The therapeutic potential of harmine and ayahuasca in depression : Evidence from exploratory animal and human studies

Flávia de Lima Osório, Ligia Ribeiro Horta de Macedo, João Paulo Machado de Sousa, Joel Porfírio Pinto, João Quevedo, José Alexandre de Souza Crippa and Jaime Eduardo C. Hallak

The Ethnopharmacology of Ayahuasca, chapitre 5, 2011, 75-85
Editor : Rafael Guimarães dos Santos

ISBN: 978-81-7895-526-1

Abstract

The high prevalence and the socio-functional impairment associated with depressive disorders, added to the limitations of currently available treatments, justify the search for novel pharmacological strategies for the management of depression. This chapter presents the major results of animal and human studies conducted by a group of Brazilian researchers concerning the antidepressant potential of harmine, an alkaloid belonging to the group of β-carbolines and present in Ayahuasca (AYA), a tea with hallucinogenic properties used for religious and medicinal purposes by peoples from the Amazon. The results obtained thus far suggest that harmine and other substances present in AYA might have antidepressant-like effects in the central nervous system of animals and human patients, pointing out the possibility of the therapeutic use of AYA in humans.

1. Depressive disorders – Clinical aspects

Depression is a highly frequent psychiatric disorder with a lifetime prevalence of 17%, being twice as prevalent among women as compared with men. Onset usually occurs in the third decade of life, but the disorder can affect individuals at any age. It is a recurring condition and around 20-25% of patients become chronically ill[1]. Depressive disorders are associated with intense suffering, high morbidity rates, and increased mortality[2]. According to a study of the World Health Organization (WHO), depression is currently the fourth leading cause of morbidity and, within a ten-year period, it might rank second among the disorders affecting productive life[1]. According to the current Diagnostic and Statistical Manual of Mental Disorders published by the American Psychiatric Association (DSM-IV)[3], the diagnosis of a depressive episode requires the presence of depressed mood and/or anhedonia for a minimum of two weeks, accompanied by at least four of the following symptoms: significant weight loss or gain (5% of body weight); psychomotor agitation or retardation; insomnia or hypersomnia; fatigue or diminished energy; low self-esteem or inappropriate feelings of guilt; difficulties to think, concentrate or make decisions; and thoughts of death and suicide ideation or attempt. The symptoms must be associated with significant suffering and/or impairment in social, occupational or other functional areas, cannot be caused by a general medical condition or substance use, or fulfill the criteria for a mixed episode (episode in which the diagnostic criteria for both depression and mania are simultaneously satisfied).

Clinically, depressive disorders are divided into single episode (if only one episode has occurred in life), recurring (when at least two episodes occurred), and chronic (if an episode lasts for two years or more)[3]. In terms of severity, depressive episodes are divided into mild, moderate, and severe. In mild episodes, few or no additional criteria besides those necessary for diagnosis are fulfilled and functional impairment is minor; in severe episodes a variety of symptoms are present, with significant functional impairment and possible association with psychotic symptoms; in moderate episodes, both the number of symptoms and the ensuing functional impairment lie on an intermediate level between the two former categories[3].

2. Etiologic factors and neurobiology of depression

The vulnerability to develop depression is connected with environmental factors such as early parental loss, childhood history of traumatic events, personality traits, family and personal history of depression, recent traumatic events, and genetic factors[1].

One of the main hypotheses to explain the neurobiology of depression was proposed following the discovery of the mechanisms of action of early antidepressant agents, which were accidentally discovered in the 1950s during the development of antihistamine (imipramine → tricyclic antidepressant) and antituberculosis (iproniazid → monoamine oxidase (MAO) inhibitor) drugs. Added to this, the comprehension of the action of three substances on the central nervous system (CNS), namely, imipramine (inhibiting neuronal reuptake of noradrenaline and serotonin), reserpine (depleting monoamines and causing depressive symptoms), and amphetamine (releasing noradrenalin and inhibiting its neuronal reuptake, causing euphoria) led to the proposition, in the 1960s, of the classic monoamine theory of depression, according to which the disorder would be caused by decreased availability of noradrenaline and serotonin in the brain[4].

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