Search Results (88)

Cancer-related cognitive impairment (CRCI)—encompassing anxiety, depression, and memory deficits—significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a Lewis lung carcinoma (3LL) mouse model. Behavioral assessments revealed heightened anxiety-like behavior and memory impairment following 3LL cell transplantation. Biochemical analysis revealed reduced tryptophan levels in both blood and hippocampal tissue, accompanied by the downregulation of serotonergic receptor genes and upregulation of pro-inflammatory cytokine genes in the hippocampus of tumor-bearing mice. Additionally, microglial density and morphological activation were markedly elevated. TBG treatment reversed these behavioral deficits, improving both anxiety-related behavior and memory performance. These effects were associated with the normalization of microglial density and morphology, as well as the restoration of serotonergic receptor and cytokine gene expression. In vitro, TBG partially suppressed neuroinflammatory gene expression in BV-2 microglial cells exposed to conditioned medium from 3LL cells. Collectively, these findings suggest that TBG alleviates CRCI-like symptoms by modulating neuroinflammation and microglial activation. This study highlights TBG as a promising therapeutic candidate for improving cognitive and emotional functioning in patients with cancer. Full article

Gas chromatography with mass spectrometry (GC-MS) is a common analytical technique used for identifying and quantifying drugs of abuse, as well as their metabolites, extracted from biological samples. Depending on the properties of the analyzed compounds, particularly in the case of metabolites, derivatization is often necessary. In this article, we will address the definition, properties, sample preparation, and GC-MS analysis of the most common drugs of abuse in their native (seized) form and their metabolites in biological samples (urine, blood, hair, and tissue). Drugs that will be described are: amphetamines and their derivatives, cannabinoids, cocaine, opioids, lysergide (LSD), benzodiazepines, gamma-hydroxybutyric acid (GHB), phencyclidine (PCP), mescaline, psilocin, and psilocybin. The literature review showed that the analysis of the drugs of abuse requires a simple extraction procedure and analysis with or without derivatization. However, the analysis of the metabolites requires removing the interferences from the matrix (proteins, other compounds, water, and other species that may interfere with the analysis or contaminate the GC-MS). This review article will provide insights into the available procedures for sample preparation and analytical methods, helping authors gain the necessary information and select the desired procedure for analysis. Full article

Several plants produce toxic and hallucinogenic metabolites, posing risks when misused due to a lack of botanical knowledge. Improper or accidental use of these plants poses a public health risk and has been associated with forensic cases involving poisoning, suicide, or drug-facilitated crimes. This review identified eight species of forensic interest that grow in southern Chile and analyzed their active compounds, mechanisms of toxicity, and documented clinical and legal cases. These selected species included both native and introduced taxa, whose main toxic agents are tropane alkaloids (atropine, scopolamine), piperidine (coniine), taxane pseudoalkaloids, and natural opiates (morphine, codeine). Most reported cases involved unintentional poisoning, mainly in children, highlighting the lack of regulation and awareness. This review revealed the need for improved forensic and clinical documentation of plant-based intoxications in Chile and greater public education regarding the toxicological risks posed by these botanical species. Full article

Background/Objectives: Hallucinogenic substances such as psilocybin, psilocin, ergometrine, ergotamine, and lysergic acid diethylamide (LSD) have been demonstrated to enhance the force of contraction (FOC), in part due to the phosphorylation of phospholamban in human atrial preparations via 5-HT₄ serotonin receptors and/or H₂ histamine receptors. However, whether psilocybin or psilocin acts at isolated mammalian ventricular preparations and whether they increase protein phosphorylation in the mammalian ventricle remains to be elucidated. Methods: To this end, the FOC and phospholamban phosphorylation in isolated perfused hearts from transgenic mice with cardiomyocyte-specific overexpression of either human 5-HT₄ receptors (5-HT₄-TG) or human H₂ receptors (H₂-TG) and their wild-type littermates (WT) were examined. Furthermore, the ergot alkaloids ergometrine, ergotamine, and LSD were used as references. Results: Psilocybin and psilocin enhanced the FOC to 137% and to 152%, respectively, and elevated the phospholamban phosphorylation in isolated perfused hearts from 5-HT₄-TG. In H₂-TG hearts, psilocybin and psilocin increased the FOC to a much lesser extent but had no effect on the phospholamban phosphorylation. In contrast, LSD increased the FOC and phosphorylation state of phospholamban in isolated hearts of both 5-HT₄-TG and H₂-TG. On the other hand, ergometrine and ergotamine increased the FOC only in H₂-TG. Ergometrine increased the phosphorylation state of phospholamban in perfused hearts from H₂-TG, but not from 5-HT₄-TG. Ergotamine failed to increase the phospholamban phosphorylation in both H₂-TG and 5-HT₄-TG. Psilocybin, psilocin, ergotamine, ergometrine, and LSD were unable to increase FOC and phospholamban phosphorylation in perfused hearts from WT. Conclusions: The increase in the phosphorylation state of phospholamban could provide a partial explanation for the positive inotropic effects and the relaxant effects of not only psilocybin and psilocin but also ergometrine and LSD in the isolated hearts of the animals used in this study. Full article

Background: Understanding immune response is essential for preparing for public health crises. COVID-19 vaccination provides robust immunity against SARS-CoV-2, but immunocompromised populations may have weaker immune responses. We assessed SARS-CoV-2 spike (trimer) total IgG/IgM/IgA (total Ig) to investigate immune response to COVID-19 vaccination in people living with HIV (PLWH), considering CD4⁺ T cell count, viral load, substance use, and comorbidities. Methods: This cross-sectional study was conducted in Miami, Florida, between May 2021 and December 2021 as part of the NIH Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) initiative (3U01DA040381-05S1) and the Miami Adult Studies on HIV (MASH) cohort (U01DA040381). Blood samples were collected and SARS-CoV-2 spike (trimer) total Ig was quantified. HIV serostatus, viral load, CD4⁺ T cell count, and COVID-19 vaccinations were abstracted from medical records. Substance use (tobacco, alcohol, and drug use [marijuana, cocaine, heroin, fentanyl, methamphetamine, amphetamine, hallucinogens, ecstasy, or misuse of prescription drugs]), and comorbidities (hypertension, diabetes, autoimmune disease, obesity, chronic kidney disease, and substance use disorders) were assessed via validated questionnaires. Drug use was confirmed via urine toxicology. Multivariable linear regression was conducted. Results: Median age (n = 1317) was 57.8 years, 49.8% were male, 50% were Black non-Hispanic, 66.2% had received ≥1 dose of a COVID-19 vaccine, and 29.6% were PLWH (71.3% virally suppressed and median CD4⁺ T cell count > 500 cells/µL). PLWH, compared to people without HIV, were more likely to have received ≥1 dose of a COVID-19 vaccine (76.2% vs. 62.0%, p < 0.001) and present with substance use (77.2% vs. 42.9%, p < 0.001) and comorbidities (72.8% vs. 48.2%, p < 0.001). Vaccinated PLWH, compared to unvaccinated PLWH, had higher CD4⁺ T cell counts (577.5 vs. 517.5, p = 0.011) and were more likely to be virally suppressed (76.4% vs. 54.8%, p < 0.001). A lower CD4⁺ T cell count (<200 vs. ≥500, β = −0.400, p = 0.033) and higher HIV viral load (≥200–<5000 vs. <200, β = −0.275, p < 0.001) were associated with lower spike (trimer) total Ig titers, indicating a diminished response to COVID-19 vaccination. Conclusions: A lower CD4⁺ T cell count and higher HIV viremia were linked to reduced SARS-CoV-2 immunogenicity in racial/ethnic minority PLWH, a population underrepresented in vaccine clinical trials. HIV care providers should target efforts to maintain viral suppression to avoid diminished responses to COVID-19 vaccination. Full article

Since its origins, the debate on the interaction between religions and psychoactives has been strongly influenced, both positively and negatively, by prejudices, policies, fashions and trends that had little to do with scientific research. Stigma and exaltation in different historical moments have equally characterized the study of the presence and use of so-called entheogens in the different declinations of the shamanic phenomenon around the world. This article attempts to shed light on the various trends regarding the state of the art, providing new epistemological elements on the basis of an ethnographic investigation among some Indigenous peoples of India. The production of alcoholic beverages (fermented and distilled, but sometimes in combination with other psychoactive or hallucinogens among the starters) is a fundamental trait of the aboriginal (ādivāsī) cultures of the Indian subcontinent. Not immune from an attempt at political instrumentalization, which occurred both in the colonial period and in the contemporary era, the discourse on the natural production of these sacred substances is today the key to understanding indigenous ontology and its traditional idea of sustainability. Far beyond the mere documentation of the induction of altered states of consciousness, this investigation involves the discovery of local pharmacopeias, as well as principles of fermentation and food preservation. Full article

Lysergic acid diethylamide (LSD) is gaining renewed interest as a potential treatment for anxiety, depression, and alcohol use disorder, with clinical trials reporting significant symptom reductions and long-lasting effects. LSD modulates serotonin (5-HT2A) receptors, which, in turn, influence dysfunctional brain networks involved in emotional processing and cognition. It has also shown promise in psychedelic-assisted psychotherapy, where mystical-type experiences are linked to improved psychological well-being. This review examines LSD’s pharmacokinetics, neurobiological mechanisms, and safety considerations, including cardiovascular risks, emotional vulnerability, and the potential for hallucinogen-persisting perception disorder (HPPD). Challenges such as small sample sizes, variable dosing protocols, and regulatory restrictions limit large-scale trials. Future research should focus on standardization, pharmacogenetic influences, and personalized treatment strategies to ensure its safe and effective integration into clinical practice. Full article

Besides the well-known hallucinogenic ketamine, various novel ketamine derivatives are available on the illicit drug market, sold as designer drugs. Minor chemical changes to the parent compound aim to circumvent existing narcotic drug laws while mimicking the effects of the original substance. Ketamine and some of its derivatives possess a chiral centre and therefore exist as two enantiomers. While differences in the effects of S- and R-ketamine are well studied, this is not the case for ketamine derivatives. Therefore, the development and adaptation of suitable enantioseparation methods for those compounds is important to face the problems of the constantly changing drug market. In this study, different chiral separation methods for capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC) were tested on 11 ketamine derivatives. Some of them were enantioseparated for the first time due to their novelty. All compounds were at least partially separated on both instruments. HPLC separations were conducted using four different polysaccharide-based chiral stationary phases. Furthermore, an optical rotation detector coupled to the HPLC enabled the determination of the enantiomer elution order. In CE analysis, enantioseparation was achieved using 2% (w/v) acetyl-β-cyclodextrin or carboxymethyl- β-cyclodextrin in 10 mM di-sodium hydrogen phosphate as the background electrolyte in capillary electrophoresis. Full article

Several authors have advanced the idea that psychedelics such as psilocybin might be effective means for achieving moral bioenhancement (MBE). Here, I discuss some reservations on this assertion from both neuropharmacological and bioethical perspectives, and surmised that there is little, if any, good justification for such a claim. The indication of psychedelics for MBE is undermined by their hallucinogenic properties and the risk of adverse psychosis. There is also a lack of sound bioethical basis for using psychedelics to enhance morality. Based on our current understanding, the use of psychedelics specifically for MBE in healthy individuals would violate the ethical principle of non-maleficence. Unless there is unequivocal demonstration that psychedelics could enhance morality, or that new non-hallucinogenic derivatives become available, an indication for psychedelics in MBE would be untenable. Full article

Psychoactive drugs are compounds that alter the function of the central nervous system, resulting in changes in perception, mood, cognition, and behavior. A subclass of psychoactive drugs, psychedelics, are hallucinogenic drugs that can trigger psychedelic experiences and possible changes in mental perception. The potential use of psychedelics as a therapeutic has led to an increase in clinical research focusing on the treatment of mental disorders including anxiety and depression. There are numerous species belonging to Psychotria and Banisteriopsis which have been reported to contain psychedelic and psychoactive compounds; however, there is a lack of validated analytical methods for raw plant material, which is crucial if these plants are to be commercially cultivated for medicines. This study provides a fully validated method using ultra-high performance liquid chromatography (UHPLC) coupled to mass spectrometry (MS) for the following six compounds: tryptamine, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), tetrahydroharmine (THH), harmaline, and harmine. The validated method was used to determine the psychoactive concentrations in Psychotria viridis, Psychotria carthagenensis, Banisteriopsis caapi, and Alicia anisopetala. Validation parameters were established; linearity (R² = 0.988–0.999), limit of detection (LOD) (0.06–0.11 ng/mL), limit of quantitation (LOQ) (0.18–0.34 ng/mL), accuracy, precision, extraction efficiency (>98%), recovery (74.1–111.6%), and matrix effect (70.6–109%) were all evaluated. All six compounds eluted within nine minutes, with a total analysis time of 20 min including column equilibration. This method establishes a high-throughput method for the robust analysis of psychedelics which may see future use in agricultural research and industry. Full article

Background: Piperazines, synthetic compounds known for their stimulant and hallucinogenic effects, have gained prominence among novel psychoactive substances (NPS) and are frequently associated with adverse psychiatric outcomes, including psychosis. Methods: A systematic review of the literature available up to 23 May 2024 was conducted, using the PubMed, Scopus, and Web of Science databases, in addition to the related gray literature, utilizing the following search strategy: “piperazines” AND (“psychosis” OR “hallucination” OR “delusion” OR “schizophrenia” OR “delusional” OR “schizoaffective”) NOT review NOT animal. Data collection adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research methods were registered with PROSPERO (CRD42024549204). Results: Out of a total of 4547 articles identified, 4 met the inclusion criteria. We observed an important relationship between piperazine abuse and the onset of acute psychotic episodes, marked by symptoms such as paranoia, auditory, and visual hallucinations. Conclusion: The complex polyreceptor action mechanism of piperazines may explain these psychopathological effects, similar to those observed with other NPS. Although studies confirm a link between piperazine use and psychosis, data on long-term outcomes are limited. Recovery is common following cessation and treatment. Further research into the effects of piperazine abuse and the development of specific treatment protocols for substance-induced psychosis is necessary. Full article

New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the literature. We sought to summarize the available evidence on NPS-related psychiatric disorders, to facilitate the interpretation of the molecular mechanism underlying their specific pathologies. A literature search of Scopus, PubMed and Google Scholar was conducted including studies published between 2013 and 2024, in which a correlation between NPS consumption and psychiatric symptoms was reported. Furthermore, the short- and long-term psychopathological effects were included. The literature search resulted in 109 NPS-related intoxication cases in which acute or chronic psychiatric symptoms were reported, mostly related to synthetic cannabinoids, followed by synthetic cathinones, hallucinogens, natural NPSs and stimulants. The most common acute symptoms were hallucinations, aggressiveness, and psychotic and bizarre behavior, related to the molecular disbalance of neurotransmitters in the central nervous systems, with different mechanisms. The lack of clear diagnostic criteria and toxicological analyses has resulted in crucial complications in psychiatric diagnoses related to NPS intoxication. Hence, the implementation of toxicological screening procedures in emergency rooms, including the main NPS classes, should support the diagnosis of acute intoxication and its proper therapeutic treatment. Finally, proper follow-up should be implemented to assess the chronic sequelae. Full article

Accurate and generalizable classification of brain states is essential for understanding their neural underpinnings and improving clinical diagnostics. Traditionally, functional connectivity patterns and graph-theoretic metrics have been utilized. However, cortical gradient features, which reflect global brain organization, offer a complementary approach. We hypothesized that a machine learning model integrating these three feature sets would effectively discriminate between baseline and atypical brain states across a wide spectrum of conditions, even though the underlying neural mechanisms vary. To test this, we extracted features from brain states associated with three meta-conditions including unconsciousness (NREM2 sleep, propofol deep sedation, and propofol general anesthesia), psychedelic states induced by hallucinogens (subanesthetic ketamine, lysergic acid diethylamide, and nitrous oxide), and neuropsychiatric disorders (attention-deficit hyperactivity disorder, bipolar disorder, and schizophrenia). We used support vector machine with nested cross-validation to construct our models. The soft voting ensemble model marked the average balanced accuracy (average of specificity and sensitivity) of 79% (62–98% across all conditions), outperforming individual base models (70–76%). Notably, our models exhibited varying degrees of transferability across different datasets, with performance being dependent on the specific brain states and feature sets used. Feature importance analysis across meta-conditions suggests that the underlying neural mechanisms vary significantly, necessitating tailored approaches for accurate classification of specific brain states. This finding underscores the value of our feature-integrated ensemble models, which leverage the strengths of multiple feature types to achieve robust performance across a broader range of brain states. While our approach offers valuable insights into the neural signatures of different brain states, future work is needed to develop and validate even more generalizable models that can accurately classify brain states across a wider array of conditions. Full article

The present study examined three hallucinogenic amphetamine derivatives, namely, 2,5-dimethoxy-4-iodoamphetamine (DOI) as well as 2,5-dimethoxy-4-methylamphetamine (DOM) and 4-methylmethcathinone (mephedrone). The objective of this study was to test the hypothesis that DOI, DOM, and mephedrone would increase the contractile force in isolated human atrial preparations in a manner similar to amphetamine. To this end, we measured contractile force under isometric conditions in electrically stimulated (1 Hz) human atrial preparations obtained during open surgery. DOI and DOM alone or in the presence of isoprenaline reduced the contractile force concentration-dependently in human atrial preparations. These negative inotropic effects of DOM and DOI were not attenuated by 10 µM atropine. However, mephedrone increased the contractile force in human atrial preparations in a concentration- and time-dependent manner. Furthermore, these effects were attenuated by the subsequent addition of 10 µM propranolol or pretreatment with 10 µM cocaine in the organ bath. Therefore, it can be concluded that amphetamine derivatives may exert opposing effects on cardiac contractile force. The precise mechanism by which DOI and DOM exert their negative inotropic effects remains unknown at present. The cardiac effects of mephedrone are probably due to the release of cardiac noradrenaline. Full article

Some species of the Orchidaceae family are used in Mexican traditional medicine. However, there are no current and critical compilations of the medicinal uses and pharmacological effects of the members of the Orchidaceae family. This review provides a current, critical, and comprehensive analysis of the traditional medicinal uses, pharmacological reports, and active compounds isolated from Mexican orchids. A total of 62 Mexican orchids with medicinal potential have been recorded, of which 14 have scientific evidence. The remaining 48 plant species have ethnomedicinal information but have not been validated with scientific studies. These orchids are distributed in 14 states of the Mexican Republic, mainly in the southern region of Mexico. The most common pharmacological activities reported are anti-inflammatory, vasorelaxant, antinociceptive, antioxidant, spasmolytic, antihypertensive, and hallucinogenic activities. It is necessary to increase the number of pharmacological, phytochemical, and toxicological studies with medicinal orchids from Mexico because there are scientific studies on only 22.5% of these species. In further studies, it will be possible to evaluate the pharmacological effects of Mexican orchids in clinical trials. In addition, the mechanisms of action by which plant extracts and their active compounds exert medicinal effects remain to be studied. Plant extracts from orchids and their active compounds show promising antinociceptive and spasmolytic effects, respectively. Full article