceeded mystical experiences. Nevertheless, the indirect effects through post-acute changes in dysfunctional attitudes did not account for all the impact of acute effects nor interact with them. These results emphasize the import of both acute and post-acute reactions, suggesting that strategies for optimizing each might maximize outcomes for psychedelic-assisted interventions. Furthermore, standard cognitive interventions that alter these cognitions could combine with psychedelics in straightforward ways. The results also support the use of multiple multivariate approaches to address the relative importance of multicollinear predictors.

Psilocybin, a major indole alkaloid found in magic mushrooms (), has recently drawn attention as a breakthrough therapy to treat major depressive disorder. This review aimed to summarize and identify knowledge gaps concerning their pharmacokinetic characteristics of psilocybin and its active metabolite, psilocin. Original studies related to pharmacokinetics of psilocybin conducted , animals, and humans were systematically collected from PubMed, Scopus, and ScienceDirect, from their inceptions to November 2023. Twenty articles were included in this work and assessed for study quality. A comprehensive review of the pharmacokinetics of psilocybin and psilocin in both animals and humans was performed. Psilocybin is considered a prodrug that is dephosphorylated to psilocin by alkaline phosphatase. Following ingestion, the peak psilocin plasma and brain levels were rapidly achieved in a dose-dependent manner. Psilocin is metabolized primarily through both Phase I and Phase II processes with the half-life of 2-3 hours. This review also identified lack of some pharmacokinetic related information and limitations of available research that may help direct future investigations to better understand the pharmacokinetics and improve study design including dose selection and dosage optimization.

We sought to identify patterns of psychedelic use among United States military veterans, compare demographic variables and perspectives of those who did and did not report use, and characterize benefits and adverse outcomes associated with use. Respondents ( = 426) were recruited to complete an online cross-sectional survey. Approximately one-half (51%) reported using psychedelics. Most did so for healing/treatment (70%) and/or spiritual purposes (48%), and most (85%) reported benefiting from use. Those who used psychedelics reported they would be more likely to use VA services ( < .001, d = 0.64) and to return to the VA for care ( < .001, d = 0.79) if psychedelic therapy was offered. Almost two-thirds (59%) reported adverse outcomes associated with use. Equivalent proportions rated their psychedelic experiences as beneficial among those who did (89%) and did not (81%) report adverse outcomes. Fewer adverse outcomes were associated with being older, using psilocybin, feeling prepared and confident in the reasons for use, being in a comfortable setting, and being able to "trust, let go, and be open" (R = 0.77;  < .001). Psychedelics may offer benefits but may also lead to adverse outcomes without proper preparation and support. Future research should examine the utility of psychedelic-based approaches for veteran mental health care.

Emerging legal frameworks in Oregon and Colorado license facilitators to support adults receiving psychedelic services. The current legal frameworks are silent regarding facilitators' personal experience with psychedelics. An e-Delphi process recruited 36 experts with at least 5 years' experience facilitating psilocybin experiences in ceremonial settings, indigenous practices, or clinical trials. Respondents completed in-depth, semi-structured qualitative interviews via secure web links. Interviews were recorded, transcribed, and analyzed using Thematic Analysis. Experts with a mean of 15.2 (SD 13.1) years' experience providing psilocybin services expressed the importance of first-hand experience with psychedelics as a qualification for the emerging workforce. One participant questioned the necessity of personal psychedelic experience. Experts suggested that personal experience may indirectly support high-quality care because it enhances facilitators' personal wellbeing, and may help facilitators understand the complexity and nature of their clients' psychedelic experiences. Novel state-legal psychedelic paradigms create a real-world opportunity to assess associations between facilitators' personal psychedelic experience and the safety and outcomes of psychedelic services.

Psychedelic-assisted therapy (PAT) has shown preliminary efficacy for psychiatric and physical health conditions. Although some people report naturalistic psychedelic use with so-called "underground" practitioners, little is known about PAT that occurs outside of controlled clinical settings or perspectives of these practitioners. We conducted an anonymous online survey of individuals who reported providing psychedelic support services (e.g. trip sitting and/or preparatory/follow-up psychotherapy) in naturalistic settings. We investigated demographics, including education and licensing, details about services provided, and reported client outcomes. Among 107 participants, 40.2% held a full or in-progress license and 44.9% had not obtained a relevant graduate degree. Almost all participants reported pre-screening clients before treatment, offering preparation, integration, and trip-sitting services, and most employed a range of therapeutic modalities, centering primarily on non-directive approaches. Participants reported that clients most commonly consumed psilocybin, and treated numerous conditions, primarily aligning with indications targeted in psychedelic clinical research. Perceptions of clients' symptom changes were largely positive, although a small proportion reported worsened personality disorder symptoms. Further research delineating client and practitioner perspectives of naturalistic PAT services is warranted, and such work may shed light on the benefits and risks specific to naturalistic PAT as well as inform best practices for practitioners.

Growing evidence suggests the tendency to act rashly under positive and negative emotions and affect-related drinking motives connect symptoms of mood disorders with alcohol-related problems. However, studies examining this sequence are scarce in Latin-American samples. The present study evaluated, in Argentinian college students ( = 403; 68.2% women; age = 21.03 ± 4.90), a sequential model of symptoms of depression, urgency traits, internal drinking motives, and problematic alcohol use. Path analysis was conducted to examine the direct and indirect associations between symptoms of depression and problematic alcohol use (heavy episodic drinking and alcohol-related negative consequences) via positive and negative urgency traits and internal drinking motives. Findings revealed indirect associations from depressive symptoms to problematic alcohol use via urgency traits and drinking motives (e.g. depression symptoms→positive [negative] urgency→enhancement [coping]→drinking problems). This suggests that students who experience more symptoms of depression may be more likely to react to these experiences of negative affect by engaging in heavy drinking episodes and encounter more alcohol-related problems. This seems to stem from a higher propensity to act rashly during intense emotional experiences and a greater motivation to drink as a means of regulating their mood. Future interventions aimed at preventing or reducing problematic alcohol use (especially among Argentinian young adults) might consider targeting these specific impulsivity traits as well as affect-related drinking motivations.