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Risk Assessment of Ritual Use of Oral Dimethyltryptamine (DMT) and Harmala Alkaloids


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To extend previous reviews by assessing the acute systemic toxicity and psychological hazards of a dimethyltryptamine and beta-carboline brew (ayahuasca/hoasca) used in religious ceremonies. A systematic literature search, supplemented by interviews with ceremony participants. No laboratory animal models were located that tested the acute toxicity or the abuse potential of ayahuasca. Separate animal studies of the median lethal dose of dimethyltryptamine (DMT) and of several harmala alkaloids indicated that a lethal dose of these substances in humans is probably greater than 20 times the typical ceremonial dose. Adverse health effects may occur from casual use of ayahuasca, particularly when serotonergic substances are used in conjunction. DMT is capable of inducing aversive psychological reactions or transient psychotic episodes that resolve spontaneously in a few hours. There was no evidence that ayahuasca has substantial or persistent abuse potential. Long-term psychological benefits have been documented when ayahuasca is used in a well-established social context. A decoction of DMT and harmala alkaloids used in religious ceremonies has a safety margin comparable to codeine, mescaline or methadone. The dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal.
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Risk assessment of ritual use of oral
dimethyltryptamine (DMT) and harmala alkaloids
Robert S. Gable
Claremont Graduate University, Claremont, CA, USA
Aim To extend previous reviews by assessing the acute systemic toxicity and psychological hazards of a dimethyl-
tryptamine and b-carboline brew (ayahuasca/hoasca) used in religious ceremonies. Method A systematic literature
search, supplemented by interviews with ceremony participants. Results No laboratory animal models were located
that tested the acute toxicity or the abuse potential of ayahuasca. Separate animal studies of the median lethal dose of
dimethyltryptamine (DMT) and of several harmala alkaloids indicated that a lethal dose of these substances in humans
is probably greater than 20 times the typical ceremonial dose. Adverse health effects may occur from casual use of
ayahuasca, particularly when serotonergic substances are used in conjunction. DMT is capable of inducing aversive
psychological reactions or transient psychotic episodes that resolve spontaneously in a few hours. There was no
evidence that ayahuasca has substantial or persistent abuse potential. Long-term psychological benefits have been
documented when ayahuasca is used in a well-established social context. Conclusion A decoction of DMT and
harmala alkaloids used in religious ceremonies has a safety margin comparable to codeine, mescaline or methadone.
The dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal.
Keywords Abuse potential, ayahuasca, dimethyltryptamine, DMT, toxicity.
Correspondence to: Robert S. Gable, 2738 Fulton Street, Berkeley, CA 94705, USA. E-mail:
Submitted 19 February 2006; initial review completed 12 June 2006; final version accepted 11 July 2006
Among substances suspected of having abuse potential,
N,N-dimethyltryptamine (DMT) has received relatively
little attention. However, in 2006, a case was decided by
the US Supreme Court that involved the question as to
whether a DMT and b-carboline plant decoction
(ayahuasca/hoasca) is safe for ceremonial use by
members of a small spiritualist Christian church [1]. The
church prevailed in a unanimous decision in part
because the government, which opposed the use of DMT,
could not meet its burden of showing that hoasca posed a
serious health risk to church members. This paper is a
review of the known acute systemic risks of oral DMT
and concomitantly ingested harmala alkaloids.
Risk refers to the quantified probability of a future
harm. The concept of risk requires a causal relationship
between a hazard (such as a drug overdose) and a known
unfavorable outcome (such as illness or death). In order
to establish this causal relationship, a stimulus must
produce an effect more often than would normally occur
in the absence of that stimulus. Thus, the probabilistic
estimate of risk is often an intrinsic aspect of the research
process by which a causal relation is demonstrated. In the
case of oral DMT, probabilistic estimates can be made for
very few of the drug’s effects at the present time. Some
effects, both favorable and unfavorable, that have been
attributed to DMT may amount to little more than plau-
sible associations. Given the limited amount of published
scientific data regarding oral DMT, this paper takes a
broad view of potential hazards with the expectation that
future research will better establish the risks that might
actually exist.
Ayahuasca (EYE-ah-WAS-ka) or hoasca (WAS-ka) is a
mixture consisting essentially of two compounds. One is
an amine—the simplest and most common being the
tryptamine DMT. The second compound is a monoamine
oxidase inhibitor (MAOI) in the form of a b-carboline
such as harmine, harmaline or tetrahydroharmine. DMT
alone has predicable and significant psychological
REVIEW doi:10.1111/j.1360-0443.2006.01652.x
© 2007 The Author. Journal compilation © 2007 Society for the Study of Addiction Addiction,102, 24–34
activity when smoked, injected or insufflated; but when
used orally it only becomes, or remains, psychoactive in
combination with an MAOI [2–4].
Ayahuasca/hoasca is prepared customarily by com-
bining the leaves from the Psychotria viridis bush along
with bark scraped from the stem of the Banisteriopsis caapi
vine [4,5]. The ingredients are boiled for several hours
and then decanted. The resulting thick, brown, oily liquid
(referred to colloquially in some locales as ‘vine of the
souls’ or ‘vine of the dead’) has been used throughout the
Amazon Basin as a medicinal and ceremonial beverage
since antiquity [6].
Various sacramental brews containing DMT and
b-carbolines, used primarily in Amazonia, are generally
known as ayahuasca. The term ‘hoasca’, a Portuguese
transliteration of ayahuasca, is limited historically and
properly to a subclass of ayahuasca beverages associated
with a specific sacramental use ([5], chapter 16, ‘Hoasca
versus Ayahuasca’). The most commonly recognized sac-
ramental use of ayahuasca occurs among members of
two churches in Brazil: the O Centro Espirita Beneficiente
Uniao Do Vegetal (UDV), founded in 1961 with approxi-
mately 8000 current members, and the Santo Daime,
founded around 1940 with approximately 2500 current
members. Hoasca preparation occurs as part of a reli-
gious ritual known as preparo in the UDV. The Santo
Daime church also uses a decoction of P. viridis and B.
cappi called santo daime or simply daime, and its prepara-
tion ritual is known as feitio [7]. In the present paper,
‘hoasca’ will refer exclusively to UDV’s sacramental
decoction of plant DMT and harmala alkaloids.
The UDV cultivates the plants that are used in their
hoasca ‘tea’ on land that the church owns and maintains
for that purpose. The preparo ceremony can involve up to
200 people working together at a UDV temple over a
period of several days. Photographs of the process appear
in Metzner ([8], pp. 20, 21, 205). In 1992, the Brazilian
Federal Narcotics Council granted legal status for the use
of hoasca in religious contexts.
The present paper extends previous reviews [9,10] that
compared the acute lethal toxicity and the abuse poten-
tial of various psychoactive substances. A simple induc-
tive and iterative procedure was used to locate English-
language serial publications, from 1969 to 2005,
accessible through six databases: Biosis Previews, Digital
Dissertations, Google, PsychAbstracts, Pubmed and
Toxline. The Science Citation Index was occasionally used
to follow-up unusually salient reports. Six primary search
terms—‘ayahuasca’, ‘hoasca’, ‘dimethyltryptamine’,
‘harmine’, ‘harmaline’ and ‘tetrahydroharmine’—were
keyed into the search engines and scanned for the topics
‘overdose’, ‘lethal dose’, ‘lethality’, ‘toxicity’, ‘death’,
‘therapeutic index’, ‘abuse potential’ and ‘dependency’.
The most relevant books, reference works and special
journal issues (e.g. [5,8,11–12]) were also consulted,
thus expanding the information sources beyond those
located only by the search descriptors. In 2003, this
author met with 16 people 2 hours before and periodi-
cally for 12 hours after an ayahuasca ceremony led by a
Peruvian shaman. In 2005, the author had access to a
detailed legal document [13] consisting of more than
1000 pages that served as the evidentiary basis for health
information about hoasca for use in the US Supreme
Court case mentioned previously [1].
An item retrieved during the literature search was
considered potentially relevant if it met at least two of
four criteria: (1) DMT or one of the monoamine oxidase
inhibitors was quantified with respect to an effective or a
toxic dose; (2) the health status of the individual was
indicated; (3) the possible use of concomitant substances
was mentioned; and (4) the data source appeared to be
technical or scholarly in nature.
Fewer than 100 scholarly articles that focused specifically
on ayahuasca/hoasca were located in English-language
serial publications. The majority of these ar ticles involved
inapplicable topics such as neurological experiments, eth-
nographic descriptions or potential medical uses. The
descriptors ‘dimethyltryptamine’, ‘harmine’, ‘harmaline’
and ‘tetrahydroharmine’ resulted in approximately 200
citations retrieved from the databases, excluding Google
and the Science Citation Index. However, after cross-
indexing the keyword ‘toxicity’ with these four descrip-
tors, the number of non-redundant citations that met the
screening criteria was fewer than 25. When all relevant
citations from serial publications were supplemented
with excerpts from scholarly books, monographs and
published reports, the total number of documents printed
and filed was approximately 140.
Description of ayahuasca/hoasca brew
The DMT alkaloid has been reported as ranging from
0.1% to 0.66% dry weight in P. viridis leaves [14]. Sur-
prisingly, the DMT in leaf samples from a single P. viridis
plant has been shown to vary from approximately 3 mg/g
to 9.5 mg/g dry weight in the course of one day. The
concentrations of the b-carboline alkaloids in B. caapi
have been reported as ranging from 0.05% to 1.95% dry
weight [15,16].
Substantial variation in concentrations and propor-
tions of the constituents of ayahuasca brews can be
expected as a consequence of the varying chemical
Risk assessment of oral DMT 25
© 2007 The Author. Journal compilation © 2007 Society for the Study of Addiction Addiction,102, 24–34
composition of the source plants as well as different
methods of preparation. Average DMT doses in assayed
ayahuasca brews have ranged from 8.8 mg [17] to 42 mg
[18]. The content of other alkaloids also varied widely
(see Table 1). This fivefold variance of DMT quantities in
ayahuasca brews might be compared to the common
fivefold variance in caffeinated beverages which range
typically from 0.2 mg/ml of caffeine in green tea to
1.0 mg/ml of caffeine in filtered coffee [19].
The ritual structure in which hoasca is ingested
provides some control of dosage and subsequent psycho-
logical effects. Because the natural sources used in prepa-
ration of the tea does not allow UDV members to
standardize their hoasca brew with respect to DMT or
b-carbolines, the person conducting the ceremony drinks
the brew before administering it to UDV members as a
means of testing for potency. Different amounts of the
brew are initially offered to individual participants and,
depending upon reactions, a participant may be offered a
second cup at his or her request.
A clear distinction must be made between prepara-
tions consisting exclusively of DMT that are injected,
smoked or insufflated versus DMT preparations that are
oral mixtures of DMT and MAOI. Injected, smoked or
insufflated DMT is noted for its very rapid activity. Peak
cognitive effects last only 3–10 minutes, and normal con-
sciousness returns within 30 minutes. In contrast, initial
somatic effects (e.g. nausea, tingling, increased body tem-
perature) after ingesting oral DMT appear in approxi-
mately 20 minutes, followed by the onset of cognitive
effects that peak between 60 and 120 minutes [20]. The
cognitive effects diminish gradually to a normal state in
approximately 4 hours. At normally used doses, the psy-
chological effects of oral DMT are less intense than those
of injected, smoked or insufflated DMT.
Acute lethality
A traditional and standard criterion for assessing the
relative toxicity of various substances has been the lethal
dose of a substance. The median lethal dose (LD50)isthe
statistically derived quantity of a substance given in a
single dose that causes death in 50% of the experimental
animals. One early study by Trevan [21] used more than
900 mice to assess the toxicity of cocaine and of insulin.
More humane standards, such as the minimal lethal dose
or the maximal non-lethal dose, are being gradually
implemented by toxicologists, although many regulatory
agencies still rely on the traditional LD50. Some test pro-
cedures have been advocated that can reduce the number
of killed animals to as few as six [22].
The criterion of single-dose acute lethality is an
extremely limited estimate of human toxicity because it
does not take into account variables such as interspecies
differences, repeated dosing, environmental conditions,
prior health status and psychological factors. None the
less, the influence that such variables might have on
an established dose–response relationship should not
obscure the fact that the LD50 is a clearly defined, repli-
cable and important benchmark of toxicity.
The LD50 of DMT in mice is reported as 47 mg/kg
intraperitoneally and 32 mg/kg intravenously [23]. No
other LD50 data on DMT are believed to be available in
the English language at this time. Five compounds
with structural resemblance to DMT—serotonin,
psilocin, psilocybin, bufotenin and 5-methoxy-N,N-
dimethyltryptamine (5-MeO-DMT)—all have an intra-
venous LD50 among rodents that are similar to, or
substantially less toxic than, DMT. In two rare studies
reporting oral lethal doses of these related compounds,
the LD50 of serotonin in mice was 60 mg/kg [23]; the
LD50 of 5-MeO-DMT in mice was 278 mg/kg [24].
The principal b-carboline alkaloids added to DMT in
ayahuasca mixtures are harmine, harmaline and tet-
rahydroharmine. In addition to the B. caapi vine, these
alkaloids can be found in the Peganum harmala (Syrian
rue) shrub, a desert plant native to Central Asia. An
aqueous extract of P. harmala seeds administered orally to
rats resulted in a LD50 of 2 g/kg [25]. Because the
b-carboline admixtures in ayahuasca appear to be less
Table 1 Quantity (in milligrams) of alkaloids in ayahuasca/hoasca brews.1
Dose size 2DMT Harmine Harmaline THH Reference
140 ml 35.6 238 28 150 [2,14,18]
237 ml 33 17 26 Not stated [75]
60 ml 36 280 25 96 [15]
Gelatin capsule 30 120 None None [4]
100 ml 9.1 47.5 Trace 4.2 [17]
100 ml38.8 9.2 Not stated 26.5 [17]
Gelatin capsule 42 71 4.8 57 [30]
200 ml 25 30 trace 10 [16]
1Adapted, in part, from Riba [76]. 2Estimated average given to a 70 kg adult in the study referenced. 3Two samples of ayahuasca reported in the same
26 Robert S. Gable
© 2007 The Author. Journal compilation © 2007 Society for the Study of Addiction Addiction,102, 24–34
toxic than DMT, our attention should focus on the DMT
A simple extrapolation of DMT lethality data from
mice to humans is obviously untenable. We are therefore
forced to make some intrepid, but not original, assump-
tions. One traditional rule for scaling unknown differ-
ences between humans and non-human animal species is
simply to assume that humans are 10 times more sensi-
tive, based on body weight, than rodents [26]. To be even
more cautious in light of the absence of LD50 data regard-
ing oral DMT, let us assume that humans are 20 times
more sensitive than rodents. This would result in a
human LD50 of 1.6 mg/kg for DMT administered intrave-
nously, or a total intravenous dose of 112 mg for a typical
70 kg person. Because we are interested in the potential
toxicity of oral DMT in ayahuasca, it is necessary to
convert our estimated intravenous LD50 dose of
1.6 mg/kg DMT to an oral equivalent. Usually, an intra-
venously administered dose of a substance is assumed to
have bioavailability of 100%. The bioavailability of an
oral dose is significantly less. An oral DMT dose of
1.0 mg/kg has been reported to increase blood pressure
and heart rate comparable to a 0.1–0.2 mg/kg intrave-
nous dose [20]. With respect to psychological reactions,
an intravenous DMT bolus of 0.4 mg/kg has been docu-
mented carefully as ‘highly psychedelic’ ([12], p. 138),
while an oral dose of DMT ‘in excess of 2.0 mg/kg’ in
ayahuasca is known to produce maximal effects ([4],
p. 175). Let us assume an intravenous-to-oral conversion
factor of 1 : 5, based on the assumption that 0.4 mg
intravenously is equivalent to approximately 2.0 mg of
oral DMT. If 1.6 mg/kg is a median lethal dose of
intravenous DMT, then a median lethal dose of oral
DMT would be 8 mg/kg, or a total dose of 560 mg for a
70 kg individual. Note, however, that 560 mg is the esti-
mated median dose, and therefore one-half of potential
DMT fatalities would occur at an oral dose less than
560 mg.
A safety ratio or safety margin for ayahuasca can be
estimated by comparing the calculated LD50 to the cus-
tomary effective dose. The average ceremonial dose of
DMT, as listed in Table 1, is about 27 mg; therefore, the
safety margin for ayahuasca is approximately 20 (560/
27 =20.7).
Cardiac stress
Intravenous DMT is known to increase heart rate
rapidly, as well as systolic and diastolic blood pressure.
Strassman & Qualls [27] reported that a 0.4 mg/kg dose
of DMT at the postinjection interval of 2 minutes raised
the heart rate approximately 26 beats per minute (bpm),
and raised systolic pressure by 35 mmHg and diastolic
pressure by 30 mmHg. DMT plus b-carbolines in
ayahuasca ingested in doses ranging from 0.48 mg/kg
to 1.0 mg/kg were shown to induce peak increases in
heart rate and blood pressure at about one-third that of
intravenous DMT after 90 and 120 minutes [3,20].
Table 2 summarizes these data along with comparisons
of some commonly used psychoactive substances. The
reference cited for each of the substances in Table 2 is
the primary, but not exclusive, source of the information
On the basis of acute heart rate and blood pressure
data, the hemodynamic effects of a typical dose of
ayahuasca appear to be less potentially hazardous than
many commonly used psychoactive substances.This ten-
tative conclusion assumes that any substance listed in
Table 2 Heart rate and blood pressure increases after administration of DMT or other psychoactive substances.
Heart rate
(mmHg) Reference2
Intravenous 0.4 2 minutes 26 35 30 [27]2
Oral 0.48 20 minutes 7.4 9.0 9.3 [3]
Oral 0.5 45 minutes 6.4 8.8 10.4 [20]
Oral 0.75 45 minutes 8.0 13.4 9.8 [20]
Oral 1.0 45 minutes 9.2 13.8 8.6 [20]
Alcohol oral 1157 15 minutes 9 -2 1 [77]
Caffeine oral33.3 15 minutes 4.0 5.0 5.0 [29]
Cocaine insufflated41.37 55 minutes 17 14 14 [78]
Marijuana smoked (98.6 ng/ml)515 minutes 11.6 (See footnote 6) [79]
MDMA oral 1.5 60 min 28 25 7 [80]
1Assumes an individual who has not developed toleranceto the indicated substance. 2The reference listed is the primary, but not the exclusive, source for
the data summarized in the table. Some original data were averaged. 3Caffeine powder mixed with grapefruit juice; caffeine dose was equivalent to two
or three cups of instant coffee. 4Administered as 120 mg of white powder (cocaine and lactose) in four ‘lines’, snorted two lines per nostril. 5Plasma THC
from 10 puffs, at 1-minute intervals, from a marijuana cigarette containing 1.75% THC. 6Typically, a slight increase in blood pressure when in a supine
position, a decrease when in an upright position.
Risk assessment of oral DMT 27
© 2007 The Author. Journal compilation © 2007 Society for the Study of Addiction Addiction,102, 24–34
Table 2 is administered once by the route and in the
quantity indicated without any concomitant pharmaco-
logically active substances. Occasional stroke, myocardial
infarction and other adverse cardiovascular events can be
expected to be associated with, even if not directly caused
by, the use of ayahuasca or other drugs or foods that
induce acute hemodynamic changes. Individual differ-
ences in metabolism and health status often result in a
wide range of reactions to psychoactive substances. For
example, the heart rate of some of the participants in the
Strassman & Qualls intravenous DMT study [27] peaked
at 150 bpm, while the heart rate of other participants
was raised no higher than 95 bpm. Furthermore, the
hemodynamic reaction to ayahuasca may depend on the
relative concentrations of DMT to the b-carbolines. In
decoctions tested by Pomilio, Vitale & Ciprian-Ollivier
[17], an exceptionally low concentration of DMT com-
pared to b-carbolines significantly decreased heart rate.
An experiment with dogs found that harmala alkaloids
decreased heart rate but were inconsistent in their effect
on blood pressure [28].
Because heart rate increases with ayahuasca are so
minimal, the differences may be the result of unrelated
physical activity of the participants. Such changes might
be put into perspective by a study conducted by Hartley,
Lovallo & Whitselt [29]. A beverage containing a 230 mg
dose of caffeine (equivalent to two or three 150 ml cups of
instant coffee) resulted in only negligible increases in
heart rate (4 bpm) and blood pressure (5 mmHg). Later in
the same study, the researchers asked the 77 study par-
ticipants to deliver a 3-minute speech ‘to a video camera
in front of 2 experimenters wearing white coats’ ([29],
p. 1023). Under this anxiety-producing condition, the
average increase in heart rate was 30 bpm; the systolic
pressure increased an average of 28 mmHg and the dias-
tolic pressure increased an average of 21 mmHg. These
increases are more than twice those occurring with oral
It is generally held that the b-carbolines in ayahuasca
are reversible and highly selective inhibitors of MAO [30].
The ayahuasca-induced blockade of MAO presumably
allows a larger quantity of serotonin to accumulate in
nerve terminals. Excessive accumulation can produce a
range of adverse physiological symptoms, a ‘serotonin
syndrome’, that includes tremor, diarrhea, autonomic
instability, hyperthermia, sweating, muscle spasms and
possible death [31].
A few irreversible or non-selective MAO inhibitors
(e.g. phenelzine, tranylcypromine) are associated
strongly with instances of severe serotonin syndrome,
but a large number of opiates, analgesics, tricyclic anti-
depressants, selective serotonin reuptake inhibitors
(SSRIs) and anti-migraine agents have also been
implicated [31]. Individuals who have recently used
ginseng, St John’s wort, dextromethorphan or 3,4-
methylenedioxymethamphetamine (MDMA: ecstasy)
should be cautious about using ayahuasca. Physical dis-
comfort or chronic pain (e.g. backache) may be exacer-
bated by ayahuasca, so potential users should be warned
of this side effect.
Table 3 lists six reported instances in which there
were severe toxic reactions to a psychoactive tryptamine
and/or a b-carboline. The death of a 25-year-old male
caused by amine intoxication [32] involved 5-MeO-DMT
in addition to DMT and b-carboline. No laboratory
animal studies were located during the present review
that compared the toxicity of orally active 5-MeO-DMT
with orally active DMT. However, 5-MeO-DMT is
reported to be more potent than DMT when smoked [5]
or taken orally with harmaline [4]. Experienced
researchers have cautioned that these substances should
not be casually interchanged in ayahuasca-like prepara-
tions. The male decedent ingested an unknown quantity
of ‘herbal tonics’ that presumably contained MAOIs in
addition to the DMT and 5MeO-DMT because he was
found to have a blood concentration of tetrahydro-
harmine three times higher than that found among 14
volunteers in a UDV hoasca study [2]. The autopsy was
performed the day after the body was discovered, so
post-mortem drug redistribution makes it difficult to
determine what the peak cardiac or peripheral blood
concentration of tetrahydroharmine or 5-MeO-DMT
might have actually been.
The briefly described fatality of a 71-year-old diabetic
female, listed in Table 3, repor ted that only tobacco leaves
and B. caapi were the constituents of the so-called
‘ayahuasca’ brew [33]. The abstract did not document
the concentration of any b-carbolines, but did report
measurements (at unstated time intervals) of
1900 ng/ml and 710 ng/ml of blood nicotine. These con-
centrations exceed by at least 20 times the average post-
mortem nicotine concentration (34 ng/ml) reported by
Ekwald & Clemedson [34]. ‘The cause of death [of the
71-year-old] was attributed to acute nicotine intoxica-
tion’ ([33], p. 287). Administration of the unorthodox
nicotine/b-carboline brew by enema to this older person,
who was a non-smoker, precludes the relevance of this
case to typical ayahuasca/hoasca use.
The quantity of P. harma seeds consumed as a single
intoxicant by the two individuals cited in Table 3 [36,37]
should be distinguished from the lower quantity of B.
caapi or P. harmala that is used customarily in an ayahua-
sca brew. These individuals ingested 15–50 times more
b-carboline alkaloids than the 3 g needed to maintain the
oral activity of DMT in an ayahuasca preparation [5].
Herraiz [38] has noted that coffee may act as a MAOI, and
the caffeine used by one of the decedents probably inten-
sified the effect of the harmala seeds.
28 Robert S. Gable
© 2007 The Author. Journal compilation © 2007 Society for the Study of Addiction Addiction,102, 24–34
The last item listed in Table 3 involved more than 30
individuals between the ages of 20 and 50 years who
‘were participating in a meditation session named
“releasing autohypnosis of forest medicine men”’ ([39],
p. 50). The published report does not detail the number of
participants who were hospitalized, their gender or their
health status following the ingestion of 100–200 ml of
herbal tea, although all the patients recovered satisfacto-
rily. Fatalities from atropine or scopolamine are rare, and
from harmine are extremely rare. The reported dose of
atropine (4 mg) and of scopolamine (78 mg) received by
the meditation session participants is eight to 13 times
less than the estimated minimal lethal dose of these sub-
stances [40,41]. The severe reactions of at least a few of
the individuals who required mechanical ventilation
was attributed by the report authors to the combined
synergistic actions of harmine, atropine and scopola-
mine. This incident provides additional evidence of the
potential danger of combining pharmacologically active
substances in non-traditional ways.
To this author’s knowledge, there have been no deaths
caused by hoasca or any other traditional DMT/b-
carboline ayahuasca brews. The probability of a toxic
overdose of ayahuasca is seemingly minimized by seroto-
nin’s stimulation of the vagus nerve which, in turn,
induces emesis near the level of an effective ayahuasca
dose. The risk of overdose appears to be related primarily
to the concurrent or prior use of an additional serotoner-
gic substance. People who have an abnormal metabolism
or a compromised health status are obviously at a greater
risk than the normal population, and might prudently
avoid the use of ayahuasca preparations.
Table 3 Acute toxic reactions to ayahuasca-related compounds.
Age/sex Primary Estimated Effects Toxicological Factors Reference
25 m5-MeO-DMT Unknown quantity
of ‘herbal tonics’
Death caused by
5-Meo-DMT 1.88
mg/l, THH
0.38 mg/l,
0.17 mg/l
Camping in park,
71 F Ayahuasca
Not reported Death caused by
Nicotine 1900 mg/l
and 710 mg/l
Non-smoker, no
emesis, brew
administered by
36 mAyahuasca
100 ml of brew Gross motor tremors,
resolved without
treatment after 4
No blood chemistry
Daily use of 20 mg
of oral fluoxetine
35 mPeganum
150 g of P. harmala
Heart rate 100 bpm,
bp 80/40 mmHg,
convulsion, stable
in few hours after
b-carbolines not
Gastric ulcer, mild
anemia but other
27 F P. harmala 50 g of P. harmala
Hallucinations, GI
resolved in a few
b-carbolines, caffeine
level not reported
Seeds ingested with
A brew of harmine
27 mg, atropine
atropine 4 mg,
78 mg
Tachycardia, coma,
all patients
with supportive
Harmine 179 mg/l,
atropine 27 mg/l
515 mg/l
Ingested alkaloids
had ‘synergistic
1Coffee brews contain b-carboline alkaloids. 2‘More than 30 people aged 20–50 years’. No information provided regarding sex or health status of
Risk assessment of oral DMT 29
© 2007 The Author. Journal compilation © 2007 Society for the Study of Addiction Addiction,102, 24–34
Psychological dysfunction
The general sequence of psychological and cognitive
responses to ayahuasca is dose-dependent and predict-
able; however, the reactions of any particular individual
at any one session are not. With a medium dose of DMT,
objects in the environment appear to vibrate and increase
in brightness. Rapidly moving patterns and scenes
emerge that are visible with eyes either open or closed.
This experience is referred to as being a ‘visionary state’
([42], p. 109). It should be noted that these altered per-
ceptions and cognitions do not usually cause users to
become unaware of their surroundings or lose the ability
to speak coherently. Many users walk to the restroom as a
result of diarrhea.
Riba and colleagues [20] described the reactions of six
volunteers after they each received doses of 0.05, 0.75
and 01.0 mg/kg of ayahuasca. Results obtained on
Addiction Research Center Inventory (ARCI) scales
showed that as the doses increased, emotions of happi-
ness, sadness, awe and amazement also increased. At
medium and high doses, the volunteers agreed that the
experience seemed similar to a dream and that the sense
of self and the passing of time were deeply affected. For
example, the awareness between individuals can become
so interlinked that typical self-centered judgements about
the contents of another person’s statement are simply
absent. With respect to time perception, some people
report that during an ayahuasca session they are swept
into a conscious state where the usual orderly pro-
gression of time becomes obviously non-existent, and
they experience ‘eternity’ ([43], p. 45). This sensation/
perception was often associated with the emotion of well-
being, but it can also be accompanied by feelings of terror.
Virtually all data sources indicate that the DMT or
ayahuasca experience has a substantial degree of unpre-
dictability with respect to both aversive and positive
aspects, depending on variables such as dosage, partici-
pant’s intention and setting. Reactions during ayahuasca
ceremonies have ranged from profound calmness [44] to
anguished cries for forgiveness [45].
In interviews with 150 informants, Shannon [46]
reported that, even among individuals without academic
education or philosophical training, the ayahuasca expe-
rience prompted users to reflect seriously on the phenom-
ena of life, nature and human consciousness. A pilot
study by Grob and colleagues [47] comparing 15
members of the UDV with a control group of 15 non-
members revealed that the UDV members showed more
rigidity, regimentation, reflection and word-recall on
various tests than non-members. According to Grob
([47], p. 90), ‘all of the 15 UDV subjects claimed that
their experience with ritual use of hoasca as a psychoac-
tive ritual sacrament had had a profound [positive]
impact on the course of their lives’. Most of the UDV
members had a history of moderate to severe alcohol use
prior to joining the UDV. This variable was not reported
for the control group, so the generalization of this study’s
result to the general population is uncertain.
Certain perceptual characteristics of the ayahuasca
experience overlap those of schizophrenia, and a few
researchers have reported that urinary or blood levels of
DMT are above normal in schizophrenic individuals
[48,49]. This has led to the hypothesis that the non-
destruction of dimethylated indolealkyalamines such as
DMT could play a role in progressive deterioration of cog-
nitive processes [50]. Other studies have produced con-
flicting results and alternative conclusions [51,52]. Jacob
& Presti ([53], p. 935) proposed that increased DMT,
acting at the G-protein-coupled trace amine receptor,
might actually serve in schizophrenics as ‘a homeostatic
response to calm or suppress psychotic activity, rather
than exacerbate it’. At present, the proposition that
endogenous DMT in schizophrenia is related biochemi-
cally to ayahuasca-induced states of consciousness
remains a speculative hypothesis.
The hallucinogenic effect of ayahuasca and other
tryptamine derivatives can precipitate severe adverse psy-
chological reactions, and this is especially true when
administered outside established ceremonial practices
[54]. For example, two cases of unsupervised use of
5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT,
‘foxy’) have been reported in which an unknown amount
of 5-MeO-DIPT caused sensory hallucinations requiring
several hours of hospitalization [55,56]. Transient psy-
chotic episodes are also known to occur with high doses
of psilocybin [57] and LSD [58]. LSD, psilocybin and
5-MeO-DIPT are, however, orally active and more potent
than DMT; thus the comparability of these three sub-
stances with DMT is somewhat problematic.
Over a period of 5 years, the medical studies section of
the UDV documented between 13 and 24 cases in which
ayahuasca might have been a contributing factor in a
psychotic incident ([13], p. 701). The incidents docu-
mented by the UDV occurred from an estimated total of
25 000 servings of the hoasca tea. Although the preva-
lence rate of psychosis or schizophrenia among adults in
the United States varies according to the way in which
diagnostic criteria are applied, the generally accepted
estimate is approximately 1.3% [59]. A reported UDV rate
of psychotic episodes under 1% suggests that the use of
hoasca is not a triggering event for sustained psychosis.
Many or most of the UDV psychotic episodes were tran-
sient in nature and resolved spontaneously ([13], p. 623).
Dependence and abuse potential
The extent to which ayahuasca might lead to physiologi-
cal dependence or compulsive drug-seeking is an
30 Robert S. Gable
© 2007 The Author. Journal compilation © 2007 Society for the Study of Addiction Addiction,102, 24–34
important public health concern. The physiological
dependence potential of DMT and ayahuasca remains to
be documented convincingly. Hallucinogenic substances
structurally similar to DMT are rarely used in a compul-
sive manner that would meet the dependence criteria of
the Diagnostic and Statistical Manual version IV (DSM-IV)
[60]. No studies were located during the present review
that reported that the termination of DMT resulted in an
abstinence syndrome.
With respect to drug tolerance, however, a few non-
human animal studies have been conducted that show
varying degrees of tolerance to behavioral and physi-
ological responses over a period of 3 or 4 weeks [61–63].
Little or no tolerance to emotional or autonomic effects
was reported in one study, where human volunteers were
administered DMT four times at 30-minute intervals
[64], and in another study where DMT was administered
twice daily for 5 days [52].
Despite the presumed absence of physiological depen-
dency and tolerance, ayahuasca might, nonetheless,
function as a positive reinforcer leading to significant
abuse potential. We would want to know, for example,
what proportion of individuals who try DMT or ayahua-
sca once or twice fall into a pattern of chronic use that
they then find difficult to quit. The UDV has reported that
15–20% of first-time participants in hoasca ceremonies
become UDV members ([13], p. 700). This subsequent
participation in the UDV church is within the reported
range of first-time visitors who become members of
Christian churches in the United States [65].
Future consumption patterns of ayahuasca are diffi-
cult of determine because, in part, the frequency of
present use in the general population is so low, but its
general psychopharmacological profile suggests that it
lacks the abuse potential of amphetamines, cocaine,
opiates or other widely abused substances. Indeed,
accounts of any strong and sustained reinforcing effects
of tryptamine compounds are rare in experimental litera-
ture. More typically, non-human animal studies conclude
that administration of tryptamine derivatives such as
mescaline, psilocybin or DMT result in erratic patterns of
self-administration indicating that ‘these compounds
have weak reinforcing effects, or alternatively, mixed rein-
forcing and aversive effects’ ([66], p. 156).
Any attempt to characterize the possible acute adverse
health effects of ayahuasca is hampered by the very
limited number of relevant scientific studies of DMT and
b-carboline decoctions. This situation invites an easy
commingling of facts, speculations, inferences, biases,
conjectures and hidden agendas. Arguments made in the
course of litigation are especially prone to linguistic
obfuscation of empirical weaknesses. None the less, legal
and policy decisions must be made in the light of what
almost always seems to be insufficient evidence. Data
available at this time indicate that the acute systemic tox-
icity of ayahuasca is, by comparison, substantially less
than alcohol. The average acute lethal dose of ethyl
alcohol is well-documented at approximately 330 g [67],
10 times the normal recreational dose. The acute lethal
dose of ayahuasca was calculated in this review as 20
times the effective dose. This safety margin is similar to
codeine, mescaline and methadone [9]. Previous esti-
mates of the LD50 of DMT have been as high as 40 or 50
times the customary dose [9,68]; the difference is prima-
rily a result of varying the safety factors that are used to
extrapolate data from non-human laboratory animal
studies to humans.
No acute health hazards, excluding potential seroton-
ergic reactions, have been documented as a routine,
serious threat from ayahuasca when ingested within the
range of customary dosages. Possible chronic health
effects of ayahuasca were not considered in the present
Most public attention is focused on hazards that we
want to avoid, such as accidents, heart attacks or bank-
ruptcy. However, there are hazards that people accept,
perhaps grudgingly, because they perceive a potential
benefit—for instance, crossing a street against the traffic
light, speeding to a hospital with a sick child, agreeing to
an adjustable mortgage. Andritzky [69] has described the
traditional use of ayahuasca in Amazonia during healing
rituals. A more contemporary North American illustra-
tion was provided by a university administrator who
reported that he previously considered Schedule I drugs
to be a taboo option until he was diagnosed with meta-
static liver cancer [70]. When potential benefits are con-
sidered, the option with the least risk is not necessarily
the best choice.
Indeed, some risks are not merely accepted, but
actively sought. Examples include hang-gliding, road
racing and alcohol drinking contests. Recently, the inter-
net has become a favored source of information for
individuals seeking drug-related experiences. Boyer,
Shannon & Hibberd [71] have profiled 12 adolescents in a
drug treatment program who reported being influenced
detrimentally by drug information, including a descrip-
tion of Syrian rue, that they found on the internet.
However, the internet also contains descriptions of
intoxicated misadventures that might serve as a caution-
ary tale (e.g. a self-reported ayahuasca overdose caused
by the user’s self-described ‘swaggering arrogance’ ([72],
p. 1). Virtually all poisoning reports with tryptamine/
MAOI mixtures involve individuals who prepared their
own brew and/or who ingested an additional psychoac-
tive substance [35,39,72,73].
Risk assessment of oral DMT 31
© 2007 The Author. Journal compilation © 2007 Society for the Study of Addiction Addiction,102, 24–34
The relative lack of abuse potential of ayahuasca in
social settings seems very plausible. The unpredictable
occurrence of frightening images and thoughts, plus pre-
dictable nausea and diarrhea, makes it a very unlikely
candidate for a ‘club drug’.
Finally, it might be noted that the discipline of toxicol-
ogy has its own queasiness—especially about spiritual
concepts such as ‘transcendence’, ‘ineffability’ and
‘grace’ that often appear in descriptions of ayahuasca
sessions by physically and psychologically healthy indi-
viduals [74]. Many reported experiences are similar to
descriptions of samadhi in advaitan Hinduism, satori in
Zen Buddhism or beatific vision in Christianity. Such
alleged beneficial experiences lie outside the pathology-
oriented realm of toxicology, but not necessarily or com-
pletely beyond the scientific requirement of falsifiability.
Variations in consciousness are, at least in theory, worthy
of serious scientific study because of their central place in
human endeavors.
This review was funded, in part, by the Life Science
Research Group, Inc., an independent non-profit research
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... The DEA report cited an animal toxicology extrapolation model estimating that the LD50 for oral DMT in humans would be 8 mg kg À1 , which is more than 20 times the dose of oral DMT (approximately 27 mg) typically consumed from ayahuasca (Gable, 2007). However, the report also omitted the researcher's explanation that "simple extrapolation of DMT lethality data from mice to humans is obviously untenable" due to differences in metabolism, physiology, and even serotonin receptor distribution and that "the dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal" (Gable, 2007). ...
... The DEA report cited an animal toxicology extrapolation model estimating that the LD50 for oral DMT in humans would be 8 mg kg À1 , which is more than 20 times the dose of oral DMT (approximately 27 mg) typically consumed from ayahuasca (Gable, 2007). However, the report also omitted the researcher's explanation that "simple extrapolation of DMT lethality data from mice to humans is obviously untenable" due to differences in metabolism, physiology, and even serotonin receptor distribution and that "the dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal" (Gable, 2007). A more recent review of animal data on ayahuasca/DMT, which was not mentioned in the DEA report, indicates that ayahuasca is toxicologically safe in ceremonial-comparable doses (Daldegan-Bueno, Simionato, Favaro, & Maia, 2023). ...
... Elevated blood pressure and heart rate normally happen transiently in most humans, including those with no measurable damage to their hearts. Gable (2007) analyzed several studies to compare changes in heart rate and blood pressure brought on by various psychoactive substances and concluded that the hemodynamic effects of ayahuasca appear less hazardous than alcohol. ...
Full-text available
On February 2023, the Drug Enforcement Administration (DEA) released a document to the legal team representing the Church of the Eagle and the Condor (“CEC”). This disclosure came two years after the church, in conjunction with Chacruna Institute, submitted two FOIA requests to the DEA and the Department of Justice requesting all records pertaining to ayahuasca. This report, titled “Ayahuasca: Risks to Public Health and Safety,” was issued in July 2020. In the present article, we challenge a number of claims made in the DEA report and highlight significant factual omissions, theoretical biases, and misinterpretations of existing data. We will demonstrate that the DEA report severely downplays the safety profile and therapeutic potential of ayahuasca and overemphasizes the risks. It also fails to include current research on ayahuasca demonstrating its potential benefits.
... Carhart-Harris, Erritzoe, et al. (2012) demonstrated that activity in these regions is significantly reduced under the acute influence of psychedelics. Psilocybin, a 5-HT2A agonist and functional analogue of DMT (Gable, 2007), and the active ingredient in so called magic mushrooms was administered to participants in a task free functional MRI (fMRI) protocol. ...
... The psychoactive effects that users experience following ingestion of ayahuasca are largely a result of dimethyltryptamine (DMT) (McKenna et al., 1984). The compound DMT itself is a functional analogue of various psychedelic tryptamines, including 5-HO-DMT, 5-MeO-DMT, 4-AcO-DMT, psilocin (4-HO-DMT), and psilocybin (4-PO-DMT), as well as a structural analogue of melatonin and serotonin (Gable, 2007). DMT is an endogenous serotonergic compound with evidence suggesting it exists within the brain, lungs, and liver of humans, with trace amounts also being prevalent in a large range of other plant and animal species (Domínguez-Clavé et al., 2016). ...
... Safety and wellbeing issues are always paramount for any intervention, therefore it is important to outline some of the wealth of research suggesting that the risks of ayahuasca use are minimal, when used appropriately. Animal studies suggest a fatal dosage of DMT would be 20 times that of the standard ritualistic ayahuasca practice (Gable, 2007). This suggests a wide therapeutic window, with neither acute nor long-term administration of ayahuasca appearing toxic in humans (Guimarães dos Santos, 2013). ...
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Ayahuasca is a psychedelic plant brew originating from the Amazon Rainforest. It is formed from two basic components, the Banisteriopsis caapi vine, and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. There has been a dramatic increase in interest surrounding ayahuasca since the turn of the millennium. Increasing numbers of tourists are travelling to the Amazon rainforest to drink the brew, with various media outlets, celebrities, and researchers describing benefit from its consumption. Ayahuasca is now present in every continent and retreat centres offering plant medicine experiences in the Amazon rainforest has become a thriving business. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. This thesis comprises five studies investigating Amazonian ayahuasca use. Initially, the pharmacology of the brew is explored in the form of a systematic review, concluding complex synergistic mechanisms may be present, although further research is needed. The remaining studies utilise observational methodology, investigating the impact of ayahuasca retreats following a traditional Shipibo lineage adapted for ayahuasca tourists in the Peruvian Amazon. The effects of the brew on personality, mental health outcomes, epigenetics, and nature relatedness are documented. Further, a phenomenological analysis of the ayahuasca experience is included. The research in this thesis is amongst the first to investigate Shipibo-style ayahuasca retreats in the Peruvian Amazon. Various ethical issues surrounding the increasing popularity of the brew and potential medicalisation are also discussed. It is hoped that this research will add to the growing body of knowledge surrounding the potential therapeutic effects of ayahuasca, whilst considering risks, ethics, and wider applications.
... Realizando una revisión de la literatura disponible no se encontraron evidencias de daño físico en personas que utilizaban regularmente ayahuasca con fines religiosos, calculándose una dosis letal estimativa en más de 20 veces la dosis comúnmente utilizada (Gable et al., 2007). ...
... Tampoco se encontró evidencia de potencia de abuso ya que solo un 15-20% de las personas que concurrían a este grupo religioso y utilizaban ayahuasca por primera vez se convertían en miembros del culto, estadística similar a la que se da en personas que concurren por primera vez a otros grupos religiosos (Gable et al., 2007). ...
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Puede consultar otros artículos publicados por los autores en la revista Psicofarmacología en Pobihuszka Damián. "Alucinógenos serotoninérgicos: posibles implicancias en el tratamiento de depresión y trastornos por ansiedad". Psicofarmacología 2017;104:9-18. Alucinógenos serotoninérgicos: posibles implicancias en el tratamiento de depresión y trastornos por ansiedad Serotonergic Hallucinogens: Possible Implications in the Treatment of Depression and Anxiety Disorders Médico (UCC), especialista en psiquiatría (UNLP y Col. Med. prov. de Bs As). Magíster en psiconeurofarmacología (Univ. Favaloro). Co-director y docente en Centro Dionysos Mar del Plata. En la actualidad existe un renovado interés por la investigación de los posibles usos terapéuticos de los alucinógenos serotoninérgicos como psilocibina, LSD, dimetiltriptamina y otros cuya investigación había cesado luego de que estas sustancias se declararan ilegales en los años setenta. En el siguiente trabajo se revisa la información disponible al momento acerca de su posible utilización en el tratamiento de la depresión y de los trastornos por ansiedad con investigaciones, tanto en modelos animales como en humanos con estas patologías. Se exploran además las diferentes hipótesis en relación a su efectividad en estos trastornos como la down-regulation de los receptores 5-HT2A en CPF, la neuroplasticidad asociada a glutamato con la activación del receptor 5-HT2A y formación de BDNF, cambios en el procesamiento emocional sesgado asociado a la depresión involucrando la amígdala y circuitos prefronto-límbicos, modulación de la Default Mode Network y del sistema inmune. Por último se evalúan cuestiones relacionadas con la seguridad de la utilización de estas sustancias. Resumen Nowadays, there is renewed interest in investigating the potential therapeutic uses of serotonergic hallucinogens such as psilocybin, LSD, dimethyltryptamine, and other serotonergic hallucinogens which no longer had been investigated after they were declared illegal in the seventies. This article provides a revision of the available information on the possible use of these serotonergic hallucinogens in depression and anxiety disorders, with investigations both in animal models as well as in human beings who suffer from these pathologies. The author also analyses the different hypotheses relating to their efficacy in these disorders, such as the 5-HT2A receptor downregulation in PFC, the neuroplasticity associated with glutamate, along with the 5-HT2A receptor activation and the BDNF formation, changes in the emotional processing bias associated with depression and involving the amygdala and prefrontal-limbic circuits, the modulation of the default mode network and the immune system. Finally, the aspects relating to the safety use of these substances are evaluated. Abstract Damián Pobihuszka Fecha de recepción: 22 de marzo de 2017 Fecha de aceptación: 12 de mayo de 2017 Palabras clave Keywords Alucinógenos serotoninérgicos-Depresión-Trastornos por ansiedad-5-HT2A-Procesamiento emocional-Default mode network-Glutamato. Serotonergic hallucinogens-Depression-Anxiety disorders-5-HT2A-Emotional processing-Default mode network-Glutamate Introducción Los alucinógenos presentes en la naturaleza han sido uti-lizados a lo largo de la historia de la humanidad con diversos fines mágicos, religiosos y curativos por culturas diversas (Hoffer, 1970). En la actualidad muchas de estas sustancias como la dimetiltriptamina contenida en la ayahuasca siguen siendo utilizadas popularmente, por ejemplo, en la región amazónica de Perú con fines medicinales (Baumeister et al., 2014) (Naranjo, 2012). Pertenecen a este grupo sustancias, algunas de origen natural , otras sintético que ejercen sus efectos principalmente a través de un agonismo o agonismo parcial sobre el receptor 5-HT2A (Nichols, 2004). En 1943 se descubrieron accidentalmente los efectos psi-coactivos el LSD, primer compuesto de esta clase de origen sintético. A partir de allí se produjo un gran interés en la comunidad científica por el estudio de estas sustancias generando una buena cantidad de estudios clínicos y publi-caciones, intentando utilizar estos compuestos en diferentes problemas clínicos, como una herramienta para el estudio del funcionamiento de la mente y como una manera de acelerar y profundizar procesos psicoterapéuticos (Vollenweider et al., 2010) (Hoffer, 1970). Se llegó a afirmar que "no sería una exageración decir que los alucinógenos utilizados adecuadamente y con los cuida-dos necesarios podrían ser para la psiquiatría lo que el microsco-pio es a la biología, o el telescopio a la astronomía. Estas herramientas hacen posible el estudio de importantes proce-sos que en circunstancias normales no están disponibles a la observación directa" (Grof, 1980). Muchos de estos estudios iniciales carecían de los requerimien-tos metodológicos actuales, por lo que es difícil extrapolar Psicofarmacología 17:104, Junio 2017
... Collectively, these findings show that DMT modulates dopaminergic activity in an indirect manner. Although DMT promotes the release of DA at high doses, it does not exhibit dependence potential when used in a well-established social context such as clinical administration (D'Souza et al., 2022) or ritual ceremonies (Gable, 2007;Bouso et al., 2012). In contrast, several observational studies of ritual ayahuasca users report remissions of substance-use disorders (Halpern et al., 2008;Fernández et al., 2014;Loizaga-Velder and Verres, 2014;Winkelman, 2014). ...
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Ayahuasca is a psychedelic plant brew originating from the Amazon rainforest. It is formed from two basic components, the Banisteriopsis caapi vine and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. Here we review the history of ayahuasca and describe recent work on its pharmacology, phenomenological responses, and clinical applications. There has been a significant increase in interest in ayahuasca since the turn of the millennium. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. The effects of the brew on personality and mental health outcomes are discussed in this review. Furthermore, phenomenological analyses of the ayahuasca experience are explored. Ayahuasca is a promising psychedelic agent that warrants greater empirical attention regarding its basic neurochemical mechanisms of action and potential therapeutic application.
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Psychedelic drugs have experienced an unprecedented surge in recreational Highlights use within the past few years. Among recreational users, the risks of psychedelic Psychedelic use is rapidly growing in use by pregnant and breastfeeding women are severely understudied and there popularity for recreational and clinical is little information on the potential teratogenic effects of these drugs. We pro- purposes, but its potential risks for preg. nant and breastfeeding women are vide an overview of the previous data on psychedelic teratogenicity from rodent currently unknown. studies and human surveys, discuss their limitations, and propose the utility of the zebrafish as a potential effective model for investigating psychedelic terato-genicity. Recent years have validated the use of zebrafish in the study of fetal exposure and developmental biology; we highlight these properties of the zebrafish for its suitability in psychedelic toxicity research.
Classic psychedelics: safety, side effects and medication interactions Given the growing scientific and social interest in the use of classic psychedelics for psychiatric disorders, physicians are increasingly confronted with patients resorting to these drugs. To this date, treatment with classic psychedelics within a medical framework is non-existent. Patients could seek such a treatment themselves by means of a retreat under the guidance of (non-)professionals in a non-official health facility in countries where the use of these substances is legalised. They could also go ‘underground’ in countries where these substances are illegal. It is important that physicians have an open conversation with their patients in order to adequately inform them and make a risk assessment. In this article, the safety, side effects and drug interactions of classic psychedelics are reported. Classic psychedelics are non-addictive and have a low toxicity. Their use under controlled conditions reduces the risk of serious unwanted effects, such as persistent psychotic symptoms, disabling flashback phenomena or increased suicidality. Under uncontrolled conditions and in the absence of psychological support, these risks are, however, real and thus the use of these drugs to treat psychological symptoms should be strongly discouraged. Interactions with other drugs are possible. This risk should be assessed individually for each patient, depending on the medication and type of psychedelic.
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Natural psychedelic compounds are emerging as potential novel therapeutics in psychiatry. This review will discuss how natural psychedelics exert their neurobiological therapeutic effects, and how different neurotransmission systems mediate the effects of these compounds. Further, current therapeutic strategies for depression, and novel mechanism of action of natural psychedelics in the treatment of depression will be discussed. In this review, our focus will be on N, N-dimethyltryptamine (DMT), reversible type A monoamine oxidase inhibitors, mescaline-containing cacti, psilocybin/psilocin-containing mushrooms, ibogaine, muscimol extracted from Amanita spp. mushrooms and ibotenic acid.
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Traditional therapies, resorting to the use of plants, have acquired a great demand over the years, both for economic reasons and the preference for natural treatments. Some studies suggest that ayahuasca may have beneficial properties in treating some physical and psychological imbalances. Thus, we carried out a systematic review of studies published up to December 2022, where these themes were addressed. The search was carried out in the PubMed database, and only studies written in English and published in peer-reviewed journals were included. Thus, 228 publications were identified, of which 66 were included in the present study. The reviewed studies suggest that ayahuasca may have beneficial effects on various physical and psychological conditions, namely in the treatment of depression, anxiety and various diseases of the neurobiological system, as well as anti-inflammatory and antimicrobial properties, demonstrating its therapeutic potential. The number of studies that address this issue has also been growing, demonstrating interest in the search for alternative treatments. However, to the best of our knowledge, this is the first systematic review where all the findings of therapeutic effects associated with the consumption of ayahuasca are reviewed.
Ayahuasca is a psychedelic plant-based tea from the Amazon used for spiritual and medicinal purposes. Research suggests its utility in the treatment of various mental health conditions. Potential risks are also being identified. Largely absent from this literature have been the perspectives of ayahuasca ceremony leaders, whose knowledge and experience are vital to understanding the potential risks and benefits of drinking ayahuasca. This qualitative study explored the perspectives of 15 ayahuasca ceremony leaders regarding facilitative ceremony conditions, contraindications, and psychedelic emergencies. An inventory of every concern related to ceremonial ayahuasca use mentioned by the leaders is also presented. The findings are useful for clinicians and policy-makers, and relevant to the application of psychedelic medicine more broadly, informing the dialogue regarding the potential utility of psychedelic-assisted mental health interventions.
Background: The psychoactive stimulant 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy, is widely used in nonmedical settings. Little is known about its cardiovascular effects. Objective: To evaluate the acute cardiovascular effects of MDMA by using transthoracic two-dimensional and Doppler echocardiography. Design: Four-session, ascending-dose, double-blind, placebo-controlled trial. Setting: Urban hospital. Patients: Eight healthy adults who self-reported MDMA use. Intervention: Echocardiographic effects of dobutamine (5, 20, and 40 μg/kg of body weight per minute) were measured in a preliminary session. Oral MDMA (0.5 and 1.5 mg/kg of body weight) or placebo was administered 1 hour before echocardiographic measurements in three weekly sessions. Measurements: Heart rate and blood pressure were measured at regular intervals before and after MDMA administration. Echocardiographic measures of stroke volume, ejection fraction, cardiac output, and meridional wall stress were obtained 1 hour after MDMA administration and during dobutamine infusions. Results: At a dose of 1.5 mg/kg, MDMA increased mean heart rate (by 28 beats/min), systolic blood pressure (by 25 mm Hg), diastolic blood pressure (by 7 mm Hg), and cardiac output (by 2 L/min). The effects of MDMA were similar to those of dobutamine, 20 and 40 μg/kg per minute. Inotropism, measured by using meridional wall stress corrected for ejection fraction, decreased after administration of dobutamine, 40 μg/kg per minute, but did not change after either dose of MDMA. Conclusions: Modest oral doses of MDMA increase heart rate, blood pressure, and myocardial oxygen consumption in a magnitude similar to dobutamine, 20 to 40 μg/kg per minute. In contrast to dobutamine, MDMA has no measurable inotropic effects.
This chapter focuses on medical toxicology, and discusses the predominantly substance-induced effects. However, the general principles of toxicology are also valid in the field of veterinary medicine, and they also apply to physical agents, such as ionizing radiation. Risk assessments for certain ecosystems are discussed with respect to human exposure because otherwise this field requires special expertise, and different priorities must be considered. The assessment of toxicological risk is a difficult process. Evaluation of the necessary clinical and experimental data requires a high degree of toxicological and medical expertise, including a solid medical education and toxicological experience acquired over many years.
A new method for the determination of N,N-dimethyl-5-hydroxytryptamine (bufotenine), N,N-dimethyltryptamine (DMT)*, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), and N-methyltryptamine (NMT) was developed using highperformance liquid chromatography-mass spectrometry (HPLC-MS). Identification of the analytes is based on liquid chromatographic retention times of analytes and two fragment ions produced by a triple quadrupole mass spectrometer. Quantification is based on electrospray ionization (ESI), and multiple reaction monitoring (MRM) was also utilized for getting better selectivity. The analytes and internal standard were separated from the urine matrix by solid-phase extraction (SPE). The method was applied for the determination of these compounds in urine samples of patients from surgical, medical and psychiatric wards. Of the dimethylated amines, only bufotenine was found in significant amounts (up to 34 w g/L). In keeping with our earlier results, the bufotenine excretion of psychiatric patients ...
Abstract The experimental psychosis observed after drinking Hoascareproduces,the pathologic transmethylationtheory of schizophrenia. The occurrence of N,N-dimethyltryptamine (DMT) in the Hoascadrink and in the urine samples of subjects supports now that the biological and neuropsychological effects are produced by this methylated indolealkylamineassisted by the β- carboline derivatives. These results further confirm that the urinary hallucinogenic compounds detected in healthy subjects (post-Hoasca, but not before) are the same as those found in the urine samples of acute psychotic unmedicated,patients. The ability of Hoascato modulate serotonergic receptors was evaluated, and thereby to which extent cortisol, prolactin and serotonin levels as well as perceptual and cognitive processes were affected. The degree of Hoascamonoamine,oxidase (MAO) inhibition was directly correlated with the concentration of MAO- inhibiting β−carbolines. The additive combination,of harmine and tetrahydroharmine (THH) accounts for the MAO inhibition exhibited by Hoasca. Molecular Medicinal Chemistry,IDECEFYN vol 1 July-October 2003, 1- 7 http// ISSN 1666-888X