Racial effects on masimo pulse oximetry: impact of low perfusion index.

PURPOSE:  Evaluate the SpO2-SaO2 difference between Black and White volunteer subjects having a low perfusion index (Pi) compared to those having a normal Pi. METHODS:  The Pi data were abstracted from electronic files collected on 7183 paired SpO2-SaO2 samples (3201 Black and 3982 White) from a recently reported desaturation study of 75 subjects (39 Black and 36 White) where SaO2 values were sequentially decreased from 100 to 70%. The Pi values from that dataset were divided into two groups (Pi ≤ 1 or Pi > 1) for analysis. A Pi value ≤ 1 was considered "low perfusion" and a Pi value > 1 was considered "normal perfusion". Statistical calculations included values of bias (mean difference of SpO2-SaO2), precision (standard deviation of the difference), and accuracy (root-mean-square error [ARMS]). During conditions of low perfusion (Pi ≤ 1, range [0.1 to 1]), overall bias and precision were + 0.48% ± 1.59%, while bias and precision were + 0.19 ± 1.53%, and + 0.91 ± 1.57%, for Black and White subjects, respectively. RESULTS:  During normal perfusion (Pi > 1, range [1 to 12]), overall bias and precision were + 0.18% ± 1.34%, while bias and precision were -0.26 ± 1.37%, and - 0.12 ± 1.31%, for Black and White subjects, respectively. ARMS was 1.37% in all subjects with normal perfusion and 1.64% in all subjects with low perfusion. CONCLUSION:  Masimo SET® pulse oximeters with RD SET® sensors are accurate for individuals of both Black and White races when Pi is normal, as well as during conditions when Pi is low. The ARMS for all conditions studied is well within FDA standards. This study was conducted in healthy volunteers during well-controlled laboratory desaturations, and results could vary under certain challenging clinical conditions.

Racial effects on Masimo pulse oximetry: a laboratory study.

Recent publications have suggested that pulse oximeters exhibit reduced accuracy in dark-skinned patients during periods of hypoxemia. Masimo SET® (Signal Extraction Technology®) has been designed, calibrated, and validated using nearly equal numbers of dark and light skinned subjects, with the goal of eliminating differences between pulse oximetry saturation (SpO2) and arterial oxygen saturation (SaO2) values due to skin pigmentation. The accuracy concerns reported in dark-skinned patients led us to perform a retrospective analysis of healthy Black and White volunteers. Seventy-five subjects who self-identified as being racially Black or White underwent a desaturation protocol where SaO2 values were decreased from 100 to 70%, while simultaneous SpO2 values were recorded using Masimo RD SET® sensors. Statistical bias (mean difference) and precision (standard deviation of difference) were - 0.20 ± 1.40% for Black and - 0.05 ± 1.35% for White subjects. Plots of SpO2 versus SaO2 show no significant visible differences between races throughout the saturation range from 70 to 100%. Box plots grouped in 1% saturation bins, from 89-96%, and plotted against concomitant SaO2 values, show that occult hypoxemia (SaO2 < 88% when SpO2 = 92-96%) occurred in only 0.2% of White subject data pairs, but not in any Black subjects. There were no clinically significant differences in bias (mean difference of SpO2-SaO2) found between healthy Black and White subjects. Occult hypoxemia was rare and did not occur in Black subjects. Masimo RD SET® can be used with equal assurance in people with dark or light skin. These laboratory results were obtained in well-controlled experimental conditions in healthy volunteers-not reflecting actual clinical conditions/patients.

Pro-Con Debate: Should Code Sharing Be Mandatory for Publication?

In this Pro-Con commentary article, we discuss whether or not code sharing should be mandatory for scientific publications. Scientific programming is an increasingly prevalent tool in research. However, there are not unified guidelines for code availability requirements. Some journals require code sharing. Others require code descriptions. Yet others have no policies around code sharing. The Pro side presented here argues that code sharing should be mandatory for all scientific publications involving code. This Pro argument comes in 2 parts. First, any defensible reason for not sharing code is an equally valid a reason for the manuscript itself not being published. Second, lack of code sharing requirements creates 2 tiers of science: one where reproducibility is required and one where it is not. Additionally, the Pro authors suggest that a debate over code sharing is itself a decade out-of-date due to the emerging availability of containerization and virtual environment sharing software. The Pro argument concludes with an appeal that authors release code to make their work more understandable by other researchers. The Con side presented here argues that computer source codes of medical technology equipment should not be subject to mandatory public disclosure. The source code is a crucial part of what makes a particular device unique and allows that device to outperform its competition. The Con authors believe that public disclosure of this proprietary information would destroy all incentives for businesses to develop new and improved technologies. Competition in the free marketplace is what drives companies to constantly improve their products, to develop new and better medical devices. The open disclosure of these "trade secret" details would effectively end that competitive drive. Why invest time, money, and energy developing a "better mousetrap" if your competitors can copy it and produce it the next day?

Correspondence to: performance of the new SmartCardia wireless, wearable oximeter: a comparison with arterial SaO2 in healthy volunteers.

In a recent publication in BMC Anesthesiology, Rincon, et al.present accuracy data for three pulse oximeters with sensors located at three different anatomic sites. Their results for the Masimo Radical with fingertip sensor are erroneous, and we present valid data here. Rincon, et al.show a Bias ± Precision of 2.02 ± 4.6, while the correct laboratory values are -0.01 ± 1.16. The most probable reason for these invalid data is that insufficient time was used at each saturation plateau to allow stabilization of SpO2 readings on a fingertip sensor. It has been shown in the literature that fingertip sensors require at least a full minute of stable oxygenation conditions before their readings will be the same as earlobe sensors.

Assessing the Psychedelic "After-Glow" in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities.

Background: Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures. Methods: Using 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose. Results: Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the "nonjudging" subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later. Conclusions: These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca.

Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans.

BACKGROUND: Salvinorin-A is a terpene found in the leaves of the plant Salvia divinorum. When administered to humans, salvinorin-A induces an intense but short-lasting modified state of awareness, sharing features with those induced by the classical serotonin-2A receptor agonist psychedelics. However, unlike substances such as psilocybin or mescaline, salvinorin-A shows agonist activity at the kappa-opioid receptor rather than at the serotonin-2A receptor. Here, we assessed the involvement of kappa-opioid receptor and serotonin-2A agonism in the subjective, cardiovascular, and neuroendocrine effects of salvinorin-A in humans. METHODS: We conducted a placebo-controlled, randomized, double-blind study with 2 groups of 12 healthy volunteers with experience with psychedelic drugs. There were 4 experimental sessions. In group 1, participants received the following treatment combinations: placebo+placebo, placebo+salvinorin-A, naltrexone+placebo, and naltrexone+salvinorin-A. Naltrexone, a nonspecific opioid receptor antagonist, was administered at a dose of 50mg orally. In group 2, participants received the treatment combinations: placebo+placebo, placebo+salvinorin-A, ketanserin+placebo, and ketanserin+salvinorin-A. Ketanserin, a selective serotonin-2A antagonist, was administered at a dose of 40mg orally. RESULTS: Inhalation of 1mg of vaporized salvinorin-A led to maximum plasma concentrations at 1 and 2 minutes after dosing. When administered alone, salvinorin-A severely reduced external sensory perception and induced intense visual and auditory modifications, increased systolic blood pressure, and cortisol and prolactin release. These effects were effectively blocked by naltrexone, but not by ketanserin. CONCLUSIONS: Results support kappa opioid receptor agonism as the mechanism of action underlying the subjective and physiological effects of salvinorin-A in humans and rule out the involvement of a serotonin-2A-mediated mechanism.

Salvinorin-A Induces Intense Dissociative Effects, Blocking External Sensory Perception and Modulating Interoception and Sense of Body Ownership in Humans.

BACKGROUND: Salvinorin-A is a terpene with agonist properties at the kappa-opioid receptor, the binding site of endogenous dynorphins. Salvinorin-A is found in Salvia divinorum, a psychoactive plant traditionally used by the Mazatec people of Oaxaca, Mexico, for medicinal and spiritual purposes. Previous studies with the plant and salvinorin-A have reported psychedelic-like changes in perception, but also unusual changes in body awareness and detachment from external reality. Here we comprehensively studied the profiles of subjective effects of increasing doses of salvinorin-A in healthy volunteers, with a special emphasis on interoception. METHODS: A placebo and three increasing doses of vaporized salvinorin-A (0.25, 0.50, and 1mg) were administered to eight healthy volunteers with previous experience in the use of psychedelics. Drug effects were assessed using a battery of questionnaires that included, among others, the Hallucinogen Rating Scale, the Altered States of Consciousness, and a new instrument that evaluates different aspects of body awareness: the Multidimensional Assessment for Interoceptive Awareness. RESULTS: Salvinorin-A led to a disconnection from external reality, induced elaborate visions and auditory phenomena, and modified interoception. The lower doses increased somatic sensations, but the highest dose led to a sense of a complete loss of contact with the body. CONCLUSIONS: Salvinorin-A induced intense psychotropic effects characterized by a dose-dependent gating of external audio-visual information and an inverted-U dose-response effect on body awareness. These results suggest a prominent role for the kappa opioid receptor in the regulation of sensory perception, interoception, and the sense of body ownership in humans.

On the transmethylation hypothesis: stress, N,N-dimethyltryptamine, and positive symptoms of psychosis.

Past research suggests a relationship between stress and positive symptoms of psychosis. However, the biological substrate of this relationship remains unknown. According to the transmethylation hypothesis, schizophrenia could result from a biochemical disruption in the stress mechanism. This biochemical disruption would lead to the production of a substance that would account for the symptoms of psychosis. Moreover, some studies have tested endogenous N,N-dimethyltryptamine (DMT) in the context of the transmethylation hypothesis. Stress has been found to elevate DMT levels in rodents. Also, elevated DMT levels have been associated with positive features of psychosis in psychiatric patients. Additionally, healthy participants treated with exogenous DMT experience predominantly positive symptoms of psychosis. The present paper examines endogenous DMT as a possible biological mediator of the relationship between stress and positive symptoms of psychosis.

Acute chest pain in contingency operations at a Role 1 facility.

Acute chest pain is a common medical presenting complaint which can be difficult to diagnose and treat outside of a fully equipped emergency department. In future contingency operations the number of personnel deployed is likely be smaller, with the medical cover appropriate for the population at risk, such that the deployed medical facilities will be smaller than the Role 3 unit with which we have become familiar over the last 10 years of operations in Afghanistan. Physician involvement in these smaller medical facilities is crucial to maintain clinical effect when dealing with patients presenting with disease and non-battle injury, which can often make up the majority of deployed healthcare work. Patients presenting with chest pain require rapid assessment and stabilisation prior to medical evacuation to a suitable definitive care unit. This article focuses on emergency acute chest pain presentations, non-cardiac causes of chest pain, risk reduction and how contingency will affect patient care.

Pharmacokinetics of single oral dose of pimobendan in Hispaniolan Amazon parrots (Amazona ventralis).

Pimobendan is a phosphodiesterase (PDE) inhibitor and calcium sensitizer with inotropic, lusitropic, and rasodilator properties used in the treatment of congestive heart failure. The mechanism of action is by inhibition of PDE III and V and by increasing intracellular calcium sensitivity in the cardiac myocardium. Pharmacokinetic and pharmacodynamic studies have been published in humans, dogs, and cats, but there are no studies in avian species. Pimobendan has been used in birds at the empirical dosage of 0.25 mg/kg q12h. To determine the pharmacokinetic parameters of pimobendan in Hispaniolan Amazon parrots (Amazona ventralis), 3 pilot studies with 2 birds, each receiving 1, 3, and 10 mg/kg PO, provided the basis for the pivotal trials with 6 birds, each receiving 10 mg/kg PO using 2 different suspensions. Blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 18 hours after drug administration. Plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (HPLC/MS) by use of electrospray ionization. Because of the erratic and low concentrations of pimobendan, pharmacokinetic parameters were calculated using naive averaged analysis. Plasma concentrations after commercial pimobendan tablet suspension at 10 mg/kg reached a Cmax of 8.26 ng/mL at 3 hours with a terminal half-life of 2.1 hours, while concentrations after the bulk chemical suspension reached a Cmax of 1.28 ng/mL at 12 hours and had a terminal half-life of 2.3 hours. Further studies evaluating the effect of oral pimobendan in parrots are needed.

Transient Acquired Amegakaryocytic Thrombocytopenia in the Setting of Severe Sepsis: A Case Report.

Acquired amegakaryocytic thrombocytopenia (AATP) is a rare disorder in which severely low platelet levels occur due to reduced or complete absence of megakaryocytes in the bone marrow. The pathophysiology of this disease is not fully understood, although anti-thyroid peroxidase antibodies (anti-TPO) binding to cellular-myeloproliferative leukemia (c-mpl) receptors is a proposed mechanism. Currently, no standard published guideline for treatment exists, but immunosuppressive therapies have been used based on the proposed mechanism and associated conditions. We present a case of a 57-year-old male who presented to the hospital with a 3-day history of progressive weakness and dysphagia. He had recently been discharged from an outside health system after evaluation for suspected gastrointestinal bleeding, although esophagogastroduodenoscopy and colonoscopy did not uncover a source of bleeding. Fifteen days later, he was admitted to our hospital for septic shock and acute renal failure with suspected lower gastrointestinal bleeding (melena on presentation). He was found to have a rapidly declining platelet count with a nadir of 0. Due to severe thrombocytopenia, filgrastim was administered. A bone marrow biopsy revealed findings consistent with amegakaryocytosis with otherwise preserved cell lines. Hematologic labs improved with the initiation of appropriate treatment for severe sepsis. After performing an extensive workup, the likely etiology of transient AATP in this case was severe sepsis-induced immune dysregulation and bone marrow suppression.

LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate.

We report a qualitative liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the simultaneous analysis of the three known N,N-dimethyltryptamine endogenous hallucinogens, their precursors and metabolites, as well as melatonin and its metabolic precursors. The method was characterized using artificial cerebrospinal fluid (aCSF) as the matrix and was subsequently applied to the analysis of rat brain pineal gland-aCSF microdialysate. The method describes the simultaneous analysis of 23 chemically diverse compounds plus a deuterated internal standard by direct injection, requiring no dilution or extraction of the samples. The results demonstrate that this is a simple, sensitive, specific and direct approach to the qualitative analysis of these compounds in this matrix. The protocol also employs stringent MS confirmatory criteria for the detection and confirmation of the compounds examined, including exact mass measurements. The excellent limits of detection and broad scope make it a valuable research tool for examining the endogenous hallucinogen pathways in the central nervous system. We report here, for the first time, the presence of N,N-dimethyltryptamine in pineal gland microdialysate obtained from the rat.

A Prospective Randomized Controlled Pilot Simulation Study to Investigate the Effect of Audiovisual Decision Support on Diagnosis and Therapeutic Interventions.

INTRODUCTION: Combining audiovisual decision support during perioperative critical events might enhance provider diagnostic and therapeutic accuracy and efficiency. METHODS: This study is a prospective, randomized controlled pilot trial studying the impact of audiovisual decision support on anesthesia professional performance at NorthShore University HealthSystem's high fidelity simulation center. Twenty anesthesia professionals (>2 years of clinical experience in the current role) were randomized to 2 groups (current care model vs. audiovisual assistance) and underwent 3 periprocedural simulation scenarios, where patient deterioration occurs: anaphylaxis, amniotic fluid embolism, and cardiac arrest during dental case. RESULTS: Overall, there was a statistically significant decrease in the mean and median pooled times to diagnosis in both the amniotic fluid embolism and pediatric dental scenarios. There was a statistically significant increase in the number of participants in the intervention group who made diagnosis 3 before the end of the scene (P = 0.03) in the amniotic fluid embolism case. In the pediatric dental case, there was a statistically significant reduction in the median time to diagnosis 1 and diagnosis 3 in the intervention group versus control (P = 0.01 and P = 0.0002). A significant increase in the number of participants in the intervention group versus control made the correct diagnosis 2 before vital sign change 3 (P = 0.03), and more participants in the intervention group made the correct diagnosis 3 before the end of the scene when compared with control (P = 0.001). The median time to start intervention 2 during the dental case was statistically significantly greater in the intervention group versus the control (P = 0.05). All other endpoints were not statistically significant among the 3 simulation scenarios. Six questions were answered by all participants upon immediate completion of the simulation scenarios and revealed that 19 of 20 participants had delivered anesthesia care to patients similar to the 3 simulation scenarios and 18 of 20 participants reported that they would prefer audiovisual assistance to detect abnormalities in vital signs that subsequently provides appropriate diagnostic and therapeutic options. CONCLUSIONS: This pilot study suggested some significant improvement in anesthesia professional time to correct diagnosis and completion of identification of the correct diagnosis before the next vital change in the audiovisual cue group versus control, particularly in the outpatient dental case. In addition, the mean and median pooled times to diagnosis were significantly reduced by approximately 1 minute in both evaluated simulation scenarios. The postsimulation survey responses also suggest the desirability of an audiovisual decision support tool among the current anesthesia professional participants. However, overall, there were no significant differences in the time to intervention between groups in all simulation scenarios.

Methodology for determining major constituents of ayahuasca and their metabolites in blood.

There is an increasing interest in potential medical applications of ayahuasca, a South American psychotropic plant tea with a long cultural history of indigenous medical and religious use. Clinical research into ayahuasca will require specific, sensitive and comprehensive methods for the characterization and quantitation of these compounds and their metabolites in blood. A combination of two analytical techniques (high-performance liquid chromatography with ultraviolet and/or fluorescence detection and gas chromatography with nitrogen-phosphorus detection) has been used for the analysis of some of the constituents of ayahuasca in blood following its oral consumption. We report here a single methodology for the direct analysis of 14 of the major alkaloid components of ayahuasca, including several known and potential metabolites of N,N-dimethyltryptamine and the harmala alkaloids in blood. The method uses 96-well plate/protein precipitation/filtration for plasma samples, and analysis by HPLC-ion trap-ion trap-mass spectrometry using heated electrospray ionization to reduce matrix effects. The method expands the list of compounds capable of being monitored in blood following ayahuasca administration while providing a simplified approach to their analysis. The method has adequate sensitivity, specificity and reproducibility to make it useful for clinical research with ayahuasca.

Pharmacokinetics of tetracycline after single-dose oral administration in the American alligator (Alligator mississippiensis).

The major objective of the study was to assess the pharmacokinetics of tetracycline administered orally to fasted and nonfasted American alligators (Alligator mississippiensis) at 50 mg/kg. Plasma levels of tetracycline were determined using high-performance liquid chromatography with ultraviolet detection. The concentration versus time curve was analyzed using a compartmental modeling technique. A one-compartment model with first-order absorption and elimination, as well as a lag time to absorption, best described the data. The area under the curve and mean residence time values differed significantly between the fasted and nonfasted groups. Based on the results of this study, tetracycline suspension administered once orally at 50 mg/kg to American alligators is not expected to reach plasma concentrations above the breakpoint minimum inhibitory concentration of 4 microg/ml for susceptible organisms.

Administration of N,N-dimethyltryptamine (DMT) in psychedelic therapeutics and research and the study of endogenous DMT.

As with all drugs, the route, form, and/or dose of a substance administered or applied can play a defining role in its overall pharmacology and use as a therapeutic. This review will focus on these factors as they relate to the psychedelic N,N-dimethyltryptamine (DMT). It will examine the positive and negative aspects of different formulations and routes of administration of DMT and the observed effects from such administrations in the form of ayahuasca teas; oral "pharmahuasca"; injections by intravenous (IV) and intramuscular (IM) routes; inhalation, insufflation; and other routes; and high-dose, low-dose, and "micro-dose" effects. The review will consider possible oral route of administration alternatives that would not require concomitant use of a monoamine oxidase inhibitor. The review will then address the current research findings for DMT from in vivo and in vitro studies as well as the possibility that these findings may be revealing the role of endogenous DMT in normal brain function.

Pharmahuasca and DMT Rescue ROS Production and Differentially Expressed Genes Observed after Predator and Psychosocial Stress: Relevance to Human PTSD.

Post-traumatic stress disorder (PTSD) is associated with cognitive deficits, oxidative stress, and inflammation. Animal models have recapitulated features of PTSD, but no comparative RNA sequencing analysis of differentially expressed genes (DEGs) in the brain between PTSD and animal models of traumatic stress has been carried out. We compared DEGs from the prefrontal cortex (PFC) of an established stress model to DEGs from the dorsolateral PFC (dlPFC) of humans. We observed a significant enrichment of rat DEGs in human PTSD and identified 20 overlapping DEGs, of which 17 (85%) are directionally concordant. N,N-dimethyltryptamine (DMT) is a known indirect antioxidant, anti-inflammatory, and neuroprotective compound with antidepressant and plasticity-facilitating effects. We tested the capacity of DMT, the monoamine oxidase inhibitor (MAOI) harmaline, and "pharmahuasca" (DMT + harmaline) to reduce reactive oxygen species (ROS) production and inflammatory gene expression and to modulate neuroplasticity-related gene expression in the model. We administered DMT (2 mg/kg IP), harmaline (1.5 mg/kg IP), pharmahuasca, or vehicle every other day for 5 days, following a 30 day stress regiment. We measured ROS production in the PFC and hippocampus (HC) by electron paramagnetic resonance spectroscopy and sequenced total mRNA in the PFC. We also performed in vitro assays to measure the affinity and efficacy of DMT and harmaline at 5HT2AR compared to 5-HT. DMT and pharmahuasca reduced ROS production in the PFC and HC, while harmaline had mixed effects. Treatments normalized 9, 12, and 14 overlapping DEGs, and pathway analysis implicated that genes were involved in ROS production, inflammation, growth factor signaling, neurotransmission, and neuroplasticity.

Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine.

Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting ß-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.