Acute effects of ayahuasca in a juvenile non-human primate model of depression

Abstract

Objective:The incidence rate of major depression in adolescents reaches approximately 14%. This disorder is usually recurrent, without remission of symptoms even after pharmacological treatment, and persists throughout adult life. Since the effects of antidepressants take approximately 2 weeks to begin, new pharmacological therapies are under continuous exploration. Recent evidence suggests that psychedelics could produce rapid antidepressant effects. In this study, we evaluated the potential antidepressant effects of ayahuasca in a juvenile non-human primate model of depression.Methods:While living with their families, juvenile marmosets (8 males; 7 females) were observed on alternate days for four weeks during a baseline phase. This was followed by 8 weeks of an induced depressive state protocol, the social isolated context (IC), in which the animals were monitored in the first and last weeks. Subsequently, five males and four females were randomly selected for treatment, first with a single administration of saline vehicle (1.67 mL/300 g of body weight, via gavage), followed by a single dose of ayahuasca (1.67 mL/300 g of body weight, via gavage). Both phases lasted 1 week and the animals were monitored daily. A third week of sampling was called the tardive-pharmacological effects phase. In all phases the marmosets were assessed for behavior, fecal cortisol levels, and body weight.Results:After IC, the animals presented typical hypocortisolemia, but cortisol recovered to baseline levels 24 h after an acute dose of ayahuasca; this recovery was not observed in vehicle-treated animals. Additionally, in males, ayahuasca, but not the vehicle, reduced scratching, a stereotypic behavior, and increased feeding. Ayahuasca treatment also improved body weight to baseline levels in both sexes. The ayahuasca-induced behavioral response had long-term effects (14 days). Thus, in this translational juvenile animal model of depression, ayahuasca presented beneficial effects.Conclusions:These results can contribute to the validation of ayahuasca as an antidepressant drug and encourage new studies on psychedelic drugs as a tool for treating mood disorders, including for adolescents with early-onset depression.

Biodiversity of β-Carboline Profile of Banisteriopsis caapi and Ayahuasca, a Plant and a Brew with Neuropharmacological Potential

“…In spite of the globalization of ayahuasca use and the substantial number of studies showing a broad spectrum of therapeutic potential of ayahuasca, B. caapi , and β-carbolines [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 39 ], there are very few studies that examined the chemical profile of the beverage and the plant obtained from different sources. The first studies that investigated the levels of β-carbolines in B. caapi were conducted in the late 1960s to the 1980s and analyzed 6–7 plant samples collected in the Peruvian Amazon [ 4 , 33 , 34 , 40 ].…”

“…B. caapi extracts showed to act against neurodegenerative diseases, such as Parkinson’s disease [ 18 , 19 , 20 , 21 ]. Furthermore, various studies have investigated the therapeutic potential of ayahuasca for depression and addiction in experimental animals [ 22 , 23 , 24 , 25 ] and humans [ 26 , 27 , 28 ].…”

Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial

“…Serotonergic psychedelics, from natural or synthetic origin, present a similar mechanism of action of current antidepressants, such as the agonism of serotonin (Sanchez, 2018). Therefore, there is an increasing number of studies testing the antidepressant effects of psychedelics in humans, particularly of psilocybin (Carhart-Harris et al, 2016; Griffiths et al, 2016; Ross et al, 2016) and ayahuasca (Osório et al, 2015; Sanches et al, 2016; Palhano-Fontes et al, 2018), including in animal models of depression (Silva et al, 2018). Moreover, recent studies have suggested that regular intake of micro-doses of psychedelics leads to benefits in mood, health and cognition, decreasing symptoms of depression and anxiety, with no reports of significant alteration of consciousness (Johnstad, 2018; Anderson et al, 2019; Polito and Stevenson, 2019).…”

Translational evidence for ayahuasca as an antidepressant: what’s next?

“…Both institutions also participated in the study by da Silva et al,1 which complements previous rodent and human studies by showing that a single dose of ayahuasca (1.67 mL/300 g) produced significant physiological and behavioral improvements in a juvenile primate model of social isolation, which is phylogenetically closer to humans. Moreover, these effects remained significant for 14 days, corroborating previous results with MDD patients (improvements lasting 7-21 days) 4,5.…”

“…The article recently published by da Silva et al in the Brazilian Journal of Psychiatry 1 reported that ayahuasca, a psychoactive decoction containing harmine and dimethyltryptamine traditionally used by Amazonian indigenous groups and Brazilian syncretic religions, produced antidepressant effects in a juvenile primate model of depression. The antidepressive effects of ayahuasca and its alkaloids have been previously demonstrated in rodent models of depression.…”