Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

Is psychedelic use associated with cancer?: Interrogating a half-century-old claim using contemporary population-level data.

BACKGROUND: In 1967, concerns about the carcinogenic potential of psychedelics arose after a study reported chromosomal damage in human leukocytes following in vitro lysergic acid (LSD) exposure. Worries were further heightened by subsequent reports of leukemia and other cancers in LSD users. Additional investigations of psychedelics' effects on chromosomes were published over the next decade, with the majority suggesting these concerns were unfounded. However, the relationship between psychedelics and cancer has been explored only minimally from an epidemiological perspective. AIMS: To determine whether associations exist between psychedelic use and either lifetime cancer or hematologic cancer diagnoses. METHODS: We analyzed data from adult participants in the 2015-2019 administrations of the National Survey on Drug Use and Health for associations between lifetime use of psychedelics and lifetime diagnosis of either any cancer or hematologic cancer. RESULTS: We identified no associations between lifetime psychedelic use and either lifetime cancer diagnosis or hematologic cancer diagnosis. Sub-analyses of lifetime lysergamide, phenethylamine, and tryptamine use also revealed no associations with lifetime cancer or hematologic cancer diagnosis. CONCLUSIONS: While laboratory studies and case reports from the 1960s and 1970s generated concerns about psychedelics' carcinogenic potential, this analysis of recent epidemiological data does not support an association between psychedelic use and development of cancer in general or hematologic cancer. Important study limitations to consider include a lack of information about psychedelic dosage, number of lifetime psychedelic exposures, and the temporal relationship between psychedelic use and cancer diagnosis.

Associations between lifetime classic psychedelic use and markers of physical health.

BACKGROUND: In recent years, there has been significant research on the mental health effects of classic psychedelic use, but there is very little evidence on how classic psychedelics might influence physical health. AIMS: The purpose of the present study was to investigate the associations between lifetime classic psychedelic use and markers of physical health. METHODS: Using data from the National Survey on Drug Use and Health (2015-2018) with 171,766 (unweighted) adults aged 18 or above in the United States, the current study examined the associations between lifetime classic psychedelic use and three markers of physical health (self-reported overall health, body mass index, and heart condition and/or cancer in the past 12 months) while controlling for a range of covariates. RESULTS: Respondents who reported having tried a classic psychedelic at least once in their lifetime had significantly higher odds of greater self-reported overall health and significantly lower odds of being overweight or obese versus having a normal weight. The association between lifetime classic psychedelic use and having a heart condition and/or cancer in the past 12 months approached conventional levels of significance, with lower odds of having a heart condition and/or cancer in the past 12 months for respondents who had tried a classic psychedelic at least once. CONCLUSION: The results of the present study suggest that classic psychedelics may be beneficial to physical health. Future research should investigate the causal effects of classic psychedelics on physical health and evaluate possible mechanisms.

Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews.

INTRODUCTION: Mood, anxiety, and substance-use disorders are among the most prevalent psychiatric disorders in the population. Although several pharmacological treatments are available, they are not effective for a significant proportion of patients and are associated with several adverse reactions. Therefore, new treatments should be explored. Recent studies suggest that serotonergic hallucinogens/psychedelics including ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) have anxiolytic, antidepressive, and antiaddictive effects. Areas Covered: A systematic review of systematic reviews assessing the efficacy, safety, and tolerability of serotonergic hallucinogens/psychedelic was performed using the PubMed data base until 11 April 2018. Systematic reviews with or without meta-analysis were analyzed, but only reviews that described at least one randomized controlled trial (RCT) were included. Expert Commentary: Psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence, and ayahuasca reduced depression symptoms in treatment-resistant depression. Although the results are promising, several studies were open label, and only few were RCTs, and most had small sample sizes and a short duration. Single or few doses of these drugs seem to be well tolerated, but long-term studies are lacking. New RCTs with bigger samples and longer duration are needed to replicate these findings.

Uso de drogas de diseño en fiestas electrónicas: aspectos clínicos, neuropsiquiátricos, epidemiológicos y de intervención prehospitalaria / Use of designer drugs in electronic parties: clinical, neuropsychiatric, epidemiological and prehospital intervention aspects

Introducción: Las llamadas "fiestas electrónicas" permitieron la generalización del uso de drogas de diseño (DdD) para disminuir el cansancio, las inhibiciones y aumentar la empatía entre los asistentes. Objetivo: Presentar los resultados de prevalencia, aspectos neuropsiquiátricos, clínicos y epidemiológicos del uso de DdD en fiestas electrónicas. Material y método: Realizamos un estudio de campo, observacional y transversal, mediante encuesta estandarizada, normatizada y anónima para consignar parámetros clínicos y neuropsiquiátricos en 138 asistentes a fiestas electrónicas que mediante demanda espontánea o requerida por terceros fueron evaluados por médicos y refirieron consumo de DdD. Se aplicaron parámetros estadísticos y se cumplieron normas éticas. Resultados: Objetivamos un alto consumo de alcohol, con alta prevalencia de uso comórbido con otras sustancias de diseño como el éxtasis y GHB. Los consumidores de GHB presentaron disminución de parámetros clínicos con un síndrome inhibitorio, en contraste con los valores aumentados en usuarios de éxtasis. Conclusión: La diferencia en las manifestaciones clínico-neuropsiquiátricas tienen sustento en aspectos neurobiológicos del mecanismo de acción y condicionan el tratamiento prehospitalario.

Introduction: The so-called "electronic parties" allowed the widespread use of designer drugs (DOD) to reduce fatigue, inhibitions and increase empathy among participants. Objective: To present the results of prevalence, neuropsychiatric, clinical and epidemiological aspects of the use of DoD in electronic parties. Material and Methods: We conducted a field study, observational and transversal, through standardized, Normatized and anonymous survey to record clinical and neuropsychiatric parameters 138 attendees electronic parties that by spontaneous or required by third application were evaluated by physicians and reported consumption of DOD. Statistical parameters were applied and ethical standards were met. Results: We objectify a high consumption of alcohol, with high prevalence of comorbid use design with other substances like ecstasy and GHB. GHB consumers had decreased clinical parameters with an inhibitory syndrome, in contrast to the values increased in users of ecstasy. Conclusions The difference in clinical and neuropsychiatric manifestations have support in neurobiological aspects of the mechanism of action and determine the prehospital treatment.

From Hofmann to the Haight Ashbury, and into the future: the past and potential of lysergic acid diethlyamide.

Since the discovery of its psychedelic properties in 1943, lysergic acid diethylamide (LSD) has been explored by psychiatric/therapeutic researchers, military/intelligence agencies, and a significant portion of the general population. Promising early research was halted by LSD's placement as a Schedule I drug in the early 1970s. The U.S. Army and CIA dropped their research after finding it unreliable for their purposes. NSDUH estimates that more than 22 million (9.1% of the population) have used LSD at least once in their lives. Recently, researchers have been investigating the therapeutic use of LSD and other psychedelics for end-of-life anxiety, post-traumatic stress disorder (PTSD), cancer, and addiction treatment. Adverse psychedelic reactions can be managed using talkdown techniques developed and in use since the 1960s.

Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases.

A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 µg of LSD (n = 8) or 20 µg of LSD with an open-label crossover to 200 µg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.

Self-inflicted testicular amputation in first lysergic acid diethylamide use.

BACKGROUND: Genital self-mutilation is a well-known phenomenon in patients with schizophrenia and has occasionally been described in patients with personality disorders or transsexuality. However, literature just provides few cases of genital self-mutilation related to the use of psychotropic substances. CASE DESCRIPTION: A previously mentally healthy man (age, 32 years) performed manual amputation of both testes after first use of lysergic acid diethylamide in combination with alcohol consumption. Follow-up examination 6 month after the event did not reveal the development of a psychiatric disorder. CONCLUSIONS: This report shows that a first and single use of lysergic acid diethylamide in combination with alcohol can cause intoxication with dramatic consequences.

Two cases of lysergamide intoxication by ingestion of seeds from Hawaiian Baby Woodrose.

We describe two cases of human consumption of seeds from Argyreia nervosa (Hawaiian Baby Woodrose), which resulted in one fatality due to falling from a building and one surviving witness. The principal psychoactive constituent of the seeds, lysergamide (LSA), was recovered from blood and urine samples by mixed-mode cation exchange solid-phase extraction and quantified by ultra performance liquid chromatography-time of flight mass spectrometry (UPLC-ToF/MS). The LSA concentrations were determined by UPLC-ToF/MS to be 4.9 microg/L in blood and 1.0mg/L in urine in the dead person and 1.8 microg/L in blood and 0.50mg/L in urine in the living person. These analytical findings were found to be in accordance with the case story, which indicated that seeds had been ingested and also noted psychological reactions, i.e. the will to jump out of the window. Other findings in the dead person were 22 microg/L THC in blood, 0.71 g/L ethanol in blood and 1.0 g/L ethanol in vitreous humor. Constituents originating from the seeds of A. nervosa, i.e. LSA, ergonovine, lysergic acid alpha-hydroxyethylamide were also identified in the biological samples. The 2-hydroxy-3-oxo metabolites of LSA and ergonovine were identified in the urine sample of the deceased.

Uso y abuso de drogas durante el embarazo: [revisión] / Illicit drug use and abuse during pregnancy: [review]

El consumo y dependencia de sustancias, es un serio problema social con alta morbilidad materno-fetal. El aumento de la oferta y el contexto social favorecedor, permitió que la difusión del consumo sustancias tóxicas ilícitas, conlleve una incidencia creciente en gestantes consumidoras de sustancias y aumento de recién nacidos afectados por las prácticas tóxicas de sus madres. La evaluación del riesgo cuando la gestación es expuesta a las drogas es difícil, los resultados pueden estar sesgados por el consumo concomitante de otros tóxicos o por factores sociológicos y socio-sanitarios desfavorables. Aunque tampoco se definió un patrón específico de anomalías congénitas, se considera que el abuso de drogas, en general, comporta mayor riego de desenlace anómalo del embarazo, por un incremento del riesgo de malformaciones congénitas, debido a la probable teratogenicidad de algunas sustancias o de la morbilidad perinatal afectando el crecimiento fetal o el normal desarrollo del embarazo. También existen posibles repercusiones a largo plazo en la capacidad de aprendizaje y comportamiento delos niños expuestos intraútero, aunque no demostró efectivamente. Por lo tanto, todo embarazo en el que se detecto un hábito tóxico se debe considerar de mayor riesgo, tomando las medidas oportunas para lograr que las pacientes se alejen de éstas prácticas, apoyadas por un equipo multidisciplinario, idealmente antes del inicio del embarazo, lo que implica la adopción de medidas profilácticas de información y concienciación de las mujeres en edad fértil y de apoyo durante el embarazo y la lactancia para el abandono de la dependencia.

Illicit drug use and dependence is a serious social problem with high maternal and fetal morbidity. Supply increase and propitious social context allowed that the diffusion of theuse of illicit toxic substances entails a growing incidence in pregnant women who use illicit drugs and an increase of newborns affected by the practices of their mothers. Risk evaluation is difficult when gestation is exposed to illicit drugs because the results could be biased by the concomitant consumption of others toxic substances or by psychological and socio-sanitary unfavorable factors. Though a specific pattern of congenital anomalies has not been defined, in general it is considered that drug abuse has an increased risk ofanomalous outcomes in pregnancies. This risk is caused by an increase in the risk of congenital malformations due to the probable teratogenicity of some substances or the perinatal morbility affecting the fetal growth or normal pregnancy development. Although it has not been demonstrated effectively, there are also possible long-term repercussions in the learning capacity and behavior of the children exposed intra uterus. In conclusion, all pregnancies exposed to illicit drugs must be considered high risk pregnancies and measures should be taken so that the patients avoid these practices supported by a multidisciplinary team. Ideally, this team should start working before pregnancy implying the adoption of preventive measures such as information and public awareness of women in fertile age and support during pregnancy and maternal lactation.

[Interferon alpha-associated agranulocytosis during clozapine treatment. Case report and status of current knowledge]. / Interferon-alpha-assoziierte Agranulozytose während Clozapin-Behandlung. Kasuistik und Wissensstand.

Little is known about possibilities of chronic hepatitis C treatment with interferon-alpha (IFN-alpha) in psychiatric patients continuously taking antipsychotics. We report on a 28-year-old hepatitis C-positive man with paranoid psychosis. He was successfully treated with clozapine, an atypical antipsychotic drug which is known for the risk of granulocytopenia and agranulocytosis. With doses up to 200 mg/day over 3 years, he showed no remarkable changes in WBC. Because of the chronic hepatitis C with genotype 3a, additional treatment was started with IFN-alpha (s.c., 3 x 6 million IU/week). After 2 months of therapy he developed a severe agranulocytosis. Both clozapine and IFN-alpha were discontinued, and his WBC returned to normal. Results from bone marrow examination were compatible with a toxic reaction possibly caused by either or both medications. We discuss possible problems with IFN-alpha during the treatment of psychiatric patients, interactions with psychiatric medication, and hematotoxic side effects like those from clozapine. We recommend combining IFN-alpha with less "toxic" antipsychotics and weekly checks of WBC.

[LSD and cannabis abuse in early pregnancy with good perinatal outcome. Case report and review of the literature]. / LSD- und Cannabis-Konsum während der frühen Schwangerschaft mit gutem perinatalen Ausgang. Fallbericht und Literaturübersicht.

This is a case report of a 27-year-old patient who had smoked a joint (cannabis) and 20 cigarettes (tobacco) daily up to the time of a positive pregnancy test at 7 4/7 weeks (p.c.). On day 20 p.c. she had an LSD minitrip. There are reports of chromosome aberrations in in vitro animal studies with LSD. In humans the main consequences are malformations of the fetal extremities and dysplasias of the eye. In both animals and humans cannabis causes changes in dopaminergic activity. Our recommendation was to continue the pregnancy, but to monitor it closely. The patient had a spontaneous term delivery-a lively boy with weight between the 5th and the 50th percentile, length between the 50th and the 90th percentile, normal umbilical arterial and venous pH values, and Apgar scores 7/9/10. There were no visible abnormalities, and behaviour was normal. If it is suspected that a pregnant patient consumes LSD, dysplasias of the fetal skeleton and eye should be checked for. With respect to LSD and to cannabis, too, the intellectual development of the child should be closely followed.

Drogas ilicitas e esquizofrenia em adolescentes / Use of illicit drugs and schizophrenia in adolescents

Este trabalho trata da investigacao dos registros medicos de todos os adolescentes hospitalizados no Departamento de Psiquiatria infantil e de adolescentes com o diagnostico de esquizofrenia ou psicose esquizoafetiva (DSM-IV) associado ao uso e abuso de drogas ilicitas...

Genetic toxicology of abused drugs: a brief review.

Although numerous studies have been conducted on abused drugs, most focus on the problems of addiction (dependence) and their neurotoxicities. Now accumulated data have demonstrated that the genotoxicity and/or carcinogenicity of abused drugs can also be detrimental to our health. In this review, commonly abused substances, including LSD, opiates (diacetylmorphine, morphine, opium and codeine), cocaine, cannabis, betel quid and khat, are discussed for their potential genotoxicity/carcinogenicity. The available literature in the field, although not as abundant as for neurotoxicity, clearly indicates the capability of abused drugs to induce genotoxicity.

[Forensic psychiatric expert evaluation of so-called drug-induced psychoses]. / Forensisch-psychiatrische Begutachtung bei sogenannten drogeninduzierten Psychosen.

A considerable number of schizophrenic persons also abuse illegal drugs. This comorbidity raises problems of diagnosis which become particularly important when concerning forensic questions. The hypothesis of a distinct psychopathological syndrome of drug induced psychosis is widely criticized in the literature. A case report is presented to demonstrate the problems of differential diagnoses and the difficulties for psychiatric expertizing arising from these problems.

Catatonia LSD induced?

The case of a patient who developed catatonia one week following Lysergic Acid Diethylamide (LSD) ingestion is presented. The psychosis developed two days after the intake. The catatonic syndrome resolved dramatically following one treatment of electroconvulsive therapy (ECT). This is perhaps the first case report of catatonia following the use of LSD. The need for a diagnostic category of organic catatonia is highlighted.

The muscle findings in the neuroleptic malignant syndrome associated with lysergic acid diethylamide.

A detailed pathological description of the muscle findings in a case of the neuroleptic malignant syndrome (NMS) following ingestion of lysergic acid diethylamide (LSD) is given, including the first ultrastructural analysis. Focal necrosis, oedema, and hypercontraction of fibres with glycogen and lipid depletion, were identified, all of which had resolved completely a year later. The findings are compared with those in malignant hyperthermia. It is suggested that the results support the view that in NMS, the muscle rigidity is due to central mechanisms and, in both this disorder and malignant hyperthermia, it is responsible for the hyperpyrexia and its life-threatening complications.