ArticlePDF Available

Abstract and Figures

A substance extracted from the Amazonian vine Banisteriopsis caapi was shown in the 1920s to alleviate parkinsonism. These pioneering studies were criticized and forgotten for a number of reasons, including questions as to the identity of the active agent and failure to conduct strictly controlled studies. We now report the first double-blind, randomized placebo-controlled trial of a Banisteriopsis caapi (BC) extract for treatment of Parkinson's disease (PD). A single dose of BC administered to de novo PD patients resulted in significant improvement in motor function evidenced by decline in the Unified Parkinson's Disease Rating Scale (UPDRS) score. The beneficial effects were maximal by the second hour and persisted until the last evaluation of the patients at 4 hours. However, tremor was not improved and in some patients tremor was exacerbated. All patients also experienced a degree of transient nausea or vomiting. We measured the concentrations of the putative active agents (harmine, harmaline, and tetrahydroharmaline), and hypothesize that the beneficial effects were primarily due to glutamate receptor antagonist actions of the harmalines.
Content may be subject to copyright.
Abstract. A substance extracted from the Amazonian
vine Banisteriopsis caapi was shown in the 1920s to alle-
viate parkinsonism. These pioneering studies were crit-
icized and forgotten for a number of reasons, including
questions as to the identity of the active agent and
failure to conduct strictly controlled studies. We now re-
port the first double-blind, randomized placebo-con-
trolled trial of a Banisteriopsis caapi (BC) extract for treat-
ment of Parkinson’s disease (PD). A single dose of BC
administered to de novo PD patients resulted in signifi-
cant improvement in motor function evidenced by de-
cline in the Unified Parkinson’s Disease Rating Scale
(UPDRS) score. The beneficial effects were maximal by
the second hour and persisted until the last evaluation of
the patients at 4 hours. However, tremor was not im-
proved and in some patients tremor was exacerbated.
All patients also experienced a degree of transient
nausea or vomiting. We measured the concentrations of
the putative active agents (harmine, harmaline, and
tetrahydroharmaline), and hypothesize that the benefi-
cial effects were primarily due to glutamate receptor an-
tagonist actions of the harmalines.
Marcos Serrano-Dueñas, MD, is in the Neurology Service of Carlos Andrade
Marín Hospital in Quito, Ecuador. Fernando Cardozo-Pelaez, PhD, and Juan R.
Sánchez-Ramos, PhD, MD, are in the Department of Neurology at the Univer-
sity of South Florida in Tampa, Florida. E-mail:
Supported in part by the Helen Ellis Research Fund.
Vol. 5, No. 3 (Summer 2001)
Marcos Serrano-Dueñas, Fernando Cardozo-Pelaez,
and Juan R. Sánchez-Ramos
combination of two plants, the vine Banisteri-
opsis caapi (BC) and the leaves of other plants, most
commonly Psychotria viridis, which contains the hallu-
cinogen dimethyltryptamine (DMT). Ayahuasca
(known as hoasca in Brazil, Yage in Colombia, and Caapi
in other parts of the Amazon basin), has a long history
of use in medico-magical-religious ceremonies by natives
of the Amazonian rain forests.1,2 More recently,
ayahuasca has been used as a religious sacrament by two
state-approved churches in Brazil (Uniao do Vegetal and
Church of Santo Daime). The banisteriopsis vine con-
tains contains
-carbolines such as harmine, harmaline,
and tetrahydroharmine,3,4,5 which normally do not pro-
duce the desired psychotropic effects unless they are used
with the DMT-containing plant. When taken orally,
DMT is metabolized by monoamine oxidase (MAO) and
is inactive, but the combination of DMT and the MAO
inhibitor banisterine results in psychotropic effects.
The active agent of the banisteriopsis vine was iden-
tified by Louis Lewin, who named it banisterine. Based on
the subjective sensations experienced by Lewin following
self-adminstration, he recommended it for treatment of
rigid-akinetic syndromes in the late 1920s in Germany;4
all the reports mention improvement in rigidity, but con-
flicting results regarding tremor. Rustige also noted im-
provement in mood and affect. Later, Halpern studied
the subjective effects on herself, and noted a sensation of
lightness of body and a belligerent, aggressive mood.
Original Research
From the 1930s to the present, the use of banisterine in
treatment of PD has been virtually forgotten.
One of us (MS-D) had previously evaluated 13 pa-
tients who admitted use of ayahuasca occasionally (every
5 or 6 months), and who felt it helped alleviate the signs
and symptoms of PD. In 4 of these patients we were able
to directly observe the effects of consumption of
ayahuasca. In one of these, extract of Banisteriopsis caapi
(BC) was taken alone (no admixture of plants) and in
the other 3 patients, the admixture of plants was in-
gested. Approximately 20 minutes after ingestion of the
beverage, there was an improvement in rigidity with ex-
acerbation of tremor and appearance of abnormal invol-
untary movements as well as the induction of a halluci-
natory state. The motor effects and hallucinations were
much less evident in the single patient who took only
the BC extract.
L-dopa is the gold standard of PD treatment, but its
use is limited by the development of motor complica-
tions, including dyskinesias, in 30 to 80% of chronically
treated patients.6As a result, additional therapies have
been developed that increase and stabilize synaptic
levels of dopamine without augmenting the adminis-
tered dosage of L-dopa, as for example by inhibiting
dopamine metabolism with MAO inhibitors or with cat-
echol-O-methyl transferase inhibitors.7,8
Based on the remarkable effects of banisterine re-
ported in the late 1920s and the dramatic effects noted
in the few patients described above, we undertook a
double-blind, randomized, placebo-controlled study of
the acute effects of a single dose of BC extract in a co-
hort of 30 de novo PD patients.
Thirty consecutive patients with newly diagnosed PD
were selected (using diagnostic criteria of Calne et al.9)
from the Neurology Service of Carlos Andrade Marín
Hospital in Quito, Ecuador. The patients were randomly
assigned to receive either banisteriopsis extract or
placebo tea (Figure 1).
All patients underwent assessment of higher cor-
tical functions with the Short Test of Mental Status
(STMS);10the Hamilton test for depression (HT);11cra-
nial CT; serum chemistry (urea, creatinine, and glucose);
hepatic enzymes (GOT, GPT, GGT); and cardiac eval-
uation including EKG.
Patients who scored more than 50% on the HT, who
scored less than 29 points on the STMS, or who exhib-
ited anomalies on the serum tests or cardiac evaluation
were excluded from the study.
BC was prepared as a liquid extract 12 hours before
administration in a standard manner: 50 g (dry weight)
of the vine was chopped into small fragments, and added
to 1500 mL of water, brought to boiling for four hours
Figure 1. Double-Blind, Placebo-Controlled Trial of a Single Dose of
Banisteriopsis caapi Extract for Treatment of Parkinson’s Disease
Consecutive de novo patients (n = 30)
Not Randomized (n= 0)
Single dose placebo tea (n= 15) Single dose banisteriopsis extract (n= 15)
Examined at 1, 2, and 4 hrs (n= 15) Examined at 1, 2, and 4 hrs (n= 15)
Withdrawn from study (n= 0) Withdrawn from study (n= 0)
until the volume was reduced to 200 mL. The solution
was filtered and adminstered in that form.
All patients came to the clinic fasting and received
200 mL of either the BC solution (BC) or placebo (P),
which consisted of 200 mL of manzanilla tea. Patients
were not allowed to eat or drink anything but water
during the course of the session.
Patients were evaluated using the motor component
of the Unified Parkinson’s Disease Rating Scale
(UPDRS)12before (baseline) and 60, 120, and 240 min-
utes after ingesting the test infusions (questions 3, 4, 9,
11, 14, 17, 32–39, and 41 of the UPDRS were not in-
cluded). Analysis of variance (ANOVA) of the data fol-
lowed by Bonferroni corrections for multiple compar-
isons was performed. An value of 0.05 was chosen and
p< 0.0125 was considered statistically significant.13
This protocol was approved by the Department of
Docencia and Research of the Andrade Marín Hospital
in Quito, Ecuador. All patients provided informed con-
Measurement of harmala alkaloids
in Banisteriopsis caapi extract
Analysis of the levels of harmala alkaloids (harmine,
harmaline, and tetrahydroharmine) present in the ban-
isteriopsis extract was performed as described previously3
with certain modifications. HPLC system: The mobile
phase was 100 mM ammonium acetate, pH 6.9, with
20% methanol and 20% acetonitrile. Flow rate was kept
at 1 mL/min using a BAS 200 series pump (BAS, W.
Lafayette, Ind, USA). The mixture of harmala alkaloids
was separated using a reverse phase YMCbasic HPLC
column (4.6 ×150 mm) with a 3-micron particle size
(YMC Inc., Wilmington, NC, USA). Harmine and har-
maline were purchased from Sigma Chemical Co. (St.
Louis, Mo, USA). Tetrahydroharmine was produced
from the reduction of harmaline with sodium borohy-
dride, as described previously.3Harmine, harmaline, and
tetrahydroharmine were detected using a LS-3B fluores-
cent detector (Perkin Elmer, Norwalk, Conn, USA).
Harmine was detected using a wavelength of 300 nm for
excitation and 360 nm for emission. Harmaline and
tetrahydroharmine were detected with wavelengths of
340 nm and 480 nm for excitation and emission, re-
spectively. A calibration curve was constructed with
known amounts of the 3 compounds and the area of the
peaks was recorded and compared to the areas produced
by the injection of the Banisteriopsis caapi extract. Levels
of harmala alkaloids were expressed as micrograms per
milliliter of extract.
The average age of the BC group was 67 ± 8.3 years and
the P group averaged 62.9 ± 7 years of age. Median du-
ration of disease was 24.8 ± 12 months in the BC group
and 25 ± 7.7 months in the P group. Fifteen patients
were male and 15 female (Table 1).
At baseline, the mean UPDRS score in the BC
group was 54.4, and 53.8 for the P group (p < 0.4). The
UPDRS scores at 60, 120, and 240 minutes were 41.4 in
the BC group compared to 46.4 in the P group; 22.4 in
the BC group compared to 52.5 in the P group; and 25.6
in the BC group compared to 53 in the P group, respec-
tively. These differences were statistically significant (p
< 0.0004; p< 0.0001; p< 0.0001) (Table 2).
Side effects were noted only in the BC group.
Nausea or vomiting was noted in 100% of the BC pa-
tients, diarrhea in 53.3%, agitation in 26.6%, and 1 pa-
tient experienced transient hallucinations. All of the
patients in the BC group experienced an exacerbation of
their resting tremor and, in addition, postural and action
tremor. Abnormal involuntary movements, choreiform
in nature, were also noted (Table 3).
Analysis of the Banisteriopsis caapi extract yielded
the following levels of harmala alkaloids (mean ± sem):
harmine 418.44 ± 11.78 mg/mL, harmaline 173.03 ±
4.13 mg/mL, and tetrahydroharmine 382.40 ± 8.38
Serrano-Dueñas, Cardozo-Pelaez, and Sánchez-Ramos: Effects of Banisteriopsis caapi Extract on Parkinson’s Disease
Table 1. Patient Characteristics
# of patients 15 15
Age mean 67 62.9
(years) SD 8.3 7
range 49–81 53–76
Duration mean 24.8 25
(months) SD 12.7 7.7
range 14–36 15–38
Depression mean 35.3 33
HT SD 10.5 10.4
(%) range 15–50 15–50
Dementia mean 34.2 33.9
STMS SD 2.4 2.3
(points) range 30–38 30–38
HT = Hamilton Scale
STMS = Short Test of Mental Status
BC = Banisteriopsis caapi Group
P = Placebo Group
In this double-blind, randomized, placebo-controlled
trial, we demonstrated that a single dose of BC adminis-
tered to de novo PD patients resulted in significant im-
provement in motor function evidenced by decline in
the motor component of the UPDRS score. The benefi-
cial effects were noted by 1 hour and motor function
continued to improve for the 4 hours during which the
patients were studied. However, all patients who re-
ceived BC experienced a worsening of resting tremor
and the development of action and postural tremors,
with some abnormal choreiform movements. All pa-
tients also experienced a degree of transient nausea or
vomiting. With the exception of the single patient who
experienced confusion and hallucinations, these side ef-
fects were much less severe than those experienced by
users of the complete ayahuasca beverage.
The levels of harmaline in the banisteriopsis extract
ingested by the subjects in this study were almost iden-
tical to those measured by Callaway and colleagues in
the preparations of ayahusaca used by members of the
Uniao de Vegetal in Brazil.3However, the mean harmine
and tetrahydroharmine levels were 25% and 35%, re-
spectively, of the levels measured in their Brazilian sub-
Table 2. Analysis of Variance of UPDRS (Baseline versus 1st, 2nd and 3rd in BC compared to P)
Evaluations Evaluations
B 1st 2nd 3rd B 1st 2nd 3rd
Mean 54.4 41.4 22.4 25.6 53.8 46.4 52.5 53
DS 3.8 2.9 3.6 0.7 2.8 2.8 4.2 1.4
Range 47–61 37–46 16–28 19–33 49–57 40–52 46–57 47–57
Variance 14.6 8.6 13.4 13.9 4.6 14.5 8.9 7.1
B vs. 1st B vs. 2nd B vs. 3rd B vs. 1st B vs. 2nd B vs. 3rd
F statistic 109.2 548.5 436.5 6.5 1.8 0.8
p< 0.001 0.0001 0.0001 0.01 0.1 0.3
BC vs. P
B vs. B 1st vs. 1st 2nd vs. 2nd 3rd vs. 3rd
F statistic 0.5 15.5 609 536.2
p< 0.4 0.0004 0.0001 0.0001
UPDRS (items excluded: 3, 4, 9, 11, 13, 14, 17, 32, 33, 34, 35, 36, 37, 38, 39, and 41)
p< 0.01 is statistically significant
BC = Banisteriopsis caapi group
P = Placebo group
B = baseline
Table 3. Adverse Effects
Nausea or vomiting m 8 of 15
s 7 of 15
total 15 of 15 = 100%
Dizziness m 6 of 15
s 6 of 15
total 12 of 15 = 80%
Diarrhea m 3 of 15
s 5 of 15
total 8 of 15 = 53.3 %
Pyschomotor agitation m 2 of 15
s 2 of 15
total 4 of 15 = 26.6%
Confusion 1 of 15 = 6.6%
Hallucinations 1 of 15 = 6.6%
AIMs m 8 of 15
Exacerb. Tremor s 7 of 15
m= moderate, s= severe
AIMS = abnormal involuntary movements
jects, who ingested the complete brew prepared from a
combination of plants.3The proportion of banisteriopsis
vine to Psychtria viridis leaves and the exact methods for
preparation of the brew were not noted in the Callaway
In the shamanic use of ayahuasca for religious, mag-
ical, or healing purposes, the infusion is prepared from a
mixture of plants. A critical component of the shamanic
beverage is the presence of the DMT-containing Psy-
chotria viridis.1,2,3 DMT is a potent hallucinogen when
given systemically or when smoked; when taken orally,
it is inactive due to its metabolism by gut and liver
MAO. BC is an inhibitor of MAO and, when ingested
orally with DMT-containing plants, allows the DMT to
produce a range of psychotropic effects, with prominent
visions, hallucinations, and illusions.1,2,5
The dramatic improvement in signs and symptoms
of PD produced by the extract of BC may be due to a
combination of two known mechanisms of action of the
harmalines, the putative active agents. Harmaline, a b-
carboline compound with a structural resemblance to
serotonin, is a known nonselective inhibitor of MAO.14
MAO inhibitors can potentiate the actions of endoge-
nous dopamine, but the symptomatic benefits in PD are
very mild, as evidenced by the study of deprenyl in de
novo patients.15 It is difficult to conceive that the dra-
matic improvement produced by BC can be due solely to
MAO inhibition. It is possible that the interaction of
harmaline at glutamatergic receptors plays a significant
role in restoring motor function in PD. Harmaline has
been shown to be an NMDA receptor antagonist.16 Har-
maline displaces [3H]MK-801, which binds to the cation
channel of the NMDA receptor, from membranes pre-
pared from rabbit brain tissue.16
Glutamate is an excitatory amino acid that plays a
role in the symptomatic expression of PD17 and that has
also been implicated in the process of neurodegeneration
of dopaminergic neurons of the substantia nigra.18 When
dopamine deficiency develops, the adaptive changes in
the striatal outflow pathways result in disinhibition of
the subthalamic nucleus. In turn, the hyperactive sub-
thalamic-pallidal glutamate projection results in de-
creased outflow from globus pallidus internal segment
(GP-int) to thalamus, to produce the clinical manifes-
tations of slowness and rigidity.19 Blockage of gluta-
matergic receptors corrects the imbalance that results
from dopamine deficiency and helps restore normal
motor function.20 In the rat, local infusion of NMDA re-
ceptor antagonists to the GP-int/SNr has been shown to
reverse the signs of parkinsonism.21 In both rats and pri-
mates, the NMDA receptor antagonist LY235959 has
been shown to potentiate the antiparkinson effects of
L-dopa, to stabilize the motor fluctuations and to alle-
viate choreiform dyskinesias. However, MK-801, a glu-
tamate NMDA receptor antagonist with hallucinogenic
side effects (similar to phencyclidine and ketamine) has
been reported to induce dystonia when used with L-dopa
in a primate model of parkinsonism.21In naive rats, MK-
801 increases locomotor activity and potentiates the
motor effects of L-dopa.23The AMPA antagonist NBZX
(2,3- dihydroxy-6-intro-7-sulfamoil-benzo-9[f]quinoxa -
line) im proved tremor, posture, and manual dexterity in
parkinsonian monkeys.24When glutamate antagonists
are given together with L-dopa, the dosage of L-dopa can
be greatly reduced without lessening motor function.20,24
To conclude, we suggest that the antiglutamate actions
of harmaline are most likely responsible for the anti -
parkinson effects observed in the BC group of patients.
The transient worsening of tremor and induction of
postural and action tremor by banisterine has been been
noted before by early investigators and, in fact, harma-
line was used in the 1960s to study the mechanism of ac-
tion tremor that could be induced by harmaline in pri-
Interestingly, L-dopa-induced dyskinesias are associ-
ated with a decrease in the activity of the glutamatergic
projection to the GP-int. Paradoxically, glutamatergic
receptors are apparently involved in these dyskinesias,
since adminstration of glutamate antagonists (of the
NMDA receptor subtype) have been shown to be useful
in controlling L-dopa-induced dyskinesias.20
There is little concern for the possibility that the
harmalines in the ayahuasca tea are cytotoxic at con-
centrations found in the tea. Harmaline and a related b-
carboline, ibogaine, are cytotoxic in rats only following
extremely high doses of 100 mg/kg or 100 mg/kg ×3.
Two recent studies clearly demonstrated that even lower
doses (25 and 40 mg/kg) given to rats did not produce
Purkinje cell degeneration.25,26
To summarize, extracts of BC were shown to have
remarkable symptomatic benefit in drug-naive de novo
patients. This was the first double-blind, randomized,
placebo-controlled trial of a BC extract for treatment of
PD. Studies with banisterine done in the late 1920s were
criticized because the benefits were believed by many to
be psychological. We measured the concentrations of
the putative active agents, and hypothesize that the ben-
eficial effects were primarily due to glutamate receptor
antagonist actions of the harmalines. The most common
side effect was transient nausea/vomiting, which could in
the future be prevented by pretreatment with domperi-
done. Hallucinations in a single case may reflect a higher
Serrano-Dueñas, Cardozo-Pelaez, and Sánchez-Ramos: Effects of Banisteriopsis caapi Extract on Parkinson’s Disease
sensitivity in that patient to the NMDA receptor an-
tagonists. A complete dose-response study needs to be
done in human volunteers in order to determine the op-
timal concentrations of b-carbolines to produce max-
imal symptomatic relief and minimal side effects.
11. Ayala Flores F, Lewis WH. Drinking the South
American hallucinogenic ayahuasca. Econ Botany. 1978;32:
12. Bennett BC. Hallucinogenic plants of the Shuar and
related indigenous groups in Amazonian Ecuador and Peru.
Brittonia. 1992;44:483–493.
13. Callaway JC, Raymon LP, Hearn WL, et al. Quanti-
tation of N,N-dimethyltryptamine and Harmala Alkaloids in
Human Plasma after Oral Dosing with Ayahuasca. J Anal Tox-
icol. 1996,20:492–498.
14. Sanchez-Ramos JR. Banisterine and Parkinson’s dis-
ease. Clin Neuropharmacol. 1991;14:391–402.
15. McKenna DJ, Towers GH, Abbott F. Monoamine ox-
idase inhibitors in South American hallucinogenic plants:
tryptamine and beta-carboline constituents of ayahuasca. J
Ethnopharmacol. 1984:10;195–223.
16. Bédard PJ, Blanchet PJ, Lévesque D, et al. Patho-
physiology of L-dopa-induced dyskinesias. Mov Disord. 1999;
14(Suppl 1):s4–s8.
17. Lang AE, Lozano AM. Parkinson’s disease. First of
two parts. N Engl J Med. 1998;339:1044–1053.
18. Lang AE, Lozano AM. Parkinson’s disease. Second of
two parts. N Engl J Med. 1998;339:1130–1143
19. Calne DB, Snow DB, Lee C. Criteria for diagnosis in
Parkinson’s disease. Ann Neurol. 1992;32:125–127.
10. Kokmen E, Naessens JM, Offord KP. A Short test of
mental status: description and preliminary results. Mayo Clin
Proc. 1987;62:281–288.
11. Hamilton M. A rating scale for depression. J Neurol
Neurosurg Psychiatry. 1960;23:56–62.
12. Fahn S, Elton RL, and members of The UPDRS de-
velopment committee. Unified Parkinson’s disease rating
scale. In: Fahn S, Marsden CD, Goldstein M, Calne DB, eds.
Recent Development in Parkinsons Disease. Vol. 2. Florham
Park, NJ: MacMillan; 1987:153–163.
13. Dawson-Saunders B, Trapp RG. Bioestadística Médica.
México DF: Editorial El Manual Moderno, 1993 [Basic and
Clinical Biostatics. Trans. Carsolio M. New York, NY: Appleton
& Lange; 1990].
14. Udenfriend S, Witkop B, Redfield BG, Weissbach
H. Studies with reversible inhibitors of monoamine oxidase:
harmaline and related compounds. Biochem Pharmacol.
15. Parkinson Study Group Effects of tocopherol and de-
prenyl on the progression of disability in early Parkinson’s dis-
ease. N Engl J Med. 1993;328:176–183.
16. Du W, Aloyo VJ, Harvey JA. Harmaline competi-
tively inhibits [3H]MK-801 binding to the NMDA receptor in
rabbit brain. Brain Res. 1997;770(1–2):26–29.
17. Ciliax BJ, Greenamyre T, Levey AI. Functional, bio-
chemistry and molecular neuropharmacology of the basal gan-
glia and motor systems. In: Watts RL, Koller WC. Movement
Disorders. Neurologic Principles and Practice. New York, NY:
McGraw-Hill; 1997:99–116.
18. Olanow CW, Jenner P, Tatton NA, Tatton WG.
Neurodegeneration and Parkinson’s disease. In: Jankovic J,
Tolosa E. Parkinson’s Disease and Movement Disorders. 3d ed.
Baltimore, Md: Williams & Kilkins; 1998:67–103.
19. Young AB, Penney JB Jr. Biochemical and functional
organization of the basal ganglia. In: Jankovic J, Tolosa E.
Parkinson’s Disease and Movement Disorders. 3rd ed. Baltimore,
Md: Williams & Kilkins; 1998:1–13.
20. Blandini F, Greenamyre JT. Prospects of glutamate
antagonists in the therapy of Parkinson’s disease. Fundam Clin
Pharmacol. 1998;12:4–12.
21. Ossowska K, Lorenc-Koci E, Konieczny J, Wolfarth S.
The role of striatal glutamate receptors in models of Parkin -
son’s disease. Amino Acids. 1998;14:11–15.
22. Starr MS. Antagonists of glutamate in the treatment
of Parkinson’s disease: from laboratory to the clinic. Amino
Acids. 1998;14:41–42.
23. Liljequist S, Ossowska K, Grabowska-Anden M,
Anden NE. Effect of the NMDA receptor antagonist, MK-
801, on locomotor activity and on the metabolism of
dopamine in various brain areas of mice. Eur J Pharmacol.
24. Lange KW, Reiderer P. Glutamatergic drugs in
Parkinson’s disease. Life Sciences. 1994;55:2067–2075.
25. Poirier LJ. The development of animal models for
studies in Parkinson’s disease. In: McDowell FH, Markham
CH, eds. Recent Advances in Parkinson’s Disease. Philadelphia,
Pa: F. A. Davis Co; 1971:83–118.
26. Molinari HH, Maisonneuve IM, Glick SD. Ibogaine
neurotoxicity: a re-evaluation. Brain Res. 1996;737(1–
27. Xu Z, Chang LW, Slikker W Jr, Ali SF, Rountree RL,
Scallet AC. A dose-response study of ibogaine-induced neu-
ropathology in the rat cerebellum. Toxicol Sci. 2000;57(1):
... Concerning the presence of beta-carbolines in the brew, these substances (especially harmine) have been investigated regarding their possible therapeutic effects such as in the treatment of Parkinson's disease due to their dopaminergic neurotransmission modulation [59][60][61]. From a toxicological perspective, betacarbolines administrated individually and in B. caapi extracts have been shown to cause hyperthermia, tingling sensations, nausea, vomiting, tremors, and learning and memory deficits [59,[62][63][64]. Furthermore, by inhibiting MAO-A function, drugdrug interactions may be more prone to happen with ayahuasca than with other psychedelics, especially concerning the metabolism of potentially toxic monoamines such as tyramine [65]. ...
... Concerning the presence of beta-carbolines in the brew, these substances (especially harmine) have been investigated regarding their possible therapeutic effects such as in the treatment of Parkinson's disease due to their dopaminergic neurotransmission modulation [59][60][61]. From a toxicological perspective, betacarbolines administrated individually and in B. caapi extracts have been shown to cause hyperthermia, tingling sensations, nausea, vomiting, tremors, and learning and memory deficits [59,[62][63][64]. Furthermore, by inhibiting MAO-A function, drugdrug interactions may be more prone to happen with ayahuasca than with other psychedelics, especially concerning the metabolism of potentially toxic monoamines such as tyramine [65]. ...
... Given this inhibition, concomitant consumption of ayahuasca with substances that are metabolized by these enzymes should also be avoided. Finally, harmine and harmaline have been demonstrated to be capable of modulating cholinergic, GABAergic, and glutamatergic neurotransmission, imbuing them, and ultimately ayahuasca, with a complex pharmacological synergy that has yet to be fully understood with regard to its relationship to the AEs and therapeutic effects induced by these substances [59,67,68]. ...
Introduction: Ayahuasca is a psychedelic brew originally used by indigenous tribes from the Amazon Rainforest and in religious rituals. Pre-clinical and observational studies have demonstrated its possible potential as an antidepressant, and open and placebo-controlled clinical trials corroborated these results. For it to become an approved treatment for depression, its safety and tolerability need to be assessed and documented. Areas covered: We have gathered data regarding occurrence of adverse events (AEs) in all reported randomized, placebo-controlled trials with healthy and clinical populations involving ayahuasca administration (n = 108 ayahuasca administrations). We systematically categorized these results, recorded their prevalence and discussed the possible mechanisms related to their emergence. Expert opinion: : There were no reports of serious AEs, indicating a relative safety of ayahuasca administration in controlled settings. Most common AEs related to ayahuasca administration included nausea, vomiting, headaches and transient increases in cardiovascular measurements. Ayahuasca research is still in its infancy, especially concerning the absence of large and robust clinical trials to verify its antidepressant effects. Dose standardization, legal prohibition of the possession of its alkaloids and how traditional communities will be compensated if ayahuasca becomes an approved medicine are the biggest obstacles to overcome for its future use in the therapeutic context.
... To overcome the comorbids in PD, i.e., depression and insomnia, clinical studies are going on Ginkgo biloba and Valerian officinalis, respectively, with adjunct to Xiaoyao pill, i.e., Bupleurum species (herb). In the clinical prospective study bySerrano-Dueñas et al. (2001), a randomized, double-blind, placebo-controlled trial of a Banisteriopsis caapi (BC) was carried out for the treatment of Parkinson's patients. After a single dose of BC administration, a significant decline is noted in the motor component of the "Unified Parkinson's Disease Rating Scale" score. ...
... Harmaline, a b-carboline compound, acts as a nonselective inhibitor of MAO, which can potentiate the actions of endogenous dopamine. Along with MAO inhibition, modulation of glutamatergic receptors is also reported to be beneficial in restoring motor function in PD(Serrano- Dueñas et al. 2001). ...
Full-text available
Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons, leading to misbalance and loss of coordination. Current therapies are claimed only for symptomatic relief, on long-term use, which causes alteration in basal ganglia, and give rise to various adverse effects like dyskinesia and extra pyramidal side effects, which is reversed and proved to be attenuated with the help of various herbal approaches. Therefore, in order to attenuate the dopaminergic complications, focus of current research has been shifted from dopaminergic to non-dopaminergic strategies. Herbs and herbal remedies seems to be a better option to overcome the complications associated with current dopaminergic therapies. In recent years, various herbs and herbal remedies based on Ayurveda, traditional Chinese and Korean remedies, have become the target of various researches. These herbs and their bioactive compound are being extensively used to treat PD in India, China, Japan, and Korea. The major focus of this current review is to analyze preclinical studies with reference to various herbs, bioactive compounds, and traditional remedies for the management of Parkinson disorder, which will give an insight towards clinical trials.
... These mixed results and the perceived weaker efficacy than solanaceous alkaloids (scopolamine, hyoscine) led to the abandonment of the studies ( Djamshidian et al., 2016 ;Sanchez-Ramos, 1991 ). More recently, in patients with Parkinson's disease, motor function improved in the B. caapi group (n = 15) compared to the placebo group (n = 15) with strongest effects after two hours lasting up to four hours; however, all patients receiving B. caapi showed tremor worsening and side effects (e.g., diarrhea, nausea) ( Serrano-Dueñas et al., 2001 ). ...
The therapeutic potential of the psychedelic brew ayahuasca has been investigated in preclinical and clinical studies. Currently, the most consistent evidence refers to depression. However, various studies suggest that ayahuasca may comprise therapeutic benefits in other health conditions. This narrative review provides a comprehensive, up-to-date overview of ayahuasca's therapeutic effects in diverse clinical conditions in human (clinical, cross-sectional, observational, and qualitative) and preclinical (animal and in vitro) studies. In addition to summarizing and discussing the most commonly studied conditions, such as depression, anxiety, and substance use disorders (SUD), we also examine less frequently studied psychiatric, neurological, and physical conditions. Moreover, we discuss evidence from epidemiological studies on the impact of regular, long-term ayahuasca use on health and psychosocial outcomes. Overall, evidence for depression and SUD is more consistent, with numerous and diverse studies. However, a growing body of evidence suggests that other conditions equally relevant to public health might be promising targets for ayahuasca's therapeutic effects. This includes preliminary studies indicating potential for grief, eating disorders, posttraumatic stress disorder, personality disorders, Parkinson's and Alzheimer's disease, and severe physical illnesses (e.g., cancer, chronic conditions). Moreover, preliminary evidence in long-term ayahuasca users does not suggest detrimental effects but possible benefits for individual and collective health. In light of the emerging evidence of psychedelic drugs as therapeutic agents, it is essential to further investigate in rigorous designs the therapeutic potential of ayahuasca in conditions other than depression.
... Also known as daime, vegetal, hoasca, caapi, natema, yagé/yajé/iajé or pindé, this beverage was originally used as a sacrament to elevate the state of consciousness by indigenous populations of the Amazon Basin and, nowadays, it is widespread among all continents (McKenna, 2004;Teixeira et al., 2008;Meneguetti and Meneguetti, 2014;Frecska et al., 2016;Oliveira et al., 2018). With the use of Ayahuasca, significant improvements have been reported for many neurological pathologies and even in drug addiction rehabilitation (Serrano-Dueñas et al., 2001;McKenna, 2004, Santos et al., 2007. ...
Ayahuasca is a traditional psychoactive beverage with pharmaceutical potential, prepared with Banisteriopsis caapi and Psychotria viridis, although the use of non-traditional plants - the so-called “Ayahuasca analogues” -, such as Banisteriopsis and related species, are also reported. These species are highly polymorphic and inconsistent in flowering periods, being difficult to identify when collecting to prepare the brew. To aid their separation in a vegetative state, some species used in Ayahuasca analogues (B. laevifolia, B. muricata and Diplopterys pubipetala) were characterized in their wood, outer bark, and leaf morphoanatomy. We also verified whether their use is supported by histochemical data and investigated other compounds of pharmaceutical importance, in comparison with B. caapi. Usual techniques and methodology were used for histochemical and histological investigations, in addition to X-ray imaging for examining crystal organization and venation patterns. The wood anatomy descriptions of these species are given for the first time, and new characters were described, such as the tangential alignment of prismatic crystals in ray cells of D. pubipetala. Vegetative characters aid the species identification when reproductive material is unavailable, as the species differed in outer bark morphology, leaf morphology and anatomy and wood anatomy. Statistical analyses based on qualitative and quantitative anatomical features reinforce the recent distinction of Banisteriopsis and Diplopterys genera. Histochemical analyses revealed the presence of important compounds of potential pharmacological use: alkaloids, saponins, essential oils, lipids, pectin, tannins and general phenolic compounds, mostly in parenchymatous tissues in the bark and lesser in the wood. Alkaloids found mainly in the bark support the use of these plants in Ayahuasca analogues, although further studies are needed to ensure its safety and to exploit their pharmacological potential. It also raises an alternative extraction technique that could use solely strips of bark for small preparations of Ayahuasca, allowing for sustainable plant management.
Full-text available
Ayahuasca is a psychoactive Amazonian plant brew. It is usually made from the Banisteriopsis caapi vine (Spruce ex Griseb. Morton, Malpighiaceae), which contains three primary harmala alkaloids, along with the leaves of Psychotria viridis (Ruiz et Pavon, Rubiaceae) in which the potent psychedelic dimethyltryptamine (DMT) is found. DMT-harmaloid concoctions have gained popularity in recent years, due to growing anecdotal and scientific reports of therapeutic benefits associated with their consumption. Ayahuasca is now ingested in a variety of different settings across the globe, from traditional ethnobotanical to so called “neo-shamanic” ceremonies. Furthermore, related preparations involving alternative sources of DMT and harmala alkaloids are becoming increasingly common as knowledge of ayahuasca continues to spread internationally. This article reviews the existing literature and draws on original qualitative data from a large cross-sectional study of ayahuasca drinkers, to propose a model of psychotherapeutic processes associated with the consumption of ayahuasca. We assert that it is these processes, facilitated by a range of neurobiological effects, that lead to beneficial mental health and wellbeing outcomes. Our proposed model identifies five key psychotherapeutic processes or effects inherent to the ayahuasca experience; somatic effects; introspection and emotional processing; increased Self-connection; increased spiritual connection, and finally the gaining of insights and new perspectives. We note some important differences in these processes compared with other classic psychedelics as well as the implications of the model for the therapeutic use of ayahuasca. Improved understanding of the psychotherapeutic processes involved with the ayahuasca experience will better equip practitioners to work with this potentially transformative concoction and enable the optimization of therapeutic treatment models for potential clinical use.
Full-text available
Ayahuasca is a blend of Amazonian plants that has been used for traditional medicine by the inhabitants of this region for hundreds of years. Furthermore, this plant has been demonstrated to be a viable therapy for a variety of neurological and mental diseases. EEG experiments have found specific brain regions that changed significantly due to ayahuasca. Here, we used an EEG dataset to investigate the ability to automatically detect changes in brain activity using machine learning and complex networks. Machine learning was applied at three different levels of data abstraction: (A) the raw EEG time series, (B) the correlation of the EEG time series, and (C) the complex network measures calculated from (B). Further, at the abstraction level of (C), we developed new measures of complex networks relating to community detection. As a result, the machine learning method was able to automatically detect changes in brain activity, with case (B) showing the highest accuracy (92%), followed by (A) (88%) and (C) (83%), indicating that connectivity changes between brain regions are more important for the detection of ayahuasca. The most activated areas were the frontal and temporal lobe, which is consistent with the literature. F3 and PO4 were the most important brain connections, a significant new discovery for psychedelic literature. This connection may point to a cognitive process akin to face recognition in individuals during ayahuasca-mediated visual hallucinations. Furthermore, closeness centrality and assortativity were the most important complex network measures. These two measures are also associated with diseases such as Alzheimer's disease, indicating a possible therapeutic mechanism. Moreover, the new measures were crucial to the predictive model and suggested larger brain communities associated with the use of ayahuasca. This suggests that the dissemination of information in functional brain networks is slower when this drug is present. Overall, our methodology was able to automatically detect changes in brain activity during ayahuasca consumption and interpret how these psychedelics alter brain networks, as well as provide insights into their mechanisms of action.
Full-text available
Background Recent research suggests that ayahuasca and its alkaloid-containing ingredients may be helpful in the treatment and prevention of certain movement and neurodegenerative disorders. However, such research is still in its infancy and more studies in normative samples seem necessary to explore effects of ayahuasca on clinically relevant brain structures, such as the corpus callosum. Aims The purpose of the present study was to investigate links between ayahuasca use and callosal structure in a normative sample. Methods Using structural imaging data from 22 ayahuasca users and 22 matched controls we compared the thickness of the corpus callosum between both groups at 100 equidistant points across the entire midsagittal surface. In addition, we investigated point-wise correlations between callosal thickness and the number of past ayahuasca sessions. Results The corpus callosum was significantly thicker within the isthmus in the ayahuasca group than in the control group. There was also a significant positive correlation between callosal thickness and the number of past ayahuasca sessions within the rostral body, albeit none of these effects survived corrections for multiple comparisons. No region was significantly thicker in the control than in the ayahuasca group, and no callosal region was negatively linked to ayahuasca use, even at uncorrected significance thresholds. Conclusion This study provides preliminary evidence of links between ayahuasca use and the corpus callosum. However, future studies need to replicate these findings, preferably using larger sample sizes and ideally also utilizing longitudinal research designs, to draw any practical conclusion and offer implications for follow-up clinical research.
Background Self-renewal and proliferation of neural progenitor cells occur throughout humans' lives. However, aging, stress, and degenerative diseases can hinder or stop the process. If you can accelerate neurogenesis in adults, this is a promising way to recover from neurodegeneration and cognitive impairments. As the demand for a safer and natural therapeutic product has increased over the past decade, medicinal plants seem to be a viable alternative to synthetic medicines. Since early human civilization, various herbs have been used as medicines and are still a basis for different modern medications. With the advancements in science, researchers can isolate the active compounds in an herb and predict these herbs' line of action when used as a drug. Our current knowledge of medicinal plants with neurological functions is many, but only a few are scientifically validated. Method A review of the scientific literature explaining plants' bioactive compounds that show neurogenesis was executed. All published data till the year 2021 have been taken to consideration. PubMed, Scopus, ScienceDirect, and Google Scholar directories were used to explore literature published using relevant keywords. Results Plants like Panax ginseng, Lycium barbarum, Acorus tatarinowii, Curcuma longa, Salvia miltiorrhiza, Centella asiatica, Bacopa monnieri, Ginkgo biloba, Cuscuta japonica, Radix Astragali, Hericium erinaceus and Banisteriopsis caapi have shown to induce neurogenesis. Conclusions The information on medicinal plants compiled in this review pertains to those with a therapeutic value that can be used for drug development to cope with neurodegenerative diseases and memory impairment.
Full-text available
Peganum harmala L. contains 17 alkaloids of quinazoline and indole structure types. Of these, harmaline, harmine, harmalol and L-peganin (vazicin) are pharmacologically active. It was established that of the alkaloids contained in the seeds, 50-95% is dominated by harmaline, harmine is dominated in the roots (67-74% of the total of extractive substances), and in the aerial part, the main mass is peganin (up to 78% of the total of alkaloids). Beta-carboline alkaloids of Peganum harmala L. inhibit monoamine oxidase, thereby exerting a neuroprotective effect. This article is devoted to the results of studies of the neurotropic action of harmine hydrochloride, when compared with the activity of the reference drug “Amitriptyline”. It was shown that the use of harmine hydrochloride helps to reduce the level of anxiety in animals under conditions of experimental psychoemotional chronic stress with prolonged administration. In the study of acute and chronic toxicity, it was determined that harmine hydrochloride belongs to the category of moderately toxic substances (hazard class II). According to the results of molecular docking, the presence of strong bonds in harmine hydrochloride with the serotonin 5-HT2C receptor, dopamine D2 receptor, as well as monoamine oxidase A and B was revealed, which indicates the implementation of the mechanism of neurotropic action of harmine hydrochloride at the level of synaptic neurotransmission of monoamines (dopamine, serotonin and others). It was also established that harmine hydrochloride eliminates haloperidol-induced catalepsy in rats, reduces oligokinesia and rigidity in the Parkinson’s test, has antihypoxic activity in the hypobaric hypoxia test, and exhibits pronounced antidepressant activity in the Porsolt’s test. In the course of the study of pharmacokinetics and bioavailability, it was revealed that with the administration of harmine hydrochloride, the quantitative content is quickly achieved and the concentration of the active substance in the blood significantly increases. The relative bioavailability of harmine hydrochloride is 112.7%.
Hoppea fastigiata (Griseb.) C.B. Clarke, an annual medicinal herb belonging to Gentianaceae, is mostly found in South-Asian countries. The genus possesses a unique class of compounds called xanthones, which are known for their potential against Alzheimer’s and Parkinson’s diseases. Three major xanthones were isolated and structurally confirmed as 1,5,7-trihydroxy-3-methoxyxanthone, 1,5-dihydroxy-3,7-dimethoxyxanthone, and 1,3,5-trihydroxy-8-methoxyxanthone from the in vitro shoot cultures which showed potential inhibitions against acetylcholinesterase, monoamine oxidase A, and monoamine oxidase B enzymes. Upon treatment with different elicitors, yeast extract (YE) was found to be most effective which led to a 20-fold increase of 1,3,5-trihydroxy-8-methoxy xanthone. YE treatment caused a rapid burst of reactive oxygen species (ROS) and the subsequent increase in xanthone contents. Phenylalanine ammonia lyase activity remained suppressed and 4-coumarate: CoA ligase activity remained unaffected after elicitation. However, shikimate dehydrogenase and shikimate kinase activities increased after elicitation. This suggested phenylalanine-independent biosynthesis of xanthones. Subsequent treatment of shoots cultures with different inhibitors of superoxide radicals (O2−), hydrogen peroxide (H2O2) generation, and calcium channel was found to suppress accumulation of xanthones. Thus, calcium mediated generation of H2O2 followed by the activation of shikimate pathway enzymes is the key early step of xanthone biosynthesis in H. fastigiata.
Full-text available
Banisteriopsis caapi, Brugmansia suaveolens, andNicotiana tabacum are the principal hallucinogens used by the Shuar and related ethnic groups in Amazonian Ecuador and Peru. These three species are common hallucinogens throughout northwestern Amazonia.Banisteriopsis caapi (natem) is the hallucinogen most frequently employed by the Shuar. The Shuar drink the juice ofN. tabacum duringnatem healing ceremonies. They also believe that smoke fromN. tabacum cigarettes repel evil spirits.Brugmansia suaveolens is the strongest Shuar hallucinogen. Considered very dangerous, it sometimes is added tonatem mixtures or it may be taken alone. Other plants used in hallucinogens or in narcotic beverages includeBrunfelsia grandiflora, Cyperus spp.,Diplopterys cabrerana, Heliconia stricta, Herrania spp., andIlex guayusa.
Full-text available
It is of historical interest that 63 years ago Louis Lewin reported the use of a hallucinogenic compound prepared from the South American vine, Banisteria Caapi, to treat Parkinson's disease (PD). This psychoactive compound, named banisterine, proved to be identical to harmine, but 30 years were to pass before it was shown to be a reversible monoamine oxidase (MAO) inhibitor. The first reports of the use of banisterine to treat postencephalitic parkinsonism in 1929 created a stir in the popular press and banisterine was hailed as a "magic drug." Despite continued studies of the harmala alkaloids by other researchers, interest in the therapeutic value of these compounds vanished during the 1930's. The story of banisterine is reviewed because it was the first MAO inhibitor to be used in parkinsonism, and illustrates the historical role of psychoactive drugs in the development of effective therapies, and in elucidating the pathophysiology of PD.
Background and Methods In 1987 we began a multicenter controlled clinical trial of deprenyl (a monoamine oxidase inhibitor) and tocopherol (a component of vitamin E that traps free radicals) in the treatment of early Parkinson's disease. We randomly assigned 800 patients to one of four treatments: placebo, active tocopherol and deprenyl placebo, active deprenyl and tocopherol placebo, or both active drugs. The primary end point was the onset of disability prompting the clinical decision to begin administering levodopa. An interim analysis showed that deprenyl was beneficial . We report the results of tocopherol treatment after a mean (±SD) follow-up of 14 ±6 months, as well as the follow-up results for deprenyl. Results There was no beneficial effect of tocopherol or any interaction between tocopherol and deprenyl. The beneficial effects of deprenyl, which occurred largely during the first 12 months of treatment, remained strong and significantly delayed the onset of disability requiring levodopa therapy (hazard ratio, 0.50; 95 percent confidence interval, 0.41 to 0.62; P<0.001). The difference in the estimated median time to the end point was about nine months. The ratings for Parkinson's disease improved during the first three months of deprenyl treatment; the motor performance of deprenyl-treated patients worsened after the treatments were withdrawn. Conclusions Deprenyl (10 mg per day) but not tocopherol (2000 IU per day) delays the onset of disability associated with early, otherwise untreated Parkin-son's disease. The action of deprenyl that accounts for its beneficial effects remains unclear.
Harmaline and related compounds have been shown to be potent inhibitors of monoamine oxidase effecting 50 per cent inhibition of serotonin metabolism at 10−6 M. Inhibition is reversible both in vitro and in vivo. Procedures have been presented for evaluating the effectiveness of monoamine oxidase inhibitors bothin vitro and in vivo.
There are few first-hand reports of drinking ayahuasca by residents of Amazonia, where use is widespread. One of us (F.A.F. ), who lives in Iquitos, took ayahuasca 30 times during a three-year period between 1972 and 1974 in an attempt to experience all levels of hallucination. Although unable to achieve the ultimate goal of telepathy and extrasensory perception, this author clearly relates his repeated experiences within the three other levels of hallucination and also correlates these experiences with those of others he observed who drank ayahuasca at the same time.
It has been suggested that the excitatory amino acid glutamate, acting as both a neurotoxin and a neurotransmitter, might play a central role in the pathophysiology of Parkinson's disease (PD). Intrinsic energetic defects of the neurons of the substantia nigra pars compacta, the brain area where the degenerative process of PD takes place, may render nigral neurons highly vulnerable to the effects of glutamate, which acts as a neurotoxin in the presence of impaired cellular energy metabolism. Degeneration of dopamine nigral neurons and striatal dopaminergic denervation cause a cascade of functional modifications in the activity of basal ganglia nuclei. Due to the close relationship that links dopaminergic and glutamatergic neurotransmission, glutamate is directly involved in the functional alterations of basal ganglia circuitry that lead to the development of parkinsonian motor symptoms. Drugs counteracting the effects of glutamate might therefore provide new protective and symptomatic strategies for therapy of PD.
Parkinson's disease evolves slowly, and there is current interest in exploring the earliest stages of the disorder, because of new approaches to studying pathogenesis and developing potential neuroprotective treatment. Recognizing early Parkinson's disease is not easy. The certainty of diagnosis increases as the disease advances. To address the problem of identifying Parkinson's disease in its initial phases of clinical expression, we propose the following designated levels of confidence for the diagnosis: (1) clinically possible, (2) clinically probable, and (3) clinically definite. Laboratory support for the diagnosis may be applied to each category. Criteria are provided as a framework underpinning this classification.