Journal of Ethnopharmacology 112 (2007) 507–513 Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members R.G. Santos a,∗, J. Landeira-Fernandez b, R.J. Strassman c, V. Motta a, A.P.M. Cruz a a Departamento de Processos Psicol´ogicos B´asicos, Instituto de Psicologia, Universidade de Bras´ılia, Asa Norte, Bras´ılia-DF 70910-900, Brazil b Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA c Departamento de Psicologia, Pontif´ıcia Universidade Cat´olica do Rio de Janeiro, PUC-RJ, Brazil Received 21 December 2006; received in revised form 16 April 2007; accepted 18 April 2007 Available online 25 April 2007 Abstract The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other plants such as Psychotria viridis, is growing in urban centers of Europe, South and North America in the last several decades. Despite this diffusion, little is known about its effects on emotional states. The present study investigated the effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that ingested ayahuasca for at least 10 consecutive years. The study was done in the Santo Daime church, where the questionnaires were administered 1 h after the ingestion of the brew, in a double-blind, placebo-controlled procedure. While under the acute effects of ayahuasca, participants scored lower on the scales for panic and hopelessness related states. Ayahuasca ingestion did not modify state- or trait-anxiety. The results are discussed in terms of the possible use of ayahuasca in alleviating signs of hopelessness and panic-like related symptoms. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Ayahuasca; Banisteriopsis caapi; Psychotria viridis; Emotional states; BHS; ASI-R 1. Introduction The word ayahuasca is used to describe the spiritual force in the beverage or the beverage itself, which is made with several Ayahuasca is a Quechua term derived from the juxtaposition species of the Banisteriopsis vine (e.g., Banisteriopsis caapi, of the terms: Aya–“soul”“dead spirit”; Waska–“rope”, “vine”, Banisteriopsis muricata) (Malpighiaceae), usually in combina- and thus is loosely translatable “vine of the souls” or “vine of tion with other plants, such as Psychotria viridis or Diplopterys the dead”. Ayahuasca refers to the vine used as the principle cabrerana (Ott, 1994). Ayahuasca also may refer to prepara- ingredient of a psychoactive beverage used by more than 70 dif- tions containing only the vine, as made by the Maku Indians, for ferent indigenous groups spread along Brazil, Colombia, Peru, example (Davis, 1997). Venezuela, Bolivia and Ecuador (Goulart, 2005; Luna, 2005). Since the beginning of the 20th century ayahuasca has been used by syncretic religious cults created in the Amazonian Brazilian states of Acre and Rondonia.ˆ These groups, of which Abbreviations: DMT, N,N-dimethyltryptamine; THH, tetrahydroharmine; Santo Daime, Barquinha and Uniao˜ do Vegetal (UDV) are the 5-HT, 5-hydroxytryptamine; MAO, monoamine oxidase; SSRIs, selective main ones, use ayahuasca as a healing tool and as a vehicle serotonin reuptake inhibitors; SPECT, single photon emission computer- ized tomography; GC/MS, gas chromatography/mass spectrometry; STAI, to gain access to the divine realm. These churches are highly state–trait-anxiety inventory; A-state, state-anxiety; A-trait, trait-anxiety; ASI- syncretic, containing influences from popular Catholicism, R, revised anxiety sensitivity index; BHS, Beck hopelessness scale; UDV,Uniao˜ European esoteric and spiritual beliefs, African cosmologies, do Vegetal and indigenous botanical knowledge. Their use of ayahuasca as ∗ Corresponding author. Current address: Centre d’Investigacio´ de Medica- sacrament resembles that of the Christian Eucharist. In the Santo ments, Institut de Recerca, Servei de Farmacologia Cl´ınica, Hospital de la Santa Creu i Sant Pau (HSCSP), St. Antoni Maria Claret, 167, Barcelona 08025, Spain. Daime and UDV rites, members drink ayahuasca usually twice Tel.: +34 93 2919019; fax: +34 93 2919286. a month, and in Barquinha it is not unusual to consume the brew E-mail address: [email protected] (R.G. Santos). four times per week (Araujo,´ 1999; Labate and Araujo,´ 2004). 0378-8741/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2007.04.012 508 R.G. Santos et al. / Journal of Ethnopharmacology 112 (2007) 507–513 Several studies (e.g., McKenna and Towers, 1981; McKenna and amphetamines), 11 with tobacco addiction, and 3 with pho- et al., 1984; Callaway, 1988; McKenna et al., 1990, 1998; bic anxiety disorders. Five of the participants with a history Callaway et al., 1999) have indicated that the main compo- of alcoholism also had histories of violent behavior associated nents of ayahuasca, the N,N-dimethyltryptamine (DMT) and with binge drinking. All of these psychiatric diagnoses remit- some beta-carbolines, are structurally similar to serotonin (5- ted following entry into the religion. All participants reported hydroxytryptamine or 5-HT), a neurotransmitter present in the that their use of ayahuasca within the religious context led to nervous system of most animal species. Correspondently, further improved mental and physical health and significant improve- observations found these ayahuasca components to display high ments in interpersonal, work, and family interactions (Grob et affinity for serotonin receptors, especially the 5-HT2 receptor al., 1996; McKenna et al., 1998). subtype (Smith et al., 1998; Grella et al., 2003). Assessing serotonergic function the authors found a signif- The beta-carbolines in ayahuasca include harmine, harma- icant up-regulation in the density of the serotonin transporter line and tetrahydroharmine (THH). DMT is an ultra-short-acting in blood platelets of the ayahuasca drinkers compared to the hallucinogenic tryptamine (Callaway et al., 1999) present in sev- control group (Callaway et al., 1994). Up- or down-regulation eral plants used as admixtures to the Banisteriopsis caapi vine in of peripheral platelet receptors is considered to reflect similar ayahuasca preparations. DMT also is present in tissues of mam- biochemical events occurring in the brain. None of the par- mals, marine animals and amphibians. In human beings it also ticipants showed evidence of any neurological or psychiatric is endogenous, being found in blood, urine and cerebrospinal deficit. fluid (Strassman, 2001). Despite being a potent psychoactive Callaway hypothesized that the causative agent of this platelet chemical, DMT is inactive following oral administration at doses effect was tetrahydroharmine (THH). In a self-experiment, he up to 1000 mg, probably due to degradation by gastrointestinal underwent single photon emission computerized tomography and liver MAO (monoamine oxidase) (McKenna et al., 1984). (SPECT) scans of his own brain 5-HT uptake receptors before However, when DMT is combined with inhibitors of the MAO and after a 6-week course of daily dosing with THH. He found enzymes, as are the beta-carbolines present in ayahuasca, it that the density of central 5-HT receptors in the prefrontal cortex becomes able to reach the systemic circulation and the cen- had increased. During recovery over the next several weeks their tral nervous system, thus producing its effects (McKenna et al., density gradually returned to previous levels. 1984). According to McKenna et al. (1998) a deficit of serotonin The beta-carbolines present in ayahuasca are potent natural, reuptake sites in frontal cortex has been found to correlate with selective, reversible, competitive inhibitors of peripheral MAO, aggressive behavior in alcoholics. If THH were able to specifi- and are more active against MAO-A than MAO-B. They also cally reverse this deficit, it may have applications in the treatment have a relatively low affinity for liver MAO compared to brain of this behavior. As mentioned previously, the majority of the MAO (McKenna et al., 1984, 1998). There is some evidence, participants in the Grob et al. study had a previous history however, that THH, the second most abundant beta-carboline in of alcoholism, some displaying violent behavior. Although the the beverage, acts as a selective inhibitor of serotonin reuptake behavioral transformation could be due to the supportive social as well as an MAO inhibitor (McKenna et al., 1998; Frecska et and psychological environment of a religious group, the finding al., 2004). The inhibition of both systems – MAO and serotonin of this long-term change in precisely the serotonin system that reuptake – by ayahuasca’s beta-carbolines may result in elevated is deficient in violent alcoholics argues that biochemical factors levels of brain serotonin (McKenna et al., 1998; Luna, 2005). also may play a role (McKenna et al., 1998). Despite the fact that the use of ayahuasca is a relatively It is well established that anxiety, panic and depressive- widespread practice in countries like Brazil, Peru and Colombia, related symptoms are significantly attenuated by 5-HT agonists, and that this practice is spreading to the United Sates, Europe and such as tricyclic antidepressants and selective serotonin reup- other