Full Text Available Bufotenine is an alkaloid derived from serotonin, structurally similar to LSD and psilocin. This molecule is able to inhibit the rabies virus infection in in vitro and in vivo models, increasing the survival rate of infected animals. Being a very promising molecule for an incurable disease and because of the fact that there is no consensus regarding its neurological effects, this study aimed to evaluate chronic treatment of bufotenine on behavior, pathophysiology, and pharmacokinetics of mice. Animals were daily treated for 21 consecutive days with 0.63, 1.05, and 2.1 mg/animal/day bufotenine and evaluated by open field test and physiological parameters during all the experiment. After this period, organs were collected for histopathological and biodistribution analysis. Animals treated with bufotenine had mild behavioral alterations compared to the control group, being dose-response relationship. On the other hand, animals showed normal physiological functions and no histological alterations in the organs. With high doses, an inflammatory reaction was observed in the site of injection, but with no cellular damage. The alkaloid could be found in the heart and kidney with all doses and in the lungs and brain with higher doses. These results show that the effective dose, 0.63 mg/day, is safe to be administered in mice, since it did not cause significant effects on the animals’ physiology and on the CNS. Higher doses were well tolerated, causing only mild behavioral effects. Thus, bufotenine might be a drug prototype for rabies treatment, an incurable disease.
Martin, Rafaela; Schürenkamp, Jennifer; Gasse, Angela; Pfeiffer, Heidi; Köhler, Helga
A method for the simultaneous extraction of the hallucinogens psilocin, bufotenine, lysergic acid diethylamide (LSD) as well as iso-LSD, nor-LSD and O-H-LSD from hair with hydrochloride acid and methanol is presented. Clean-up of the hair extracts is performed with solid phase extraction using a mixed-mode cation exchanger. Extracts are measured with liquid chromatography coupled with electrospray tandem mass spectrometry. The method was successfully validated according to the guidelines of the 'Society of Toxicological and Forensic Chemistry' (GTFCh). To obtain reference material hair was soaked in a solution of the analytes in dimethyl sulfoxide/methanol to allow incorporation into the hair. These fortified hair samples were used for method development and can be employed as quality controls. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Martin, Rafaela; Schürenkamp, Jennifer; Gasse, Angela; Pfeiffer, Heidi; Köhler, Helga
A validated method for the simultaneous determination of psilocin, bufotenine, lysergic acid diethylamide and its metabolites in serum, plasma and urine using liquid chromatography-electrospray ionization/tandem mass spectrometry was developed. During the solid-phase extraction procedure with polymeric mixed-mode cation exchange columns, the unstable analytes were protected by ascorbic acid, drying with nitrogen and exclusion of light. The limits of detection and quantitation for all analytes were low. Recovery was ≥86 % for all analytes and no significant matrix effects were observed. Interday and intraday imprecisions at different concentrations ranged from 1.1 to 8.2 % relative standard deviation, bias was within ±5.3 %. Processed samples were stable in the autosampler for at least 2 days. Furthermore, freeze/thaw and long-term stability were investigated. The method was successfully applied to authentic serum and urine samples.
Moretti, Christian; Gaillard, Y.; Grenand, Pierre; Bevalot, F.; Prevosto, J.M.
This paper is the first thorough analysis of takini, a hallucinogen used by the shamans of several peoples in Suriname, French Guiana, and the region east of the Para in Brazil. The drug is contained in the latex of the Brosimum acutifolium tree, and until now, its psychotropic properties appeared inconsistent with the more general medicinal uses of the tree in the surrounding region. Our chemical and botanical studies reveal that the active ingredient of takini is bufotenine; and that this c...
Moretti, Christian; Gaillard, Yvan; Grenand, Pierre; Bévalot, Fabien; Prévosto, Jean-Michel
This paper is the first thorough analysis of takini, a hallucinogen used by the shamans of several peoples in Suriname, French Guiana, and the region east of the Para in Brazil. The drug is contained in the latex of the Brosimum acutifolium tree, and until now, its psychotropic properties appeared inconsistent with the more general medicinal uses of the tree in the surrounding region. Our chemical and botanical studies reveal that the active ingredient of takini is bufotenine; and that this compound is only contained in the subspecies Brosimum acutifolium Huber subsp. acutifolium C.C. Berg that is found in the same area of the eastern Guianas.
... Administrator, in turn, has redelegated this function to the Deputy Administrator, pursuant to 28 CFR 0.104. The...-methylthiofentanyl 2 g Alpha-methyltryptamine (AMT) 25 g Aminorex 25 g Benzylmorphine 2 g Betacetylmethadol 2 g Beta-hydroxy-3-methylfentanyl 2 g Beta-hydroxyfentanyl 2 g Betameprodine 2 g Betaprodine 2 g Bufotenine 3 g...
... Administrator, in turn, has redelegated this function to the Deputy Administrator, pursuant to 28 CFR 0.104. DEA... Alpha-methyltryptamine (AMT) 12 g Aminorex 12 g Benzylmorphine 2 g Betacetylmethadol 2 g Beta-hydroxy-3-methylfentanyl 2 g Beta-hydroxyfentanyl 2 g Betameprodine 2 g Betamethadol 2 g Betaprodine 2 g Bufotenine 3 g...
Full Text Available D06750 Crude ... Drug Toad venom (JP17) Hellebrin [CPD:C08868], Resibufogenin [CPD...:C17058], Cinobufagin [CPD:C16931], Bufalin [CPD:C16922], Bufotalin [CPD:C16923], Cinobufotalin [CPD:C16932], Gamabufo...C16921], Cardenolides, Bufotenine [CPD:C08299], Bufotenidine [CPD:C13664], Epiren...aginol, Marinobufagin, Resibufagin, Serotonine, Bufothionine, Dehydrobufotenine, Bufotoxin, Cholesterol [CPD...terol [CPD:C01694], Campesterol [CPD:C01789], Sitosterol [CPD:C01753] ... Bufo bufo gargagrizans [TAX:30331], Bufo
Full Text Available E00121 Toad venom (JP17) Crude drug Hellebrin [CPD:C08868], Resibufogenin [CPD:C17...058], Cinobufagin [CPD:C16931], Bufalin [CPD:C16922], Bufotalin [CPD:C16923], Cinobufotalin [CPD:C16932], Gamabufo...talin [CPD:C16962], Telocinobufagin [CPD:C17072], Hellebrigenin [CPD:C16969], Bufadienolides [CPD:C16921], Cardenolides, Bufo...tenine [CPD:C08299], Bufotenidine [CPD:C13664], Epirenamin...ol, Marinobufagin, Resibufagin, Serotonine, Bufothionine, Dehydrobufotenine, Bufotoxin, Cholesterol [CPD:C00
Full Text Available Natural psychoactive substances have fascinated the curious mind of shamans, artists, scholars and laymen since antiquity. During the twentieth century, the chemical composition of the most important psychoactive drugs, that is opium, cannabis, coca and "magic mushrooms", has been fully elucidated. The mode of action of the principal ingredients has also been deciphered at the molecular level. In the past two decades, the use of herbal drugs, such as kava, kratom and Salvia divinorum, began to spread beyond their traditional geographical and cultural boundaries. The aim of the present paper is to briefly summarize recent findings on the psychopharmacology of the most prominent psychoactive natural products. Current knowledge on a few lesser-known drugs, including bufotenine, glaucine, kava, betel, pituri, lettuce opium and kanna is also reviewed. In addition, selected cases of alleged natural (or semi-natural products are also mentioned.
Ciprian-Ollivier, J; Cetkovich-Bakmas, M G
Interest in the role of indolamines in the pathogenesis of psychoses has been renewed in recent years by the development of atypical antipsychotic drugs such as clozapine, olanzapine, and risperidone, which act on serotonin receptors. Discovery of the hallucinogenic compounds called methylated indolealkyalamines (MIAs) (e.g. N,N-dimethylserotonin, or bufotenin, and N,N-dimethyltryptamine, or DMT) led proponents of the transmethylation hypothesis of schizophrenia to theorize that through some inborn error of metabolism, serotonin or tryptamine might undergo the addition of extra methyl radicals, thereby forming MIAs with hallucinogenic properties. Various studies have attempted to detect the excretion of MIAs, especially DMT, in the body fluids of psychotic patients and normal controls. Some of these studies have demonstrated elevated MIA concentrations in psychotic patients, including those with schizophrenia, compared with normal persons, and others have not. A number of variables may account for these contradictory findings. The mechanism whereby the beverage ayahuasca, which is used in certain cure and divination rituals in the Amazon Basin, exerts its hallucinogenic effects may serve as a model to explain the mechanism underlying hallucinogenic symptoms in schizophrenia and may lend support to the transmethylation hypothesis. Certain studies suggest that specific perceptual disturbances manifested by schizophrenic patients could contribute to progressive deterioration and negative symptomatology. All these findings point to the need for further study of the neurophysiology of MIAs and their pathogenetic role in endogenous psychoses.
Rico, María; Andrés-Costa, María Jesús; Picó, Yolanda
Wastewater can provide a wealth of epidemiologic data on common drugs consumed and on health and nutritional problems based on the biomarkers excreted into community sewage systems. One of the biggest uncertainties of these studies is the estimation of the number of inhabitants served by the treatment plants. Twelve human urine biomarkers -5-hydroxyindoleacetic acid (5-HIAA), acesulfame, atenolol, caffeine, carbamazepine, codeine, cotinine, creatinine, hydrochlorothiazide (HCTZ), naproxen, salicylic acid (SA) and hydroxycotinine (OHCOT)- were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to estimate population size. The results reveal that populations calculated from cotinine, 5-HIAA and caffeine are commonly in agreement with those calculated by the hydrochemical parameters. Creatinine is too unstable to be applicable. HCTZ, naproxen, codeine, OHCOT and carbamazepine, under or overestimate the population compared to the hydrochemical population estimates but showed constant results through the weekdays. The consumption of cannabis, cocaine, heroin and bufotenine in Valencia was estimated for a week using different population calculations. Copyright Â© 2016 Elsevier B.V. All rights reserved.
The drug Viagra (sildenafil) has drawn public attention to aphrodisiacs. The search for such substances dates back millennia. Aphrodisiacs can be classified by their mode of action into 3 types: those that increase (1) libido, (2) potency, or (3) sexual pleasure. Various substances of animal and plant origin have been used in folk medicines of different cultures; some have been identified pharmacologically, allowing for understanding of their mechanisms of action. For increasing libido, ambrein, a major constituent of Ambra grisea, is used in Arab countries. This tricyclic triterpene alcohol increases the concentration of several anterior pituitary hormones and serum testosterone. Bufo toad skin and glands contain bufotenine (and other bufadienolides), a putative hallucinogenic congener of serotonin. It is the active ingredient in West Indian "love stone" and the Chinese medication chan su. The aphrodisiac properties are likely of central origin, as are the other effects of the drug. For increasing potency, Panax ginseng used in traditional Chinese medicine, works as an antioxidant by enhancing nitric oxide synthesis in the endothelium of many organs, including the corpora cavernosa; ginsenosides also enhance acetylcholine-induced and transmural nerve stimulation-activated relaxation associated with increased tissue cyclic guanosine monophosphate, hence the aphrodisiac properties. For increasing sexual pleasure, cantharidin ("Spanish fly") is a chemical with vesicant properties derived from blister beetles, which have been used for millennia as a sexual stimulant. Its mode of action is by inhibition of phosphodiesterase and protein phosphatase activity and stimulation of beta-receptors, inducing vascular congestion and inflammation. Morbidity from its abuse is significant. The ingestion of live beetles (Palembus dermestoides) in Southeast Asia and triatomids in Mexico may have a basis similar to cantharidin. It is of paramount importance for the physician to be
Hungen, K V; Roberts, S; Hill, D F
Investigations were carried out on the interactions of the hallucinogenic drug, D-lysergic acid diethylamide (D-LSD), and other serotonin antagonists with catecholamine-sensitive adenylate cyclase systems in cell-free preparations from different regions of rat brain. In equimolar concentration, D-LSD, 2-brono-D-lysergic acid diethylamide (BOL), or methysergide (UML) strongly blocked maximal stimulation of adenylate cyclase activity by either norepinephrine or dopamine in particulate preparations from cerebral cortices of young adult rats. D-LSD also eliminated the stimulation of adenylate cyclase activity of equimolar concentrations of norepinephrine or dopamine in particulate preparations from rat hippocampus. The effects of this hallucinogenic agent on adenylate cyclase activity were most striking in particulate preparations from corpus striatum. Thus, in 10 muM concentration, D-LSD not only completely eradicated the response to 10 muM dopamine in these preparations but also consistently stimulated adenylate cyclase activity. L-LSD (80 muM) was without effect. Significant activation of striatal adenylate cyclase was produced by 0.1 muM D-LSD. Activation of striatal adenylate cyclase of either D-LSD or dopamine was strongly blocked by the dopamine-blocking agents trifluoperazine, thioridazine, chlorpromazine, and haloperidol. The stimulatory effects of D-LSD and dopamine were also inhibited by the serotonin-blocking agents, BOL, 1-methyl-D-lysergic acid diethylamide (MLD), and cyproheptadine, but not by the beta-adrenergic-blocking agent, propranolol. However, these serotonin antagonists by themselves were incapable of stimulating adenylate cyclase activity in the striatal preparations. Several other hallucinogens, which were structurally related to serotonin, were also inactive in this regard, e.g., mescaline, N,N-dimethyltryptamine, psilocin and bufotenine. Serotonin itself produced a small stimulation of adenylate cyclase activity in striatal preparations and
Andres-Costa, M. Jesus; Andreu, Vicente; Picó, Yolanda
The presence of drugs of abuse in the aquatic environment has been recognized as an important issue for the ecosystem due their possible negative effect on it (Richardson, 2011). Incomplete removal of these substances during wastewater treatment could be one of the causes of their release in the environment (Zuccato and Castiglioni, 2009). Pollution by illicit drug residues at very low concentrations is generalized in populated areas, with potential risks for human health and the environment (Zuccato, 2008; Castiglioni et al 2007).The aim of this study was to screen and quantify 44 drugs of abuse and metabolites of wastewater samples using a hybrid quadrupole time-of-flight tandem mass spectrometry and furthermore carry out a post-target screening to identify additional compounds present in the water samples. Wastewater samples were collected from the influent and effluent of three wastewater treatment plants (WWTPs) in Valencia and river water samples form Turia River Basin. Illicit drugs were extracted by solid-phase extraction (SPE). The chromatography was performed with an Agilent 1260 Infinity ultra high performance liquid chromatography (UHPLC). The UHPLC system was coupled to a hybrid quadrupole time-of-flight ABSciex Triple TOFTM 5600. All analytes were analyzed in positive mode. Acquiring full scan MS data was employed for quantification of drugs of abuse, and automatic data dependent information product ion spectra (IDA-MS/MS) was checked for identifying emerging illicit drugs and other compounds in water samples. The use of a database containing 1212 compounds achieved high confidence results for a wide number of contaminants. In the present study, the presence of compounds that belong to amphetamines group (amphetamine, methamphetamine, ephedrine, MDMA, MDA and MDEA), tryptamines (bufotenine), pirrolidinophenone group (α-PVP and 4'-MePHP), arylcyclohexylamines (ketamine), cocainics (cocaine, benzoylecgonine, cocaethylene and ecgonine methyl ester) and