Effects of repeated ayahuasca administration on behaviour and c-Fos expression in male rats exposed to the open field.

Considering the long-lasting effects of ayahuasca on the brain and emotional processing, the objective of this study was to evaluate the behavioural and neurobiological effects of repeated ayahuasca administration in an animal model of exploratory behaviour related to novel-environment anxiety. Male Wistar rats received water, 120, 240, 480 or 3600 mg/kg of resuspended freeze-dried ayahuasca by gavage once a day for 30 days; there was also a non-manipulated homecage group. One hour after the last administration, animals were placed individually in the open field for 20 min. We analysed the weight gain, the behavioural response through a stochastic analysis, and c-Fos immunoreactive levels in the hippocampus, amygdala, pre-frontal and barrel field cortex. Ayahuasca at 120 mg/kg increased ambulation, and at 3600 mg/kg decreased vertical exploration and reduced weight gain. Aya3600 had higher c-Fos expression in regions of the hippocampus and infralimbic cortex than homecage, water or aya120 groups. Water-receiving animals had less c-Fos expression in the anterior basolateral amygdala than others groups. Our results show different behavioural effects of ayahuasca: a stimulant-like effect in small doses, and decreased activity in extreme high-dose, probably due to adverse effects. Higher activation of areas involved in emotional processing and the serotonergic pathway adds to the neurobiological literature on repeated/chronic ingestion of ayahuasca. Our data do not support an anxiolytic effect of repeated ayahuasca related to exploring new anxiogenic-environment but suggest that low ayahuasca doses should be further studied. The absence of severe impairment and behavioural syntax alteration reinforce ayahuasca safety.

Exposure to ayahuasca induces developmental and behavioral alterations on early life stages of zebrafish.

Ayahuasca is a psychoactive concoction prepared from the plants Banisteriopsis caapi and Psychotria viridis which are used ancestrally by Amazonian Indian populations and more recently, by Christian religious groups in Brazil and other countries. The aims of the present study were to identify the effects of ayahuasca on zebrafish embryo development and neurobehavior. Toxicity and developmental endpoints for zebrafish embryos were assessed from 0 to 1000 mg/L over 96 h of exposure. The effects on locomotor activity of zebrafish larvae were assessed using a video tracking system (ZebraBox) from 0 to 20 mg/L and after 120 and 144 h of exposure. The LC50 of ayahuasca in zebrafish was determined as 236.3 mg/L. Ayahuasca exposure caused significant developmental anomalies in zebrafish embryos, mainly at the highest concentration tested, including hatching delay, loss of equilibrium, edema and the accumulation of red blood cells. Embryo behavior was also significantly affected, with decreased locomotor activity at the highest concentration tested. These results are in accordance with data obtained in mammal studies highlighting the possible risks of uncontrolled use of ayahuasca. Further research employing more specific behavior analysis could provide additional data on both therapeutic benefits and possible toxicological risk of ayahuasca.

The effect of Banisteriopsis caapi (B. caapi) on the motor deficits in the MPTP-treated common marmoset model of Parkinson's disease.

Banisteriopsis caapi (B. caapi) contains harmine, harmaline, and tetrahydroharmine, has monoamine oxidase inhibitory activity, and has reported antiparkinsonian activity in humans when imbibed as a tea; however, its effects are poorly documented. For this reason, motor function was assessed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets following administration of B. caapi extract (28.4-113.6 mg/kg; po), harmine (0.1 and 0.3 mg/kg; sc), and selegiline (10 mg/kg; sc), alone or with a submaximal dose of L-3,4-dihydroxyphenylalanine (L-DOPA; 4-7 mg/kg). L-DOPA reversed motor disability, increased locomotor activity, and induced moderate dyskinesia. B. caapi did not increase locomotor activity or induce dyskinesia but at 56.8 and 113.6 mg/kg improved motor disability. The L-DOPA response was unaltered by co-administration of B. caapi. Harmine (0.1 and 0.3 mg/kg) produced a mild improvement in motor disability without affecting locomotor activity or dyskinesia but had no effect on the L-DOPA-induced antiparkinsonian response. Selegiline (10 mg/kg) alone improved motor function to the same extent as L-DOPA, but with only mild dyskinesia, and did not alter the response to L-DOPA, although dyskinesia was reduced. The findings suggest that B. caapi alone has a mild antiparkinsonian effect but does not enhance the L-DOPA response or reduce dyskinesia.

Metabolic pathways of the psychotropic-carboline alkaloids, harmaline and harmine, by liquid chromatography/mass spectrometry and NMR spectroscopy.

The ß-carboline alkaloids, harmaline and harmine, are present in hallucinogenic plants Ayahuasca and Peganum harmala, and in a variety of foods. In order to establish the metabolic pathway and bioactivities of endogenous and xenobiotic bioactive ß-carbolines, high-performance liquid chromatography, coupled with mass spectrometry, was used to identify these metabolites in human liver microsomes (HLMs) in vitro and in rat urine and bile samples after oral administration of the alkaloids. Three metabolites of harmaline and two of harmine were found in the HLMs. Nine metabolites for harmaline and seven metabolites for harmine, from the rat urine and bile samples, were identified. Among them, four in vivo metabolites were isolated and fully characterised by NMR analysis. For the first time, harmaline is shown transforming to harmine by oxidative dehydrogenation in rat. Five metabolic pathways were therefore proposed, namely, oxidative dehydrogenation, 7-O-demethylation, hydroxylation, O-glucuronide conjugation and O-sulphate conjugation.

Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of Ayahuasca: a longitudinal study.

Ayahuasca is an Amazonian psychoactive plant beverage containing the serotonergic 5-HT(2A) agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting alkaloids (harmine, harmaline and tetrahydroharmine) that render it orally active. Ayahuasca ingestion is a central feature in several Brazilian syncretic churches that have expanded their activities to urban Brazil, Europe and North America. Members of these groups typically ingest ayahuasca at least twice per month. Prior research has shown that acute ayahuasca increases blood flow in prefrontal and temporal brain regions and that it elicits intense modifications in thought processes, perception and emotion. However, regular ayahuasca use does not seem to induce the pattern of addiction-related problems that characterize drugs of abuse. To study the impact of repeated ayahuasca use on general psychological well-being, mental health and cognition, here we assessed personality, psychopathology, life attitudes and neuropsychological performance in regular ayahuasca users (n = 127) and controls (n = 115) at baseline and 1 year later. Controls were actively participating in non-ayahuasca religions. Users showed higher Reward Dependence and Self-Transcendence and lower Harm Avoidance and Self-Directedness. They scored significantly lower on all psychopathology measures, showed better performance on the Stroop test, the Wisconsin Card Sorting Test and the Letter-Number Sequencing task from the WAIS-III, and better scores on the Frontal Systems Behavior Scale. Analysis of life attitudes showed higher scores on the Spiritual Orientation Inventory, the Purpose in Life Test and the Psychosocial Well-Being test. Despite the lower number of participants available at follow-up, overall differences with controls were maintained one year later. In conclusion, we found no evidence of psychological maladjustment, mental health deterioration or cognitive impairment in the ayahuasca-using group.