Long-term effects of ayahuasca in patients with recurrent depression : a 5-year qualitative follow-up
Rafael G. dos Santos, Rafael Faria Sanches, Flávia de Lima Osório, Jaime E.C. Hallak
Archive of Clinical Psychiatry, 2018, 45, 1, 22-4
Background : Ayahuasca is a botanical hallucinogenic preparation traditionally used by indigenous populations of Northwestern Amazonian countries for ritual and therapeutic purposes. It is rich in β-carboline alkaloids and N,N-dimethyltryptamine (DMT). Preclinical, observational, and experimental studies suggest that ayahuasca and its alkaloids have anxiolytic and antidepressive effects. We recently reported in an open-label trial that ayahuasca administration was associated with significant decreases in depression symptoms for 2-3 weeks after the experimental session in 17 patients with treatment resistant major depressive disorder.
Objectives : To investigate if the experiment had any long-lasting effects on patients
Methods : Eight patients were interviewed 4 to 7 years after ayahuasca intake.
Results : Our results suggest that ayahuasca was well tolerated and that symptom reductions were limited to a few weeks. Importantly, most patients believed that the experience was among the most important of their lives, even 4-7 years later.
Discussion : To the best of our knowledge, this is the first long-term follow-up of a clinical sample that participated in an ayahuasca trial. Further studies with different and repeated dosing should be designed to further explore the antidepressive and anxiolytic effects of ayahuasca.
Keywords : Hallucinogens, psychedelics, ayahuasca, depression, safety.
Ayahuasca is a botanical hallucinogenic preparation traditionally used by indigenous populations of Northwestern Amazonian countries for ritual and therapeutic purposes (1), and also as a sacrament and therapeutic tool by Brazilian syncretic religions such as the Santo Daime, Barquinha and União do Vegetal (2,3). It is usually prepared by the prolonged concoction of the bark of the vine Banisteriopsis caapi together with the leaves of the shrub Psychotria viridis. The vine is rich in β-carboline alkaloids such as harmine, tetrahydroharmine (THH), and harmaline, and P. viridis contains N,N-dimethyltryptamine (DMT). The β-carbolines act as reversible inhibitors of monoamine oxidase (MAO)-A, and DMT act as a 5-HT1A/2A/2C agonist4. DMT by itself is not orally active due to degradation by peripheral MAO-A, but MAO-A inhibition by the β-carbolines renders DMT active by allowing it to reach the brain (4-6). The neural basis of the effects of ayahuasca seem to involve modulation of frontal and midline brain structures, such as the default mode network (DMN) (5-9).
Preclinical, observational, and experimental studies suggest that ayahuasca and its alkaloids have anxiolytic, antidepressive, and antiaddictive effects (2,3,10-14), and studies with healthy volunteers (2-8) and psychiatric patients (10,11) show that it is well tolerated. Previous observational studies assessing the mental health of members of Brazilian ayahuasca churches described the potential effects of regular ayahuasca use on anxiety, depression and dependence symptoms (2,14). Moreover, the first double-blind, controlled study showing that a single ayahuasca dose induced significant reductions on paniclike and depressive symptoms was conducted among Santo Daime members3. We recently reported that administration of a single oral dose of ayahuasca (dose: 2.2 mL/kg; alkaloid content in the sample: 0.8 mg/mL DMT, 0.21 mg/mL harmine, no harmaline was detected, and THH was not analyzed due to a lack of analytical requirements) in an open-label trial to 17 patients with treatment-resistant major depressive disorder (MDD) was associated with significant decreases in depression symptoms assessed with the Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Åsberg Depression Rating Scale (MADRS) from 80 minutes to day 2110,11. Average baseline score in the HAM-D scale was 19.24 (SD = 5.52), and at day 21 the average score was 7.56 (SD = 4.7). We recently replicated these results in a parallel arm, double-blind, randomised, placebocontrolled trial with 35 patients with treatment-resistant MDD (15). Compared to placebo, HAM-D scores at day 7 were significantly lower in patients treated with ayahuasca (Cohen’s d = 0.98), and MADRS scores were significantly reduced in the ayahuasca group at days 1, 2 and 7. After the publication of the open-label study10,11; we were interested in interviewing the volunteers after a long-time period to ask if the experiment had any long-lasting effects on them. To the best of our knowledge, this is the first long-term follow-up of a clinical sample that participated in an ayahuasca trial.