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Tripping Nemo: Zebrafish on Ayahuasca

Does ayahuasca use affect our brains? Researchers ask our fishy friends.

Maybe you’ve heard of ayahuasca, a mind-altering brew that many travel to South America to sample. Over the last few years public interest in this beverage—whose active ingredients are a combination of β-carbolines in the ayahuasca vine and psychoactive compound dimethyltryptamine (DMT) from the chacruna shrub—has skyrocketed.

It’s possible you’ve read a blog post about someone’s “life-changing” experience with ayahuasca, or seen an interview with a celebrity who returned from a self-reported “mind-altering” retreat.

Although illegal in many countries, including the United States, ayahuasca plays an integral role in many South American communities. About a decade ago, Peru's government officially recognized its cultural importance with regard to Amazonian tribe identities.

Gordon Johnson/Pixabay
Source: Gordon Johnson/Pixabay

Small studies have indicated a possible therapeutic benefit, with links to reducing depression. This would make a lot of neurological sense because DMT is a potent activator of receptors for “feel good” neurotransmitters serotonin and dopamine.

On the surface, this probably sounds great, but quite a bit of apprehension surrounding the use of ayahuasca remains—and for good reason: we don’t know its long-term effects or how chronic use could alter cognitive abilities.

A push for larger-scale studies to determine the benefits of the drug in human subjects is still ongoing, and so scientists are turning to different model systems to start answering some of these questions. Last year, one group of researchers at Universidade Federal do Rio Grande do Norte in Brazil gave ayahuasca to fish.

Yes, fish. Zebrafish to be exact.

Source: NOAA

Zebrafish are tropical fish that are common models for science research and they’re exceptionally cool. They reproduce far more quickly than model systems like mice, an ideal quality for researchers hoping to do long-term studies. They’re also transparent, so developmental biologists love using them to visualize how their bodies develop under certain conditions or perturbations. Heck, zebrafish have even gone to space.

The Brazil-based research team set out to evaluate the effects of chronic versus acute ayahuasca exposure in these fish. They obtained ayahuasca brew from a religious group in Brazil and used it at two different concentrations for their experimentation.

Zebrafish were divided into five treatment groups: a control group, two acute exposure groups, and two chronic exposure groups.

Fish in the chronic treatment groups were transferred to tanks containing an ayahuasca concentration of either 0.1 ml/L or 0.5 ml/L for 60 minutes and then transferred back to a holding tank. This was repeated once a day for 13 consecutive days.

For the acute treatment, fish followed the same protocol, but the tanks were ayahuasca-free. On day 14, the acute exposure groups were placed in tanks containing an ayahuasca concentration of either 0.1 ml/L or 0.5 ml/L for 60 minutes, shortly before their first cognitive test.

Source: Semevent/Pixabay

The researchers tested cognition of the fish using a one-trial object discrimination test, a memory test commonly used for a variety of model systems to assess a range of cognitive functions. For this test, fish are first habituated to a tank and then presented objects in that tank. In this study, Lego® blocks were used. One of the blocks was eventually replaced by another block of similar shape but of a different color. Fish in each test group were given time to explore the new object. Throughout each stage of the test, the behavior of the fish was recorded and each fish’s average swimming speed, maximum swimming speed, total distance traveled, freezing, and time exploring each object were analyzed.

The researchers found that the fish acutely exposed to ayahuasca did not show changes in object memorization or discrimination compared to the control group, but that was not the case for the chronically exposed groups.

Zebrafish chronically exposed to ayahuasca showed increased overall activity but decreased exploration behavior. The amount of time taken to explore a new object indicates if a fish recognizes the object's novelty, so these results indicated that the chronically-treated fish were not discriminating between the old and new objects. Increased overall activity is a trait previously shown to be linked to anxiety in zebrafish and is perhaps the result of excessive activation of the dopamine and serotonin receptors mentioned earlier.

Although more complex tests need to be done, and on systems beyond just zebrafish, these creatures have provided us a window into understanding the dangers of prolonged ayahuasca use, which suggests negative effects to memory and learning.