Case Report
Intoxication Associated with Ayahuasca Consumption, Characterization, and Comparative Analysis of the Beverage's Components: A Case Report
Intoxicación asociada con el consumo de ayahuasca, caracterización y análisis comparativo de los componentes de la bebida: un caso clínico
Edgar A. Estrella-Parraa, José G. Avila-Acevedoa, Ana M. García-Boresa, José C. Rivera-Cabrerab, Edgar F. Alarcón-Villaseñorc, Ivone Alejandre-Garcíad, Francisco J. Alarcón-Aguilare,
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a Laboratorio de Fitoquímica, UBIPRO, FES-Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
b Escuela Médico Militar, Departamento de Farmacología, Laboratorio de Cromatografía de Líquidos, Ciudad de México, Mexico
c ISSSTE, Ciudad de México, Mexico
d Instrumentos y Equipos Falcón, S.A. de C.V., Ciudad de México, Mexico
e Laboratorio de Farmacología, Departamento Ciencias de la Salud, Universidad Autónoma Metropolitana, Unidad Iztapalapa, Ciudad de México, Mexico
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Estrella-Parra, José G. Avila-Acevedo, Ana M. García-Bores, José C. Rivera-Cabrera, Edgar F. Alarcón-Villaseñor, Ivone Alejandre-García, Francisco J. Alarcón-Aguilar" "autores" => array:7 [ 0 => array:3 [ "nombre" => "Edgar A." "apellidos" => "Estrella-Parra" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "José G." "apellidos" => "Avila-Acevedo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Ana M." "apellidos" => "García-Bores" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "José C." 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"apellidos" => "Alarcón-Aguilar" "email" => array:1 [ 0 => "aaaf@xanum.uam.mx" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Laboratorio de Fitoquímica, UBIPRO, FES-Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Escuela Médico Militar, Departamento de Farmacología, Laboratorio de Cromatografía de Líquidos, Ciudad de México, Mexico" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "ISSSTE, Ciudad de México, Mexico" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Instrumentos y Equipos Falcón, S.A. de C.V., Ciudad de México, Mexico" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Laboratorio de Farmacología, Departamento Ciencias de la Salud, Universidad Autónoma Metropolitana, Unidad Iztapalapa, Ciudad de México, Mexico" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Intoxicación asociada con el consumo de ayahuasca, caracterización y análisis comparativo de los componentes de la bebida: un caso clínico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1837 "Ancho" => 3341 "Tamanyo" => 298315 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Chromatogram of different samples. <span class="elsevierStyleBold">I</span>. Blood plasma of young man. <span class="elsevierStyleBold">II</span>. Ayahuasca introduced and ingested by the young man. <span class="elsevierStyleBold">III</span>. Ayahuasca from Tamabioy path, municipality of Sibundoy, Putumayo, Colombia. <span class="elsevierStyleBold">IV</span>. Ayahuasca from path río Blanco Sur, Department of Cauca, Colombia (Nasa ethnic group). <span class="elsevierStyleBold">1</span>. 5-Methoxy-N,N-dimethyltryptamine (5-Meo-DMT); <span class="elsevierStyleBold">2</span>. harmaline; <span class="elsevierStyleBold">3</span>. harmol; <span class="elsevierStyleBold">4</span>. N,N-dimethyltryptamine (DMT); <span class="elsevierStyleBold">5</span>. harmine; <span class="elsevierStyleBold">6</span>. bufotenin (5-OH-DMT); <span class="elsevierStyleBold">7</span>. tetrahydroharmine (THH). *Not identified compound. UV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>260<span class="elsevierStyleHsp" style=""></span>nm.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The ayahuasca beverage (caapi or yajé) is a decoction derived from the bark of the liana <span class="elsevierStyleItalic">Banisteriopsis caapi</span> or <span class="elsevierStyleItalic">B. inebrians</span> (Malpighiaceae) and the leaves of <span class="elsevierStyleItalic">Psychotria viridis</span>.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> Ayahuasca contains β-carbolines such as harmine, harmaline, and tetrahydro harmine; and tryptamine derivatives, particularly dimethyltryptamine (DMT), as the principal constituents.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> DMT is a psychoactive compound that has been under international control since 1971. However, the cultural uses and beneficial effects have led to legal use being permitted in the origin countries.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> Since the principal constituents in ayahuasca interact with several neuronal systems at the central level, it has been suggested that it may be effective in treating conditions including depression, anxiety, Alzheimer's disease, and Parkinson's disease, and for the treatment of pharmacodependence.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The debate surrounding the beneficial and harmful effects of ayahuasca has been significant. Ayahuasca has been used in the syncretic religions,<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> whose followers have consumed ayahuasca for more than 30 years without adverse health effects.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> Several reports show that ayahuasca's tolerability and psychological effects result in a pleasant and satisfactory experience,<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> and that it is apparently safe, producing divergent creative thinking, a reduction in fear, the forgiveness of others/oneself, and self-acceptance in the users.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3,9,10</span></a> Ayahuasca's effects after its acute use begins approximately 40<span class="elsevierStyleHsp" style=""></span>min following ingestion, peaking between 60 and 120<span class="elsevierStyleHsp" style=""></span>min, with subjective effects fading by approximately 4<span class="elsevierStyleHsp" style=""></span>h. Approximately 30<span class="elsevierStyleHsp" style=""></span>min after ingestion, users note changing perceptions; at the same time, users report nauseas, intense vomiting, and in some cases diarrhea.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11,12</span></a> Users remain aware of their surroundings and can speak.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Users also experiment visual effects like vibrating objects, increased intensity of colors, moving geometric patterns and intricate images with eyes open or closed.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> Visual phenomena may be related to neurochemical changes in the visual cortex and the claustrum. Synesthesia is common, particularly auditory to visual synesthetic effects and usually are associated with music.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> Several studies have used the Hallucinogen Rating Scale (HRS) developed by Dr. Rick Strassman in which there were found positive response to 14 selected items with a dose of 0.85<span class="elsevierStyleHsp" style=""></span>mg of DMT/kg of body weight that caused increase in activation, euphoria, and well-being.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> Some of the psychological effects are powerful sense of self-confidence, a new perspective and reinterpretation of intrapsychic conflicts.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Ayahuasca use has spread worldwide. The increase in its popularity has led to the apparition of a significant number of “healing centers” within and outside several Latin American countries, resulting in cases of ayahuasca ingestion without appropriate precautions.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> Although ayahuasca has a reputation as a beverage with low toxicity, specific potential contraindications and susceptibility phenomes for ayahuasca consumption have been reported.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> Also have been reported psychotropic and adverse effects after ingestion of ayahuasca combined with antidepressants,<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> suggesting that some care should be taken concerning its interaction with other drugs. This case report refers to an intoxicated young man with ayahuasca and other drugs that were deduced of an informatic analysis by KNIME 4.4.2 version, based on OpenMS.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Case report</span><p id="par0025" class="elsevierStylePara elsevierViewall">A 24-year-old man, apparently in good physical condition, without any allergies, transfusions, surgeries, or fractures arrived at emergency room presenting cognitive decline and a fluctuating course of delirium, stupor, and disorientation.</p><p id="par0030" class="elsevierStylePara elsevierViewall">He stated that he started using recreational drugs at 17 years old. He was not accepted for higher-level studies due to poor school performance, leading to constant episodes of depression and anxiety. The patient indicated a dysfunctional family and reported growing up with feelings of hatred and violence toward his mother. He experienced a crisis and conflict with his mother when she sent him to his maternal grandparents’ home in Oaxaca, México, where he started consuming ayahuasca at 21 years old. After several initiation rituals, he began consuming ayahuasca as a habit.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The patient returned to Mexico City as a ‘therapist’ (declaring himself to be an ayahuasca “guru” or “ayahuasquero”), charging $96.44 US per user, purchasing ayahuasca in Peru and other South American countries, and transporting it to Mexico disguised as a clothing dye. During a two years period, he made five suicide attempts. Psychological states of psychosis and violence were also detected during five psychotherapy sessions alongside his mother. The patient expressed a desire to experiment with higher doses of ayahuasca and ultimately presented in a state of suspect ayahuasca intoxication. He never mentioned being taking any medicine.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Physical examination findings were language disfunction (aphasia), pink cheeks, miosis, conjunctival hyperemia, exophthalmia, and visual and auditory hallucinations, responding intermittently to external stimuli. With scary faces, he expressed incomprehensive phrases while trying to grab hold of a person or object and not recognizing his parents. To spontaneous eye-opening (Glasgow 4 points), without verbal response (Glasgow 1 point) and an abnormal limb flexion motor response (Glasgow 3 points), obtaining a Glasgow Coma Scale score severe of 8/15. Oxygen saturation was 86%. The patient showed sinus tachycardia, a heart rate of 120<span class="elsevierStyleHsp" style=""></span>beats/min, blood pressure of 150/110<span class="elsevierStyleHsp" style=""></span>mmHg, 35<span class="elsevierStyleHsp" style=""></span>°C body temperature, and 22 spontaneous breaths/min. He also presented diaphoresis, pale skin, and cyanosis on the lips and hands. Bronchoconstriction and wheezing in both pulmonary fields were noted.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The patient received supplemental oxygen (6<span class="elsevierStyleHsp" style=""></span>L/min) in the ‘semi-Fowler’ position and was canalized with Hartmann solution (120<span class="elsevierStyleHsp" style=""></span>mL/min). The main components of ayahuasca were analyzed in the patient's blood to determine the ayahuasca's involvement in the poisoning by HPLC. Also, the blood sample (Sample 1) of the patients was submitted to a bioinformatics analysis by KNIME 4.4.2 version, based on OpenMS, an open-source software library for LC/MS data management and analyses. In addition, this Sample 1 was compared with the extract consumed, the different samples of ayahuasca donated for investigation from Colombia, and the standard compounds, harmine and harmaline (Sigma-Aldrich), which were analyzed by HPLC–ESI-MS. The traditional ayahuasca samples analyzed were Sample 2: ingested ayahuasca sample introduced to Mexico by the patient; Sample 3: traditional ayahuasca beverage from Vereda Tamabioy, Municipality of Sibundoy, Putumayo, Colombia; Sample 4: traditional ayahuasca beverage from Vereda Rio Blanco Sur, Department of Cauca, Colombia (Nasa ethnic group). These samples were donated for purposes of investigation.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">HPLC/DAD</span><p id="par0050" class="elsevierStylePara elsevierViewall">The HPLC (Thermo Dionex ultimate 3000; Sunnyvale, CA, USA) consisted of a PDA detector (at 220–330<span class="elsevierStyleHsp" style=""></span>nm). The column was an Accucore QC18, 150<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>4.6<span class="elsevierStyleHsp" style=""></span>mm, particle size 2.6<span class="elsevierStyleHsp" style=""></span>μm, (Thermo Scientific). The samples were analyzed using a gradient of water (v/v) (A), acetonitrile (v/v) (B) and methanol (v/v) (C), all solvents with 0.1% formic acid: starting with 10% A, 90% B and 0% C, from −5 to 0<span class="elsevierStyleHsp" style=""></span>min. Then, with 50% A, 50% B, and 0% C, from 1–4<span class="elsevierStyleHsp" style=""></span>min. After, 2% A, 98% B and 0% C, from 5 to 6<span class="elsevierStyleHsp" style=""></span>min, ending with 10% A, 90% B and 0% C until 23<span class="elsevierStyleHsp" style=""></span>min. The flow rate was 0.3<span class="elsevierStyleHsp" style=""></span>mL/min. The following compounds were used for identification: harmine (catalog number: 286044-1G; Lot # BCBS6157V) and harmaline (catalog number: 51330-1G; Lot # BCBP4993V) purchased from Sigma-Aldrich. The injection volume was 40<span class="elsevierStyleHsp" style=""></span>μl. Concentrations were expressed in mg/1<span class="elsevierStyleHsp" style=""></span>mg of extract of the plant, with three different experiments. Ayahuasca compound concentration was determined from the peak area ratio of the target analyte to that of the internal standard. Different concentration of harmine and harmaline were prepared at 0.001, 0.005, 0.010, 0.020, 0.030, 0.040, mg/1<span class="elsevierStyleHsp" style=""></span>mL of mass water. Lineal regression of harmine (<span class="elsevierStyleItalic">Y</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>670.32<span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>4609.6; <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.95) and harmaline (<span class="elsevierStyleItalic">Y</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1533.9<span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2133.4; <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.94) were calculated.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Mass detector</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Full mass</span><p id="par0055" class="elsevierStylePara elsevierViewall">An Orbitrap Fusion Tri-hybrid system was used with an ESI source controlled by Xcalibur Software (Thermo Scientific Xcalibur V. 4.1.5.0). Method duration (min): 23; ion source type: H-ESI; spray voltage: static; positive ion (V): 3900.00; negative ion (V): 2500.00; sheath gas (Arb): 43; aux gas (Arb): 15; sweep gas (Arb): 0; ion transfer tube temp. (°C): 260; vaporizer temp. (°C): 350; cycle time (s): 3. Master Scan. Detector type: ion trap; ion trap scan rate: normal; mass range: normal; use quadrupole isolation: true; RF lens (%): 60; AGC target: 3.0e<span class="elsevierStyleSup">4</span>; maximum injection time (ms): 10; microscans: 1; data type: profile; polarity: positive; mass range (<span class="elsevierStyleItalic">m/z</span>): 50–1000; intensity threshold: 5.0e<span class="elsevierStyleSup">4</span>. Exclusion duration (s): 10; mass tolerance: ppm; low: 10.00; high: 10.00. Nitrogen and helium of ultra-high purity (99.99%) were used as nebulizing gases. The experimental spectral mass was compared to harmine and harmaline (purchased from Sigma-Aldrich), databases HMDB, SDBS, METLIN, NIST, and MassBank as well as spectrometric inferences.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">MS<span class="elsevierStyleSup">2</span>/MS<span class="elsevierStyleSup">3</span> experiments</span><p id="par0060" class="elsevierStylePara elsevierViewall">Isolation mode: quadrupole; CID collision energy (%): 40 (MS<span class="elsevierStyleSup">2</span>) and 50 (MS<span class="elsevierStyleSup">3</span>); activation Q: 0.25; detector type: Orbitrap; scan range mode: auto: <span class="elsevierStyleItalic">m/z</span> normal; Orbitrap resolution: 30,000; AGC target: 5.0e<span class="elsevierStyleSup">4</span>; maximum injection time (ms): 100; microscans: 1; data type: centroid; decision: data dependent mode: top N; precursor priority: most intense.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Bioinformatic analysis</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">KNIME workflow</span><p id="par0065" class="elsevierStylePara elsevierViewall">We used KNIME 4.4.2 version, based on OpenMS, a comprehensive open-source software library for the analysis of MS data. The metabolite identification is based on matching the accurate masses against the theoretical mass of databases as Human Metabolome Database (HMDB) (version 4). We performed three experiments independently.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The compounds identified in the patient's blood plasma and the ayahuasca beverages from different regions were similar: (1) harmaline, (2) harmol, (3) N,N-dimethyltryptamine (DMT), (4) harmine, (5) bufotenin (5-OH-DMT) and (6) tetrahydroharmine (THH) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), which presented the mass spectra fragmentations patterns shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>. The patient's ayahuasca beverage (Sample 2) contained 0.05<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">−6</span><span class="elsevierStyleHsp" style=""></span>mg/L of harmaline and 0.27<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.003<span class="elsevierStyleHsp" style=""></span>mg/L of harmine in each case per mg of extract.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Other drugs in the patient's blood plasma deduced from bioinformatics analysis by KNIME 4.4.2 were DMT, narcotoline, methamphetamine, norcocaine, 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol, dimethyl amphetamine, 3,4-methylenedioxy amphetamine, 4-hydroxy amphetamine, carbamazepine, demoxepam, atorvastatin, ketoprofen, naproxen, oseltamivir, diazepam, ciprofloxacin, magnesium salicylate, aspirin, and disulfiram, among other metabolites (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Once the toxic agents were identified in the plasma, including narcotoline, an opiate agent, the patient received naloxone (1<span class="elsevierStyleHsp" style=""></span>mg intravenous), improving the Glasgow Coma Scale score from severe (8/15) to moderate (9/15) after 5<span class="elsevierStyleHsp" style=""></span>min as well as improving his verbal response. At 10<span class="elsevierStyleHsp" style=""></span>min, the Glasgow Coma Scale score increased to 10/15, recovering the verbal response. At 30<span class="elsevierStyleHsp" style=""></span>min, the patient presented a blood pressure of 100/65<span class="elsevierStyleHsp" style=""></span>mm Hg, heart rate of 70<span class="elsevierStyleHsp" style=""></span>beats/min, respiratory rate of 14 spontaneous breaths/min, the body temperature of 37<span class="elsevierStyleHsp" style=""></span>°C, and saturation of O<span class="elsevierStyleInf">2</span> (100%) with nasal tips (3<span class="elsevierStyleHsp" style=""></span>L/min). At 4<span class="elsevierStyleHsp" style=""></span>h, the Glasgow Coma Scale score was standard (15/15).</p><p id="par0085" class="elsevierStylePara elsevierViewall">The patient's course was cataloged substance/medication-induced psychotic disorder. Treatment to support the patient and offer gastric protection was initiated with omeprazole (20<span class="elsevierStyleHsp" style=""></span>mg), dexamethasone (8<span class="elsevierStyleHsp" style=""></span>mg), and ondansetron (8<span class="elsevierStyleHsp" style=""></span>mg). The patient also was prescribed escitalopram (10<span class="elsevierStyleHsp" style=""></span>mg every night for 8 months) to control episodes of depression and anxiety. Later, the patient reported feeling guilty and handed in his remaining ayahuasca extract, indicating that he would stop being a ‘guru or travel master.’ He attends his psychotherapies punctually, showing a good evolution without relapse for at least six months.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The patient presented the same blood plasma chemical composition as the ayahuasca beverage. The traditional samples of ayahuasca contained harmaline, harmol, DMT, harmine, and derivatives. In addition, the patient's blood sample presented metabolites that were not reported at the medical inspection, such as methamphetamine and derivatives, norcocaine, 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol, carbamazepine, demoxepam, and other anti-inflammatories, analgesic, and antacids agents; inclusive disulfiram, an aldehyde dehydrogenase inhibitor.</p><p id="par0095" class="elsevierStylePara elsevierViewall">DMT and harmaline induce more tremors/convulsions than other β-carbolines, as they are more active than tryptamine derivatives.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> This activity may partly explain the patient's clinical state on arrival at the emergency room. However, the patient's clinical state was induced not only by the ayahuasca beverage's metabolites but also by the pharmacological activity of the other drugs that were not reported in the clinical history, evidenced by bio-informatic analysis of his plasma metabolome.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Amphetamines and their derivatives were present in plasma. People addicted to methamphetamine showed detriment to neural and psychological faculties.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> In a case report, a treated person with disulfiram showed psychosis or mania with psychotic symptoms like agitation, labile and anxious affect, decreased sleep, pressured and rapid speech, increased self-esteem, tangential and racing thought, ideas of reference, suspiciousness.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> These symptoms are like the reported in this report. Among other metabolites detected, they were also cannabinoid derivatives, which induce anxiety, psychosis induction or aggravation, ataxia, and generalized depression of the SNC.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Carbamazepine, in case of an overdose and interaction with other drugs, may cause severe cardiovascular effects, restlessness, muscular twitching, tremor, dilated pupils, nystagmus, psychomotor disturbances, among other neurological symptoms that may occur.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> Finally, the side effects most reported for diazepam are drowsiness, fatigue, muscle weakness, ataxia, restlessness, acute hyperexcited states, anxiety, agitation, aggressiveness, irritability, rage, hallucinations, psychoses, spasticity, inappropriate behavior, and other adverse behavioral effects.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The data indicate that the patient consumed a traditional ayahuasca beverage. The amount of ayahuasca consumed by mouth is around 100<span class="elsevierStyleHsp" style=""></span>mL, containing variable concentrations of DMT; nevertheless, in some ayahuasca beverages, the amount of DMT is ten times higher than the usual doses,<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> representing a high risk of intoxication by overdoses or hypersusceptibility phenomena. Either way, there are few cases of intoxication associated with ayahuasca consumption alone.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> The reported cases of intoxication by ayahuasca have been associated with interactions with other drugs, such as serotonergic drugs,<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> cannabis, and mushrooms (<span class="elsevierStyleItalic">Psilocybe</span> spp.), alcohol, and tobacco.<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">26,27</span></a> Therefore, the pharmacological interactions of the components in the ayahuasca beverage can be the leading causes of poisoning, which can be deduced from the bioinformatic analysis.</p><p id="par0115" class="elsevierStylePara elsevierViewall">In addition, the intoxication of ayahuasca also has been associated with specific psychiatric pathologies in the users, such as bipolar disorder with manic episodes and mood disorder episodes,<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">26,28</span></a> as well as previous cardiac and hepatic pathologies.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> Therefore, the psychiatric pathologies of the young Mexican patient could have also influenced the intoxication. Considering the participation of psycho-environmental factors in the patient and his clinical background as a consumer of other narcotic drugs together with ayahuasca, we conclude that all this may have led to him being hyper susceptible, contributing to increased toxicological response and the observed clinical state.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Ayahuasca is traditionally used in Latin American countries like Brazil, Peru, Colombia, and Ecuador. However, today its use has spread worldwide, particularly in Mexico, Spain, the Netherlands, New Zealand, Australia, the USA, and western Asia.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> Unfortunately, the management, preparation, and healing services associated with the ayahuasca beverage are now, in many cases, performed by non-indigenous people, also known as “neo-ayahuasqueros,” who perform rituals illegally and solely for financial purposes.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> The services are disseminated using the internet and often promote the potential usefulness of the beverage in numerous diseases.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> This situation has led to the ingestion of ayahuasca without appropriate precautions, as occurred in the presented case.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In agreement with Callaway and Grob,<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> it is necessary to establish parameters for ayahuasca's optimal use and safety due to its rising popularity. Furthermore, considering that the ayahuasca may be prepared with other potentially toxic botanical species, regulation of the consumption of ayahuasca worldwide is mandatory.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Funding</span><p id="par0130" class="elsevierStylePara elsevierViewall">PRODEP-SEP Postdoctoral Fellowship supported this work at <span class="elsevierStyleGrantSponsor" id="gs1">Universidad Autónoma Metropolitana (UAM)</span> under grant <span class="elsevierStyleGrantNumber" refid="gs1">14612857</span>.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflict of interest</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1886026" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Clinical case" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1633443" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1886025" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Caso clínico" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1633444" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "HPLC/DAD" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Mass detector" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Full mass" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "MS/MS experiments" ] ] ] 8 => array:3 [ "identificador" => "sec0035" "titulo" => "Bioinformatic analysis" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "KNIME workflow" ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 10 => array:2 [ "identificador" => "sec0050" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "xack662894" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-10-17" "fechaAceptado" => "2023-02-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1633443" "palabras" => array:5 [ 0 => "Ayahuasca" 1 => "Intoxication" 2 => "Psychotropic alkaloids" 3 => "DMT" 4 => "β-Carbolines" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1633444" "palabras" => array:5 [ 0 => "Ayahuasca" 1 => "Intoxicación" 2 => "Alcaloides psicotrópicos" 3 => "DMT" 4 => "β-Carbolinas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Ayahuasca is a psychotropic beverage from South America, derived from <span class="elsevierStyleItalic">Banisteriopsis caapi</span> and <span class="elsevierStyleItalic">Psychotria viridis.</span> The beverage contains alkaloids such as β-carbolines and dimethyltryptamine (DMT), which alter the psychoactive functions associated with perception and thought processes. Its consumption in the countries of origin, such as Brazil, Colombia, and Peru, is prevalent. Its use has been popularized worldwide, especially in the European Union and North America, where the ayahuasca samples are introduced from South America.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This article presents the case report of a Mexican ayahuasca user with clinical symptoms of poisoning.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Clinical case</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A 24-year-old man, habitual consumer of ayahuasca, arrived at emergency room presenting cognitive decline and a fluctuating course of delirium, stupor, and disorientation. The patient's blood samples were compared using HPLC/ESI-MS/MS with the extract consumed, with other traditional Colombian ayahuasca samples, and with standard chemicals, aiming to determine whether the components of ayahuasca were present in the patient's blood. The same blood sample was subjected to a bioinformatics analysis (KNIME 4.4.2-version, based on OpenMS) to detect other drugs probably consumed by the patient.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The principal components of ayahuasca in the blood sample were identified: DMT, harmaline, harmine, harmol, bufotenine, and tetrahydro harmine. In addition, other narcotic drugs, such as 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol, amphetamine, and norcocaine, were also detected. The poisoning can be associated with ayahuasca consumption and its interaction with other drugs.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Clinical case" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Ayahuasca es una preparación psicotrópica sudamericana de <span class="elsevierStyleItalic">Banisteriopsis caapi</span> y <span class="elsevierStyleItalic">Psychotria viridis.</span> El preparado contiene β-carbolinas y dimetiltriptamina (DMT), alcaloides que alteran las funciones psicoactivas asociadas con procesos de la percepción y el pensamiento. Su consumo es prevalente en los países de origen, como Brasil, Colombia y Perú. Sin embargo, su uso se ha popularizado mundialmente, sobre todo en Europa y en Estados Unidos.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Este artículo presenta el caso clínico de un mexicano usuario de ayahuasca con síntomas clínicos de envenenamiento.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Caso clínico</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Un hombre de 24 años, consumidor habitual de ayahuasca, llegó a la sala de emergencias presentando deterioro cognitivo y un curso fluctuante de delirio, estupor y desorientación. La muestra sanguínea del paciente fue comparada con el extracto consumido, con otras muestras tradicionales de ayahuasca provenientes de Colombia y con estándares de carbolinas usando HPLC/ESI-MS/MS, con el objetivo de determinar si los componentes de ayahuasca estaban presentes en la sangre del paciente. La misma muestra sanguínea se sometió a un análisis bioinformático (KNIME versión 4.4.2, basada en OpenMS) para detectar otras drogas posiblemente consumidas por el paciente.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En la sangre del paciente se lograron identificar los principales componentes de ayahuasca: DMT, harmalina, harmina, harmol, bufotenina y tetrahidro-harmina. Entre otras drogas de abuso, también se detectaron: 11-nor-9-carboxi-Δ-(9)-tetrahidrocannabinol, anfetamina y norcocaína. Aunque es posible asociar el envenenamiento del paciente con el consumo de ayahuasca, es necesario considerar que consumió también otras drogas.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Caso clínico" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1837 "Ancho" => 3341 "Tamanyo" => 298315 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Chromatogram of different samples. <span class="elsevierStyleBold">I</span>. Blood plasma of young man. <span class="elsevierStyleBold">II</span>. Ayahuasca introduced and ingested by the young man. <span class="elsevierStyleBold">III</span>. Ayahuasca from Tamabioy path, municipality of Sibundoy, Putumayo, Colombia. <span class="elsevierStyleBold">IV</span>. Ayahuasca from path río Blanco Sur, Department of Cauca, Colombia (Nasa ethnic group). <span class="elsevierStyleBold">1</span>. 5-Methoxy-N,N-dimethyltryptamine (5-Meo-DMT); <span class="elsevierStyleBold">2</span>. harmaline; <span class="elsevierStyleBold">3</span>. harmol; <span class="elsevierStyleBold">4</span>. N,N-dimethyltryptamine (DMT); <span class="elsevierStyleBold">5</span>. harmine; <span class="elsevierStyleBold">6</span>. bufotenin (5-OH-DMT); <span class="elsevierStyleBold">7</span>. tetrahydroharmine (THH). *Not identified compound. UV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>260<span class="elsevierStyleHsp" style=""></span>nm.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 4215 "Ancho" => 3258 "Tamanyo" => 991967 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Full mass and UV absorbance of metabolites detected in the blood plasma of the user as well as ingested ayahuasca. <span class="elsevierStyleBold">1</span>. 5-Meo-DMT (MW: 219.07 [M+H]); <span class="elsevierStyleBold">2</span>. harmaline (MW: 214.97 [M+H]); <span class="elsevierStyleBold">3</span>. harmol (MW: 199.10 [M+H]); <span class="elsevierStyleBold">4</span>. DMT (MW: 189.13 [M+H]); <span class="elsevierStyleBold">5</span>. harmine (MW: 213.10 [M+H]); <span class="elsevierStyleBold">6</span>. bufotenin (MW: 205.10 [M+H]). <span class="elsevierStyleBold">7</span>. tetrahydroharmine (THH) (MW: 216.97 [M+H]). Ion trap as mass analyzer and quadrupole as ion filter. Positive mode [M+H].</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "fx1.jpeg" "imagenAlto" => 3347 "imagenAncho" => 3258 "imagenTamanyo" => 1182724 ] ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Metabolomic identification of young man plasma sample using KNIME analysis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drinking the South American hallucinogenic ayahuasca" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F.L. 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Mariano Guetio (Greater Milwaukee Area, U.S.A.), Gustavo Ramos Burbano (Neuroscience Lab. at ARP Seguro Social, Valle del Cauca, and Professor of Neurology from the Universidad del Valle and of the Universidad Libre de Cali, Colombia), and to the shaman Juan Mutumbajoy Jacanamijoy from the Vereda Tamabioy, Municipality of Sibundoy, Putumayo, Colombia, for their assistance and donation of the samples for purposes of investigation.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/00347450/unassign/S0034745023000240/v1_202304191237/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/00347450/unassign/S0034745023000240/v1_202304191237/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0034745023000240?idApp=UINPBA00004N" ]
