Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats

This rodent study (2015) found that long-term administration of ayahuasca can interfere with the contextual association of emotional events in rats.

Abstract

“Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.”

Authors: Vanessa M. Favaro, Maurício Yonamine, Juliana C. K. Soares & Maria G. M. Oliveira

Summary

RESEARCH ARTICLE

Ayahuasca, a hallucinogenic beverage, activates brain areas involved with episodic memory, contextual associations and emotional processing. Long-term administration of ayahuasca can interfere with the contextual association of emotional events in rats.

Introduction

Ayahuasca was originally used by indigenous communities in the upper Amazon and the Andes for healing, spiritual development and divination. It has since been incorporated into modern syncretic religious movements.

Ayahuasca tea is prepared by boiling the bark and stems of Banisteriopsis caapi together with various admixture plants. The tea contains the psychoactive agent DMT and beta-carbolines, which inhibit the metabolic breakdown of DMT by visceral MAO.

Recently, it has been shown that the administration of tea to rats changes the serotonin levels and increases dopamine and noradrenaline levels.

Ayahuasca consumption increases blood flow to the parahippocampal gyrus, the anterior cingulate cortex and the amygdala, regions involved in memory, contextual associations and emotional processing. Long-term ayahuasca users report improved memory, concentration and a sense of meaning in their lives.

Animal studies can complement human findings in evaluating some cognitive or behavioral impact of long-term consumption of ayahuasca. We used well-established paradigms to investigate the long-term effects of ayahuasca on memory and anxiety processes in rats.

Subjects

Wistar rats were housed in groups of 5 in a room with constant temperature and a 12 hour light/dark cycle.

Ayahuasca

Ayahuasca tea was derived from a religious institution and the alkaloids were determined using a gas chromatography method. The tea was concentrated and freeze-dried and stored at 4°C.

Doses and groups

Animals were given freeze-dried ayahuasca extract doses of 120, 240 and 480 mg/kg orally by gavage.

Apparatus

Morris water maze: A 200cm diameter pool was filled with water at 23°C and a platform was placed in the center of one of the quadrants.

The conditioning chamber consisted of aluminum walls, Plexiglas rear wall, ceiling, and hinged front door, and was situated in sound-attenuating cabinets in an isolated room. The floor of the chamber consisted of 19 stainless steel rods connected to a shock source during training and contextual fear conditioning test.

Experimental procedures

In experiment 1, rats received ayahuasca (120, 240 or 480 mg/kg) for 30 days and were then placed on an elevated plus maze (EPM) and conditioned with five tone – footshock pairings (30 minutes after EPM). Contextual fear conditioning was assessed by freezing the rats in the conditioning chamber, and tone fear conditioning was assessed by placing the rats in a modified chamber and presenting five tones with 25s intertrial intervals.

Long-term ayahuasca administration affected performance in the elevated plus maze and fear conditioning foreground followed by repeated sessions. The rats were placed in the conditioning chamber 48 hours after the last administration and freezing time was assessed for 300s.

Four groups of animals received ayahuasca administration for 30 days. The animals were trained on the Morris water maze spatial version for 48 hours after the last administration, and the time spent in the target quadrant was used to determine the spatial memory.

Discussion

The present study investigated whether long-term ayahuasca administration influences the behavior of rats in elevated plus maze, fear conditioning and Morris water maze paradigms. The results showed that the behavior changes observed were acquired in off-drug state.

The concentration of ayahuasca components in gas chromatography was similar to those values found in the literature, and the doses used were determined by considering the animal weight and the DMT concentration in the religious ceremony.

The lower dose of ayahuasca used in the present study had an impact on the performance of the animals in the fear conditioning test. The results show that the nature of context being salient or not during the learning and memory process is affected by long-term ayahuasca administration.

The same dose that enhanced contextual fear conditioning increased the fear response in the tone fear conditioning test for both before and after tone presentation. This effect could be due to increased sensitization to the shock experience. The second experiment tested the hypothesis that the higher freezing performed in the pre-CS moment during TFC was due to similarities between contexts, leading to a conditioned response to the common contextual elements.

A control experiment was conducted to determine whether the effect observed in Experiments 1 and 2 was due to ayahuasca administration or to a residual effect of the last single dose administered 48 hours before training.

Long-term ayahuasca administration did not interfere with spatial learning or memory in animals in an off-drug state, suggesting that it may interfere with the contextual association with emotional events that only occurs in classical conditioning.

Ayahuasca tea drinkers have reported remission of anxiety disorders after beginning to drink the tea in the religious context. However, there is no evidence of an anxiety effect after a long-term treatment, and the relation between religiosity and anxiety is difficult to examine.

The present study has some limitations, such as administering ayahuasca for 30 days to maximize the possibility of observing altered behaviors, and giving an interval between the last day of treatment and the first day of training.

These data suggest that long-term ayahuasca administration in rats may interfere with the contextual association with emotional events necessary for contextual conditioning. This knowledge is essential for a better understanding of long-term ayahuasca effects.

Study details

Compounds studied
Ayahuasca

Topics studied
Anxiety

Study characteristics
Animal Study

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