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Lysergic acid diethylamide (LSD) is a synthetic psychedelic compound with potential therapeutic value for psychiatric disorders. This study aims to establish Caenorhabditis elegans as an in vivo model for examining LSD's effects on locomotor behavior. Our results demonstrate that LSD is absorbed by C. elegans and that the acute treatment reduces animal speed, similar to the role of endogenous serotonin. This response is mediated in part by the serotonergic receptors SER-1 and SER-4. Our findings highlight the potential of this nematode as a new experimental model in psychedelic research.

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Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use has expanded to other cultures. Hallucinogens are natural or synthetic substances that alter the perception of reality at nontoxic doses, producing intense psychological and physiological effects. The initial research on hallucinogens began in the 1950s. However, their non-medical use, studies without proper controls, and negative social opinion resulted in legal restrictions that limited their use for clinical and preclinical research for more than two decades. A renewed interest in studying hallucinogens as potential therapeutic agents for treating different psychiatric conditions has recently re-emerged. This review summarizes the effects of main hallucinogen drugs and their therapeutic potential. Classic hallucinogens such as LSD, dimethyltryptamine, psilocin, and mescaline have chemical structures similar to serotonin and directly activate 5-hydroxy-tryptamine (5-HT2A) receptors. Ketamine is a dissociative anesthetic with antagonist effects at the glutamatergic N-methyl-D-aspartate receptor, indirectly activating 5-HT2A receptors. Ketamine has rapid antidepressant effects and reduces suicidal ideation, but its effects are short-lasting. Other hallucinogens are under study. It is necessary to continue this research with a more rigorous methodology and include studying the long-term effects of psychedelics use.

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ABSTRACT Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use has expanded to other cultures. Hallucinogens are natural or synthetic substances that alter the perception of reality at nontoxic doses, producing intense psychological and physiological effects. The initial research on hallucinogens began in the 1950s. However, their non-medical use, studies without proper controls, and negative social opinion resulted in legal restrictions that limited their use for clinical and preclinical research for more than two decades. A renewed interest in studying hallucinogens as potential therapeutic agents for treating different psychiatric conditions has recently re-emerged. This review summarizes the effects of main hallucinogen drugs and their therapeutic potential. Classic hallucinogens such as LSD, dimethyltryptamine, psilocin, and mescaline have chemical structures similar to serotonin and directly activate 5-hydroxy-tryptamine (5-HT2A) receptors. Ketamine is a dissociative anesthetic with antagonist effects at the glutamatergic N-methyl-D-aspartate receptor, indirectly activating 5-HT2A receptors. Ketamine has rapid antidepressant effects and reduces suicidal ideation, but its effects are short-lasting. Other hallucinogens are under study. It is necessary to continue this research with a more rigorous methodology and include studying the long-term effects of psychedelics use.

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PURPOSE: We have developed and validated a high-sensitivity method to quantify lysergic acid diethylamide (LSD) and 2-oxo-3-hydroxy-LSD (OH-LSD) in oral fluid samples using liquid-liquid extraction and liquid chromatography-tandem mass spectrometry (LC‒MS/MS). The method was applied to the quantification of both substances in 42 authentic oral fluid samples. METHODS: A liquid-liquid extraction was performed using 500 µL each of samples (oral fluid samples collected using Quantisal™ device) and dichloromethane/isopropanol mixture (1:1, v/v). Enzymatic hydrolysis was evaluated to cleave glucuronide metabolites. RESULTS: The limit of quantification was 0.01 ng/mL for both LSD and OH-LSD. The linearity was assessed between 0.01 and 5 ng/mL. Imprecision and bias were not higher than 10.2% for both analytes. Extraction recovery was higher than 69%. The analytes were stable in the autosampler at 10 °C for 24 h, and up to 30 days at 4 and -20 °C. The method was applied to the analysis of 42 oral fluid samples. LSD was detected in all samples (concentrations between 0.02 and 175 ng/mL), and OH-LSD was detected in 20 samples (concentrations between 0.01 and 1.53 ng/mL). CONCLUSIONS: A high-sensitive method was fully validated and applied to authentic samples. To our knowledge, this is the first work to report concentrations of LSD and OH-LSD in authentic oral fluid samples.

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Parkinson´s disease is the most important neuromotor pathology due to the prominent loss of dopaminergic neurons in the substantia nigra pars compacta. There is an inherent deficiency of dopamine in Parkinson´s disease, which is aggravated when neuroinflammatory processes are present. Several biomolecules are interesting candidates for the regulation of inflammation and possible neuroprotection, such as valerenic acid, one of the main components of Valeriana officinalis. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced mouse model of Parkinson's disease was developed to evaluate the motor effects of valerenic acid. The evaluation was carried out with four tests (an invert screen test for muscle strength, cross beam test, open field mobility test and lifting on hind legs test). Subsequently, the neuroinflammatory process was evaluated through ELISA of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α and IFN-γ). The decreases in the inflammatory and neurodegenerative processes were evaluated by Western blot and immunohistochemistry analyses of the tissues, which included an evaluation of the tyrosine hydroxylase and GFAP proteins. Finally, the predicted mechanism of action of valerenic acid was supported by molecular docking calculations with the 5-HT5A receptor. The results indicate that the use of valerenic acid as a co-treatment decreases the neuroinflammation in Parkinson's disease induced by MPTP and provides evidence of a decrease in the evaluated pro-inflammatory cytokines and in the amount of GFAP in the mesencephalic area. Valerenic acid prevents neuroinflammation in a Parkinson's disease mouse model, which might reflect the neuroprotection of dopaminergic neurons with the recovery of motor ability.

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Introdução: A maculopatia ou retinopatia solar é uma lesão foto-traumática da mácula causada pela observação direta ou indireta de fontes luminosas intensas, que ocorre comumente na presença de distúrbios psíquicos ou após o uso de drogas recreativas. O prognóstico visual varia e a conduta é expectante. Descrição do caso: Paciente V.V.A.M., sexo masculino, 20 anos, estudante, com queixa de escotoma central em ambos os olhos. Nega antecedentes patológicos e oculares. Solicitaram-se tomografia de coerência óptica (OCT) e retinografia, que revelaram uma lesão central, bilateral e simétrica na retina externa. Paciente relatou ter feito uso de Dietilamida de ácido lisérgico (LSD) e, sob influência da droga, ter olhado de forma direta para o sol por aproximadamente 40 minutos. Discussão: O prognóstico da retinopatia solar é variável e relaciona-se com o tempo de exposição e com o comprimento da onda da fonte de luz. A etiopatogênese é explicada pelo dano causado ao epitélio pigmentar da retina (EPR) pela radiação. Conclusões: Deve haver maior orientação ao público sobre os possíveis efeitos danosos de exposição a fontes de luz de origens diversas. Além disso, destaca-se a importância do OCT para a identificação da maculopatia solar. (AU)

Introduction: Solar maculopathy or retinopathy is photo-traumatic damage created on the macula, caused by direct or indirect observation of intense light sources, commonly occurring in the presence of psychic disorders or after the use of recreational drugs. The visual prognosis varies. There is currently no known treatment. Case report: A 20-year-old male with no previous complaints reported central scotoma in both eyes despite 20/20 uncorrected vision. Bilateral, symmetric, central changes could be seen in the macula in fundoscopy. Optical coherence tomography (OCT) confirmed loss of the external retina suggestive of Solar Maculopathy. The patient later claimed to have spent 40 minutes looking directly into the sun after use of Lysergic Acid Diethylamide (LSD). Discussion: The prognosis of solar retinopathy is related to the exposure time and to the wavelength of the light source, with those between 300-350 nm being the most harmful. Its etiopathogenesis is explained by damage caused to the retinal pigment epithelium (EPR) caused by radiation, interrupting the interdigitations between this layer and the external segment of the photoreceptors. Ophthalmoscopically, solar maculopathy is characterized by a small foveolar lesion that might become yellowish in the days following exposure, in the form of exudate or edema, followed by loss of foveal reflex and thinning of the fovea. The initial yellowed lesions are subsequently replaced by a spotted EPR or even by a lamellar orifice. Conclusions: There should be public guidance on the possible harmful effects of exposure to sources of light from diverse origins, as it usually occurs during solar eclipses, after exposure to certain types of lasers or observation of fires since this habit can cause severe and sometimes irreversible visual loss. (AU)

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In a recent issue of the BMC Psychiatry, the evidence of effectiveness of treatments for psychiatric conditions in end-stage cancer patients was reviewed (Johnson, 2018). The review was comprehensive, and included traditional and non-traditional/alternative treatments, including herbal medicines and spirituality. However, evidence showing that classic or serotonergic hallucinogens/psychedelics such as psilocybin and lysergic acid diethylamide (LSD) could be effective treatments for depressive and anxiety disorders in end-stage cancer was not included. In this commentary, we expand the information available on the original article by briefly reviewing data from recent placebo-controlled, double-blind, cross-over clinical trials showing evidence that administration of single (or few) doses of LSD and psilocybin was associated with rapid and sustained reductions in depressive and anxiety symptoms in patients with end-stage cancer and other life-threatening diseases (e.g., Bechterew's disease, Parkinson's disease, Celiac disease). Since these substances seem to produce rapid and sustained therapeutic effects with single (or few) doses and well tolerated, large-scale, prospective, multi-site studies of end-stage cancer and classical/serotonergic hallucinogens/psychedelics should be performed to improve our understanding of the therapeutic potentials of these drugs and their use on clinical practice.

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BACKGROUND: Recognition of emotions in facial expressions (REFE) is a key aspect of social cognition. Anxiety and mood disorders are associated with deficits in REFE, and anxiolytics and antidepressants reverse these deficits. Recent studies have shown that serotonergic hallucinogens (i.e. ayahuasca, dimethyltryptamine, psilocybin, lysergic acid diethylamide [LSD], and mescaline) have anxiolytic and antidepressant properties, but their effects on REFE are not well understood. The purpose of the study was to conduct a systematic review analyzing the effects of serotonergic hallucinogens on REFE in humans. METHODS: Studies published in the PubMed, PsycINFO, and Web of Science databases until 19 October 2018 which analyzed the effects of serotonergic hallucinogens on REFE in humans were included. RESULTS: Of the 62 studies identified, 8 studies were included. Included studies involved the administration of a single or a few doses of LSD or psilocybin, and most trials were randomized and controlled with placebo. LSD and psilocybin reduced the recognition of negative emotions in most studies and modulated amygdala activity to these stimuli, which was correlated with antidepressive effects in patients. Both drugs were well tolerated. CONCLUSIONS: Serotonergic hallucinogens reduced the recognition of negative emotions by modulating amygdala activity. Despite the small sample sizes, results suggest that serotonergic hallucinogens show promising beneficial effects on deficits in REFE.

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Gender dysphoria (GD) (DSM-5) or transsexualism (ICD-10) refers to the marked incongruity between the experience of one's gender and the sex at birth. In this case report, we describe the use of LSD as a triggering factor of confusion in the gender identity of a 39-year-old male patient, with symptoms of psychosis and 25 years of substance abuse, who sought psychiatric care with the desire to undergo sex reassignment surgery. The symptoms of GD/psychosis were resolved by two therapeutic measures: withdrawal of psychoactive substances and use of a low-dose antipsychotic. We discuss the hypothesis that the superior parietal cortical area may be an important locus for body image and that symptoms of GD may be related to variations underlying this brain region. Finally, this case report shows that some presentations of GD can be created by life experience in individuals who have underlying mental or, synonymously, neurophysiological abnormalities.

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