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ORIGINAL ARTICLE
Antidepressant effects of a single dose of ayahuasca in
patients with recurrent depression: a preliminary report
Fla´via de L. Oso´rio,
1,2
Rafael F. Sanches,
1,3
Ligia R. Macedo,
1
Rafael G. dos Santos,
1
Joa˜ o P. Maia-de-Oliveira,
4
Lauro Wichert-Ana,
1
Draulio B. de Araujo,
5,6
Jordi Riba,
3,7,8,9
Jose´ A. Crippa,
1,2
Jaime E. Hallak
1,2
1
Department of Neurosciences and Behavior, Ribeira˜ o Preto Medical School, Universidade de Sa˜o Paulo (USP), Ribeira˜o Preto, SP, Brazil.
2
National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil.
3
Centre d’Investigacio´ de Medicaments, Servei de
Farmacologia Clı´nica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
4
Department of Clinical Medicine, Universidade Federal do Rio
Grande do Norte (UFRN), Natal, RN, Brazil.
5
Hospital Universita´ rio Onofre Lopes, UFRN, Natal, RN, Brazil.
6
Brain Institute, UFRN, Natal, RN,
Brazil.
7
Human Experimental Neuropsychopharmacology, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
8
Department of Pharmacology and Treatment, Universitat Auto`noma de Barcelona, Spain.
9
Centro de Investigacio´ n Biome´ dica en Red de
Salud Mental, CIBERSAM, Barcelona, Spain.
Objectives: Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich
in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore
have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six
volunteers with a current depressive episode.
Methods: Open-label trial conducted in an inpatient psychiatric unit.
Results: Statistically significant reductions of up to 82% in depressive scores were observed between
baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale
for Depression (HAM-D), the Montgomery-A
˚sberg Depression Rating Scale (MADRS), and the
Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration
resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking
disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or
hypomania in patients with mood disorders and that modifications in thought content, which could
indicate psychedelic effects, are not essential for mood improvement.
Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in
patients with a depressive disorder.
Keywords: Psychedelic agents; dimethyltryptamine; harmine; monoamine oxidase inhibitors;
therapeutic use
Introduction
Depression is a highly prevalent disorder andis associated
with intense personal suffering, increased mortality, and
high morbidity.
1,2
Although its etiology is unknown, some
theories suggest that biological factors may be implicated.
3
One such theory is the monoamine hypothesis, which
suggests that an imbalance in cerebral monoamines such
as dopamine, norepinephrine, and, especially, serotonin is
responsible for depressive symptomatology.
3
The mono-
amine hypothesis is the theory on which the leading
commercially available antidepressants are based.
3
Currently available treatments have limitations that can
lead to low therapeutic effectiveness, especially related to
low response rates, as well as adverse effects and
latency to onset of therapeutic action.
3
Thus, new
interventions, particularly those that with the potential
for acute effect, would have a huge impact on the
treatment of depression. The N-methyl-D-aspartate
(NMDA) receptor antagonist ketamine, for example, has
rapid and potent antidepressant effects in treatment-
resistant major depressive disorder (MDD) and bipolar
depression, and its use is considered one of the most
exciting areas in contemporary psychiatric research.
4,5
Ayahuasca (AYA), a botanical hallucinogen tradition-
ally used by indigenous groups of the Northwest Amazon
region for ritual and medicinal purposes,
6,7
is a potential
candidate for this new generation of antidepressant
research focusing on new pharmacological treatments
that produce immediate and more pronounced effects.
AYA is prepared by prolonged decoction of the bark of the
vine Banisteriopsis caapi with the leaves of the shrub
Psychotria viridis.
6,7
B. caapi contains the b-carboline
alkaloids harmine, tetrahydroharmine (THH), and harma-
line, which act as monoamine oxidase A inhibitors
Correspondence: Jaime E. C. Hallak, Departamento de Neurocieˆncias
e Cieˆ ncias do Comportamento, Faculdade de Medicina de Ribeira˜o
Preto, Universidade de Sa˜ o Paulo, Hospital das Clı´nicas, 36andar,
Av. Bandeirantes, 3900, Ribeira˜o Preto, SP, Brazil.
E-mail: jhallak@fmrp.usp.br
Submitted Jun 20 2014, accepted Aug 08 2014.
Revista Brasileira de Psiquiatria. 2015;37:13–20
ß2015 Associac¸a˜ o Brasileira de Psiquiatria
doi:10.1590/1516-4446-2014-1496
(MAOI), while P. viridis is rich in the psychedelic
tryptamine N, N-dimethyltryptamine (DMT).
6,8-11
The psychoactive effects of AYA are produced by a
combined action of peripheral (gastrointestinal and liver)
monoamine oxidase A (MAO-A) inhibition by harmine and
central 5-HT
1A/2A/2C
agonist action of DMT on frontal and
paralimbic brain areas.
8,9,12
Studies conducted among
long-term (i.e., years or decades) members of religious
groups that use AYA ritually suggest that this population
does not present evidence of psychological, neuropsy-
chological, or psychiatric harm caused by AYA.
13-15
In
fact, there are several reports describing reduced mental
health problems in AYA users.
13-15
Nevertheless, given
the small number of studies, most with a limited number
of participants, there is insufficient information to allow a
definitive conclusion on this topic, and more studies on
the potential long-term toxicity of AYA are required.
An increasing number of studies report antidepressive
potential for AYA alkaloids in animals.
16-24
Furthermore,
a double-blind, placebo-controlled animal study reported
reduced hopelessness and panic-related signs after
acute AYA administration,
25
and preliminary data in
humans also support an antidepressive action for AYA.
26
The agonist action of AYA alkaloids on serotonergic
receptors and its inhibitory effects on MAO-A, associated
with field and laboratory evidence suggesting that AYA
causes a sensation of well-being, led to the hypothesis
that this substance could be useful in the treatment of
depression in humans. Thus, the objective of the present
preliminary, open-label study was to evaluate the acute
effects of a single dose of AYA in patients diagnosed with
depression and to test whether AYA administration could
produce an acute antidepressant effect.
Methods
Volunteers
Six volunteers (two men and four women, mean age
44.16613.55 years) with a diagnosis of recurrent MDD
participated in the study. Within this group, two volunteers
were experiencing a current mild depressive episode,
three were experiencing a moderate episode, and one
was experiencing a severe depressive episode. None of
the volunteers were experiencing depressive episodes
with psychotic symptoms.
Participants were recruited through local advertise-
ments and by referrals from private psychiatric clinics.
Volunteers were not taking any psychopharmaceuticals
at the time of recruitment; they were patients that did not
exhibit a significant therapeutic response to their latest
medication and were in the process of switching to a new
agent. Patients participated in the study before the
introduction of the new medication.
None of the participants had ever used illicit drugs or
AYA, as assessed by a medical interview, and had no
evidence of current clinical conditions or pregnancy, as
assessed by medical interview, physical examination,
and laboratory tests. A diagnosis of bipolar disorder and
a previous history of mania or hypomania induced by
antidepressants/substance use were considered exclu-
sion criteria.
The study was conducted in accordance with the
Declarations of Helsinki and Tokyo concerning human
subject research and approved by the Research Ethics
Committee of Hospital das Clı´nicas da Faculdade de
Medicina de Ribeira˜ o Preto da Universidade de Sa˜o
Paulo, Ribeira˜ o Preto, state of Sa˜ o Paulo, Brazil (HC-RP
process no. 2484/2008). The volunteers received detailed
information on the nature of AYA, the general psycholo-
gical effects of hallucinogens, and its possible adverse
effects, as reported in the psychiatric literature. All volunteers
gave their written informed consent to participate.
Drug
We obtained a standard sample of AYA prepared by
members of the Santo Daime community, consisting of the
stalks of B. caapi (rich in harmine, THH, and harmaline)
combined with the washed leaves of P. viridis (rich in
DMT), boiled and concentrated for several hours. The
resulting brew was stored in plastic bottles at room
temperature at the Santo Daime community and sub-
sequently in a refrigerator in the Department of
Neurosciences and Behavior, Ribeira˜ o Preto Medical
School, Universidade de Sa˜o Paulo, Ribeira˜ o Preto,
Brazil. AYA was stored under refrigeration until the day
of the experimental session. All AYA used in the present
study was from this original batch.
Each subject drank 120-200 mL of AYA (2.2 mL/kg
body weight). The AYA batch used in the experiment
contained 0.8 mg/mL DMT, 0.21 mg/mL harmine, and no
harmaline at the chromatography detection threshold of
0.02 mg/mL. To quantify the content of each alkaloid, a
1-mL sample of AYA was homogenized with sodium
acetate buffer solution (pH = 9), extracted with 5 mL
diethyl ether in a shaker (20 min), and centrifuged at
3,000 rpm for 15 min. The organic phase was collected
and evaporated under a nitrogen stream. The residue
was dissolved in 1 mL methanol and 1 mL of the resulting
solution was analyzed by gas chromatography/mass
spectrometry (GC/MS), performed using a Varian
CP3800 gas chromatograph coupled to a Varian Saturn
2000 ion trap mass spectrometer (Varian Inc.). A capillary
column (DB-5MS, 30 m 60.25 mm i.d. 60.25 mm film
thickness; Agilent) was used. The chromatographic
conditions were as follows: injector temperature 2506C
in splitless mode and oven temperature program 806C for
1 min, ramped at 56C/min to 2206C and held for 10 min,
and then to 3006C for 5 min. Helium at a flow rate of 0.8
mL/min was used as carrier gas.
Medical interview and laboratory tests
A general clinical examination; a laboratory workup
consisting of a complete blood cell count; evaluation of
blood glucose levels; measurement of plasma sodium
and potassium, urea, creatinine, urinary beta-HCG (in
women of childbearing age), bilirubin, and liver enzymes;
and an electrocardiogram were performed.
FL Oso´rio et al.14
Rev Bras Psiquiatr. 2015;37(1)
Psychometric instruments
Structured Clinical Interview for DSM-IV (SCID-IV)
This interview was used to assess whether potential
patients met the inclusion and exclusion criteria.
27,28
Brief Psychiatric Rating Scale (BPRS)
This clinician-administered scale was used to evaluate
four symptom dimensions: 1) Withdrawal-Retardation;
2) Thinking Disorder; 3) Anxious-Depression; and
4) Activation.
29,30
Young Mania Rating Scale (YMRS)
This clinician-administered scale was used to assess
manic symptoms.
31,32
Hamilton Rating Scale for Depression (HAM-D)
This clinician-administered scale was used to assess and
quantify depressive symptoms in patients with a previous
diagnosis of mood disorder.
33,34
Montgomery-A
˚sberg Depression Rating Scale (MADRS)
This clinician-administered scale was used to assess the
severity of depressive symptoms.
34,35
Assessment of tolerability
Systolic blood pressure (SBP) and diastolic blood
pressure (DBP) were measured at the following time
points: 10 minutes (-10) before AYA administration
(baseline) and 40 min (+40), 80 min (+80), 140 min
(+140), and 180 min (+180) after AYA administration.
Blood pressure was measured using a mercury sphyg-
momanometer (Becton Dickinson, Brazil).
Adverse effects were not systematically assessed.
Dysphoric effects were recorded by means of sponta-
neous verbal reports.
Experimental procedure
Volunteers were admitted to an inpatient psychiatric unit
for 2 weeks prior to AYA administration as part of an
open-label trial. During this time, volunteers were not
under the influence of any psychiatric medication or
recreational drugs. The experimental session, which was
performed individually, lasted on average 4 h and
consisted of AYA intake followed by administration of
the scales. During measurements, volunteers remained
seated in a comfortable recliner in a quiet, dimly lit room.
After the end of the session, patients remained under
observation for 24 h; if no complications were observed,
they were discharged.
The BPRS, YMRS, HAM-D and MADRS scales were
completed by a psychiatrist with clinical experience and
training in the use of these scales, at the following time
points: 10 minutes (-10) before AYA administration
(baseline); 40 min (+40), 80 min (+80), 140 min (+140),
and 180 min (+180) after AYA administration; and on
days 1 (D1), 7 (D7), 14 (D14), and 21 (D21) after AYA
administration.
Data analysis
After verification of data distribution, descriptive statistics
and repeated-measures analysis of variance (ANOVA)
were used for statistical analysis. Significance was set at
p,0.05.
Results
The clinical and demographic characteristics of the study
participants are presented in Table 1.
Regarding depressive symptoms, the average baseline
HAM-D score of the volunteers was 17.5667.73, which
was classified according to the scale guidelines as a
moderate level of depression. At D1, there was a 62%
decrease in the mean score, which was statistically
significant (p = 0.01) (Figures 1 and 2). This decrease
was even more pronounced by D7 (72%, p = 0.01).
However, on D14, the level of symptoms increased, and
although the symptom score remained 45% below base-
line, this difference was not statistically significant (p =
0.11). On D21, there was a further significant decrease in
depressive symptoms (p = 0.01). The greatest score
changes were observed for items related to depressed
mood, feelings of guilt, suicidal ideation, and difficulties at
work/activities, i.e., those associated with typical depres-
sive symptoms.
Regarding MADRS scores, results were similar to
those observed for the HAM-D scale. The average
baseline score of the volunteers was 23.5611.14 points.
At +180, there was a significant decrease in MADRS
scores (38%, p = 0.01) (Figures 1 and 3). On D1, a more
robust decrease was observed (p = 0.003), and the
average score on D7 was 82% below baseline (p =
0.009). On D14, a significant increase in symptoms was
observed (p = 0.001), although a subsequent significant
decrease occurred on D21 (p = 0.002). As observed with
the HAM-D scale, the most significant score changes
were observed for items related to apparent and
Table 1 Clinical and demographic characteristics of patients with recurrent major depressive disorder (n=6)
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
Age (years)/sex 47/female 61/female 28/female 58/male 31/female 36/male
Severity of current depressive episode Moderate Mild Severe Mild Moderate Moderate
HAM-D score 16 11 29 7 20 20
MADRS score 18 16 39 9 27 32
HAM-D = Hamilton Rating Scale for Depression; MADRS = Montgomery-A
˚sberg Depression Rating Scale.
Antidepressant effects of ayahuasca 15
Rev Bras Psiquiatr. 2015;37(1)
expressed sadness, pessimistic thinking, suicidal idea-
tion, and difficulty concentrating.
Regarding the BPRS scale, volunteers were generally
asymptomatic on the withdrawal-retardation (BPRS-WR),
thinking disorder (BPRS-TD), and activation (BPRS-A)
subscales at baseline (Figure 4). AYA administration
produced nonsignificant increases in the scores of these
subscales, with effect peaking at 80 min. After this time
point, scores decreased and returned to baseline at 180
min. Generally, the symptoms expressed referred to
disorientation/confusion, conceptual disorganization, psy-
chomotor retardation, and emotional withdrawal. Although
nonsignificant, the increase in the scores of these sub-
scales at 80 min after AYA administration suggests that
AYA produced mild psychoactive effects.
On the Anxious-Depression BPRS subscale (BPRS-
AD), volunteers demonstrated higher scores at baseline,
likely due to the presence of depressed mood, feelings of
guilt, and psychic anxiety, which are typical symptoms of
the underlying psychopathology. Throughout the experi-
ment, the presence of these symptoms varied, but values
remained lower as compared to baseline. At +140, these
symptoms were significantly reduced (p = 0.02) and
remained so (72% below baseline) until D7, when they
began to increase but still remained significantly lower
than baseline values (Figure 4).
Regarding the YMRS scale, volunteers exhibited no
significant changes in symptoms throughout the experi-
ment (Figure 1). However, irritability and decreased
capacity for insight and sleep were more prevalent during
the first 80 minutes following AYA administration, which
was likely associated with the peak period of the sub-
jective effects of AYA.
AYA was well tolerated by all patients. With the
exception of vomiting, volunteers did not spontaneously
report any other adverse effect. Volunteers considered the
effects of AYA on thought content and sensory perception
mild and short-lived, and none reported dysphoric mani-
festations associated with the psychoactive effects of AYA.
Blood pressure increased moderately and nonsignificantly
(Table 2).
Vomiting was reported by 50% of the volunteers.
However, patients were informed before the experimental
session that AYA could induce vomiting, and this emetic
Figure 1 Temporal distribution of scores (means from six volunteers) on the Hamilton Rating Scale for Depression (HAM-D),
Montgomery-A
˚sberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS). HAM-D: *p,0.05;
MADRS:
{
p,0.05,
{
p,0.01. Error bars denote one standard error of the mean.
Figure 2 Temporal distribution of individual scores on the Hamilton Rating Scale for Depression (HAM-D) (n=6).
FL Oso´rio et al.16
Rev Bras Psiquiatr. 2015;37(1)
effect was considered by patients as an integral part of
the effects produced by AYA. Patients did not consider
vomiting as causing severe discomfort.
Discussion
The results of the present investigation demonstrate that
AYA has significant and quite impressive acute antide-
pressive effects. Score reductions were observed in both
the HAM-D and MADRS scales on D1 and D7, and these
effects lasted for several days. It is noteworthy that these
changes showed a profile that was very similar across
volunteers, regardless of the prior level of depression, i.e.,
the severity of the current depressive episode. The
antidepressant potential of AYA was previously demon-
strated in a study that reported a decrease in hope-
lessness symptoms after acute AYA intake.
25
The average time necessary for the onset of therapeu-
tic action of commercially available antidepressants is
2 weeks.
3
Considering currently available medications,
the fast antidepressant action of AYA is promising, as it
may provide faster reductions in depressive symptoms.
Moreover, the antidepressant effects of AYA alkaloids
may inspire a new area of depression research.
Interestingly, symptoms increased on D14 as measured
by the HAM-D and MADRS scales, although a subsequent
significant decrease occurred on D21 in both scales.
Although increased, HAM-D scores still remained 45%
below baseline values, but this difference was nonsignifi-
cant. On the other hand, MADRS scores on D14 were
significantly increased.
The decreases and increases in depressive symptoms
after AYA administration could reflect complex intracellular
events that remain active after the acute effects of AYA
have subsided. The acute antidepressive effects of keta-
mine, for instance, may be sustained for weeks to months
and are associated with increased synaptogenesis and
spine formation, which seem to be related with increases in
brain-derived neurotrophic factor (BDNF) protein levels.
4,5
Studies conducted in rodents by our group and by others
using doses of 10-15 mg/kg harmine have demonstrated
antidepressive effects for this compound, which were
associated with increases in BDNF levels.
17,19,21
Furthermore, harmine, THH, and harmaline are potent
natural, selective, reversible, and competitive inhibitors of
Figure 3 Temporal distribution of individual scores on the Montgomery-A
˚sberg Depression Rating Scale (MADRS) (n=6).
Figure 4 Temporal distribution of scores (means from six volunteers) on the Brief Psychiatric Rating Scale (BPRS) subscales
(WR = Withdrawal-Retardation; TD = Thinking Disorder; AD = Anxious-Depression; and A = Activation). *p,0.05. Error bars
denote one standard error of the mean.
Antidepressant effects of ayahuasca 17
Rev Bras Psiquiatr. 2015;37(1)
the MAO enzyme, especially of the MAO-A subtype.
9,36
THH acts as a selective serotonin reuptake inhibitor as
well as an MAOI.
9,37
Inhibition of both systems –
–
MAO
and serotonin reuptake –
–
may result in elevated levels of
brain serotonin and other monoamines, producing anti-
depressant effects.
9,25,38
The statistically significant reductions in BPRS-AD
scores from D1 to D21 suggest that AYA produced anti-
depressive and anxiolytic effects. A previous study
reported decreased panic-related signs after acute AYA
intake.
25
AYA administration did not produce statistically sig-
nificant sensory, cognitive, or affective modifications as
assessed by the BPRS and YMRS scales. Although
nonsignificant, in the present study these effects were
observed during a period ranging from 80 to 140 min after
AYA administration, which is the time point when the
subjective effects of AYA are peaking, as are DMT
plasma levels.
8-12
The absence of statistically significant effects on
BPRS-TD scores could be explained by the DMT con-
centration found in our AYA batch (0.08 mg/mL), which is
lower than DMT doses used in previous studies that
reported significant psychotropic effects of AYA (0.53 mg/
mL DMT).
9,12
The nonsignificant effects of AYA on the
BPRS-TD subscale suggest that changes in sensory
perception and thought content may not be essential for
therapeutic effects.
AYA was well tolerated by all patients, suggesting that
it can be safely administered to depressed patients. This
result corroborates previous studies reporting a good
tolerability profile for AYA administration to healthy
volunteers.
8-12,15,25,39
In the present study, the psychoac-
tive effects of AYA were considered by participants as
mild and short-lived, corroborating the nonsignificant
effect of AYA on the BPRS-TD subscale. The nonsigni-
ficant increases in blood pressure replicate previous
findings in human studies suggesting that AYA produces
moderate cardiovascular effects.
8-12,15,25,39
Early academic research on classical hallucinogens
was designed considering the powerful influences of set
(psychological state) and setting (environment) on the
effects of this class of substances.
40
Considering this
background, in the present study volunteers were kept as
comfortable as possible, remaining seated in a recliner
in a quiet, dimly lit room throughout the experimental
session. Investigator interference was minimal, allowing
patients to concentrate on the effects of AYA. This safe
environment may have reduced the probability of
dysphoric reactions.
40
Vomiting was the only adverse effect reported by
volunteers (50%). Patients were informed before the
experimental session that vomiting was a possible effect
of AYA, as nausea and vomiting are the most frequently
reported adverse effects in clinical trials of acute AYA
administration.
8-12,15,39
In the present study, vomiting
apparently did not have a significant influence on the
antidepressive effects of AYA. Patients did not consider
this emetic effect to be a severe discomfort, a result that
is in line with previous studies of acute AYA administra-
tion to healthy volunteers, which reported that most
participants regarded their AYA experience as pleasant
despite the occurrence of vomiting.
8-12,15,39
In future studies, it would be interesting to try to reduce
the emetic effect of AYA by premedicating with an
antiemetic. However, this possibility should be explored
with caution, considering that AYA alkaloids could interact
with antiemetic drugs. Another possibility could be to
administer AYA in different formulations. Freeze-dried
AYA appears to produce less vomiting than oral
AYA.
8,11,15,39
Interestingly, variable degrees of nausea,
vomiting, and, occasionally, simultaneous diarrhea are
common in AYA rituals. In these contexts, however, these
purgative effects are considered positive and cleansing.
7
Important limitations of the present open-label study
include the small sample size, the absence of a
systematic inquiry about side effects, and the lack of
placebo and control groups. Although patients did not
spontaneously report adverse effects other than vomiting,
the lack of a systematic assessment of adverse effects
may have reduced the likelihood of registering more
subtle effects, such as impacts on cognition. Future
studies should assess the possible adverse effects of
AYA in clinical populations by using other subjective
measures, such as visual analogue scales and other
scales that measure hallucinogenic effects, and by
exploring other variables that could be modified by AYA
administration as reported in previous studies, such as
neuropsychological, neurophysiological, autonomic, neu-
roendocrine, and immunological parameters.
8,10,11,14,15
Ideally, future studies involving AYA and depressed
patients or other clinical populations should also be
designed to include a control group. This group could
receive a placebo, a comparator drug with an established
therapeutic indication, or AYA preceded by pretreatment
with a 5-HT
2A
receptor antagonist to investigate possible
Table 2 Systolic/diastolic blood pressure measurements in patients with recurrent major depressive disorder (n=5)*
Mean 6SD Median Minimum Maximum
SBP (baseline) 118614.83 120 100 140
SBP (140 min) 119623.02 120 85 150
DBP (baseline) 79.469.31 80 70 90
DBP (140 min) 76.4613.74 80 60 90
HR (baseline) 78611.48 78 68 96
HR (140 min) 72.267.69 70 64 84
DBP = diastolic blood pressure; HR = heart rate; SBP = systolic blood pressure; SD = standard deviation.
*Data missing for one patient.
The 140-min time point was chosen because the subjective effects of AYA peak around this time, as do DMT plasma levels.
8-12
All blood
pressure values expressed in mmHg. HR values expressed in beats per minute.
FL Oso´rio et al.18
Rev Bras Psiquiatr. 2015;37(1)
mechanisms of action. Regarding the small number of
patients, additional studies with larger sample sizes and
using neuroimaging techniques (single photon emission
tomography, SPECT) are underway in our laboratory.
The aforementioned limitations should be considered
taking into account the novelty of this research and
its preliminary nature. To our knowledge, the use of AYA
in a controlled clinical setting in patients with current
depression –
–
or in any other clinical population –
–
has
never been investigated. Moreover, the results of the
present study, although preliminary, are corroborated
by mounting research showing antidepressive potentials
for AYA alkaloids in nonhuman animals
16-24
and in
humans.
13,25,26
Finally, the reported results may prompt novel research
into substances with faster therapeutic actions than
currently available pharmacological resources, thus mak-
ing antidepressive treatment more effective.
The findings of this preliminary study demonstrate the
potential antidepressant and anxiolytic effects of AYA,
effects that, importantly, have an earlier onset of action
when compared to traditional antidepressants. These
findings suggest that AYA may represent a powerful new
substance for the treatment of depressive and anxiety
symptoms. However, these results deserve careful
analysis, given the inherent limitations of an uncontrolled,
open-label study with a small sample size. Other studies
are needed to replicate these preliminary observations
and to test, for example, the most effective dose (or
doses) of AYA and the safety, tolerability, and effective-
ness of AYA administration over a longer period of time.
Acknowledgements
This study was conducted at the Department of
Neurosciences and Behavior, Ribeira˜ o Preto Medical
School, Universidade de Sa˜ o Paulo, Ribeira˜ o Preto,
Brazil. RFS is a Fellow of the Science without Borders
Program, Brazil (process no. 245447/2012-1).
Disclosure
The authors report no conflicts of interest.
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