This study (n=24) found that experienced users showed less detrimental effects on higher cognition following ayahuasca intake than occasional users.
Abstract
“Background: Ayahuasca, a South American psychotropic plant tea containing the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine, has been shown to increase regional cerebral blood flow in prefrontal brain regions after acute administration to humans. Despite interactions at this level, neuropsychological studies have not found cognitive deficits in abstinent long-term users. Objectives: Here, we wished to investigate the effects of acute ayahuasca intake on neuropsychological performance, specifically on working memory and executive function. Methods: Twenty-four ayahuasca users (11 long-term experienced users and 13 occasional users) were assessed in their habitual setting using the Stroop, Sternberg, and Tower of London tasks prior to and following ayahuasca intake. Results: Errors in the Sternberg task increased, whereas reaction times in the Stroop task decreased and accuracy was maintained for the whole sample following ayahuasca intake. Interestingly, results in the Tower of London showed significantly increased execution and resolution times and number of movements for the occasional but not the experienced users. Additionally, a correlation analysis including all subjects showed that impaired performance in the Tower of London was inversely correlated with lifetime ayahuasca use. Conclusions: Acute ayahuasca administration impaired working memory but decreased stimulus–response interference. Interestingly, detrimental effects on higher cognition were only observed in the less experienced group. Rather than leading to increased impairment, greater prior exposure to ayahuasca was associated with reduced incapacitation. Compensatory or neuromodulatory effects associated with long-term ayahuasca intake could underlie preserved executive function in experienced users.”
Authors: José C. Bouso, Josep M. Fábregas, Rosa M. Antonijoan, Antoni Rodríguez-Fornells & Jordi Riba
Summary
Ayahuasca, a psychoactive plant tea from South America, increases cerebral blood flow in the prefrontal brain regions.
We investigated the effects of acute ayahuasca intake on neuropsychological performance in 24 ayahuasca users. The results showed that performance in the Stroop, Sternberg, and Tower of London tasks decreased following ayahuasca intake.
Acute ayahuasca administration impaired working memory but decreased stimulus-response interference. However, long-term ayahuasca use may have compensatory effects that preserve executive function.
Introduction
Serotonergic psychedelics, such as psilocybin and DMT, have been shown to act as serotonin (5-HT) 2A/1A/2C receptor agonists, and are being proposed as tools to investigate the role of 5-HT2A receptors in higher cognitive function.
Prefrontal and other cortico-subcortical networks involved in cognitive control are responsible for complex cognitive tasks such as working memory, response execution, and executive functions. 5-HT2A receptors are highly expressed in pyramidal cells of the prefrontal cortex.
Studies in animals have shown that 5-HT2A receptor activation induces excitatory postsynaptic potentials in the frontomedial cortex, an effect mediated by glutamate release. Neuroimaging studies in humans have shown that the medial prefrontal/anterior cingulate cortex is involved in the effects of psychedelics.
In a recent investigation, neuropsychological performance was assessed in a large sample of long-term ayahuasca users. The ayahuasca plant decoction contains -carboline alkaloids with monoamine oxidase-inhibiting properties that block the metabolic break-down of the labile DMT and render it orally active. In a long-term user study, 127 ayahuasca users scored better on neuropsychological tests than 115 controls, despite the fact that the prefrontal cortex is a key region targeted by psychedelics.
In the present study, we investigated the acute effects of ayahuasca on neuropsychological performance. We also explored the role of prior experience with ayahuasca in the degree of impairment observed.
Materials and methods
We studied 24 individuals who had taken ayahuasca between 8 and 60 times in the past 3 years to assess the role of prior ayahuasca use in current neuropsychological performance after acute ayahuasca intake. All participants abstained from ayahuasca for at least 15 days before the first of two experimental sessions, and were evaluated in the same setting where they usually take ayahuasca. Their verbal and fluid IQ scores were recorded, and an informed consent was obtained prior to participation.
Two hours after ayahuasca intake, participants were assessed in a separate and quiet room. Computerized tasks were executed on portable computers under the supervision of one of the authors, while a noncomputerized test was administered by another author.
The Sternberg working memory task
A computerized version of Sternberg’s verbal working memory test was used. Subjects had to indicate whether a target letter was present or not in a series of consonants by pressing a button. Two initial training trials were presented followed by 42 test trials. Reaction time for correct responses and performance quality were evaluated after each of the two training trials.
The Stroop color and word test
A modified computerized version of the Golden 1978 task was used to measure selective attention, cognitive flexibility, conflict monitoring, and resistance to interference. The task has been associated with activation in the anterior cingulate cortex and the dorsolateral prefrontal cortex.
The Tower of London
The Shallice task measures different components of executive function such as planning, inhibition, impulsivity, and working memory. Post-ayahuasca subjects were required to solve only the three most difficult problems from the total 13 problems used in the pre-ayahuasca assessment the previous day.
The mean pre- and post-ayahuasca scores and standard deviations (SD) were calculated from individual scores for each target variable, and correlations with lifetime ayahuasca use were calculated using Pearson’s correlation coefficient.
Results
We studied 24 ayahuasca users, 12 women, and found that experienced users had taken ayahuasca on an average of 179 occasions compared to 33 occasions for occasional users. No differences were found in years of education or in intelligence scores between the two groups.
The neuropsychological tests showed that all participants experienced intense psychotropic effects following ayahuasca administration. The results were not significantly different between experienced users and occasional users.
The statistical analysis of the data from the Sternberg task showed that there was a main effect of drug (pre vs. postadministration) for total errors, and a trend interaction between drug and group. There were no other main effects or interactions for the other variables.
The GLM analysis of data from the Stroop task showed that reaction times were shorter under the effects of ayahuasca, and the mean number of omitted responses also decreased.
One subject was lost during the analysis, so 23 participants were used. The analysis did not show any main effects of drug, but significant interactions were found between drug and group.
The correlational analysis showed that lifetime ayahuasca use was negatively correlated with mean execution time, mean resolution time, mean number of movements, and mean differential number of movements in the Tower of London test.
To rule out confounds associated with age, partial correlations were calculated controlling for this variable. Effects were maintained in all four instances.
Control experiment
A control experiment was conducted to assess the influence of practice on the performance of the administered tasks. No statistical differences were found between the control group and the two main study samples for any of the demographic variables assessed.
No statistically significant differences were observed between the first and second assessment for the Sternberg or Tower of London tasks.
Discussion
Ayahuasca intake led to a disruption of verbal working memory, increased stimulus-response interference, increased speed in the Stroop task, and decreased impulsive and inaccurate responses in both participant groups.
Prior research has found that psilocybin and DMT impair sustained attention, visual-spatial attention, alertness, binocular rivalry, global motion perception, time perception and temporal control, time interval reproduction, model object completion, and inhibition of return, but not all studies show detrimental effects.
Ayahuasca has mixed effects on neuropsychological performance, with improved performance on the Stroop task and detrimental performance on the Sternberg and Tower of London tasks. Experienced users may have developed compensatory mechanisms to compensate for the acute impairing effects of ayahuasca on executive function.
Long-term ayahuasca users showed greater prefrontal activations when conducting attention and inhibition tasks, and greater functional connectivity between frontal and occipitoparietal brain regions in an interference task compared to occasional users. This could explain the observed resistance to impairment.
Chronic ayahuasca intake could lead to neural changes that facilitate learning by increasing the expression of brain-derived neurotrophic factor in the prefrontal cortex. This could explain the faster learning effects observed in experienced users.
The present study had several limitations, such as being conducted under field conditions and not using balanced groups. However, even if learning effects were present, they did not prevent us from detecting detrimental effects in working memory and a selective impairing effect in the Tower of London.
Ayahuasca administration led to mixed effects on neuropsychological performance, negatively affecting working memory but not stimulus-response interference. Negative correlations between lifetime ayahuasca use and impaired cognitive abilities were not observed.
Study details
Participants
24