Can you expand your cognitive toolkit with psychedelics?

Are you a fan of mental exercise? Perhaps you often have your eyes glued to your Duolingo app, in an attempt to learn a new language or two as a way to keep your mind sharp. A simple Google search of “how to improve your memory” generates about one billion results in 0.54 seconds. Would it surprise you if within this sea of suggestions, Google advised you to take a psychedelic drug? (Maybe not.)

Whether or not this possibility appeals to you personally, the thought may very well be irresistible to many. Over the past decades, psychedelics have had a love-hate relationship with American society. Psychedelic research flourished and was widely embraced during the 1950’s but became taboo during the 60s after psychedelics became conflated with psychotic breaks and anti-establishment views. Despite this, psychedelic research has recently reemerged, with increasing interest in the effects of psychedelics on cognitive functioning. It’s worthwhile that researchers are exploring this especially since not all psychedelics are a modern phenomenon: a number of psychedelic substances are naturally found in a variety of plants throughout the world and have been ingested for centuries.

Source: Brittanica

One such example is ayahuasca, a psychoactive tea made from the Banisteriopsis caapi and Psychotria viridis plants, which has traditionally been used by indigenous communities of Ecuador, Columbia, Peru, and Brazil (Jiménez-Garrido et al., 2020). Ayahuasca contains several psychoactive substances such as DMT, which along with other psychedelics, binds to and activates the serotonin receptor 5HT2A, causing changes in consciousness such as hallucinations (Rifkin, Maraver, & Colzato, 2020). Because psychedelics induce an altered perception of reality, you might expect that memory would be affected in some way. Since humans have used ayahuasca over the course of history, isn’t it high time that we understand its effects on memory? To put things another way, imagine if little was known about how alcohol, which has been consumed for millenia, affects cognition—we would be in a precarious situation today, to say the least.

So how have researchers thought about the relationship between ayahuasca and memory? Well, there are different types of memory, with short and long-term memory being two broad types. It’s well established that in terms of the general relationship between ayahuasca and long-term memory, ayahuasca may cause users to recall autobiographical memories—memories of events from, and knowledge about one’s life—during their psychedelic experience, which is supported by increased blood flow to the anterior cingulate cortex and the amygdala (Favaro et al., 2015). And what do we know about the interaction between ayahuasca and short-term memory? Regular users of ayahuasca claim that the beverage improves their memory (Lobao-Soares et al., 2018), however self-reports are not completely reliable. Bouso et al. (2013) investigated these claims by examining the effect of acute ayahuasca intake on working memory (which is similar to short-term memory) among 24 people who were either long-term or occasional users of the psychedelic. Based on a working memory task completed before and during ayahuasca use, occasional users experienced more memory impairment than long-term users. Somewhat counterintuitively, this might mean that long term use of ayahuasca might shield against working memory impairment to some extent, but this would still mean that ayahuasca negatively affects short-term memory. 

Source: Brittanica

If ayahuasca really does impair memory in this way, does other research agree? Although the above study is more methodologically sound than simply relying on self-reports, the presence of expectancy effects poses a hurdle to psychedelic research. A person’s surroundings as well as their mindset play a huge role in the type of psychedelic experience they will have, especially if they have used the drug before (Rifkin et al., 2020). One way for researchers to try to control for expectancy effects is to study animals and not just humans. This approach would be especially helpful for studying memory because controlling for these effects should help, not hinder, confidence in research findings. Lobao-Soares and colleagues (2018) did just this by investigating both acute and chronic ayahuasca exposure in 100 zebrafish, measuring longer-term memory based on their exploration of legos! Compared to acutely exposed fish, those exposed to ayahuasca for 13 days weren’t able to distinguish between legos as well. Despite this impairment in long-term memory, a rodent model examining longer-term memory didn’t reveal any significant changes caused by long-term ayahuasca exposure (Favaro et al., 2015), adding to uncertainty about the negative effects of ayahuasca on memory.

Research findings continue to reveal mixed evidence for this relationship; in a study that administered harmine, a psychoactive substance found in ayahuasca, to mice, exposure to this ingredient actually improved their short-term memory, based on their exploration toward new and familiar objects (Santos & Hallak, 2017). This actually conflicts with findings that ayahuasca impairs short-term memory in humans, yet it’s worth mentioning that these studies may not be absolutely comparable because of inconsistency surrounding whether ayahuasca itself, or an isolated ingredient, was administered to subjects. Differing findings may indicate that the psychoactive ingredients in ayahuasca may affect memory differently when isolated versus combined. Nonetheless, animal models are still a useful tool for ensuring that the subjectivity involved in psychedelic experiences does not unexpectedly influence the effect of ayahuasca on memory.

If ayahuasca does indeed alter memory processes in different ways, how might this be reflected in the brain? The studies that I’ve mentioned so far are helpful for understanding the relationship between ayahuasca and memory, but they are limited because they only focus on behavior—it’s equally important that we get a glimpse into the workings of the brain. Using magnetic resonance imaging (MRI), Bouso et al. (2015) compared the brains of 22 regular ayahuasca users (used ayahuasca at least once every other week) to 22 non-users, matching pairs based on demographics such as age and sex, and the findings are fascinating! According to their findings, ayahuasca users show thinning in several structures near the midline of the brain such as the posterior cingulate cortex (PCC) and thickening in the anterior cingulate cortex (ACC).  Even though we can’t definitively say that ayahuasca caused these differences in neuroanatomy based on this study, this research helps bridge the gap between the way ayahuasca interacts with the brain and behavior. Interestingly though, both the PCC and ACC play a role in attention and cognitive control, and the PCC is known to be involved in the default mode network (DMN) which is involved in working memory (Bouso et al., 2015). Add to this that ayahuasca has also been associated with decreased functional connectivity within the DMN and it’s possible that thinning within the PCC may then explain impairments in working memory task performance (Healy, 2021).  

All of this considered, it is most clear that ayahuasca interacts with memory in interesting ways, but this relationship yearns for much more exploration. Even though research with animals is helpful for studying the effects of ayahuasca on memory, comparing these studies to human research is tricky. One problem is that scientists don’t seem to be studying certain types of memory with the specific aim of comparing the effects of ayahuasca on memory humans vs. animals. Until this happens, we won’t be able to fully understand the impact of ayahuasca on different types of memory, but research seems to broadly suggest that ayahuasca’s effects teeter in the negative direction. Despite how long ayahuasca has been around for, its effect on memory surprisingly isn’t well known so if you’re looking to improve your memory with psychedelics, ayahuasca may not be as reliable as you had hoped it would be.

Bouso, J. C., Fábregas, J. M., Antonijoan R. A.,  Rodríguez-Fornells, A., & Riba, J. (2013). Acute effects of ayahuasca on neuropsychological performance: differences in executive function between experienced and occasional users. Psychopharmacology, 230, 415-424. https://doi.org/10.1007/s00213-013-3167-9 

Bouso, J. C., Palhano-Fontes, F., Rodríguez-Fornells, A., Sanches, R., Crippa, J. A. S., Hallak, J. E. C., de Araujo, D. B., & Riba, J. (2015). Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans. European Neuropsychopharmacology, 25, 483-492. http://dx.doi.org/10.1016/j.euroneuro.2015.01.008

Dos Santos, R. G. & Hallak, J. E. C. (2017). Effects of the Natural β-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies. Journal of Psychoactive Drugs, 49(1), 1-10. http://dx.doi.org/10.1080/02791072.2016.1260189 

Favaro V. M., Yonamine M., Soares J. C. K., Oliveira M. G. M. (2015). Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats. PLoS ONE, 10(12), 1-10. doi:10.1371/ journal.pone.0145840 

Healy, C. J. (2021). The acute effects of classic psychedelics on memory in humans. Psychopharmacology, 238, 639-653. https://doi.org/10.1007/s00213-020-05756-w 

Jiménez-Garrido, D. F., Gómez-Sousa, M., Ona, G. Dos Santos, R., Hallak, J. E. C.,  Alcázar-Córcoles, M. A., & Bourso, J. C. (2020). Effects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination. Sci Rep, 10, 1-12. https://doi.org/10.1038/s41598-020-61169-x

Lobao-Soares, B., Eduardo-da-Silva, P., Amarilha, H., Pinheiro-da-Silva, J. Silva, P. F., & Luchiari, A. C. (2018). It’s Tea Time: Interference of Ayahuasca Brew on Discriminative Learning in Zebrafish. Frontiers in Behavioral Neuroscience, 12, 1-10. doi: 10.3389/fnbeh.2018.00190 

Rifkin, B. D., Maraver, M. J., & Colzato, L. S. (2020). Microdosing psychedelics as cognitive and emotional enhancers. Psychology of Consciousness: Theory, Research, and Practice, 7(3), 316–329. https://doi.org/10.1037/cns0000213

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