Search

There has been renewed interest in the use of 3,4-methylenedioxy-methamphetamine (MDMA) and serotonergic psychedelics in the treatment of multiple psychiatric disorders. Many of these compounds are known to produce prosocial effects, but how these effects relate to therapeutic efficacy and the extent to which prosocial effects are unique to a particular drug class is unknown. In this article, we present a narrative overview and compare evidence for the prosocial effects of MDMA and serotonergic psychedelics to elucidate shared mechanisms that may underlie the therapeutic process. We discuss 4 categories of prosocial effects: altered self-image, responses to social reward, responses to negative social input, and social neuroplasticity. While both categories of drugs alter self-perception, MDMA may do so in a way that is less related to the experience of mystical-type states than serotonergic psychedelics. In the case of social reward, evidence supports the ability of MDMA to enhance responses and suggests that serotonergic psychedelics may also do so, but more research is needed in this area. Both drug classes consistently dampen reactivity to negative social stimuli. Finally, preclinical evidence supports the ability of both drug classes to induce social neuroplasticity, promoting adaptive rewiring of neural circuits, which may be helpful in trauma processing. While both MDMA and serotonergic psychedelics produce prosocial effects, they differ in the mechanisms through which they do this. These differences affect the types of psychosocial interventions that may work best with each compound.

Objective: In recent years, there has been a renewed interest in investigating the use of classic psychedelics such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of mental disorders and substance use disorders. However, knowledge about the epidemiology of classic psychedelics in the Nordic countries is limited. Methods: We recruited adult, Norwegian participants who have had a memorable experience after taking a classic psychedelic substance. They filled in an anonymous internet survey with 119 items covering matters related to recreational use of psychedelics using a secure, web-based application. Data are presented by using descriptive statistics (frequencies, means, and standard deviations). Results: We recruited 841 participants, 770 (72% male; 88% 45 years or younger) of which were included in the data analysis. The intentions behind taking the psychedelic substance were mainly recreational (46.1%) or therapeutic (42.3%). Most participants reported that their most memorable experience was with psilocybin. As in modern era clinical trials, most participants were well-prepared before, did processing during, and did integration work after the experience, whereas only a minority were supported by a therapist. Self-perceived symptoms of various mental disorders and substance use disorders were prevalent in the sample. Most subjects reported improvements in their condition. Although adverse reactions were usually mild and short-lived, 4.2% lasted for 1 year or more. Persisting flashbacks were present for a year or more among 2.9% of the participants. Conclusion: In this cross-sectional sample of Norwegian, self-selecting adults, we shed light on what characterizes the most memorable experience with a classic psychedelic substance, including short- and long-term risks and benefits. For the most part, the psychedelic experience led to improvements in selfperceived symptoms of mental disorders and substance use disorders. However, a small subset experienced persisting adverse reactions. [ABSTRACT FROM AUTHOR]

ObjectiveIn recent years, there has been a renewed interest in investigating the use of classic psychedelics such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of mental disorders and substance use disorders. However, knowledge about the epidemiology of classic psychedelics in the Nordic countries is limited.MethodsWe recruited adult, Norwegian participants who have had a memorable experience after taking a classic psychedelic substance. They filled in an anonymous internet survey with 119 items covering matters related to recreational use of psychedelics using a secure, web-based application. Data are presented by using descriptive statistics (frequencies, means, and standard deviations).ResultsWe recruited 841 participants, 770 (72% male; 88% 45 years or younger) of which were included in the data analysis. The intentions behind taking the psychedelic substance were mainly recreational (46.1%) or therapeutic (42.3%). Most participants reported that their most memorable experience was with psilocybin. As in modern era clinical trials, most participants were well-prepared before, did processing during, and did integration work after the experience, whereas only a minority were supported by a therapist. Self-perceived symptoms of various mental disorders and substance use disorders were prevalent in the sample. Most subjects reported improvements in their condition. Although adverse reactions were usually mild and short-lived, 4.2% lasted for 1 year or more. Persisting flashbacks were present for a year or more among 2.9% of the participants.ConclusionIn this cross-sectional sample of Norwegian, self-selecting adults, we shed light on what characterizes the most memorable experience with a classic psychedelic substance, including short- and long-term risks and benefits. For the most part, the psychedelic experience led to improvements in self-perceived symptoms of mental disorders and substance use disorders. However, a small subset experienced persisting adverse reactions.

Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain axis, may also have a role in mediating the positive effects of psychedelics on behaviour. In this review, we present existing evidence that the composition of the gut microbiota may be responsive to psychedelic drugs, and in turn, that the effect of psychedelics could be modulated by microbial metabolism. We discuss various alternative mechanistic models and emphasize the importance of incorporating hypotheses that address the contributions of the microbiome in future research. Awareness of the microbial contribution to psychedelic action has the potential to significantly shape clinical practice, for example, by allowing personalised psychedelic therapies based on the heterogeneity of the gut microbiota., Competing Interests: Declaration of Competing Interest WAJ is a founder and shareholder of the University of British Columbia Start-up Mynd Life Sciences. All other authors declare no known competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Accumulating clinical evidence shows that psychedelic therapy, by synergistically combining psychopharmacology and psychological support, offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and/or maladaptive habitual patterns of emotion, cognition and behavior, notably, depression (MDD), treatment resistant depression (TRD) and addiction disorders, but perhaps also anxiety disorders, obsessive-compulsive disorder (OCD), Post-Traumatic Stress Disorder (PTSD) and eating disorders. Despite the emergent transdiagnostic evidence, the specific clinical dimensions that psychedelics are efficacious for, and associated underlying neurobiological pathways, remain to be well-characterized. To this end, this review focuses on pre-clinical and clinical evidence of the acute and sustained therapeutic potential of psychedelic therapy in the context of a transdiagnostic dimensional systems framework. Focusing on the Research Domain Criteria (RDoC) as a template, we will describe the multimodal mechanisms underlying the transdiagnostic therapeutic effects of psychedelic therapy, traversing molecular, cellular and network levels. These levels will be mapped to the RDoC constructs of negative and positive valence systems, arousal regulation, social processing, cognitive and sensorimotor systems. In summarizing this literature and framing it transdiagnostically, we hope we can assist the field in moving toward a mechanistic understanding of how psychedelics work for patients and eventually toward a precise-personalized psychedelic therapy paradigm. [ABSTRACT FROM AUTHOR]

Accumulating clinical evidence shows that psychedelic therapy, by synergistically combining psychopharmacology and psychological support, offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and/or maladaptive habitual patterns of emotion, cognition and behavior, notably, depression (MDD), treatment resistant depression (TRD) and addiction disorders, but perhaps also anxiety disorders, obsessive-compulsive disorder (OCD), Post-Traumatic Stress Disorder (PTSD) and eating disorders. Despite the emergent transdiagnostic evidence, the specific clinical dimensions that psychedelics are efficacious for, and associated underlying neurobiological pathways, remain to be well-characterized. To this end, this review focuses on pre-clinical and clinical evidence of the acute and sustained therapeutic potential of psychedelic therapy in the context of a transdiagnostic dimensional systems framework. Focusing on the Research Domain Criteria (RDoC) as a template, we will describe the multimodal mechanisms underlying the transdiagnostic therapeutic effects of psychedelic therapy, traversing molecular, cellular and network levels. These levels will be mapped to the RDoC constructs of negative and positive valence systems, arousal regulation, social processing, cognitive and sensorimotor systems. In summarizing this literature and framing it transdiagnostically, we hope we can assist the field in moving toward a mechanistic understanding of how psychedelics work for patients and eventually toward a precise-personalized psychedelic therapy paradigm.

BackgroundObservational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), including opioid use disorder (OUD).AimsThe study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduction in other substance use.MethodsAn anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings.ResultsFour hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption.ConclusionsWhile these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD.

Lysergic acid diethylamide (LSD) was studied from the 1950s to the 1970s to evaluate behavioral and personality changes, as well as remission of psychiatric symptoms in various disorders. LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction. However, most of the studies were not performed under contemporary standards, and it has taken several decades for a resurgence of interest in LSD research and its therapeutic potential for psychiatry. The aim of this review is to identify controlled and randomized clinical trials that assess the potential use of LSD in psychiatry. PRISMA guidelines for systematic review were followed. A literature search of PubMed and Psychedelic bibliography from Multidisciplinary Association for Psychedelic Studies (MAPS) databases was performed as well as a manual search of references from evaluated studies. Only randomized-controlled clinical trials were included. Study quality was systematically calculated by using the Cochrane Collaboration Tool for assessing risk of bias. A final selection of 11 articles was made after considering inclusion and exclusion criteria. LSD was administered to 567 patients in a dose ranging from 20 to 800 mcg. Despite the design heterogeneity of clinical trials, positive results were observed, thus revealing the therapeutic potential of LSD to reduce psychiatric symptomatology, mainly in alcoholism. The vast majority of authors describe significant and positive short-term changes in patients, despite the fact that in some studies an important homogenization was observed between the LSD treatment group and control group at long-term follow-up. Multiple variables regarding LSD treatment therapeutic approach and quality of experience were revealed and related to therapeutic outcomes. LSD is revealed as a potential therapeutic agent in psychiatry; the evidence to date is strongest for the use of LSD in the treatment of alcoholism. Despite the difficulty of designing proper double blind clinical trials with this substance, new studies that conform to modern standards are necessary in order to strengthen our knowledge on its use and open new doors in the future.

Lysergic acid diethylamide (LSD) is a potent hallucinogenic substance that was extensively investigated by psychiatrists during the 1950s and 1960s. Researchers were interested in the unique effects induced by this substance, some of which resemble symptoms seen in schizophrenia. Moreover, during that period LSD was studied and used for the treatment of several mental disorders such as depression, anxiety, addiction and personality disorders. Despite this long history of research, how LSD induces its specific effects on a neuronal level has been relatively unclear. In recent years there has been a revival of research in hallucinogenic drugs and their possible clinical applications. These contemporary studies in the UK and Switzerland include neuroimaging studies using functional magnetic resonance imaging (fMRI). In this review, we collect and interpret these recent neuroimaging findings. Overall, previous results across studies indicate that LSD administration is associated with extensive alterations in functional brain connectivity, measuring the correlated activities between different brain regions. The studies mostly reported increases in connectivity between regions and, more specifically, consistently found increased connectivity within the thalamocortical system. These latter observations are in agreement with models proposing that hallucinogenic drugs exert their effects by inhibiting cerebral filtering of external and internal data. However, studies also face several limitations, including potential biases of neuroimaging measurements.

Despite many different kinds of substances available for depression treatment, depression itself still appears to be a clinical challenge. Recently, formerly illicit substances came to scientists’ attention, including lysergic acid diethylamide (LSD), psilocybin and dimethyltryptamine (DMT). Some studies suggest that these substances might be effective in depression treatment. The aim of this study was to evaluate the efficiency of LSD, psilocybin and DMT in depression treatment in the light of current medical literature. The authors followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for this systematic review. The authors searched the PubMed and Cochrane Library databases to identify relevant publications. Finally, 10 papers were included. Most of the selected studies showed significant correlation between psilocybin and DMT use and reduction in depression symptom intensity. By analyzing qualified studies, it can be concluded that psilocybin and DMT could be useful in depression treatment, but further observations are still required.

Background: Observational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), including opioid use disorder (OUD). Aims: The study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduction in other substance use. Methods: An anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings. Results: Four hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption. Conclusions: While these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD. [ABSTRACT FROM AUTHOR]

Lysergic acid diethylamide (LSD) was studied from the 1950s to the 1970s to evaluate behavioral and personality changes, as well as remission of psychiatric symptoms in various disorders. LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction. However, most of the studies were not performed under contemporary standards, and it has taken several decades for a resurgence of interest in LSD research and its therapeutic potential for psychiatry. The aim of this review is to identify controlled and randomized clinical trials that assess the potential use of LSD in psychiatry. PRISMA guidelines for systematic review were followed. A literature search of PubMed and Psychedelic bibliography from Multidisciplinary Association for Psychedelic Studies (MAPS) databases was performed as well as a manual search of references from evaluated studies. Only randomized-controlled clinical trials were included. Study quality was systematically calculated by using the Cochrane Collaboration Tool for assessing risk of bias. A final selection of 11 articles was made after considering inclusion and exclusion criteria. LSD was administered to 567 patients in a dose ranging from 20 to 800 mcg. Despite the design heterogeneity of clinical trials, positive results were observed, thus revealing the therapeutic potential of LSD to reduce psychiatric symptomatology, mainly in alcoholism. The vast majority of authors describe significant and positive short-term changes in patients, despite the fact that in some studies an important homogenization was observed between the LSD treatment group and control group at long-term follow-up. Multiple variables regarding LSD treatment therapeutic approach and quality of experience were revealed and related to therapeutic outcomes. LSD is revealed as a potential therapeutic agent in psychiatry; the evidence to date is strongest for the use of LSD in the treatment of alcoholism. Despite the difficulty of designing proper double blind clinical trials with this substance, new studies that conform to modern standards are necessary in order to strengthen our knowledge on its use and open new doors in the future. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a mental health condition that can occur following exposure to a traumatic experience. An estimated 12 million U.S. adults are presently affected by this disorder. Current treatments include psychological therapies (e.g., exposure-based interventions) and pharmacological treatments (e.g., selective serotonin reuptake inhibitors (SSRIs)). However, a significant proportion of patients receiving standard-of-care therapies for PTSD remain symptomatic, and new approaches for this and other trauma-related mental health conditions are greatly needed. Psychedelic compounds that alter cognition, perception, and mood are currently being examined for their efficacy in treating PTSD despite their current status as Drug Enforcement Administration (DEA)- scheduled substances. Initial clinical trials have demonstrated the potential value of psychedelicassisted therapy to treat PTSD and other psychiatric disorders. In this comprehensive review, we summarize the state of the science of PTSD clinical care, including current treatments and their shortcomings. We review clinical studies of psychedelic interventions to treat PTSD, trauma-related disorders, and common comorbidities. The classic psychedelics psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) and DMT-containing ayahuasca, as well as the entactogen 3,4-methylenedioxymethamphetamine (MDMA) and the dissociative anesthetic ketamine, are reviewed. For each drug, we present the history of use, psychological and somatic effects, pharmacology, and safety profile. The rationale and proposed mechanisms for use in treating PTSD and traumarelated disorders are discussed. This review concludes with an in-depth consideration of future directions for the psychiatric applications of psychedelics to maximize therapeutic benefit and minimize risk in individuals and communities impacted by trauma-related conditions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Lysergic acid diethylamide (LSD) is one of the most widely abused hallucinogens, which can alter consciousness, produce mental disorder, and cause harmful behavior. 1-Propionyl-LSD (1 P-LSD), a novel derivative of LSD, has the similar hallucinogenic effect. It is a control substance in several countries. 1 P-LSD can act as a prodrug for LSD and is rapidly hydrolyzed to LSD in humans. Therefore, LSD use should be confirmed by the absence of 1 P-LSD and in the detection of LSD. Here, we describe a LC–MS/MS method for the simultaneous extraction of LSD, iso-LSD, 2-oxo-3-hydroxy-LSD, and 1 P-LSD from hair. Hair samples (25 mg) were pulverized by cryogenic grinding in methanol. The limits of detection were 0.2–1 pg/mg and the limits of quantification were 0.5–2 pg/mg. This method was validated and applied to hair samples from 18 suspects who may have used LSD. Segmental hair analysis revealed a decrease in the LSD concentrations from the proximal to the distill end, while 1 P-LSD was not detected in any hair segments. The interpretation of hair analysis results of LSD still remains difficult. Nevertheless, concentrations of LSD and iso-LSD in human hair from 18 LSD users were reported. LSD concentrations were from

Introduction Self-administration procedures are the gold standard for investigating the reinforcing effects of drugs. The notable exception to good correspondence between laboratory self-administration studies and human drug taking behavior has historically been the classic hallucinogens. Method The present study used a well-established daily access procedure, followed by a novel intermittent access procedure, to investigate the reinforcing effects of LSD in baboons. Results Rates of self-injection in the daily access procedure were minimal. One baboon self-administered 0.001 mg/kg and a second baboon self-administered 0.0032 mg/kg above vehicle levels, though rates of self-injection were clearly low and neither of the two remaining baboons self-administered any LSD dose tested in the daily access procedure. Rates of self-injection using an intermittent access procedure with discriminative stimuli resulted in two doses of LSD being self-administered above vehicle levels in two of three baboons tested (0.01 and 0.032 mg/kg in one baboon; 0.0032 and 0.01 mg/kg in a second). In addition, the number of self-injections at these doses was higher (range = 3–6 injections) in the intermittent access procedure than in the daily access procedure (range = 1–2 injections). Discussion The present study is the first to demonstrate LSD self-administration in a laboratory animal, and though the results are limited, they indicate intermittent access procedures with discriminative stimuli may provide a reliable and valid method for investigating the reinforcing effects of IV self-administered hallucinogens in laboratory animals. The usefulness of such procedures should be further evaluated in a larger number of subjects. [ABSTRACT FROM AUTHOR]

Moving towards a systems psychiatry paradigm embraces the inherent complex interactions across all levels from micro to macro and necessitates an integrated approach to treatment. Cortical 5-HT 2A receptors are key primary targets for the effects of serotonergic psychedelics. However, the therapeutic mechanisms underlying psychedelic therapy are complex and traverse molecular, cellular, and network levels, under the influence of biofeedback signals from the periphery and the environment. At the interface between the individual and the environment, the gut microbiome, via the gut-brain axis, plays an important role in the unconscious parallel processing systems regulating host neurophysiology. While psychedelic and microbial signalling systems operate over different timescales, the microbiota-gut-brain (MGB) axis, as a convergence hub between multiple biofeedback systems may play a role in the preparatory phase, the acute administration phase, and the integration phase of psychedelic therapy. In keeping with an interconnected systems-based approach, this review will discuss the gut microbiome and mycobiome and pathways of the MGB axis, and then explore the potential interaction between psychedelic therapy and the MGB axis and how this might influence mechanism of action and treatment response. Finally, we will discuss the possible implications for a precision medicine-based psychedelic therapy paradigm., (© 2022 The Authors.)

Highlights: [•] Drugs of abuse detected in waters from two rivers in the Madrid Region. [•] Concentrations measured are comparatively higher than in Europe. [•] Ephedrine, benzoylecgonine, EDDP and lorazepam are the most abundant compounds. [ABSTRACT FROM AUTHOR]

Despite many different kinds of substances available for depression treatment, depression itself still appears to be a clinical challenge. Recently, formerly illicit substances came to scientists' attention, including lysergic acid diethylamide (LSD), psilocybin and dimethyltryptamine (DMT). Some studies suggest that these substances might be effective in depression treatment. The aim of this study was to evaluate the efficiency of LSD, psilocybin and DMT in depression treatment in the light of current medical literature. The authors followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for this systematic review. The authors searched the PubMed and Cochrane Library databases to identify relevant publications. Finally, 10 papers were included. Most of the selected studies showed significant correlation between psilocybin and DMT use and reduction in depression symptom intensity. By analyzing qualified studies, it can be concluded that psilocybin and DMT could be useful in depression treatment, but further observations are still required. [ABSTRACT FROM AUTHOR]

It has often been suggested in the popular and academic literature that the psychedelic state qualifies as a higher state of consciousness relative to the state of normal waking awareness. This article subjects this proposal to critical scrutiny, focusing on the question of what it would mean for a state of consciousness to be 'higher'. We begin by considering the contrast between conscious contents and conscious global states. We then review the changes in conscious global state associated with psychedelic drug use, focusing on the effects of two serotonergic hallucinogens: psilocybin and lysergic acid diethylamide. Limiting our review to findings obtained from lab-based experiments and reported in peer-reviewed journals, we prioritize the more common and reliably induced effects obtained through subjective questionnaires and psychophysical measures. The findings are grouped into three broad categories (sensory perception, cognitive function, and experiences of unity) and demonstrate that although certain aspects of consciousness are improved or enhanced in the psychedelic state, many of the functional capacities that are associated with consciousness are seriously compromised. Psychedelic-induced states of consciousness are indeed remarkable in many ways, but it is inappropriate to regard them as 'higher' states of consciousness. The fact that psychedelics affect different aspects of consciousness in fundamentally different ways provides evidence against the unidimensional (or 'level-based') view of consciousness, and instead provides strong support for a multidimensional conception of conscious states. The final section of the article considers the implications of this analysis for two prominent theories of consciousness: the Global Workspace Theory and Integrated Information Theory.