Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice

Abstract

The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old) received ayahuasca or water (1.5 mL/kg, orally) twice a week for 12 months and were tested in the Morris water maze (MWM), open field and elevated plus maze (EPM) tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition) of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.

Ayahuasca‐enhanced extinction of fear behaviour: Role of infralimbic cortex 5‐HT2A and 5‐HT1A receptors

“…Accordingly, male rats presented relatively more enclosedarm entries 1 h after oral administration of AYA containing 1.0 mgÁkg À1 of DMT. On the other hand, avoidance and risk assessment, two anxiety-related behaviours remained unchanged, which confirms results obtained in mice and rats showing that DMT could only be anxiogenic with a 10-fold higher dose (Cameron et al, 2018(Cameron et al, , 2019Correa-Netto et al, 2017;Daneluz et al, 2022;Favaro et al, 2015;Pic-Taylor et al, 2015). Treating male and female rats (see also Table S1)…”

“…Studies have also investigated the effects of AYA, DMT and the β‐carbolines on the expression of anxiety and fear/threatening memories. Systemically administered DMT and AYA containing DMT at the dose range of 0.24–9.0 mg·kg −1 produced no changes in anxiety and general exploratory activity, as measured in rats and mice exposed to the elevated plus‐maze test (Cameron et al, 2019; Correa‐Netto et al, 2017; Daneluz et al, 2022; Favaro et al, 2015; Pic‐Taylor et al, 2015). However, administering 10 mg·kg −1 of DMT was anxiogenic (Cameron et al, 2018).…”

The current state of ayahuasca research in animal models: A systematic review

“…Similar to other studies, no microscopic alteration in organs and on hepatic, pancreatic, renal and lipid metabolising functions was found (data not shown) (Santos et al, 2017). Twice a week ayahuasca administration (1.5[1x]ml/kg) in six-month-old mice for one year did not alter body weight (Correa-Netto et al, 2017a).…”

“…Mice in different stages of the development treated twice a week with ayahuasca (1.5ml/kg[1x]) had no locomotor activity alteration in the open field, tested one day after administration (t[14 to 20]=-1.8456 to 1.1527, p=0.084 to 0.804); however, ayahuasca-treated infant mice spent more time in risk assessment behaviour in the elevated plus-maze test, suggesting increased anxiety (t[19]=-3.2684; p=0.004), and adolescents spent less time in and crossed fewer times the platform quadrant of the Morris water maze (t[20]=-2.6937 and -2.3350, p<0.05), indicating a memory impairment (Correa-Netto et al, 2017b). Using the same dose, ayahuasca administration twice a week in six-month-old mice for one year did not alter ageing or anxiety parameters evaluated by open field, elevated plus maze, and Morris water maze test (all p>0.05) tested before the start of treatment and one day after the last administration (Correa-Netto et al, 2017a). In zebrafishes, embryos who had their eggs exposed to ayahuasca (0.064, 0.032, 0.16, 0.8, 4, and 20mg/l) for 96h right after fertilization and tested 120 and 144 hours post-fertilization showed reduced locomotion at 4, and 20mg/l (Andrade et al, 2018).…”

The risk of chronic psychedelic and MDMA microdosing for valvular heart disease

“…Other repeat-dose toxicology studies have been performed with daily dosing up to 70 days, but did not include histological evaluation (e.g., Santos et al, 2017). Some rodent studies have dosed ayahuasca on intermittent schedules for 2 months and even up to 1 year (e.g., Cameron et al, 2019; Correa-Netto et al, 2017), but did not include cardiac assessments.…”