Ibogaína: un psicodélico atípico con potencial antiadictivo / Ibogaine: an atypical psychedelic with anti-addictive potential

El trastorno por uso de sustancias es una enfermedad crónica de graves consecuencias. Actualmente, los tratamientos farmacológicos no apuntan a corregir los cambios neurobiológicos generados en el cerebro por el uso crónico de sustancias de abuso, sino que se enfocan principalmente en la atenuación de algunos de los síntomas que padece el consumidor. La ibogaína es un psicodélico atípico que, tanto en estudios observacionales como en ensayos clínicos abiertos, ha mostrado una propiedad antiadictiva que perdura en el tiempo. Sin embargo, su delicado perfil de toxicidad cardíaca, así como su uso en entornos sin adecuadas medidas de seguridad, han limitado su progresión en las investigaciones clínicas. Los efectos antiadictivos de ibogaína han disparado diversas líneas de investigación básica, preclínica y clínica, que buscan confirmar su efectividad, entender sus mecanismos de acción y delimitar su perfil de seguridad. Dada la poca información disponible para los profesionales de salud sobre esta sustancia, esta revisión busca aportar información acerca de su potencial terapéutico, posibles mecanismos de acción y riesgos asociados a su administración.

Substance use disorder is a chronic disease with severe consequences. Currently, pharmacological treatments do not aim to correct the neurobiological changes generated in the brain by the chronic use of substances of abuse, but rather focus mainly on attenuating some of the user's symptoms. Ibogaine is an atypical psychedelic that has shown long-lasting and interesting antiaddictive properties in both observational studies and open-label clinical trials. However, its delicate profile of cardiac toxicity, as well as its use in settings without adequate safety measures, have limited its progression in clinical research. The anti-addictive effects of ibogaine have triggered diverse scientific research in basic, preclinical, and clinical areas, which seek efficacy confirmation and to fully understand ibogaine´s underlying mechanisms of action and its safety profile. Given that there is little information available to health professionals about ibogaine and its antiaddictive properties, this review aims to provide published data about its therapeutic potential in drug addiction, its mechanisms of action, and risks associated with its administration.

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice

Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy) in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group). The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05) effects: a) a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b) decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c) increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d) increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e) increased serum corticosterone levels, and f) increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.

Alcaloides e o chá de ayahuasca: uma correlação dos "estados alterados da consciência" induzido por alucinógenos / Alkaloids and ayahuasca tea: a correlation of hallucinogen-induced "altered states of consciousness"

Dentre as inúmeras plantas alucinógenas utilizadas por populações indígenas da bacia amazônica, talvez nenhuma delas seja mais interessante ou complexa em termos botânicos, químicos ou etnográficos, como a bebida alucinógena conhecida como ayahuasca, hoasca, medicina, vegetal ou daime. Ayahuasca é bebida psicotrópica da América do Sul de destacado uso no xamanismo de muitas tribos indígenas da Amazônia, obtida pela fervura da casca do cipó de Banisteriopis caapi com a mistura de folhas de Psycotria, principalmente P. viridis. No Brasil, ocupa posição de destaque na etnomedicina. A natureza química dos compostos ativos, bem como, a maneira de utilização faz com que essa bebida ocupe posição de destaque nos atuais estudos da neurofarmacologia, neurofisiologia e psiquiatria. Alucinógenos e substâncias relacionadas constituem poderosa base experimental para investigar a correlação biológica dos estados alterados de consciência. O estudo de alucinógenos em humanos é de suma importância porque as substâncias com essas propriedades afetam certas funções cerebrais que tipicamente caracterizam a mente humana, incluindo a cognição, volição, ego e auto-percepção. As várias manifestações dos "desequilíbrios do ego" são especialmente características psicodélicas proeminentes, que acabam naturalmente criando psicoses. Sumarizamos nessa revisão alguns aspectos importantes no estudo do chá de ayahuasca em humanos, as indicações e contra-indicações para fins terapêuticos e religiosos.

Among the numerous hallucinogenic plants utilized by indigenous populations of the Amazon Basin, perhaps none is as interesting or complex in terms of botany, chemistry or ethnography as the hallucinogenic beverage known as ayahuasca, hoasca, medicine, vegetable or daime. Ayahuasca is a South American psychotropic beverage that is prominent in the shamanism of many indigenous Amazonian tribes and is obtained by boiling the bark of the liana Banisteriopsis caapi together with the mixture of leaves of Psychotria, principally P. viridis. In Brazil, it occupies a central position in ethnomedicine. The chemical nature of its active constituents and the manner of its use makes it relevant to contemporary studies in neuropharmacology, neurophysiology, and psychiatry. Hallucinogens and related substances constitute a powerful experimental basis to investigate the biological correlation of altered states of consciousness. The study of hallucinogens in humans is important because these substances affect a number of brain functions that typically characterize the human mind, including cognition, volition, ego, and self-consciousness. The several manifestations of "ego disorders" are especially prominent psychedelic features that naturally lead to psychoses. In the present review, we summarize some of the important aspects in the study of ayahuasca tea in humans, its indications and contraindications for therapeutic and religious purposes.

Ayahuasca: uma revisão dos aspectos farmacológicos e toxicológicos / Ayahuasca: a review of pharmacological and toxicological aspects

A ayahuasca é uma bebida psicoativa originariamente utilizada em rituais de tribos indígenas da região amazônica. Esta bebida é preparada pela infusão de caules da Banisteriopsis caapi Morton, que contém Beta-carbolinas que são inibidoras da monoaminoxidase (MAO), e de folhas da Psychotria viridis Ruiz & Pavón, que contém o alucinógeno N,N-dimetiltriptamina (DMT). A enzima MAO degrada a DMT no fígado e intestino. No Brasil, a ayahuasca tem sido incorporada em rituais de grupos sincréticos religiosos e seu uso dentro do contexto religioso é amparado por lei federal. Atualmente, esses grupos têm se espalhado na Europa e Estados Unidos, chamando a atenção de pesquisadores internacionais quanto aos efeitos da ayahuasca. Estudos têm indicado que a ayahuasca poderia ter aplicações terapêuticas como no tratamento da farmacodependência e até sugerem seu uso seguro por adultos sadios. Entretanto, poucos estudos têm sido conduzidos para melhor avaliação de suas propriedades. O objetivo do artigo é mostrar uma revisão geral da história até as recentes descobertas envolvendo a farmacologia e a toxicologia da ayahuasca.

Ayahuasca (or caapi in Brazil) is a psychoactive plant beverage initially used by shamans in religious rituals practiced by indigenous peoples in the Amazon region. It is prepared by infusing the pounded stems of Banisteriopsis caapi Morton, a liana which contains beta-carbolines, alkaloids that are potent monoamine oxidase (MAO) inhibitors, together with the leaves of Psychotria viridis Ruiz & Pavón, which contains the psychedelic agent N,N-dimethyltryptamine (DMT). The enzyme MAO normally degrades DMT in the liver and gut. In Brazil, the use of ayahuasca within religious ceremonies is protected by law and it has been incorporated into rituals of syncretic religious groups. Some of these groups have established themselves in the United States and European countries, attracting international research interest in the effects of ayahuasca. Studies suggest that it may have therapeutic applications, such as in the treatment of drug addiction, and that it can be used safely by healthy adults. However, too few studies have been performed for a good assessment of its properties to be made. The aim of this article is to present a review of the history of ayahuasca, up to the recent discoveries concerning its pharmacology and toxicology.

Anesthetic implications of acute methylenedioxymethamphetamine intoxication in a patient with traumatic intracerebral hemorrhage

The use of the street drug methylenedioxymethamphetamine [MDMA], commonly referred to as ecstasy, has become increasingly prevalent amongst teenagers and young adults in the United States and many other parts of the world. While most anesthesiologists are facile with the intricacies of managing patients intoxicated by alcohol, cocaine and narcotics the new "club" drugs present a challenge, especially under emergency conditions. MDMA, in particular, is the most commonly abused club drug and potentially one of the most dangerous in the perioperative period. We present a case report of traumatic subarachnoid hemorrhage in a patient with acute MDMA intoxication and a review of the anesthetic implications

Modelado molecular de n-isopropil lisergamidas analogas al LSD, utilizando calculos de mecanica molecular y mecanica cuantica / Molecular modeling of n-isopropyl lisergamides using molecular mechanisms and quantum mechanical calculations

Molecular mechanics and quantum mechanics were used to study the preferred conformations, electron densities and frontier orbitals of d-LSD and their analogs with the isopropyl amide group, compounds with reported activity over the serotonin receptor. Electron densities and frontier orbitals for isopropyl analogs were similar to d-LSD, so these properties can not be related with the changes in biological activity previously reported. It was found that isopropyl analogs have preferred conformations similar to d-LSD with small variation in the alkylamide group. The variation in the alkylamide group causes small variations in the orientation of the carbonyl amide group, our study suggests that this variation could affect the binding with the hydrophobic region of the receptor.

Psychopharmacologicals: mechanism of action

Sinopse a respeito deos usos terapêuticos e teorias mais recentes que tentam explicar o mecanismo de açäo, a nível molecular, dos seguintes agentes psicotrópicos: sedativos-ansiolíticos (principalmente os benzodiazepínicos), antipsicóticos, antidepressivos, liberadores indiretos de catecolaminas, psicodislépticos e antagonistas de serotonina