Search

Introduction: Despite considerable efforts, tobacco use disorder persists as a significant public health issue. The effectiveness of current smoking cessation therapies is limited, leading to a growing interest in alternative treatment approaches such as psychedelics. Aim: The aim of this review is to evaluate the scientific evidence regarding the role of psychedelics in smoking cessation. Methods: To identify relevant literature on psychedelics and smoking cessation, a search was conducted in four academic literature databases PubMed, MEDLINE, PsycINFO, and Embase. Databases were searched from their inception up to March 24, 2024. Results: Out of the 1073 articles identified in databases, 8 publications (both clinical and non-clinical studies) met the inclusion criteria, of which a total of 4 publications originated from a single study. The majority of the studies focused on psilocybin (n = 7), for which supportive evidence was suggested for the treatment of tobacco use disorder. Additionally, research was conducted with other psychedelics for smoking cessation, such as ayahuasca, mescaline, peyote, lysergic acid diethylamide (LSD), lysergic acid amide (LSA) and (dimethyltryptamine (DMT), but the evidence base for these psychedelics is too small to draw definitive conclusions. Conclusions: There is, although limited, evidence that psychedelics, in particular psilocybin, may offer a potential avenue for combating tobacco use disorder, though more research is needed to understand their effectiveness and safety fully. [ABSTRACT FROM AUTHOR]

Background and aims Design and setting Cases Measurements Findings Conclusion Drugs sold on cryptomarkets are thought to have lower levels of adulteration and higher strength compared with those sourced off‐line. The present study aimed to determine whether cryptomarket and off‐line‐sourced 3,4‐methylenedioxy‐N‐methamphetamine (MDMA), cocaine, amphetamine, methamphetamine and lysergic acid diethylamide (LSD) differed in adulteration and strength.A between‐groups design was used to compare cryptomarket versus off‐line‐sourced drugs. Regression analyses controlling for year and service were conducted. Drug‐checking services were conducted in Spain (Energy Control) and the Netherlands (Drugs Information and Monitoring System).The cases comprised drug samples that underwent drug checking between 2016 and 2021 and were expected to contain MDMA (tablets; n = 36 065; powder: n = 6179), cocaine (n = 11 419), amphetamine (n = 6823), methamphetamine (n = 293) and LSD (n = 1817).Drugs were measured for (1) matching the advertised substance (i.e. containing any amount of the expected substance); (2) strength; (3) presence of adulteration; and (4) number of adulterants.The expected drug was more likely to be identified when sourced from cryptomarkets versus off‐line for MDMA tablets [adjusted odds ratio (AOR) = 2.10, 95% confidence interval (CI) = 1.28–3.43], MDMA powder (AOR = 2.64, CI = 1.55–4.51), cocaine (AOR = 3.65, CI = 1.98–6.71) and LSD (AOR = 1.75, CI = 1.13–2.72). Cryptomarket‐sourced MDMA powder (β = 0.03, P = 0.012), cocaine (β = 0.08, P < 0.001) and methamphetamine (β = 0.15, P = 0.028) were statistically significantly higher in strength than substances from off‐line sources. Conversely, MDMA tablets (β = −0.01, P = 0.043) and amphetamine (β = −0.07, P < 0.001) from cryptomarkets were statistically significantly lower in strength than from off‐line sources. MDMA powder (AOR = 0.53, CI = 0.33–0.86) and cocaine (AOR = 0.66, CI = 0.55–0.79) were statistically significantly less likely to be adulterated if sourced from cryptomarkets. However, amphetamine (AOR = 1.54, CI = 1.25–1.90) and LSD (AOR = 1.31, CI = 1.00–1.71) were found to be more likely to be adulterated when purchased from cryptomarkets. Cocaine from cryptomarkets exhibited fewer adulterants (incidence rate ratio = 0.71, CI = 0.60–0.85).The relationship between on‐line drug market‐places and substance quality varies depending on both the specific substance and the dynamics of the cryptomarket. [ABSTRACT FROM AUTHOR]

Accumulating evidence has shown that some hallucinogens, such as LSD, have fast and persistent effects on anxiety and depression. According to a proposed mechanism, LSD activates the TrkB and HTR2A signaling pathways, which enhance the density of neuronal dendritic spines and synaptic function, and thus promote brain function. Moreover, TrkB signaling is also known to be crucial for neural stem cell (NSC)-mediated neuroregeneration to repair dysfunctional neurons. However, the impact of LSD on neural stem cells remains to be elucidated. In this study, we observed that LSD and BDNF activated the TrkB pathway in human NSCs similarly to neurons. However, unlike BDNF, LSD did not promote NSC proliferation. These results suggest that LSD may activate an alternative mechanism to counteract the effects of BDNF-TrkB signaling on NSCs. Our findings shed light on the previously unrecognized cell type-specificity of LSD. This could be crucial for deepening our understanding of the mechanisms underlying the effects of LSD. [ABSTRACT FROM AUTHOR]

A variety of LSD analogs have emerged in recent years with dual purposes of avoiding prosecution from possession while providing new options for those willing to experiment with hallucinogenic drugs. In this study, a previously published automated sample preparation method for LSD and its primary metabolite (OH‐LSD) was utilized to extract LSD, OH‐LSD, and nine LSD analogs from urine. The liquid chromatography tandem mass spectrometry (LC–MS/MS) method was modified from the previously published LC conditions to utilize a different analytical column and gradient elution program. Mobile phases of 10 mM ammonium formate with 0.1% formic acid in deionized water (mobile phase A) and 0.1% formic acid in methanol (mobile phase B) were employed. The method was validated to ANSI/ASB Standard 036 with a 0.1 ng/mL limit of detection for all analytes and was utilized for the analysis of 325 urine specimens. Although no LSD analogs were observed in the samples analyzed, this validated method was demonstrated to be suitable for the analysis of these compounds in laboratories seeking to expand their testing scope. Automated sample preparation allows for the efficient analysis of these analytically challenging compounds with minimal manual handling. Additionally, there was no increased analytical time burden when the LC column and gradient were modified to target nine additional analytes. Detection may improve as new reference standards are developed to allow laboratories to focus on the metabolic products of these analogs. For now, this validated procedure can assist with the routine analysis and surveillance of these emerging substances. [ABSTRACT FROM AUTHOR]

With the discovery of the antidepressive effects of ketamine and the increasing withdrawal of the pharmaceutical industry from the development of new psychotropic drugs, the psychiatric research into the clinical application of hallucinogens in psychiatry has literally blossomed in the last two decades. Promising results for various treatment approaches with psychedelic agents, such lysergic acid diethylamide (LSD) and psilocybin, and dissociative agents, such as ketamine and esketamine, have raised great hopes among researchers, clinicians and patients in recent years, so that there was already talk of a new era in psychiatry. As one of the first of these substances, in December 2019 intranasal esketamine was approved in the USA and the EU for the treatment of treatment-resistant depression and Switzerland followed in 2020. Recently, psilocybin was approved in Australia, Canada and Switzerland for compassionate use in exceptional cases for the treatment of depression, while large approval studies with various psychedelic agents are currently ongoing worldwide. The medical application of psychedelic agents and ketamine/esketamine is considered to be safe; however, as with all new forms of treatment it is of crucial importance that, in addition to the hopes, the specific challenges of these new treatment approaches must also be carefully considered and assessed. Excessive expectations and an insufficient risk-benefit estimation are detrimental to the patients and the reputation of the treating physician. Although a possible paradigm shift in the care of mental health is already being discussed, this review article consciously concentrates on the possible risks of treatment and the methodological weaknesses of the studies carried out so far. [ABSTRACT FROM AUTHOR]

Background and aims: Lysergic acid diethylamide (LSD) and psilocybin are used as recreational drugs, and there is renewed interest in their clinical use. The current study aimed to (1) determine the circumstances of death and case characteristics of LSD‐ and psilocybin‐related death in Australia, 2000–23; and (2) determine the toxicological profile and major autopsy findings of these cases. Methods: This was a retrospective exploratory study of all cases of LSD‐ and psilocybin‐related death in Australia, 2000–23, retrieved from the National Coronial Information System. Results: A total of 43 cases were identified: 33 LSD and 10 psilocybin. The median ages were 24 years [interquartile range (IQR) = 13, range = 16–53] (LSD) and 26 years (IQR = 18.5, range = 20–58) (psilocybin), and fewer than five cases were female. The most common circumstance of death among both groups was traumatic accident (LSD 36.4%, psilocybin 40.0%). There were 12 cases of self‐harm, all of which involved LSD, all by physical means. In a fifth, death was attributed to multiple drug toxicity (LSD 18.2%, psilocybin 20.0%). In one case, death was attributed solely to LSD toxicity, while in a further two cases death was attributed to a cardiovascular event following LSD consumption (one LSD only, one multiple drug toxicity). In four psilocybin cases, the cause of death was undetermined. The most common clinical presentation was severe agitation (LSD 27.3%, psilocybin 20.0%). Median blood concentrations were LSD 0.8 μg/l (IQR = 1.7, range = 0.1–3), psilocin 20 μg/l (IQR = 53.5, range = 6–83). LSD was the only drug present in 25.0% of LSD cases and psilocybin in 20.0% of psilocybin cases. Pre‐existing organ pathology was uncommon. Conclusions: Lysergic acid diethylamide (LSD)‐ and psilocybin‐related death in Australia from 2000 to 2023 was primarily due to traumatic injury, whether through accident or self‐harm. Cases of acute toxic reactions that were attributed solely to LSD were rare. [ABSTRACT FROM AUTHOR]

Although the current data are scarce and fragmentary, the misuse of electronic cigarette devices (ENDSs) for smoking illicit drugs poses a serious emergent threat to public health. This review emphasises the use of ENDSs as new tools for smoking illicit drugs. A comprehensive search using the terms "illicit drugs", "vape", and "electronic cigarettes" was conducted in PubMed, web-based drug forums, chat sites and grey literature combined with theterms tobacco, nicotine, smoking, cigarettes, cannabis, marijuana, opiate, opioid, heroin, cocaine, synthetic opioids/cannabinoids, cathinones, LSD, dimethyltryptamine (DMT), 3,4 methylenedioxymethamphetamine (MDMA), methamphetamine (Meth), vape/vaping, e-liquid and addiction. Studies were included if they met the following criteria: 1) involved human participants (Female, male, intersex); 2) consumed any type of illicit drug using electronic cigarette; 3) all ages were taken into consideration. We used all combinations of search terms from each category for articles published between January 2013 and October 2023 a long period due to the fact that in the last years ENDS cigarettes have undergone improvements in their structure having the ability to regulate the evaporation temperature and facilitate the potential for use of these devices to 'vape' illicit drugs. In addition to nicotine, the main vaped drugs were cannabis, cocaine and new psychoactive substances (NPSs), which included synthetic cannabinoids, synthetic opioids, hallucinogens and stimulant drugs. An increase in the risk of overdose and death with the use of NPSs is reported. Further work is urgently needed for a better understanding on the effect of vaping illicit drugs in the population. It is confirmed that ENDSs are becoming popular devices among both young and older individuals, with a mean age of use of 46.26 ± 16.8 years, as a new way of taking illicit drugs. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) poses a significant global health burden with available treatments limited by inconsistent efficacy and notable side effects. Classic psychedelics, including lysergic acid diethylamide (LSD), have garnered attention for their potential in treating psychiatric disorders. Microdosing, the repeated consumption of sub-hallucinogenic doses of psychedelics, has emerged as a self-treatment approach for depression within lay communities. Building upon preliminary evidence and the successful completion of an open-label pilot trial of microdosing LSD for depression (LSDDEP1), this protocol outlines a phase 2b randomised controlled trial (LSDDEP2). The main objective of LSDDEP2 is to assess the modification of depressive symptoms, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), following a regimen of LSD microdoses versus placebo. Methods: This is a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients meeting DSM-5 criteria for major depressive disorder. Participants will undergo an 8-week LSD microdosing regimen using the titratable MB-22001 formulation taking two doses a week. All doses will be self-administered at home and will be titratable from 4 to 20 μg based on subjective perception and tolerability. In addition to depression symptoms, outcome will include psychiatric and personality inventories, sleep and activity tracking, electroencephalography (EEG), blood biomarkers, semi-structured interviews, and safety (e.g. adverse event, laboratory exam) measures. Discussion: This study will be the first randomised controlled trial to administer controlled microdoses of LSD for treatment of MDD in participants' naturalistic environment. The measures included are designed to assess the drug's safety, mechanism, and treatment efficacy over placebo in this population. The results of this study will be important for assessing the viability of psychedelic microdosing as an additional treatment option and for informing the direction of future clinical trials. Trial registration: ANZCTR, ACTRN12624000128594. Prospectively Registered on 13 February 2024. [ABSTRACT FROM AUTHOR]

Psychedelic substances, which can occasion mystical experiences, are sometimes used for religious and spiritual reasons. Despite strong links between psychedelics and spirituality, no previous systematic review has investigated connections between psychedelics and indicators of long-term spiritual growth. Thus, 34 empirical studies were analyzed with 19,724 total participants from 32 independent samples. A variety of methodologies were used among the reviewed studies, and some studies included international samples. Results showed that psychedelics—especially classic psychedelics (e.g., psilocybin, LSD, and DMT)—have been studied more often in this context than other substances. Findings indicate that psychedelic use is linked with a variety of subjective indicators of spiritual growth, including stronger perceived connections with the divine, a greater sense of meaning, increased spiritual faith, increased engagement in religious and spiritual practices, an increase in feelings of unity and self-transcendence, positive changes in worldview, increased connectedness with others, and reduced fear of death. Many studies that reported on one of these indicators also reported on others, implying a co-occurrence of these facets during and after psychedelic experiences. Spiritual growth was often related to mystical experiences, with higher mystical experience ratings associating positively with perceived spiritual growth. [ABSTRACT FROM AUTHOR]

LSD is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. This is the first study to follow the developmental changes in brain structure and function following LSD exposure in periadolescence. We hypothesized LSD given during a time of heightened neuroplasticity, particularly in the forebrain, would affect cognitive and emotional behavior and the associated underlying neuroanatomy and neurocircuitry. Female and male mice were given vehicle, single or multiple treatments of 3.3 µg of LSD by oral gavage starting on postnatal day 51. Between postnatal days 90–120 mice were imaged and tested for cognitive and motor behavior. MRI data from voxel-based morphometry, diffusion weighted imaging, and BOLD resting state functional connectivity were registered to a mouse 3D MRI atlas with 139 brain regions providing site-specific differences in global brain structure and functional connectivity between experimental groups. Motor behavior and cognitive performance were unaffected by periadolescent exposure to LSD. Differences across experimental groups in brain volume for any of the 139 brain areas were few in number and not focused on any specific brain region. Multiple exposures to LSD significantly altered gray matter microarchitecture across much of the brain. These changes were primary associated with the thalamus, sensory and motor cortices, and basal ganglia. The forebrain olfactory system and prefrontal cortex and hindbrain cerebellum and brainstem were unaffected. The functional connectivity between forebrain white matter tracts and sensorimotor cortices and hippocampus was reduced with multidose LSD exposure. Does exposure to LSD in late adolescence have lasting effects on brain development? The bulk of our significant findings were seen through changes is DWI values across 74 brain areas in the multi-dose LSD group. The pronounced changes in indices of anisotropy across much of the brain would suggest altered gray matter microarchitecture and neuroplasticity. There was no evidence of LSD having consequential effects on cognitive or motor behavior when animal were evaluated as young adults 90–120 days of age. Neither were there any differences in the volume of specific brain areas between experimental conditions. The reduction in connectivity in forebrain white matter tracts with multidose LSD and consolidation around sensorimotor and hippocampal brain areas requires a battery of tests to understand the consequences of these changes on behavior. [ABSTRACT FROM AUTHOR]

Psychedelics like LSD (Lysergic acid diethylamide) and psilocybin are known to modulate perceptual modalities due to the activation of mostly serotonin receptors in specific cortical (e.g., visual cortex) and subcortical (e.g., thalamus) regions of the brain. In the visual domain, these psychedelic modulations often result in peculiar disturbances of viewed objects and light and sometimes even in hallucinations of non-existent environments, objects, and creatures. Although the underlying processes are poorly understood, research conducted over the past twenty years on the subjective experience of psychedelics details theories that attempt to explain these perceptual alterations due to a disruption of communication between cortical and subcortical regions. However, rare medical conditions in the visual system like Charles Bonnet syndrome that cause perceptual distortions may shed new light on the additional importance of the retinofugal pathway in psychedelic subjective experiences. Interneurons in the retina called amacrine cells could be the first site of visual psychedelic modulation and aid in disrupting the hierarchical structure of how humans perceive visual information. This paper presents an understanding of how the retinofugal pathway communicates and modulates visual information in psychedelic and clinical conditions. Therefore, we elucidate a new theory of psychedelic modulation in the retinofugal pathway. [ABSTRACT FROM AUTHOR]

Some recent research and commentary have suggested that most or all the effects reported by people who microdose psychedelics may be explained by expectations or placebo effects. In this rapid review, we aimed to evaluate the strength of evidence for a placebo explanation of the reported effects of microdosing. We conducted a PubMed search for all studies investigating psychedelic microdosing with controlled doses and a placebo comparator. We identified 19 placebo-controlled microdosing studies and summarised all positive and null findings across this literature. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The reviewed papers indicated that microdosing with LSD and psilocybin leads to changes in neurobiology, physiology, subjective experience, affect, and cognition relative to placebo. We evaluate methodological gaps and challenges in microdosing research and suggest eight reasons why current claims that microdosing is predominately a placebo are premature and possibly wrong: (1) there have been only a small number of controlled studies; (2) studies have had small sample sizes; (3) there is evidence of dose-dependent effects; (4) studies have only investigated the effects of a small number of doses; (5) the doses investigated may have been too small; (6) studies have looked only at non-clinical populations; (7) studies so far have been susceptible to selection bias; and (8) the measured impact of expectancy is small. Considering the available evidence, we conclude that it is not yet possible to determine whether microdosing is a placebo. [ABSTRACT FROM AUTHOR]

Background: The recreational use of LSD, a synthetic psychedelic drug, has surged in recent years, coinciding with a renewed research focus on its potential psychotherapeutic properties. Aim: This study aims to describe the experiences and perceptions of individuals engaging in LSD use for the first time, derived from a large international sample. Methods: This study utilised 2018 Global Drug Survey data collected from 6 November 2017 to 10 January 2018. Participants who initiated LSD use in the preceding 12 months answered questions on their experiences, social settings, harm-reduction behaviours, and demographics. Descriptive statistics were employed, and characteristics of those seeking emergency medical treatment (EMT) and those not planning further LSD use were compared with other respondents. Results: Among 3340 respondents who used LSD in the past year, their first-time experiences generally exceeded expectations, with 97.7% expressing excitement. Adverse and unwanted side effects were rarely reported, and only 17 individuals needed EMT. Feelings of fear were reported by most (64.1%), but only very mildly and not enough to put them off from wanting to use LSD again. Discussion: Although the occurrence of unwanted side effects seems low and the LSD experience is generally pleasurable, vigilance amid the rising illicit use of LSD through harm-reduction education is still important in preventing possible risks. [ABSTRACT FROM AUTHOR]

This editorial discusses the diagnostic process for rhabdomyolysis, a condition characterized by muscle breakdown. The authors conducted a study and found that genetic testing was effective in diagnosing the condition in 15 out of 66 patients. They suggest that genetic testing should be the first step in diagnosing unprovoked rhabdomyolysis. The authors also emphasize the importance of distinguishing between triggers and underlying genetic susceptibility and propose using the RHABDO acronym to identify those at risk. They provide a flowchart for referral and diagnostic screening and call for further research on the predictive value of the acronym. They also highlight the need for a different diagnostic approach for children and adolescents and stress the importance of safe return to physical exercise and prevention of triggers after rhabdomyolysis. [Extracted from the article]

Psychoactive substances obtained from botanicals have been applied for a wide variety of purposes in the rituals of different cultures for thousands of years. Classical psychedelics from N,N′‐dimethyltryptamine, psilocybin, mescaline and various lysergamides cause specific alterations in perception, emotion and cognition by acting through serotonin 5‐HT2A receptor activation. Lysergic acid diethylamide, the first famous breakthrough in the field, was discovered by chance by Albert Hoffman in the Zurich Sandoz laboratory in 1943, and studies on its psychoactive effects began to take place in the literature. Studies in this area were blocked after the legislation controlling the use and research of psychedelic drugs came into force in 1967, but since the 1990s, it has started to be a matter of scientific curiosity again by various research groups. In particular, with the crucial reports of psychotherapy‐assisted psilocybin applications for life‐threatening cancer‐related anxiety and depression, a new avenues have been opened in the treatment of psychiatric diseases such as treatment‐resistant depression and substance addictions. An increasing number of studies show that psychedelics have a very promising potential in the treatment of neuropsychiatric diseases where the desired efficiency cannot be achieved with conventional treatment methods. In this context, we discuss psychedelic therapy, encompassing its historical development, therapeutic applications and potential treatment effects—especially in depression, trauma disorders and substance use disorders—within the framework of ethical considerations. [ABSTRACT FROM AUTHOR]

In the past few years, psilocybin, a psychedelic compound found in “magic mushrooms” (psilocybin mushrooms), has undergone decriminalization in numerous cities across the US and has been legalized in Oregon and Colorado. Proponents of psilocybin decriminalization have emphasized its therapeutic potential in treating mental health disorders. Furthermore, psilocybin mushrooms are considered the safest psychedelic option, with lower potency and a reduced risk of overdoses and emergency hospitalizations compared to other prevalent psychedelics, such as LSD (lysergic acid diethylamide) and MDMA (3,4-methylenedioxymethamphetamine). We analyzed the impact of psilocybin reforms on public interest in psilocybin, as well as their cross-commodity effects on LSD and MDMA, utilizing extensive web-based search data. We observe a significant increase in psilocybin search volume and a notable reduction in search volume associated with LSD and MDMA. Our results are consistent nationwide across states, irrespective of their stance on psilocybin reforms. The shift in public interest toward psilocybin, which is considered the safest psychedelic, away from LSD and MDMA, carries positive implications for public health. [ABSTRACT FROM AUTHOR]

The therapeutic use of psilocybin in psychedelic-assisted therapy models is currently being tested for a variety of indications, necessitating the training of hundreds of therapists. At present, training programs do not include the provision of a psilocybin experience for therapists, and the last time such an experience was offered with a similar compound was through the Spring Grove LSD Training Study between 1969 and 1974. This article explores archival Spring Grove data to inform training programs and efforts to establish or provide training experiences with psilocybin or otherwise include experiences with nonordinary states of consciousness in the training of psychedelic therapists. [ABSTRACT FROM AUTHOR]

Purpose: To examine the associations of age when first substance use and early-onset substance use before age 18 with age at onset (AAO) of hypertension. Methods: This study included 19,270 individuals with AAO of hypertension from the 2015–2019 National Survey on Drug Use and Health. Age when first use of 10 substance use variables included alcohol, daily cigarettes, cigars, smokeless tobacco, marijuana, cocaine, hallucinogens, lysergic acid diethylamide (LSD), inhalants, and methamphetamine use. The outcome was AAO of hypertension and variable cluster analysis was used to classify the exposures and outcome. Substance use status was classified into three categories: early-onset substance use (first used substance before age 18), late-onset substance use (first used substance after age 18), and never used. Results: The mean AAO of hypertension was 42.7 years. Age when first use of 10 substance use variables had significant correlations with AAO of hypertension (all p values < 0.001). Individuals with early-onset alcohol, cigars, smokeless tobacco, marijuana, hallucinogens, inhalants, cocaine, LSD, and methamphetamine use revealed significantly earlier onset of hypertension than those never used. Compared with never used substances, the Cox regression model showed that early-onset alcohol, smokeless tobacco, marijuana, inhalants, and methamphetamine use had an increased risk of AAO of hypertension [hazard ratio (HR) (95%CI) = 1.22 (1.13, 1.31), 1.36 (1.24, 1.49), 1.85 (1.75, 1.95), 1.41 (1.30, 1.52), and 1.27 (1.07,1.50), respectively]. Conclusion: These findings suggest that intervention strategies or programs focusing on preventing early-onset substance use before age 18 may delay the onset of adult hypertension. [ABSTRACT FROM AUTHOR]

Studies of psychedelic-assisted therapy with LSD, psilocybin, MDMA, and related substances show clinical promise but inadequately assess side effects. Measuring side effects is challenging because they are not always easily differentiated from treatment effects or disease symptoms and show high heterogeneity, variable duration and impact, and sensitivity to context. A systematic questionnaire describing important characteristics of side effects of psychedelics and MDMA would greatly improve on previous methods. We aimed to create a standardized tool for recording clinically relevant side effects of psychedelics and MDMA, including their severity, duration, impact, and treatment-relatedness. We constructed the Swiss Psychedelic Side Effects Inventory (SPSI) based on insights from previous research. It was pilot tested in 145 participants from three studies. Structured feedback from an expert panel was used to improve validity and feasibility. The final SPSI contains 32 side effects and standardized follow-up questions about their severity, impact, treatment-relatedness, and duration. It is compatible with any study design and can be administered as an interview or self-report at any timepoint after treatment with psychedelics or MDMA. The SPSI omits relatively unimportant side effects for brevity's sake, though space for additional symptoms is given. Future studies are needed to confirm its validity in different contexts. The SPSI is available in English and German for collecting systematic data on side effects from psychedelics and MDMA. This information is vital for improving clinical decisions, informed consent, and patient safety. • Psychedelics and MDMA can cause a unique profile of side effects which are not well-captured by the methods used in previous studies. • Psychedelic side effects vary in their severity, duration, and subjective impact. • Using previous studies, pilot data, and expert feedback, we developed the Swiss Psychedelic Side Effects Inventory (SPSI). • The SPSI contains 32 side effects and assesses their severity, impact, duration, and treatment-relatedness. • The SPSI can be used at any timepoint after psychedelic administration in any study of psychedelics or MDMA. [ABSTRACT FROM AUTHOR]

Mental health disorders and substance use disorders (SUDs) in particular, contribute greatly to the global burden of disease. Psychedelics, including entactogens and dissociative substances, are currently being explored for the treatment of SUDs, yet with less empirical clinical evidence than for other mental health disorders, such as depression or post-traumatic stress disorder (PTSD). In this narrative review, we discuss the current clinical research evidence, therapeutic potential and safety of psilocybin, lysergic acid diethylamide (LSD), ketamine, 3,4-methylenedioxymethamphetamine (MDMA) and ibogaine, particularly in the context of the SUD treatment. Our aim was to provide a balanced overview of the current research and findings on potential benefits and harms of psychedelics in clinical settings for SUD treatment. We highlight the need for more clinical research in this particular treatment area and point out some limitations and challenges to be addressed in future research. [ABSTRACT FROM AUTHOR]

This article provides an overview of the psychological and neural mechanisms of psychedelic compounds and their potential use in treating mental health and medical conditions. It discusses the therapeutic effects of psychedelics on various mental health conditions, including depression, anxiety disorders, autism, PTSD, and substance use disorders. The article explores the cellular, molecular, network, and circuit-level mechanisms through which psychedelics work, as well as the psychological and behavioral effects they produce. It also highlights the role of mystical experiences, reactivations, ayahuasca-induced personal death experiences, and environmental factors in psychedelic therapy. The article concludes by emphasizing the importance of interdisciplinary research and responsible use of psychedelics in psychiatry and mental health. The document includes references to studies and clinical trials that investigate the use of psychedelics in the treatment of mental health conditions, such as depression, anxiety, and alcohol dependence. These studies suggest that substances like ayahuasca, psilocybin, and MDMA may have positive effects on symptoms and outcomes for individuals with these conditions. However, further research is needed to fully understand the efficacy and safety of these treatments. [Extracted from the article]

Recent studies on classic psychedelics have suggested that their use is associated with psychological strengths and resilience, thereby conferring users a type of psychological protection relative to non-users. However, this idea has been brought into question by recent findings suggesting that lifetime users of lysergic acid diethylamide (LSD) report worse mental health during stressful experiences. The current study addresses these mixed findings by examining whether LSD use prior to a stressful experience buffers against the psychological distress experienced in the wake of the stressful experience. This study draws on openly-available data from the National Survey on Drug Use and Health (2008–2019) on 5,067,553 (weighted) unemployed, job seeking individuals experiencing job loss. Using purposeful respondent exclusion criteria to establish temporal precedence of the variables under investigation, this study offers a straightforward test of whether LSD use confers psychological resilience to naturalistic users. LSD use prior to job loss was associated with a higher likelihood of severe psychological distress following job loss, regardless of whether sociodemographic variables were controlled for or not. In sum, this study fails to find evidence for LSD-conferred psychological resilience in naturalistic users in the wake of a stressful experience. [ABSTRACT FROM AUTHOR]

Electrophysiologic measures provide an opportunity to inform mechanistic models and possibly biomarker prediction of response. Serotonergic psychedelics (SPs) (i.e., psilocybin, lysergic acid diethylamide (LSD)) and ketamine represent new investigational and established treatments in mood disorders respectively. There is a need to better characterize the mechanism of action of these agents. We conducted a systematic review investigating the spectral signatures of psilocybin, LSD, and ketamine in persons with major depressive disorder (MDD), treatment-resistant depression (TRD), and healthy controls. Ketamine and SPs are associated with increased theta power in persons with depression. Ketamine and SPs are also associated with decreased spectral power in the alpha, beta and delta bands in healthy controls and persons with depression. When administered with SPs, theta power was increased in persons with MDD when administered with SPs. Ketamine is associated with increased gamma band power in both healthy controls and persons with MDD. The studies included in our review were heterogeneous in their patient population, exposure, dosing of treatment and devices used to evaluate EEG and MEG signatures. Our results were extracted entirely from persons who were either healthy volunteers or persons with MDD or TRD. Extant literature evaluating EEG and MEG spectral signatures indicate that ketamine and SPs have reproducible effects in keeping with disease models of network connectivity. Future research vistas should evaluate whether observed spectral signatures can guide further discovery of therapeutics within the psychedelic and dissociative classes of agents, and its prediction capability in persons treated for depression. • Serotonergic psychedelics (SPs) decreased gamma power in healthy controls. • Ketamine & SPs increased theta power in persons with depression. • Ketamine & SPs decreased alpha, beta, and delta power in healthy and MDD persons. • Ketamine increased gamma power in both healthy and MDD persons. [ABSTRACT FROM AUTHOR]

Urinalysis of lysergic acid diethylamide (LSD) poses a challenge due to its rapid metabolism, resulting in little to no LSD detectable in urine. Instead, its primary metabolite, 2-oxo-3-hydroxy-LSD, is predominantly detected. In this study, we observed several urine profiles with iso-LSD detected together with 2-oxo-3-hydroxy-LSD. Iso-LSD is derived from illicit preparation of LSD as a major contaminant, and it was detected at higher abundance than LSD and 2-oxo-3-hydroxy-LSD in certain urine samples. Therefore, the metabolism of iso-LSD and its potential as a viable urinary biomarker for confirming LSD consumption is of interest. For metabolism studies, LSD and iso-LSD were incubated in human liver microsomes (HLMs) at 0 min, 60 min and 120 min to characterize their metabolites using LC–QTOF-MS. For urinary analysis, 500 µL of urine samples underwent enzymatic hydrolysis and clean-up using supported-liquid extraction (SLE) prior to analysis by LC–QTOF-MS. From HLM incubation study of LSD, the metabolites detected were dihydroxy-LSD, 2-oxo-LSD, N -desmethyl-LSD (nor-LSD) and 2-oxo-3-hydroxy-LSD with LSD levels decreasing significantly throughout all time points, consistent with the existing literatures. For HLM study of iso-LSD, metabolites eluting at retention times after the corresponding metabolites of LSD were detected, with iso-LSD levels showing only a slight decrease throughout all time points, due to a slower metabolism of iso-LSD compared to LSD. These findings corroborate with the urinalysis of 24 authentic urine samples, where iso-LSD with 2-oxo-3-hydroxy-LSD was detected in the absence of LSD. Based on our findings, iso-LSD is commonly detected in urine (18 out of 24 samples) sometimes with traces of possible 2-oxo-3-hydroxy-iso-LSD. The slower metabolism and high detection rate in urine make iso-LSD a viable urinary biomarker for confirming LSD consumption, especially in the absence of LSD and/or 2-oxo-3-hydroxy-LSD. [ABSTRACT FROM AUTHOR]

Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine [MDMA]), and classical psychedelics (e.g. psilocybin, lysergic acid diethylamide [LSD], and N,N-dimethyltryptamine [DMT/ayahuasca]) in conjunction with assisted therapy (AT) for psychiatric disorders. A notable methodological challenge in psychedelic AT, however, is the complexity of blinding procedures. The lack of efficacious blinding can introduce considerable response bias, reduce internal validity, and compromise participant retention. This systematic review examines design and blinding techniques in RCTs utilizing psychedelics and placebo for the treatment of psychiatric disorders. The aim of this work is to identify factors that may inform future RTC design for conducting psychedelics research. We conducted a systematic review of PubMed, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Psycinfo, Embase, and Web of Science Core Collection to examine: (1) placebo selection, (2) study design, and (3) integrity of blinding measures. Sixteen publications were identified as meeting the criteria for a systematic review. Our findings suggest that traditional placebo administration is insufficient to control for expectancy confounds. Consequently, experimental methodology that limits personnel unblinding and the use of an active placebo are important considerations when designing prospective clinical studies involving psychedelics. [ABSTRACT FROM AUTHOR]

Prodrugs are an important strategy for the development and design of therapeutic drugs. They involve the addition of an easily removable group (such as an ester) to a molecule in order to chemically protect it from metabolism, hydrolysis, or interaction with tissues. In the therapeutic drug market, prodrugs may reduce adverse effects, lead to more accurate tissue delivery, increase bioavailability and duration of effects. The same strategy has, however, been used in the illicit drug market. Internationally controlled drugs such as LSD, MDMA and benzodiazepines have been detected in the market with the addition of alkyl chain that can be removed in physiological conditions. Cyclical analogues may also be used, as is the case for 1cP‐LSD and GBL (a prodrug of GHB). Adequate detection requires increased care with extraction and analytical conditions—as the parent drugs may be formed as artifacts during these processes—and an in‐depth knowledge of metabolic pathways to avoid erroneous detection and allow for adequate identification of the drug used. Legislative updates may also be necessary to ensure prodrugs can be controlled at the same level as other illicit drugs. This article is categorized under:Toxicology > New Psychoactive SubstancesToxicology > Drug AnalysisToxicology > Analytical [ABSTRACT FROM AUTHOR]

This article provides a historical overview of the use of LSD in therapy and its connection to social issues in the 1960s and 1970s. It discusses how LSD was initially supported by the media and medical establishment, but also used in attempts to change or suppress homosexuality. The article explores the ethical considerations and impact of LSD on understandings of gender, behavior, and sexuality. It also examines the migration of LSD to the urban gay party scene and its role in shaping gay culture. The text emphasizes the prevailing social attitudes and prejudices of the time, as well as the influence of psychiatric theories on the treatment of homosexuality. It concludes by suggesting the importance of considering organic culture and social relationships when evaluating the legitimacy of psychedelics. [Extracted from the article]

This article discusses the ethical considerations surrounding informed consent in psychedelic-assisted psychotherapy (PAP). PAP involves the use of psychedelic substances in conjunction with psychotherapy to treat conditions such as posttraumatic stress disorder and major depressive disorder. The article highlights the importance of supporting participants during challenging psychedelic experiences and the need for clear guidelines on the use of rescue medications. It also explores issues related to capacity and consent during the psychedelic experience and suggests strategies for strengthening the informed consent process, such as the use of psychiatric advance directives and dynamic consent. The article emphasizes the importance of trustworthiness and cultural responsiveness in the therapeutic relationship and calls for further research on consent models and the termination of psychedelic sessions. [Extracted from the article]

Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the therapeutic effects of these drugs remains unclear. In this study, we ethopharmacologically analyzed the role of 5-HT2A in the occurrence of anxiolytic- and antidepressant-like effects of serotonergic psychedelics such as psilocin, an active metabolite of psilocybin, DOI, and TCB-2 in mice 24 h post-treatment. Mice with acute intraperitoneal psychedelic treatment exhibited significantly shorter immobility times in the forced swimming test (FST) and tail-suspension test (TST) than vehicle-treated control mice. These effects were eliminated by pretreatment with volinanserin, a 5-HT2A antagonist. Surprisingly, the decreasing immobility time in the FST in response to acute psilocin treatment was sustained for at least three weeks. In the novelty-suppressed feeding test (NSFT), the latency to feed, an indicator of anxiety-like behavior, was decreased by acute administration of psilocin; however, pretreatment with volinanserin did not diminish this effect. In contrast, DOI and TCB-2 did not affect the NSFT performance in mice. Furthermore, psilocin, DOI, and TCB-2 treatment did not affect the spontaneous locomotor activity or head-twitch response, a hallucination-like behavior in rodents. These results suggest that 5-HT2A contributes to the antidepressant effects of serotonergic psychedelics rather than anxiolytic effects. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic‐assisted therapy with psilocybin and lysergic acid diethylamide has garnered significant attention in the treatment of AUD. Yet, they require significant amounts of therapist input due to prolonged subjective effects (~4–12 h) leading to high costs and impeding implementation. Accordingly, there is an increasing interest in the rapid and short‐acting psychedelic 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing the current literature on 5‐MeO‐DMT. Primarily, 5‐MeO‐DMT is able to induce mystical experiences and ego‐dissolution together with increases in psychological flexibility and mindfulness. This could decrease AUD symptoms through the alleviation of psychiatric mood‐related comorbidities consistent with the negative reinforcement and self‐medication paradigms. In addition, preliminary evidence indicates that 5‐MeO‐DMT modulates neural oscillations that might subserve ego‐dissolution (increases in gamma), psychological flexibility and mindfulness (increases in theta), and the reorganization of executive control networks (increases in coherence across frequencies) that could improve emotion regulation and inhibition. Finally, animal studies show that 5‐MeO‐DMT is characterized by neuroplasticity, anti‐inflammation, 5‐HT2A receptor agonism, and downregulation of metabotropic glutamate receptor 5 with clinical implications for AUD and psychiatric mood‐related comorbidities. The paper concludes with several recommendations for future research to establish the purported therapeutic mechanisms of action. [ABSTRACT FROM AUTHOR]

The global use of certain classical psychedelics has increased in recent years, but little is known about their spectrum of toxicity within Australia. We aim to describe calls to New South Wales Poisons Information Centre relating to exposures to classical psychedelics including lysergic acid diethylamide, psilocybin, N,N-dimethyltryptamine, ayahuasca, mescaline and ibogaine. This is a retrospective observational study of calls to New South Wales Poisons Information Centre between January 2014 and December 2022. We identified exposures to classical psychedelics within New South Wales Poisons Information Centre database and measured the annual number of exposures, source of call (hospital, health care worker, member of the public), co-ingested substances, clinical features and advice given. There were 737 calls related to relevant psychedelic exposures; 352 (47.8 per cent) to lysergic acid diethylamide, 347 (47.0 per cent) to psilocybin, 28 (3.8 per cent) to N,N-dimethyltryptamine, 4 (0.5 per cent) to ayahuasca, 4 (0.5 per cent) to mescaline and 2 (0.3 per cent) to ibogaine. Cases were predominantly male (77.2 per cent) and aged between 20 and 74 years (65.6 per cent). Psychedelic calls more than doubled from 45 in 2014 to 105 in 2022 and 625 (85 per cent) of all calls were either from or referred to hospital. Co-ingestion of psychedelics with another substance occurred in 249 (33.8 per cent) of calls and the most frequent clinical features related to single substance psychedelic exposures were hallucinations (27.6 per cent), gastrointestinal symptoms (21.7 per cent) and tachycardia (18.1 per cent). Seizures occurred in 2.9 per cent of single substance psychedelic exposures. Increasing incidence of psychedelic exposure calls, including those reporting significant toxicity, likely reflects increasing community use. This may in part be driven by increasing interest in psychedelic assisted psychotherapy trials subsequently increasing public awareness. Relatively high poisoning severity contrasts with safety within clinical trials of psychedelic assisted psychotherapy that may relate to the uncontrolled nature of community use which is mitigated within clinical trial environments. Education about safe use may be useful. [ABSTRACT FROM AUTHOR]

Psychedelics, substances known to alter perception, mood, and consciousness, have been used across various cultures for centuries, often in religious ceremonies to facilitate spiritual experiences. Lysergic acid diethylamide (LSD) was used clinically from the 1950s until its ban in 1967. Recently, there has been a resurgence of interest in psychedelics for treating mental health disorders such as PTSD, anxiety, depression, and substance use disorders. The FDA has designated several psychedelic compounds as "breakthrough therapies," acknowledging their potential for safety and effectiveness. Psychedelics like Psilocybin, LSD, DMT/Ayahuasca, MDMA, Peyote, and Ketamine work through various mechanisms, including agonism at 5HT2A receptors and NMDA antagonism. These substances promote neuroplasticity and can disrupt pathological activity patterns in the brain's default mode network (DMN), facilitating new perspectives and emotional processing. Psychedelic-assisted therapy leverages these properties to help patients gain insight into repressed conflicts and reduce maladaptive defenses. The therapeutic process involves preparation, support during dosing, and integration phases. Safety concerns include hallucinogen persisting perception disorder (HPPD), serotonin toxicity, and potential boundary violations. Despite promising early results, comprehensive research is needed to fully understand the therapeutic potential and limitations of psychedelics. Psychedelic-assisted therapy could offer hope and transformation for millions suffering from mental illnesses if proven safe and effective. [ABSTRACT FROM AUTHOR]

Adolescent substance use continues to be a global concern. Research has shown that two consistent predictors of this behavior are self-control and peer substance use. The objective of this study was to determine if these two variables interact to affect the frequency of substance use among young people. The analysis utilized three years of data from the Second International Self-Report Delinquency study (2005-2007) (ISRD-2), which gathered information from youth, ages 12-17, residing in 30 nations (n = 72,206). Illicit substance use included cannabis, ecstasy, stimulants, and other substances. A zero-inflated negative binomial model that adjusts for selection effects was estimated to predict the frequency of substance use. The results showed that adolescents with low self-control who associated with substance using peers tended to be the most frequent substance users. Yet, youth with higher levels of selfcontrol were likely to report no or low frequency use regardless of the number of their friends who used illicit substances. Self-control affects substance use among adolescents and can attenuate the influence of peer substance use. Research using longitudinal data is needed to disentangle changes in self-control, peer substance use, and one's own substance use. [ABSTRACT FROM AUTHOR]

The article argues for safety monitoring systems and regulation of services when expanding access to psychedelics to reduce harm, with reference to a study which characterized lysergic acid diethyl acid dietylamide and psilocybin-related deaths in Australia. It urges for better systems for assessing population risks in regulated and unregulated settings, tracking of adverse effects and benefits, and enrollment of people who use psychedelics in secure data collection systems.

This document is an editorial published in Frontiers in Pharmacology titled "Recent advances in the treatment of epilepsy." It discusses the complexities of epilepsy and the different treatment options available. The editorial highlights the use of anti-seizure medications as the first line of treatment, but acknowledges that some patients are resistant to these medications. It explores new pharmacological and non-pharmacological approaches, such as specific drugs, neurostimulation techniques, and the ketogenic diet. The editorial also mentions the potential role of the gut microbiota and natural compounds in epilepsy treatment. It provides valuable insights for clinicians and researchers in the field of neuroscience. The article titled "Nutrients" published in Frontiers in Pharmacology emphasizes the importance of nutrients in maintaining good health. It discusses the role of various nutrients in supporting bodily functions and preventing diseases. The article provides a comprehensive overview of different types of nutrients, their sources, and their impact on specific health conditions. It is a valuable resource for library patrons interested in understanding the significance of nutrients in their diet and overall well-being. [Extracted from the article]

Objective: This study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Methods: The Preferred Reporting Items for Systematic Reviews (PRISMA) was used as a guide to structure and report the findings for this review. A literature search included the MEDLINE database up until December 2022. We included randomized or open-label human studies of MDMA, psilocybin, mescaline, LSD, DMT, or cannabis reporting non-emotionally charged neurocognitive outcomes ("cold cognition") measured through validated neuropsychological tests. Results: A total of 43 full-text papers on MDMA (15), cannabis (12), LSD (6), psilocybin (9), DMT/ayahuasca (1), and mescaline (0) were included, mostly on healthy subjects. A single article on MDMA's effects on cognition in subjects with PTSD was included; there were no studies on psychedelics and neurocognition in MDD. Most of the studies on healthy subjects reported detrimental or neutral effects on cognition during the peak effect of psychedelics with a few exceptions (e.g., MDMA improved psychomotor function). Performance on the type of neurocognitive dimension (e.g., attention, memory, executive function, psychomotor) varies by type of psychedelic, dosage, and cognitive testing. Conclusions: Small samples and a lack of uniformed methods across studies preclude unequivocal conclusions on whether psychedelics enhance, decrease, or have no significant effect on cognitive performance. It is foreseen that psychedelics will soon become an available treatment for various psychiatric disorders. The acute and long-term effects on cognition caused by psychedelics should be assessed in future studies. [ABSTRACT FROM AUTHOR]

• First clinical trial evaluating inhaled DMT's effects in a controlled setting. • No serious adverse event were observed, indicating potential safety. • Profound, yet manageable, subjective psychological effects reported by participants. • Inhaled DMT offers a rapid, non-invasive, and cost-efficient tool for psychiatry. Psychedelics are being increasingly examined for their therapeutic potential in mood disorders. While the acute effects of ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) last over several hours, inhaled N,N-Dimethyltryptamine (DMT) effects last around 10 min, which might provide a cost- and time-effective alternative to the clinical application of oral psychedelics. We aimed at investigating the safety and tolerability of inhaled DMT (BMND01 candidate). We recruited 27 healthy volunteers to receive a first, lower dose and a second, higher dose (5/20 mg, 7.5/30 mg, 10/40 mg, 12.5/50 mg, or 15/60 mg) of inhaled DMT in an open-label, single-ascending, fixed-order, dose-response study design. We investigated subjective experiences (intensity, valence, and phenomenology), physiological effects (blood pressure, heart rate, respiratory rate, blood oxygen saturation, body temperature), biochemical markers (liver, kidney, and metabolic functions), and adverse events during the acute and post-acute effects of DMT. DMT dose-dependently increased intensity, valence and perceptual ratings. There was a mild, transient, and self-limited increase in blood pressure and heart rate. There were no changes in safety blood biomarkers and no serious adverse events. DMT dose-dependently enhanced subjective experiences and positive valence. Inhaled DMT might be an efficient, non-invasive, safe route of administration, which might simplify the clinical use of this substance. This is the first clinical trial to test the effects of inhaled DMT (BMND01 candidate). [ABSTRACT FROM AUTHOR]

Though microdosing psychedelics has become increasingly popular, its long-term effects on cardiac health remain unknown. Microdosing most commonly involves ingesting sub-threshold doses of lysergic acid diethylamide (LSD), psilocybin, or other psychedelic drugs 2–4 times a week for at least several weeks, but potentially months or years. Concerningly, both LSD and psilocybin share structural similarities with medications which raise the risk of cardiac fibrosis and valvulopathy when taken regularly, including methysergide, pergolide, and fenfluramine. 3,4-Methylenedioxymethamphetamine, which is also reportedly used for microdosing, is likewise associated with heart valve damage when taken chronically. In this review, we evaluate the evidence that microdosing LSD, psilocybin, and other psychedelics for several months or more could raise the risk of cardiac fibrosis. We discuss the relationship between drug-induced cardiac fibrosis and the 5-HT2B receptor, and we make recommendations for evaluating the safety of microdosing psychedelics in future studies. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) is a complex mental disorder that involves alterations in signal transmission across multiple scales and structural abnormalities. The development of effective antidepressants (ADs) has been hindered by the dominance of monoamine hypothesis, resulting in slow progress. Traditional ADs have undesirable traits like delayed onset of action, limited efficacy, and severe side effects. Recently, two categories of fast-acting antidepressant compounds have surfaced, dissociative anesthetics S-ketamine and its metabolites, as well as psychedelics such as lysergic acid diethylamide (LSD). This has led to structural research and drug development of the receptors that they target. This review provides breakthroughs and achievements in the structure of depression-related receptors and novel ADs based on these. Cryo-electron microscopy (cryo-EM) has enabled researchers to identify the structures of membrane receptors, including the N-methyl-D-aspartate receptor (NMDAR) and the 5-hydroxytryptamine 2A (5-HT2A) receptor. These high-resolution structures can be used for the development of novel ADs using virtual drug screening (VDS). Moreover, the unique antidepressant effects of 5-HT1A receptors in various brain regions, and the pivotal roles of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and tyrosine kinase receptor 2 (TrkB) in regulating synaptic plasticity, emphasize their potential as therapeutic targets. Using structural information, a series of highly selective ADs were designed based on the different role of receptors in MDD. These molecules have the favorable characteristics of rapid onset and low adverse drug reactions. This review offers researchers guidance and a methodological framework for the structure-based design of ADs. [ABSTRACT FROM AUTHOR]

Introduction Alcohol use can be significantly associated with negative social, professional, and health outcomes. Even more so, alcohol use disorder (AUD) is a critical public health issue and major avoidable risk factor. This study aimed to examine the effect of a naturalistic psychedelic experience on alcohol use and related measures. Methods A retrospective online survey was conducted on 160 individuals who reported a psychedelic experience and a concomitant drinking habit but did not necessarily have an AUD. Demographic data, characteristics of the psychedelic experience, and changes in alcohol consumption and psychological flexibility were surveyed. Results: The mean number of drinking days per week and AUDIT scores significantly decreased after the psychedelic experience (P  < .001). Subjects who quit or reduced drinking had a more severe AUD (P  < .01) and lower psychological flexibility (P  = .003) before the psychedelic session. Alcohol use reduction was significantly associated with the intensity of the mystical experience (P  = .03). Psychological flexibility increased more in participants who reduced their alcohol use (P  < .001), and the change in psychological flexibility was one of the predictors of alcohol use improvement (P  = .003). Conclusion: Our findings suggest that a naturalistic psychedelic experience could be associated with a reduction in alcohol use and dependency. Such positive health outcomes can be associated with the intensity of the mystical experience as well as an increase in psychological flexibility. [ABSTRACT FROM AUTHOR]

Introduction: Amid a lack of effective chronic pain treatments, psychedelics have gained attention as a potential solution, although their Schedule 1 classification poses challenges. Psychedelics, such as lysergic acid diethylamide (LSD) and psilocybin, have gained popularity as alternatives and adjuncts for chronic pain treatment. Studies suggest that they may modulate pain processing through agonism primarily at the serotonin receptor, 5-HT2A. One of the first of its nature, we present an artificial intelligence (AI)-powered scoping review primarily focusing on evaluating psychedelics for chronic pain conditions such as cluster headache, phantom limb pain, and fibromyalgia. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we used an AI-powered comprehensive search strategy utilizing the ChatGPT4.0 Bing chat to search Medline, Embase, Cochrane, and Google Scholar for articles addressing chronic pain. The query was performed on June 1, 2023, focusing on psychedelics for chronic, non-cancer pain including headache disorders. Inclusion criteria were English-only, peer-reviewed articles involving human participants > 18 years, focusing on chronic pain conditions (eg, phantom limb pain and cluster headache), using LSD, 2.5-dimethoxy-4-bromophenethylamine (2C-B), N, N-dimethyltryptamine (DMT), psilocybin, or mescaline. Exclusion criteria were reviews, editorials, and opinion articles and studies focusing on tetrahydrocannabinol/cannabis and/or ketamine. Results: A total of 186 unique database entries were retrieved, of which nine studies were included in the scoping review. These included four case reports/series, an open-label study, a cohort study, two online surveys, and a randomized, double-blind, placebo-controlled trial. They comprised three studies addressing phantom limb pain, four addressing cluster headaches, and two addressing fibromyalgia, spinal cord injury, complex regional pain syndrome, and lumbar radiculopathy. Conclusion: Psychedelics may have potential in alleviating pain symptoms secondary to a multitude of chronic pain conditions. However, further randomized, double-blind, placebo-controlled trials are needed to further explore and evaluate the role of psychedelics in chronic, non-cancer pain. [ABSTRACT FROM AUTHOR]

Hallucinogenic drugs are used because they have effects on the central nervous system. Their hallucinogenic effects probably occur via stimulation of serotonin receptors, namely, 5-HT2A-serotonin receptors in the brain. However, a close study reveals that they also act on the heart, possibly increasing the force of contraction and beating rate and may lead to arrhythmias. Here, we will review the inotropic and chronotropic actions of bufotenin, psilocin, psilocybin, lysergic acid diethylamide (LSD), ergotamine, ergometrine, N,N-dimethyltryptamine, and 5-methoxy-N,N-dimethyltryptamine in the human heart. [ABSTRACT FROM AUTHOR]

Background: An advanced cancer diagnosis can be associated with a significant profile of distress. Psychedelic compounds have shown clinically significant effects in the treatment of psychological distress in patients with advanced-stage cancer. Given the challenges of delivering timely and effective intervention in the advanced cancer context, it is possible that an alternative, more pragmatic, approach lies in psychedelic 'microdosing'. Microdosing refers to repeated administration of psychedelics in sub-hallucinogenic doses. The purpose of this study is to evaluate the feasibility of conducting a full-scale randomised controlled trial comparing psychedelic microdose-assisted–meaning-centred psychotherapy (PA-MCP) to standard meaning-centred psychotherapy (MCP) in New Zealand indigenous (Māori) and non-indigenous people with advanced cancer and symptoms of anxiety and/or depression. Although MCP is a well-established psychotherapeutic treatment in advanced cancer populations, the potential efficacy and effectiveness of this therapy when delivered alongside a standardised microdose regimen of a psychedelic compound have not been investigated. Methods: Participants with advanced-stage cancer and symptoms of anxiety and/or depression (N = 40; 20 Māori, 20 non-Māori) will be randomised under double-blind conditions to receive 7 sessions of MCP alongside 13 doses of either an LSD microdose (4–20 µg) (PA–MCP) or inactive placebo (placebo-MCP). The feasibility, acceptability, and safety of this intervention and physiological and psychological measures will be recorded at baseline, at each session of MCP, and at a 1-month and 6-month follow-up. Discussion: Our findings will evaluate the feasibility, acceptability, and safety of a larger randomised controlled trial and provide an initial indication of the potential benefits of psychedelic microdosing for psychological distress in advanced-stage indigenous and non-indigenous cancer patients. Trial Registration: NZCTR, ACTRN12623000478617. Registered 11 May 2023. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385810&isReview=true. [ABSTRACT FROM AUTHOR]

Background: Microdosing psychedelics is a phenomenon with claimed cognitive benefits that are relatively untested clinically. Pre-clinically, psychedelics have demonstrated enhancing effects on neuroplasticity, which cannot be measured directly in humans, but may be indexed by non-invasive electroencephalography (EEG) paradigms. This study used a visual long-term potentiation (LTP) EEG paradigm to test the effects of microdosed lysergic acid diethylamide (LSD) on neural plasticity, both acutely while on the drug and cumulatively after microdosing every third day for six weeks. Healthy adult males (n = 80) completed the visual LTP paradigm at baseline, 2.5 h following a dose of 10 µg of LSD or inactive placebo, and 6 weeks later after taking 14 repeated microdoses. Visually induced LTP was used as indirect index of neural plasticity. Surface level event-related potential (ERPs) based analyses are presented alongside dynamic causal modelling of the source localised data using a generative thalamocortical model (TCM) of visual cortex to elucidate underlying synaptic circuitry. Results: Event-related potential (ERP) analyses of N1b and P2 components did not show evidence of changes in visually induced LTP by LSD either acutely or after 6 weeks of regular dosing. However modelling the complete timecourse of the ERP with the TCM demonstrated changes in laminar connectivity in primary visual cortex. This primarily included changes to self-gain and inhibitory input parameters acutely. Layer 2/3 to layer 5 excitatory connectivity was also different between LSD and placebo groups. After regular dosing only excitatory input from layer 2/3 into layer 5 and inhibitory input into layer 4 were different between groups. Conclusions: Without modulation of the ERPs it is difficult to relate the findings to other studies visually inducing LTP. It also indicates the classic peak analysis may not be sensitive enough to demonstrate evidence for changes in LTP plasticity in humans at such low doses. The TCM provides a more sensitive approach to assessing changes to plasticity as differences in plasticity mediated laminar connectivity were found between the LSD and placebo groups. Trial registration: ANZCTR registration number ACTRN12621000436875; Registered 16/04/2021 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381476. [ABSTRACT FROM AUTHOR]

Psychedelic drugs, such as lysergic acid diethylamide (LSD), are psychoactive substances used in different sociocultural contexts and which, in recent decades, have gained special attention regarding the possibility of their use in the psychiatric treatment of some mental disorders. In this context, the objective of the present study was to review the scientific literature in order to elucidate the neurobiological mechanisms of action of psychoactive drugs and discuss their possible use as psychiatric therapy. To this end, a bibliographical search was carried out in the MEDLINE, LILACS and Embase databases. After selecting studies published between 2017 and 2023, five articles were included in the present review. The results of the work carried out indicate the involvement of psychedelic drugs in the release of serotonin and norepinephrine without toxic effects on the brain. Furthermore, the studies analyzed that evaluated the efficacy and safety of the use of LSD and other psychedelic studies showed promising results, with improved quality of life and disruptive symptoms, in addition to presenting some side effects. However, the proven samples are still small and some aspects, such as the dose to be used and the treatment time, have not yet been well elucidated. Therefore, the use of psychoactive drugs appears as a viable therapeutic proposal for some mental disorders, but it needs to be better investigated, with the analysis of more variables and an increase in the samples used. [ABSTRACT FROM AUTHOR]

Although studies have demonstrated that the use of lysergic acid diethylamide (LSD) is on the rise in the United States, it remains unclear how this trend looks across the hierarchical ladder of the American workforce. This is relevant given that LSD is increasingly being touted as a means of boosting creativity and performance, with mounting anecdotal evidence that business managers in particular are turning to it for inspiration and insight. Using pooled cross-sectional data from the National Survey on Drug Use and Health (2006–2014) on 168,920 adults in the United States employed full-time (weighted = 117,270,940), this study investigates how temporal trends in past year LSD use differ among business managers and non-managers. The results suggest that the prevalence of past year LSD use increased over time at a greater rate among business managers than non-managers and that this difference cannot be accounted for by changes in business managers' perceived risk of LSD use or general substance use relative to non-managers. The study's findings indicate that temporal trends in past year LSD use depend on employees' hierarchical rank in their organization and suggest that business managers, regardless of gender, are becomingly increasingly interested in the potential competitive advantages that LSD may offer. [ABSTRACT FROM AUTHOR]