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Journal of Psychoactive Drugs

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Ayahuasca Preparations and Serotonin Reuptake

Inhibitors: A Potential Combination for Severe
Adverse Interactions
a b
James C. Callaway & Charles S. Grob
a
Department of Pharmaceutical Chemistry, University of Kuopio, Finland
b
Department of Psychiatry, Harbor/UCLA Medical Center, Torrance, California, 90509

To cite this article: James C. Callaway & Charles S. Grob (1998): Ayahuasca Preparations and Serotonin Reuptake
Inhibitors: A Potential Combination for Severe Adverse Interactions, Journal of Psychoactive Drugs, 30:4, 367-369

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 Ayahuasca Preparations and
Serotonin Reuptake Inhibitors:
A Potential Combination for
Severe Adverse Interactions
Downloaded by [Universite De Paris 1] at 21:03 17 May 2013

James C. Callaway, Ph.D.* & Charles S. Grob, M.D.**

Abstract-The Amazonian psychoactive plant beverage ayahuasca has attracted increasing interest
in recent years. Little attention has been given, however, to potentially dangerous interactions with
other drugs. In particular, the interaction between the potent monoamine oxidase-inhibiting harmala
alkaloids in ayahuasca and the selective serotonin reuptake inhibitor (SSRI) class of antidepressants
may induce a serotonin syndrome with potentially grave outcome. Caution is advised when combining
ayahuasca with certain pharmaceutical drugs.

Keywords-ayahuasca, drug interactions, harmala alkeloids, selective serotonin reuptake inhibitor

(SSRI), serotonin syndrome

Ayahuasca (a Quechua word meaning "vine of the enzyme's action is not intrinsically life threatening, lethali­
soul") is a psychoactive beverage that has been use<J for ties from combinations of MAO type-A inhibitors (MAOls)
religious purposes throughout the Amazon and Orinoco with specific serotonin reuptake inhibitors (SSRis) have
River Basins since prehistoric times (Schultes & Hofmann been reported (Neuvonen et al. 1 993). Contraindications
1 992). Also known as hoasca, daime, yage, caapi, natema, between serotonergic drugs and harmala alkaloids, how­
and by many other local names, this beverage characteris­ ever, have not been included in the medical literature.
tically contains harmala alkaloids, which are derived from The use of this beverage has not been limited to indig­
the vine Banisteriopsis caapi (Callaway et al. 1 996; Ott enous groups, and regular use by members of syncretic
1 994, 1 993; Luna & Amaringo 1 9 9 1 ). These alkaloids, religious movements from the urban populations of Brazil
primarily harmine and harmaline, are capable of blocking was already established over 70 years ago (Ott 1 994 ).
the enzymatic activity of monoamine oxidase (MAO) for Proponents of its use contend that ayahuasca benefits
several hours, and consequently inhibit the metabolic break­ the individual, the fam i l y and soc iety. An official
down of neurotransmitters. While the inhibition of this i nvestigation of ayahausca-based religions by the Brazil­
ian health and drug authorities-the Brazilian Divisao de
*Department of Pharmaceutical Chemistry, University of Kuopio,
Finland. Medicamentos do Ministerio da Saude (Dimed) and
•• Associate Professor of Psychiatry, Department of Psychiatry, Conselho Federal de Entorpecentes (Confen), respec­
Harbor/UCLA Medical Center, Torrance, California 90509. tively-eventually led to legislation that protects the use
Please address correspondence and reprint requests to James C.
Callaway, Ph.D., Department of Pharmaceutical Chemistry, University of ayahuasca in Brazil for religious purposes as of August,
of Kuopio POB 1 627, FIN-702 1 1 Kuopio, Finland. 1 987.

Journal of Psychoactive Drugs 367 Volume 30 (4), October - December 1998

 Callaway & Grob Ayahuasca Preparations and Serotonin Reuptake Inhibitors

Recent psychological and biomedical investigations Initially, emergency medical procedures may not
into the long- and short-term effects of ayahuasca have not appear to be indicated, as the initial symptoms of eupho­
shown evidence of adverse physical or psychiatric sequelae ria or confusion, vomiting and tremor are also common
(Callaway et a!. in press; Callaway et a!. 1 996; Grob et a!. with typical doses of ayahuasca (according to the authors'
1 996). In addition, an increased density of [3H]citalopram observations). In serious cases, antidotal therapy is indi­
binding sites on blood platelets suggests a neurophysiologic cated, and treatment should be aggressive, as death can
compensation for the periodic increases in serotonin levels follow within only a few hours. A serotonin antagonist,
following regular (typically biweekly) use of this beverage such as methysergide or cyproheptadine, may be used to
(Callaway et a!. 1 994 ). block symptoms of serotonin syndrome (Copland &
The detrimental consequences of combining MAOis Gorman 1 993). Additional measures may include cooling
with certain foods or medications have been known for sev­ blankets for hyperthermia, artificial ventilation for respi­
eral decades (Goldberg 1964; Blackwell 1963). One aspect ratory i n sufficien c y, a n d the admi n i stration of
of this reaction, known as the "serotonin syndrome" anticonvulsants for possible seizures (Stern back 1 99 1 ).
(Sternback 1 99 1 ), is characterized by excessive levels of Dantrolene may also be indicated to reduce muscle rigid­
the neurotransmitter serotonin (5-hydroxytryptamine, ity and hyperpyrexia (Feighner et a!. 1 990).
5 - HT). Symptoms are typically initial euphoria, nausea and
confusion followed by tremors, vomiting, convulsions and CASE STUDY
loss of consciousness, possibly leading to death in extreme
Downloaded by [Universite De Paris 1] at 21:03 17 May 2013

cases. Therefore, patients are warned of such contra­ J.M, a 36-year-old white male, had been undergoing
i ndications before using MAOis, and physicians typically treatment for mild depression for several months with
scrutinize potential complications with known concurrent fluoxetine (20 mg taken orally each morning) when he
medications. Still, adverse and fatal interactions between participated in a ceremonial ayahuasca session. One hour
combinations of MAOis with SSRis continue to be reported after ingesting approximately 1 00 mi. of ayahuasca, J.M.
(PDR Editors 1 996; Copland & Gorman 1 993; Neuvonen began to experience tremors, sweating, shivering and con­
et a!. 1 993; Peterson 1 99 1 ). Paradoxically, such combina­ fusion. As his symptoms rapidly intensified, he staggered
tions have intentionally been used in the treatment of out of the religious ceremony and collapsed on the ground
intractable cases of depression, where severely attenu­ outside. For the next three hours J.M. reported that he con­
ated serotonin activity is thought to be the underlying cause tinued to sweat profusely, display gross motor tremors and
(Peterson 199 1 ). The combination of MAOis with SSRis experience severe nausea and vomiting. In addition to
blocks two essential pathways for serotonin (centrally, in being disoriented, J.M. also later reported that he had
the neuron): its specific metabolism by MAO-A and its endured profound despair and anguish which were associ­
reuptake into presynaptic nerve terminals, respectively. The ated with mental imagery of his wife. J.M. stated "I
production of serotonin continues unabated (neither increas­ experienced being m y wife during the time I had been
ing or decreasing); only its main pathways of metabolism unfaithful to her, and I went through this horrible pain
are shut down, thus levels increase because nothing is which I knew was the pain she had experienced." J.M.
metabolized, as production continues. However, seroton­ would later describe his experience as having been over­
ergic activity can pass from therapeutic to fatal levels if its whelming, yet valuable in catalyzing a rapprochement with
unchecked production becomes excessive. his wife. Although J.M. reports having been physically
The ability of MAO Is to activate novel drug combina­ incapacitated for several hours and having received no
tions has recently been described to audiences in Europe treatment, he rapidly became asymptomatic after the four­
and North America, through popular magazines, books and hour post-ayahuasca ingestion point. There were no
internet discussion groups related to recreational drug use apparent long-term adverse sequelae.
(Dobkin de Rios 1 994; Ott 1 994; Krajick 1 992). The
potential for adverse and possibly lethal consequences from C ONCLUSI ON
combinations of ayahuasca with serotonergic medications,
however, has received little consideration. In addition, an With the growing popularity of ayahuasca throughout
insidious potential for adverse effects from active metabo­ the Americas and in Europe, there is a need to establish
lites may remain up to five weeks after discontinuing certain clear parameters for optimal efficacy and safety. Although
SSRis (Copland & Gorman 1 993). Under these circum­ a pilot Phase 1 study of short- and long-term effects of
stances, it is conceivable that some of the increasing ayahuasca in the Brazilian Amazon found subjects to be in
numbers of individuals who have already had SSRis pre­ good psychological and physical health (Callaway et a!. in
scribed for them and also try ayahuasca-perhaps as an press; McKenna, Callaway & Grob 1 998; Grob et a!. 1 996;
adjunct to psychotherapy or in the hope of personal devel­ Callaway et a!. 1 996; Callaway et a!. 1 994 ), further inves­
opment-may consequently develop an adverse or lethal tigation is called for. One particular area in need of scrutiny
serotonin syndrome. is the risk of adverse interaction between the monoamine

Journal of Psychoactive Drugs 368 Volume 30 (4), October - December 1 998

 Callaway & Grob Ayahuasca Preparations and Serotonin Reuptake Inhibitors

oxidase-inhibiting harmala alkaloids and other drugs. Given is not insignificant. Those interested in using ayahuasca
that millions of individuals worldwide are currently under­ are strongly cautioned not to combine this ancient plant
going treatment with selective serotonin reuptake inhibitors, medicine with certain classes of modern psychoactive
the potential for incurring a dangerous serotonin syndrome drugs.

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