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Can Ayahuasca Treat Depression? - Clinical Insights

What is ayahuasca?

Ayahuasca is a psychedelic brew originating from the Amazon, originally used by indigenous populations and later involved for local syncretic purposes. Since it’s origins, ayahuasca has spread across the world and has developed a more varied list of uses. The two hallmark ingredients of ayahuasca are:

1) the leaves of the Psychotria viridis

2) bark of the Banisteriopsis caapi.

The former contains the psychoactive ingredient, N-N-dimethyltryptamine, while the latter contains monoamine oxidase inhibitors, which serve to prevent the degradation of monoamine neurotransmitters (norepinephrine, serotonin, dopamine) – subsequently amplifying the psychoactive effects. These two are mixed and boiled together for hours (or days), eventually culminating in an odorous, brownish brew.

Antidepressant Effects of Ayahuasca

Since 2006, Dr. Flavia de L. Osorio has been leading an investigation regarding the antidepressant effects of a single dose of ayahuasca in patients with recurrent depression[1]. In a 2015 preliminary report of six psychiatric patients, they found significant depression reductions at one day, seven days, and 21 days after ayahuasca dosing as measured by the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS).

In 2016, the same research group conducted a much larger-scale study with 70 patients suffering from recurrent depression[2]. In addition to the aforementioned scales, they also conducted a cerebral blood flow assessment eight hours after the ayahuasca session. The results from the scale assessments showed similar findings, with significant antidepressant effects shown from soon after administration until the last measurement at 21 days. The cerebral blood flow analysis showed increased blood flow in the nucleus accumbens, amygdala, insula, and left subgenual area – regions associated with mood and emotional regulation. The only reported adverse effect was vomiting (47% of participants) – an expected and consistent effect of ayahuasca consumption. These encouraging results set the basis for a subsequent study that was randomised, double-blinded, and placebo-controlled[3].

The following study involved baseline measurements of psychiatric scales, neuropsychological scales, MRI, fMRI, and a sleep ECG. Throughout the four-day dosing session, psychiatric and psychedelic scales were completed, in addition to saliva and blood sample collection. These same measurements were also completed at one-day and two-days post-dosing session, while psychiatric assessments were also conducted at seven days. Within this study, the researchers intended to assess whether the subjective psychedelic effects were integral to the antidepressant outcomes. Using the Hallucination Rating Scale (HRS), intensity, somaesthesia, volition, cognition, perception, and affect within the psychedelic experience were assessed. Interestingly, the researchers found that visual perception scores were significantly positively associated with MADRS changes between baseline and day seven. Of the reported biomarkers, the study found that depression-associated changes in cortisol levels[4], serum brain-derived neurotrophic factor (BDNF)[5], and inflammatory markers[6] were alleviated by ayahuasca consumption.

Ultimately, these findings present evidence that ayahuasca has a rapid-acting antidepressant effect with a complex underlying mechanism consisting of both biochemical and subjective perception changes. This research has provided encouraging evidence for the potential of an ayahuasca depression treatment if administered in a safe and appropriate setting.

Dr. Fernanda Palhano-Fontes is a professor at the Brain Institute at the Federal University of Rio Grande do Norte, Natal, Brazil. She has been studying the therapeutic use of ayahuasca since 2010, specifically in treatment-resistant depression.

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