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F. da Silva

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

June 4, 2019 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).

Almeida, R. N., Galvão, A. C. D. M., Da Silva, F. S., Silva, E. A. D. S., Palhano-Fontes, F., Maia-de-Oliveira, J. P., … & Galvão-Coelho, N. (2019). Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca: observation from a randomized controlled trial. Frontiers in psychology, 10, 1234., https://doi.org/10.3389/fpsyg.2019.01234
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Acute effects of ayahuasca in a juvenile non-human primate model of depression

November 8, 2018 / Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / By / , , , , , ,

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.
da Silva, F. S., Silva, E. A., Sousa Jr, G. M. D., Maia-de-Oliveira, J. P., Soares-Rachetti, V. D. P., de Araujo, D. B., … & Galvão-Coelho, N. L. (2018). Acute effects of ayahuasca in a juvenile non-human primate model of depression. Brazilian Journal of Psychiatry, (AHEAD), 0-0. 10.1590/1516-4446-2018-0140
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Acute antidepressant effect of ayahuasca in juvenile non-human primate model of depression

January 25, 2018 / Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The incidence of major depression in adolescents, aged between 15 to 18 years, reaches approximately 14%. Usually, this disorder presents a recurrent way, without remission of symptoms even after several pharmacological treatments, persisting through adult life. Due to the relatively low efficacy of commercially available antidepressant, new pharmacological therapies are under continuous exploration. Recent evidence suggests that classic psychedelics, such as ayahuasca, produce rapid and robust antidepressant effects in treatment-resistant depression patients. In this study, we evaluated the potential of antidepressant effects of ayahuasca in a juvenile model of depression in a non-human primate, common marmoset (Callithrix jacchus). The model induces depressive-like symptoms by chronic social isolation (60 days) and antidepressant effects monitoring included fecal cortisol, body weight, and behavioral parameters. The animals presented hypocortisolemia and the recovery of cortisol to baseline levels started already at 24h after the ingestion of ayahuasca, but not the vehicle. Moreover, in males, ayahuasca, and not the vehicle, reduced the scratching, a stereotypic behavior, and increased the feeding. Ayahuasca also improving body weight to baseline levels in male and female common marmosets. The behavioral response induced by ayahuasca shows long effect, lasting 14 days. Therefore, for this translational animal model of juvenile depression, it could be proposed that ayahuasca treatment presented more notable antidepressant effects than tricyclic antidepressant nortriptyline, investigated by our group, using this same protocol in an anterior study. Ayahuasca produced faster and more durable effect on reversion of physiological changes and depressive-like symptoms. Therefore, the results found for ayahuasca treatment corroborates in the validation of this substance as an effective antidepressant drug and encourages the return of studies with psychedelic drugs in the treatment of humor disorders, including adolescents with early-age depression.

da Silva, F. S., dos Santos Silva, E. A., de Sousa Junior, G. M., Maia-de-Oliveira, J. P., Rachetti, V. D. P. S., de Araujo, D. B., … & Galvao-Coelho, N. L. (2018). Acute antidepressant effect of ayahuasca in juvenile non-human primate model of depression. bioRxiv, 254268. 10.1101/254268
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