Minireview

Hallucinogenic botanicals of America: A growing need for focused drug

education and research

John H. Halpern

a,

*, R. Andrew Sewell

b

a

Biological Psychiatry Laboratory, Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital,

115 Mill Street, Belmont, MA 02478, USA

b

Clinical Research Program, Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital,

115 Mill Street, Belmont, MA 02478, USA

Abstract

Botanical sources for medicines in America have been known since long before the arrival of Columbus. Nevertheless, both scientists and the

general public are often unaware that some of these botanical drugs are also potent intoxicants. We provide a quick overview of hallucinogenic and
dissociative drugs harvested from nature or that are openly and legally cultivated in the United States. Examples of harmful outcomes reported in
the media are contrasted with existing responsible ingestion by others, some of whom have the protected right to do so for traditional or
sacramental religious purposes. Despite an ongoing and expensive effort to warn people of the potential harms of recreational drug use, little is
known about the extent of use of these psychoactive botanicals, and the recent explosion of information available via the Internet could herald a
storm of morbidity to come. Mounting more targeted research and educational efforts today may reduce later use and abuse, inform society about
the special circumstances of religious use, and better prepare clinicians and other health care providers about the issues involved when people
choose to indigenously source psychoactive drugs for human consumption.
D

2005 Elsevier Inc. All rights reserved.

Keywords: Hallucinogens; Drug abuse; Religion; Salvia divinorum; Kava lactones; Atropine; Muscimol

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

520

Selected herbal intoxicants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

520

N,N-Dimethyltriptamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

520

Psilocybin and psilocin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

521

Mescaline. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

521

Salvinorin A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

521

Lysergic acid amide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

522

Atropine and scopolamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

522

Ibotinic acid and muscimol. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

522

Kava lactones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

523

Examples of abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

523

Religious use in the US . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

523

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

524

Acknowledgements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

524

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

524

0024-3205/$ - see front matter D 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.lfs.2005.09.005

* Corresponding author. Tel.: [phone]; fax: [phone].

E-mail address: [e-mail] (J.H. Halpern).

Life Sciences 78 (2005) 519 – 526

www.elsevier.com/locate/lifescie

Introduction

Nature retains a vast reservoir of medicines and intoxicants,

many yet to be discovered or fully profiled for safety, efficacy,
or drug interactions. Naturally occurring plant-based psycho-
active drugs are also now gaining popularity in part due to the
ready availability of publicity and information about them
through the Internet (

Halpern and Pope, 2001; Boyer et al.,

2001

). Some are emerging drugs of abuse and others have side

effect profiles that make enduring popularity unlikely. In all
cases, however, these plants are easily identifiable, have well-
defined geographic distributions, or can be legally purchased.
The increase in use and abuse of such psychoactive plants by
young Americans and the ease by which often inaccurate or
incomplete information about them is obtainable means that
clinicians, parents, educators, law enforcement, and policy-
makers need to become increasingly aware of the risks of their
use and abuse. At the same time, there is ample evidence that
the Internet can also be a potent force for drug education
(

Boyer et al., 2005

).

Consider, for example, the herb Salvia divinorum. It

contains a diterpene alkaloid, salvinorin A, which is a kappa-
opiate agonist with known hallucinogenic and dissociative
properties (

Roth et al., 2002

). It already is illegal to market S.

divinorum as a street drug alternative, but should the Food and
Drug Administration in conjunction with the National Institutes
of Health’s National Institute on Drug Abuse (NIDA) and the
Office of Dietary Supplements be offering guidance on herbs
such as this one when they are successfully marketed as
‘‘dietary supplements’’ or as products not sold for human
consumption? A potential purchaser intending to ingest
psychoactive herbs currently will find little official information
from government sources about safety and administration.

This paper offers summaries on several psychoactive

botanicals that can be easily obtained from nature or by
cultivation. Cannabis spp., which contain the psychoactive D

9

-

tetrahydrocannabinol, are already well-publicized, illegal, and
the subject of targeted anti-drug and research efforts, and so are
not addressed in this paper. We offer some examples of harm
from misuse as well as an update on the evolving recognition
that sacramental use may be a constitutionally protected
religious freedom. Taken together, the extent of use and abuse
of botanicals for their psychoactive properties suggests that
research and educational efforts are presently needed to address
a form of substance ingestion that is literally ‘‘home grown.’’

This paper is a byproduct of a presentation given by one of

the authors (JHH) at the NIDA sponsored workshop ‘‘Natur-
eceuticals (Natural Products), Nutraceuticals, Herbal Botani-
cals, and Psychoactives: Drug Discovery and Drug – Drug
Interactions’’ held November 5 – 7, 2004 in Baltimore, MD.

Selected herbal intoxicants

N,N-Dimethyltriptamine

N,N-Dimethyltriptamine (DMT) has been used by humans

in the Amazon for thousands of years in the form of

ayahuasca, a brewed tea containing a mixture of DMT-
containing leaves of the plant Psychotria viridis and the vine
Banisteriopsis caapi (

Schultes and Hofmann, 1992

) which

provides reversible monoamine oxidase inhibitors (MAOIs)—
the h-carbolines harmine, harmaline, and tetrahydroharmine—
without which the DMT would be inactivated in the gut
(

Naranjo, 1979

). Other Amazonian botanical sources of DMT

are the seeds of the Anadenanthera peregrina and bark of the
Virola trees. DMT is hallucinogenic when smoked, inhaled, or
injected but is orally inactive when ingested without an MAOI.
In the United States, DMT has never been a common drug of
abuse. Smoked DMT—the most common method when
illicitly consumed—causes a hallucinogenic experience that
peaks within 2 to 4 min and remits entirely in 20 (

Shulgin and

Shulgin, 1997

), leading it to be referred to as the ‘‘business-

man’s trip’’ during the 1960s because it could in theory be
taken over the course of a lunch break. The acute effects of
ayahuasca and similar oral preparations peak within the first
hour of ingestion, last 3 to 4 h, and are associated with a
considerable amount of nausea and vomiting (

Riba et al.,

2001

). To adherents of faiths in which ayahuasca is sacra-

mentally consumed in religious ceremony, purging is viewed as
a process of spiritual cleansing and physical detoxification.
Many native people of Latin America, especially of Brazil,
Columbia, and Peru, continue to use ayahuasca for traditional
and shamanic purposes, but syncretic faiths blending traditional
beliefs with Christianity also took hold in the last century, most
notably the Santo Daime and Uniao do Vegetal (UDV), both of
which have members residing in many countries outside of the
Amazon (See also ‘‘Religious use in the US’’ below).
Ayahuasca is regarded by these traditional people as well as
members of these religions as an important medicine, used
among other things to assist those in recovery from alcoholism
and drug addiction, although little scientific research has
evaluated these claims to date (

de Rios et al., 2002

).

A synthetic powder, DMT is found in and can be extracted

from common plants growing in much of the United States.
Canary grass (Phalaris aquatica) and related Phalaris tuberosa
and Phalaris arundinacea grow commonly in fallow fields,
lawns, alongside roads, and even in sidewalk cracks (

USDA,

2004

), and many strains also contain variable amounts of DMT

(

Baxter and Slaytor, 1972; Mack et al., 1988

). Known high-

concentration strains of Phalaris can even be legally ordered
over the Internet (

Halpern and Pope, 2001

). The root bark of

another plant common to most of America, the prairie
bundleflower (Desmanthus illinoensis), has been found to be
as much as 0.34% DMT (

Thompson et al., 1987

), making it a

more concentrated natural source of DMT than even the
Psychotria spp. used in the Amazon for ayahuasca.

Although a chemical extraction is beyond the means of most

people without a scientific background, it is relatively easy to
combine American DMT-containing plants with botanical
MAOIs available in this country to concoct an approximation
of the ayahuasca tea used in the Amazon, and people have
reported their self-experimentations on the Internet (

www.

erowid.org/experiences/subs/exp_Ayahuasca.shtml

). The same

h

-carbolines found in ayahuasca are present in Syrian rue

J.H. Halpern, R.A. Sewell / Life Sciences 78 (2005) 519 – 526

520

(Peganum harmala), which grows wild throughout the western
US, and passionflower (Passiflora incarnata), which grows
throughout the Southeast and much of the Midwest (

USDA,

2004

), and recipes for identifying and preparing these plants

are also readily located online. Popular interest in ayahuasca is
increasing in the United States, in part because of aggressive
marketing of Amazonian ‘‘eco-tours’’ which promise an
ayahuasca experience as part of the package, but also because
of the increasing prominence of Santo Daime and UDV
members seeking legal protection—with some success—for
their religious use of ayahuasca in the United States and
Europe. Although no deaths have been reported from
ayahuasca or tryptamine/MAOI combinations, already one
case has been reported of an adolescent who followed
instructions he obtained on the Internet for combining Syrian
rue with the DMT analog 5-methoxydimethyltryptamine (5-
MeO-DMT) and subsequently suffered from MAOI poisoning
(

Brush et al., 2004

).

Psilocybin and psilocin

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and

its lipophilic psychoactive metabolite, psilocin (4-hydroxy-
N,N-dimethyltryptamine) are present in Psilocybe cubensis and
related species of ‘‘magic mushrooms’’ which are found in
many regions of the world including the United States
(

Stamets, 1996

). Coprophagic, they typically grow on cow

and horse manure in the pastures of Florida through to the
southern Gulf States to Texas, and also in the Pacific Northwest
from California into Canada. Sacramental use of psilocybin
pre-dates the reign of the Aztecs (

Wasson, 1961

), and use

continues among some indigenous tribes of the Oaxaca region
of Mexico. The mushroom is illegal to possess when collected
for intoxication and is legal to possess when collected for
legitimate non-consumable purposes such as a genuine hobby
or scientific study of mushroom foraging and identification.
Psilocybe spp. spore prints, which contain no active drug, are
legal in all states except California and Georgia, and are
sometimes packaged in ‘‘home-grow’’ kits available for
purchase through the Internet or classified advertisements of
some ‘‘counter-culture’’ magazines.

One gram of dried mushroom typically contains 10 to 12 mg

of psilocybin, which is orally active at doses of 40 Ag/kg and
can either be eaten or drunk in the form of a tea. The
hallucinogenic experience peaks within 2 h and diminishes
over the next 3 to 4 h (

Stamets, 1996

). The mushrooms are not

lethal and ingestion does not appear to have any lasting health
consequences, although misidentification sometimes leads to
the accidental ingestion of mushrooms that are poisonous
rather than just psychoactive (

Arora, 1986

). There is only one

death reported from P. cubensis ingestion, likely because the
predicted lethal dose of psilocybin—6 g—is much more than
any person could reasonably ingest (

Gable, 2004

). More

concerning are deaths of people who inadvertently consume
toxic mushrooms believing them to be Psilocybe. Three deaths
in the last 30 years have been reported— one from accidental
ingestion of Galerina autumnalis and two from accidental

ingestion of Psilocybe baeocystis (

McCawley et al., 1962

),

although this was likely also a misidentification.

Mescaline

Mescaline (h-3,4,5-trimethoxyphenethylamine) is the prin-

cipal hallucinogenic constituent of the peyote cactus (Lopho-
phora williamsii), constituting up to 1.5% of its dry weight,
although over 60 other alkaloids contribute to its effect
(

Kapadia and Fayez, 1973

). Peyote grows in the desert along

the Texas – Mexico border, and is recognizable as a small
‘‘button’’ or crown visible above the earth and a longer carrot-
like tuber descending into the earth. Properly harvested, the
remaining root will slowly re-grow several buttons available
for future harvest. Peyote is peeled and eaten fresh, dried, or
powered, or the dried powder is reconstituted into a tea or
slurry, but peyote is never smoked. Its taste is bitter and acrid
enough to induce nausea and vomiting, but in doses of 4 mg of
mescaline per kg of body weight will produce a potent
intoxication that peaks within 2 – 4 h and resolves over the
subsequent 4 – 6.

Peyote is consumed chiefly in the context of religious

ceremonies of the Native American Church (NAC), the
300,000 members of whom participate in all-night peyote
ceremonies as frequently as once a week or as infrequently as a
few times a year, with average participation occurring monthly.
The NAC does not prohibit the practice of other traditional and
religious beliefs by its members, but all alcohol and drug use is
proscribed. Ceremonies take place in a tipi or other traditional
structure and bring together families, neighbors, special guests,
and other visitors. Ceremonies mark special occasions such as
a child returning from college or a birthday, or serve a
particular purpose such as promoting the health of a loved one,
resolving conflict within a family, or ensuring the safety of
church members serving in the military. Peyote ingestion is not
required in order to participate in the ceremony—as little as a
few drops might be placed on a child’s lips in order to serve as
a blessing—but typically adults will consume several teas-
poons or more of the tea (

Stewart, 1997

).

Mescaline is found not just in peyote but in other cacti such

as San Pedro (Trichocereus pachanoi) and Peruvian torch
(Trichocereus peruvianus), the former of which contains
0.33% – 2.4% mescaline (

Crosby and McLaughlin, 1973;

Helmlin and Brenneisen, 1992

) and can be purchased online

or from most local garden shops.

Salvinorin A

Salvinorin A is a diterpine alkaloid structurally unrelated to

any other hallucinogen that is a potent and selective agonist at
the kappa opioid receptor (

Roth et al., 2002

). It is found in the

glandular trichromes of the mint S. divinorum, a plant initially
only cultivated in gardens of a few Mazatec shamans of
Oaxaca, Mexico but now grown by amateur ethnobotanists to
commercial sellers of the leaves or extract (

Siebert, 2004

). The

Mazatec typically chew fresh leaves or drink the juice of the
leaves to orally absorb salvinorin A (

Valdes et al., 1983

), but in

J.H. Halpern, R.A. Sewell / Life Sciences 78 (2005) 519 – 526

521

the US, users also smoke it. S. divinorum smoked is active
for about 15 min at doses of 200 to 500 Ag of salvinorin A, but
oral administration results in an hour or longer intoxication
(

Siebert, 1994; Valdes et al., 1983

). Although S. divinorum is

not scheduled, it is being closely monitored by the Drug
Enforcement Administration (DEA) as a potentially emerging
drug of abuse (

National Drug Intelligence Center, 2003

).

Because of an increasing problem of abuse in the community,
the town of St. Peters, Missouri became the first to ban sale
of S. divinorum to under-eighteen year olds in January of
2003 with escalating fines starting at $25 (

http://www.usdoj.

gov/ndic/pubs3/3842/

). In addition, the Hallucinogen Control

Act of 2002 (House Resolution 5607) contained provisions
to regulate Salvia and salvinorin A but was not voted on
by the 107th Congress. S. divinorum does not appear to be
reinforcing and there have been no reported health risks,
although poor preparation or the resultant impaired judgment
of intoxication could lead to a number of health and safety
problems. Salvinorin A extract is available over the Internet
for $100 – $300 an ounce and the plants themselves sell for
$20 – $45 each.

Lysergic acid amide

Lysergic acid amide (LSA), a relative and precursor to

lysergic acid diethylamide (LSD), is found in the seeds of
the Hawaiian baby woodrose (Argyreia nervosa) and
morning glory (Ipomoea violacea), which can be crushed,
eaten, or soaked and drunk to provide a 4 to 8 h intoxication
that is similar to that provided by LSD, though there are
reportedly consistent qualitative and quantitative differences
(

Schultes and Hofmann, 1980

). Five to 10 woodrose seeds,

which are 0.14% LSA by dry weight (

Al-Assmar, 1999

), or

150 – 200 morning glory seeds (0.02% LSA) provide 2 to 5
mg of the compound—an active dose (

Weber and Ma, 1976

).

Sleepygrass (Stipa robustum), which grows in the South-
western United States contains even higher concentrations of
LSA, although unlike Ipomoea, which has been used for
thousands of years by Central American Indians in shamanic
and traditional ceremonies, it appears to have no history of
use or abuse in such a manner (

Petroski et al., 1992

).

Morning glory and Hawaiian baby woodrose seeds are
available commercially but are usually coated with an emetic
to discourage ingestion; instructions for removing this
coating are found on the Internet, or the erstwhile user can
patiently grow these striking flowers in the garden for later
seed harvest.

Atropine and scopolamine

Atropine and scopolamine are found in jimson weed

(Datura stamonium), nightshade (Atropa belladonna) and
mandrake (Mandragora officionarum), and scopolamine
alone is found in henbane (Hyoscyamus niger) (

Brown and

Taylor, 2001

), all of which are popularly grown as orna-

mental flowers, although Datura, a sprawling herbaceous
shrub with fragrant, trumpet-shaped flowers, grows wild in

every state except Wyoming and Alaska. The seeds are the
most potent part of the plants, followed by the roots, stems,
leaves, and flowers, and as few as ten seeds are sufficient for
psychoactivity. Dissociative rather than wholly hallucinogen-
ic, both chemicals act as central nervous system depressants
and competitively antagonize muscarinic cholinergic recep-
tors. They have considerable application in ophthalmology to
dilate pupils, anesthesia to decrease secretions and treat
bradycardia, toxicology to treat organophosphate and nerve
gas poisoning, and in emergency medicine for cardiac arrest.
Scopolamine is also used as a treatment for motion sickness.
The Zuni Indians use Datura inoxia as a poultice and
analgesic, as do the Yucateco and Lacondon Maya (

Litzinger,

1994

), and there are records of the Aztecs using it for skin

ulcers, hemorrhoids, and anesthesia. Nevertheless, in over-
dose, the plants can cause a toxic delirium that lasts hours to
days, marked by amnesia, confusion, dissociation, hallucina-
tions, delusions, euphoria, and sometimes episodes of bizarre
self-injury (

Grinspoon and Bakalar, 1997

). Some symptoms

such as headache and mydriasis can persist for weeks.
Shamanic use amongst Native Americans and other indige-
nous people throughout the world dating back four thousand
years is well described (

Litzinger, 1981

), but recreational use

is uncommon because of the frightening adverse side effect
profile and is usually limited to teenagers who do not heed
the warnings. Popular accounts of Datura use such as Carlos
Castaneda’s infamous book, ‘‘The Teachings of Don Juan:
Yaqui Way of Knowledge’’ (

Castaneda, 1968

) indirectly

encourage dangerous use by describing several different
Datura preparations without containing adequate warnings
of the side effects.

Ibotinic acid and muscimol

Ibotinic acid and muscimol are the key psychoactive

ingredients in the fly agaric (Amanita muscaria) and panther
cap (Amanita pantherina), members of a class of mushrooms
that contain some deadly varieties. Ibotinic acid is a glutamate
receptor agonist, muscimol a g-aminobutyric acid (GABA)-
receptor agonist, and together they produce a state remarkable
for powerful hallucinations and delusions, slurred speech and
incoordination, headaches, nausea and vomiting, unconscious-
ness, and an alcohol-like euphoria. Ironically, despite the
species name muscaria, anticholinergic effects are actually
minimal. Ingestion leads to psychoactivity that starts within 30
min and peaks over the next 2 – 3 h (

Waser, 1979

), and the

ibotinic acid is excreted unmetabolized in the urine, leading to
some shamanic practices of reserving and drinking of urine
from individuals who have consumed Amanita ceremonially
(

Wasson, 1979

). The mushrooms grow wild throughout the

United States and continue to be used in the traditions of some
indigenous people of the Arctic Circle and some Native
American tribes. Amanita poisoning through recreational use
is rare, and the chief risk appears to be misidentification and
ingestion of more toxic species such as death cap (Amanita
phalloides), which commonly grows in close proximity to
muscaria and other Amanita spp.

J.H. Halpern, R.A. Sewell / Life Sciences 78 (2005) 519 – 526

522

Kava lactones

The dried roots and rhizomes of the shrub Piper methysti-

cum are known as kava (or kava kava), and by grinding these
and making a tea, native Polynesians for centuries have been
brewing a mildly intoxicating beverage that has been found
to relieve menstrual cramps to toothaches and has hypnotic,
anxiolytic, and muscle relaxant properties (

Singh, 1992

). The

effects of the kava intoxication are commonly descri- bed as
‘‘dream-like’’ by users, which may explain why some
mistakenly assert that it is mildly hallucinogenic. It is
potentiated by alcohol, barbiturates, and opiates and can in
excess cause ‘‘kavaism,’’ a form of icthyosis combined with
red, irritated eyes (

Ruze, 1990

) as well as hepatitis and liver

failure (

Stickel et al., 2003

). There are six active ingredients in

kava including methysticin, and all are closely related mono- or
di-unsaturated a-pyrones (‘‘kava lactones’’) that make up
between 5% – 10% of the resin extracted from kava roots. All
are potent, centrally acting skeletal muscle relaxants, and their
antipyretic, anxiolytic, and anesthetic effects are thought to
occur through their actions on voltage-dependent ion channels
(

Cairney et al., 2002

) and actions at the glutamate and GABA

receptors (

Grunze et al., 2001

). Cognitive side effects are not

typically observed, in contrast with other hypnotics (

Bilia et al.,

2002

). Although the Food and Drug Administration (FDA)

issued a federal advisory in early 2002 warning people to
discontinue taking kava until the risks of liver damage were
further quantified (

Anonymous, 2002

), and several European

countries have banned it because of the risks of liver toxicity, it
continues to be widely available and even recommended in
health food stores (

Mills et al., 2004

) and is the seventh best-

selling herbal supplement in the US (

Morris and Avorn, 2003

).

Prior to 1980 it was almost entirely restricted to the islands of
Vanuatu, but kava bars appeared in Hawaii in 1999 and have
since begun to appear on the mainland — suggesting that kava
abuse, while still relatively restricted to Polynesians, may be
poised to make inroads into the US population. 6.6% of herbal-
supplement taking adults use kava kava (

Barnes et al., 2004

),

and kava’s inhibition of virtually all cytochrome P-450
enzymes make potentially harmful drug interactions almost
certain with many medications (such as many serotonin-
selective reuptake inhibitor antidepressants). Fewer than half
of those using herbal supplements think to disclose information
to their physicians (

Eisenberg et al., 1998

), making it all the

more important for health care providers to query patients
about their use of dietary supplements and herbal cures, and the
extent to which they rely on the Internet for health-related
information.

Examples of abuse

Reports in the media and especially in the scientific

literature about the botanicals described above are uncommon.
A few examples of these reports follow, but data on the
population of users and the extent of use has not been fully
quantified by researchers or in surveys of drug use such as the
Monitoring the Future survey (

Johnston et al., 2004

) or the

National Survey on Drug Use and Health (

Wright and Sathe,

2005

). Similarly, the Substance Abuse and Mental Health

Services Administration’s Drug Abuse Warning Network
survey of emergency room visits has yet to issue a special
topic report or feature data specific to the ingestion of
psychoactive herbs (see

http://dawninfo/samhsa.gov

).

S. divinorum has escaped the shaman’s medicine bag and is

purchasable online and through smoke shops throughout the
United States. Most media reports sensationalize this access,
but abuse appears limited, in part, because salvinorin A is
apparently non-addictive and the intense effects of the
intoxication appear to be so disturbing as to be a disincentive
for repeat purchases (

Halpern, 2003

). Nevertheless, concerns

are being expressed about what impact S. divinorum could
have upon adolescents and others, should the herb become a
much more ‘‘attractive’’ and popular intoxicant (

Bu¨cheler et al.,

2005

).

Datura intoxications by teens sometimes prove lethal. Two

teenagers died in Texas in 1994 after mixing jimson weed with
alcohol (

Anonymous, 1995

), another died in Greece after

eating pure seeds (

Boumba et al., 2004

).

Harm is occasionally reported about users of psilocybin-

containing mushrooms and a pattern of factors appear related to
these negative outcomes. Risk factors include youth, male sex,
ignorance of the effects of psilocybin, and intoxication in a
public setting with little or no supervision. A Cleveland
teenager who was shot to death after attacking a police
officer with a knife had apparently triggered a psychosis by
consuming mushrooms the previous day (

Tinsley, 2003

). A

New York university student with no history of mental illness
combined psilocybin with marijuana then leaped to his death
from the tenth floor of a library (

Arenson, 2003

). A sixteen-

year-old Californian taking mushrooms for the first time died
after falling from a highway overpass (

Erwin, 2003

). A Florida

teen developed liver failure from drinking a tea from what he
thought was P. cubensis that he had picked but drank instead A.
phalloides (

Woitas, 1997

). One 17-year-old girl in Los Angeles

left her house after consuming ‘‘magic mushrooms’’ and was
struck and killed when she wandered onto a highway (

Salliant,

2004

). In all cases, deaths occurred from mistaken ingestion of a

toxic mushroom or lack of supervision while intoxicated rather
than from pharmacological effects of psilocybin.

Kava has caused eleven cases of hepatotoxicity, including

four that proved lethal (

Clouatre, 2004

). Interestingly, it has

been suggested that it is the lack of glutathione in kava extracts
that is responsible rather than the natural botanical itself
(

Whitton et al., 2003

).

Religious use in the US

Peyote use continues to be protected for traditional and

sacramental purposes for members of federally recognized
Native American tribes (further details on religious use and
about the psychoactive botanicals that grow in America can
also be obtained from a published paper resulting from the
NIDA and Office of Natural Products sponsored workshop
‘‘Psychoactive Botanical Products’’ (

Halpern, 2004

)). The

J.H. Halpern, R.A. Sewell / Life Sciences 78 (2005) 519 – 526

523

Native American Church holds peyote as their holy sacrament
and has more members than any other single religion among
this racial minority. Protected status for the NAC’s access to
peyote is established through the American Indian Religious
Freedom Act Amendments of 1994, and the Code of Federal
Regulations expressly states at 21 CFR 1307.31 (as of February
11, 2005) that ‘‘the listing of peyote as a controlled substance in
Schedule I does not apply to the nondrug use of peyote in bona
fide religious ceremonies of the Native American Church, and
members of the Native American Church so using peyote are
exempt from registration.’’

Gaining increasing media attention, however, is the use of

ayahuasca by the UDV in the United States. The American
branch of this religion has succeeded in obtaining a federal
judicial injunction against the US Department of Justice and
more specifically the Drug Enforcement Administration from
enforcing drug laws against UDV members who ingest
ayahuasca as part of the religious ceremonies of the church.
This injunction also orders the government to enter into
negotiations with the UDV about how to safely import
sacramental ayahuasca without increasing a risk for diversion.
In late 2004, the full 10th Circuit Court of Appeals ruled 8 – 5
in favor of the UDV with Circuit Judge Seymour writing in his
opinion that ‘‘this case satisfies even the heightened standard
for preliminary injunctions. The applicable statute

. . .sets

a

most demanding burden of proof for the government: the
compelling interest test. The factual findings of the district
court, which are not challenged on appeal, make it clear that the
government has not and cannot meet that burden on this record,
and that the balance of equities is overwhelmingly in favor of
the movant’’ (UDV). Not surprisingly, the government has filed
an appeal to the Supreme Court, and, if accepted, the case
would be argued in the 2005 – 2006 docket. This litigation
apparently is poised to clarify whether even religious persecu-
tion is acceptable when the government claims that it is more
important to combat illicit drug use than to protect freedom of
religion.

Conclusion

Hallucinogens and dissociatives are not just clandestinely

manufactured for illicit distribution, but also occur naturally
in plants that either grow wild or are easily cultivated or
obtainable from nurseries or over the Internet. Accidental
ingestion, misidentification, and use despite ignorance of
correct dosages do lead to morbidity and emergency room
visits. Although the extent of illicit recreational use of these
botanicals appears to be minimal in comparison to more
dangerous drugs of abuse such as cocaine or heroin,
psilocybin use is fairly common and S. divinorum use is
becoming increasingly popular to the point that it is attracting
the attention of law enforcement authorities. These botanicals
are attractive alternates to harder-to-find psychedelics such as
LSD because these herbs are for the most part legal and
easily available, and with the advent of the Internet,
information on acquisition, cultivation, dosage, and adminis-
tration is not hard to come by. Intoxication with these

botanicals likely will become increasingly popular and the
occasional reports of harm could become much more
frequent. And yet, as noted above, none of the national
surveys on drug abuse attempt to capture data on those who
ingest these psychoactive herbs.

In contrast to those seeking only drug intoxication,

legitimate use of psychoactive botanicals in religious ceremo-
nies do exist in the United States. The NAC has an exemption
to federal drug laws prohibiting ingestion of peyote for use in
religious ceremonies, and practitioners of this religion do so
without any need for law enforcement or medical supervision.
The UDV and Santo Daime churches now are seeking similar
protections for their religious use of ayahuasca, and, remark-
ably, the UDV has so far prevailed in federal court.

Many botanicals, such as S. divinorum and kava kava, that

were initially geographically restricted are now widely
available; others grow ubiquitously and are quickly identified
by any determined individual. Drug education efforts need to
expand awareness among physicians of the potential sequelae
of such unauthorized use, and care must be taken to
distinguish legitimate sacramental use from irresponsible
and potentially harmful casual use. Education efforts should
also become more specific to those botanicals expected in a
given geographic region. Although Internet-based information
with inadequate notification of potential side effects and
interactions is an increasing problem also in need of more
focused drug education efforts, when properly used, the
Internet already is an invaluable health resource and drug
education tool.

Acknowledgements

This work was supported in part by a Career Develop-

ment Award (K23-DA00494) (JHH) and a National Research
Scholars Award (T32-DA07252014) (RAS) from the National
Institute on Drug Abuse, National Institutes of Health, Rock-
ville, MD, and a grant from the Multidisciplinary Association
for Psychedelic Studies, Sarasota, FL.

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