A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity.

N,N-dimethyltryptamine (DMT) is classified as a naturally occurring serotonergic hallucinogen of plant origin. It has also been found in animal tissues and regarded as an endogenous trace amine transmitter. The vast majority of research on DMT has targeted its psychotropic/psychedelic properties with less focus on its effects beyond the nervous system. The recent discovery that DMT is an endogenous ligand of the sigma-1 receptor may shed light on yet undiscovered physiological mechanisms of DMT activity and reveal some of its putative biological functions. A three-step active uptake process of DMT from peripheral sources to neurons underscores a presumed physiological significance of this endogenous hallucinogen. In this paper, we overview the literature on the effects of sigma-1 receptor ligands on cellular bioenergetics, the role of serotonin, and serotoninergic analogues in immunoregulation and the data regarding gene expression of the DMT synthesizing enzyme indolethylamine-N-methyltransferase in carcinogenesis. We conclude that the function of DMT may extend central nervous activity and involve a more universal role in cellular protective mechanisms. Suggestions are offered for future directions of indole alkaloid research in the general medical field. We provide converging evidence that while DMT is a substance which produces powerful psychedelic experiences, it is better understood not as a hallucinogenic drug of abuse, but rather an agent of significant adaptive mechanisms that can also serve as a promising tool in the development of future medical therapies.

Enhancement of creative expression and entoptic phenomena as after-effects of repeated ayahuasca ceremonies.

Studying the effect of psychedelic substances on expression of creativity is a challenging problem. Our primary objective was to study the psychometric measures of creativity after a series of ayahuasca ceremonies at a time when the acute effects have subsided. The secondary objective was to investigate how entoptic phenomena emerge during expression of creativity. Forty individuals who were self-motivated participants of ayahuasca rituals in Brazil completed the visual components of the Torrance Tests of Creative Thinking before and the second day after the end of a two-week long ceremony series. Twenty-one comparison subjects who did not participate in recent psychedelic use also took the Torrance tests twice, two weeks apart. Repeated ingestion of ayahuasca in the ritual setting significantly increased the number of highly original solutions and phosphenic responses. However, participants in the ayahuasca ceremonies exhibited more phosphenic solutions already at the baseline, probably due to the fact that they had more psychedelic experiences within six months prior to the study than the comparison subjects did. This naturalistic study supports the notion that some measures of visual creativity may increase after ritual use of ayahuasca, when the acute psychoactive effects are receded. It also demonstrates an increased entoptic activity after repeated ayahuasca ingestion.

Midazolam reduction with pre-operative melatonin in abdominal hysterectomy: double-blind randomized clinical trial.

INTRODUCTION: Midazolam is a benzodiazepine used for sedation, however, can cause respiratory depression and increases morbidity in patients. Melatonin is an effective alternative to manage anxiety in the perioperative period and could help to reduce the use of benzodiazepines during surgery. The aim of this clinical trial was to determine the efficacy of pre-operative sedation with a single-dose melatonin to reduce intraoperative use of midazolam in women under total abdominal hysterectomy (TAH). MATERIALS AND METHODS: This is a double-blind randomized clinical trial conducted in women over 25 years, scheduled for TAH, with American Society of Anesthesiologists Grade I or II. Each patient was randomly assigned to receive 5 mg of melatonin prolonged-release oral capsules or placebo. Midazolam use for anesthetic management was the decision of the treating anesthesiologist and sedation status was determined using the observer's assessment of alertness/sedation scale. RESULTS: In patients receiving melatonin, the use of midazolam during surgery was less than in patients receiving placebo. In addition, melatonin produces sedation 30 min after administration, the sedative effect was maintained at 60- and 90-min. Furthermore, hospital stay was shorter in patients who received melatonin (p = 0.006). CONCLUSION: Melatonin is effective for reduces intraoperative midazolam consumption and hospital stay in women undergoing TAH.

INTRODUCCIÓN: El midazolam es una benzodiazepina utilizada para la sedación, sin embargo, puede causar depresión respiratoria y aumentar la morbilidad en los pacientes. La melatonina es una alternativa eficaz para controlar la ansiedad en el período perioperatorio y podría ayudar a reducir el uso de benzodiazepinas durante la cirugía. El objetivo de este ensayo clínico fue determinar la eficacia de la sedación preoperatoria con una dosis única de melatonina para reducir el uso intraoperatorio de midazolam en mujeres sometidas a histerectomía abdominal total (HTA). MATERIAL Y MÉTODOS: Se trata de un ensayo clínico aleatorizado doble ciego realizado en mujeres mayores de 25 años, programadas para TAH, con American Society of Anesthesiologists Grado I o II. Cada paciente fue asignado al azar para recibir 5 mg de cápsulas orales de liberación prolongada de melatonina o placebo. El uso de midazolam para el manejo anestésico fue decisión del anestesiólogo tratante y el estado de sedación se determinó mediante la escala OAA/S. RESULTADOS: En las pacientes que recibieron melatonina, el uso de midazolam durante la cirugía fue menor que en las pacientes que recibieron placebo. Además, la melatonina produce sedación 30 min después de la administración, el efecto sedante se mantuvo a los 60 y 90 min. Además, la estancia hospitalaria fue más corta en los pacientes que recibieron melatonina (p = 0.006). CONCLUSIÓN: La melatonina es eficaz para reducir el consumo de midazolam intraoperatorio y la estancia hospitalaria en mujeres sometidas a HTA.

Effects of the Amazonian psychoactive beverage Ayahuasca on binocular rivalry: interhemispheric switching or interhemispheric fusion?

An early theoretical analysis supposed changes in hemispheric integration as the basis of altered state of consciousness induced by psychoactive drugs. Brain imaging studies revealed right cortical activation after administration of hallucinogens. Recent studies on binocular rivalry suggest that interhemispheric switching is the neural substrate of the perceptual oscillations observed during dichoptic stimulus presentation. The current study tested perceptual alternation in ceremonial participants, who ingested the South American hallucinogenic beverage ayahuasca, to examine the claim that there might be changes in interhemispheric function under the influence of hallucinogens. Ingestion of ayahuasca resulted in a decrease of rivalry alternation rates, increased length of one percept and there was evidence of phenomenal fusion. The findings are in line with results of brain activation studies and support the concept of interhemispheric fusion in altered states of consciousness.