PEYOTE ON THE BRAIN

Is the Secret to Alcoholism and Other Addictions Locked Up in the
Hallucinogenic Drugs?

Even with several tablespoons of peyote in me, by 3 in the morning I'm
fading. For almost six hours I have been sitting in a tepee in the Navajo
Nation, the largest Indian reservation in the United States, with 20 Navajo
men, women, and children. They belong to the Native American Church, which
has 250,000 members nationwide. Everyone except the four children has eaten
the ground-up tops, or buttons, of peyote, Lophophora williamsii. U.S. law
classifies the squat cactus and its primary active ingredient, mescaline, as
Schedule 1 substances, illegal to sell, possess, or ingest. The law exempts
members of the Native American Church, who revere peyote as a sacred
medicine.

A barrelchested man wearing a checked shirt and cowboy boots stands over the
cedarwood fire and murmurs a prayer in Dine, the Navajo language. As this
roadman, or leader of the service, sprinkles sage on the coals, my eyelids
close. I smell the sage and hear it hiss, and I see the roiling geometric
patterns, called form constants, generated by compounds such as mescaline.
Then the balding white man on my right nudges me and tells me to keep my
eyes open. The Navajo might be offended, he whispers, if they think I have
fallen asleep. Later, he shakes his head when I lean on an elbow to relieve
the ache in my back. Too casual, he says.

My guide to the etiquette of peyote ceremonies is John Halpern, a
34-year-old psychiatrist from Harvard Medical School. For five years he has
been coming here to the Navajo Nation -- 27,000 square miles of
sage-speckled desert stretching from northern Arizona into New Mexico and
Utah -- to carry out a study of peyote. Funded by the National Institute of
Drug Abuse, the study probes members of the Native American Church for
deficits in memory and other cognitive functions. Halpern has brought me
here to help me understand him and his mission, which is to provoke a
reconsideration of the pros and cons of hallucinogenic drugs, commonly
referred to as psychedelics.

Coined in 1956 from the Greek roots for "mind revealing," the term
psychedelic refers to the broad range of drugs that include peyote, LSD, and
psilocybin, the primary active ingredient in so-called magic mushrooms.
Three decades ago the federal government shut down most research on
psychedelics, and The Journal of the American Medical Association warned
that they can cause permanent "personality deterioration," even in
previously healthy users. Halpern says this blanket indictment is "alarmist"
but agrees that there are documented dangers associated with the
recreational use of the drugs. When ingested recklessly in large doses,
psychedelics can generate harrowing short-term experiences, and they can
precipitate long-term psychopathology in those predisposed to mental
illness. Nonetheless, more than 20 million Americans have tried a
psychedelic at least once, and 1.3 million are users of the drugs, by far
the most popular of which is now MDMA, or Ecstasy. Halpern undertook his
peyote research in part to test persistent fears that those who repeatedly
use psychedelics run a high risk of brain damage.

While recognizing that psychedelics are toxic substances that should not be
treated lightly, Halpern thinks some of the drug compounds could have
beneficial uses. "There are medicines here," he says, that could prove to be
"fundamentally valuable." He hopes the mind-revealing power of psychedelics
can be harnessed to help alleviate the pain and suffering caused by two
deadly diseases that have long been notoriously resistant to treatment:
alcoholism and addiction. More than 12 million Americans abuse alcohol, and
another 1 million abuse cocaine or heroin.

Halpern's conviction that psychedelics might help alcoholics and addicts is
based both on research by others and on his personal observations of members
of the Native American Church. Although Indians in central and northern
Mexico, peyote's natural habitat, have ingested it for spiritual purposes
for thousands of years, only in the last century did this practice spread to
tribes throughout North America in the form of rituals of the Native
American Church.

All the subjects of Halpern's research are Navajo, who account for roughly
10 percent of the church's membership and hold key leadership positions.
Even though tribal leaders have banned alcohol from their reservation,
alcoholism is still rampant. For the Navajo and other tribes, rates of
alcoholism are estimated to be more than twice the national average. Those
in the Native American Church say their medicine helps keep them sober and
healthy in body and mind, and Halpern suspects they are right.

He first took peyote himself five years ago, shortly after presenting his
research plan to leaders of the Native American Church. "It would have been
supremely insulting to them if I didn't try it. So I tried it." Halpern also
hoped that firsthand experience would help him understand how peyote
ceremonies might benefit church members. He checked beforehand with the U.S.
Drug Enforcement Agency, which told him that it would not object to peyote
use by non-Indians for serious scientific, educational, or journalistic
purposes. Halpern has participated in five services in all, including the
one we both attend, and these experiences have imbued him with respect for
the Indians and their faith. When I expressed curiosity about the
ceremonies, he said the best way to appreciate them is to participate in
one. He warned me that the ceremonies are in no way recreational or fun, and
our session in Arizona bears that out.

Like most Native American Church services, this one has been called for a
specific purpose -- in this case, to help a wife and husband burdened with
medical and financial problems, all too common on the reservation. Except
for Halpern and me, everyone is a friend or relative of this couple; some
have traveled hundreds of miles to be here. The meeting lasts for ten hours
with only a single 10-minute break, and it unfolds in a rhythm of rituals:
smoking tobacco rolled in corn husks; singing hymns in Dine or other Native
American languages to the pounding of a deerskin drum; eating peyote and
drinking peyote tea passed around in bowls, three times in all.

There is a spellbinding beauty in the incantations of the roadman, in the
sparks spiraling up from the bed of coals toward the tepee's soot-blackened
roof, in the stoic expression of the elder who adds cedar logs to the fire
and rakes the coals into a half circle. But none of the worshippers seems
lost in blissful aesthetic reveries. Far from it. For much of the night, the
mood is solemn, even anguished. Two people vomit, including the wife. Both
she and her husband sob as they confess their fears and yearnings. So do
others as they listen, offer prayers, or divulge their own troubles --
usually in Dine, but occasionally in English.

The power of these ceremonies, Halpern tells me later, is only partly
pharmacological. After all, worshippers usually eat just a few tablespoons
of peyote, which amounts to less than 100 milligrams of mescaline -- enough
to induce a stimulant effect but not full-fledged visions. Peyote, Halpern
speculates, serves primarily as an amplifier of emotions aroused by the
ceremony's religious and communal elements. He cannot prove this conjecture
yet, nor can he say how or if the putative benefits of these sessions might
be achieved by non-Indians in more conventional psychotherapeutic settings,
"A lot more work needs to be done to answer such questions," he says.

His creeping baldness notwithstanding, Halpern looks younger than his age.
He can be brash too. During our weekend in Navajo country -- where we visit
a substance-abuse clinic and meet a Native American Church leader as well as
attend the peyote session -- he exults in displaying his knowledge of
psychedelic chemistry and his talent for mimicry. A nightclub owner once
said his impressions were good enough for a stage act, he boasts. (Actually,
he is good, especially at obscure sitcom characters like Colonel Klink's
irritable commander in Hogan's Heroes: "Kleenk, you EE-dee-ot!")

Halpern says he does have "an abrasive, sarcastic side." But he also has an
earnest, idealistic side that comes to the fore when he talks about his
upbringing. Raised in a Jewish home in an affluent New York suburb, he was
never particularly religious, but he inherited a passion for healing from
his psychiatrist father and his psychologist mother. They convinced him that
"medicine is the highest profession you can have, because it's such a
privilege to work with human beings and to heal them."

He traces his interest in psychedelics to the early 1990s. Interning at a
psychiatric hospital in Brooklyn, New York, he became frustrated that he
could not offer better treatments for alcoholic or drug-addicted patients.

During a weekend at his parent's home, he vented to a visiting family
friend, Chunial Roy, an Indian-born psychiatrist who had settled in western
Canada. Roy recalled that in the 1950s, he did a survey of alcoholism among
Indians in British Columbia and found low rates among members of the Native
American Church. Roy added that psychedelics such as LSD had once been
considered promising treatments for addiction and other disorders.

"I was so fascinated that I did all this research," says Halpern, who had
never taken psychedelics and knew little of their history. He learned that
LSD, mescaline, and psilocybin, initially viewed as mimickers of the
symptoms of mental illness, came to be seen as potential treatments. From
1950 to the mid-1960s, journals published more than 1,000 papers describing
the treatment with psychedelics of 40,000 patients afflicted with alcoholism
and various other disorders.

One early advocate of psychedelic therapy was William Wilson, known more
familiarly as Bill W., who founded Alcoholics Anonymous in 1935. After
observing alcoholics undergoing LSD treatment and taking the drug himself in
1956, Wilson became convinced that it might benefit alcoholics by triggering
religious experiences like the one that had helped him stop drinking. The
studies that instilled these hopes in Wilson and others were largely
anecdotal, lacking controls, or flawed; they were nonetheless suggestive
enough, Halpern thought, to merit follow-up investigations.

After Halpern began his residency training at Harvard Medical School in
1996, he found a mentor: Harrison G. Pope Jr., a professor of psychiatry who
had investigated marijuana and other psychotropic drugs. Halpern and Pope
have coauthored several papers, notably one that considers whether
hallucinogens cause permanent neurocognitive damage, as some early critics
claimed. "At present," they wrote, "the literature tentatively suggests that
there are few, if any, long-term neuropsychological deficits attributable to
hallucinogen use." They contended that most studies linking psychedelics to
neurocognitive toxicity examined too few subjects and did not control
adequately for pre-existing mental illness of for consumption of other, more
toxic substances, such as amphetamines and alcohol.

It was to help resolve this lingering controversy that Halpern and Pope
decided to examine the Native American Church, which offered a large
population that consumes a psychedelic substance while avoiding other drugs
and alcohol. Halpern and Pope won grants for their project not only from the
National Institute on Drug Abuse but also from Harvard Medical School and
two private foundations that support research on psychedelics: the
Multidisciplinary Association for Psychedelic Studies and the Heffter
Research Institute (named after the German chemist who isolated mescaline
from peyote and discovered its psychoactive properties in the late 1800s).

Obtaining the cooperation of Native American Church officials turned out to
be more difficult. Many disliked the idea of having their faith scrutinized
by a scientist, especially a white one. After Halpern gave his pitch to one
church gathering, a tribal elder harangued the crowd in Navajo for 20
minutes. Finally he turned to Halpern and, angrily evoking the specter of
Christopher Columbus, exclaimed: "1492!" Another difficult moment came
during his first peyote session. The roadman kept insisting that Halpern
take more peyote, until finally he vomited. Halpern felt that the roadman's
implicit message was, "You want to learn about peyote? I'll teach you about
peyote."

Halpern persisted, coming to meetings bearing gifts of sweet grass and flat
cedar, aromatic herbs prized by Indians. "I was trying to show I took the
trouble to learn something about their culture." He trolled for volunteers
for his research by putting up ads in Laundromats and handing out flyers at
a flea market in Gallup, New Mexico. (The $100 promised to those who
completed the study helped too.)

One church leader who persuaded others in the flock to trust Halpern was
Victor J. Clyde, vice president of the Native American Church of North
America and an elected state judge. During our trip to the Navajo Nation,
Halpern and I visited Clyde in Lukachukai, Arizona, where he lives with his
wife and three children. Clyde is compact and broad-shouldered, and he
speaks with the tough self-assurance of a former prosecutor.

When I asked what the Native American Church stands to gain from Halpern's
work, Clyde replied that scientific evidence of peyote's safety should
protect church members. Just last year, the Pentagon cited concerns about
"flashbacks" -- recurrences of a psychedelic's effects long after it has
vanished from the body -- in barring servicemen in the Native American
Church from sensitive nuclear assignments. Didn't Clyde ever worry that
Halpern's research might turn up harmful effects? Clyde eyed me momentarily
before responding to my question. If peyote was harmful, he said firmly, his
people would have noticed by now.

Clyde's belief that peyote does not harm church members has been
corroborated by Halpern's research. He estimates that he spoke to 1,000
Navajo before finding 210 who met his criteria. The subjects fall into three
categories: Roughly one-third have taken peyote at least 100 times but have
minimal exposure to other drugs or alcohol; one-third are not church members
and have consumed little or no alcohol or drugs; and one-third are former
alcoholics who have been sober for at least three months.

Halpern and several research assistants administered a battery of tests --
of memory, IQ, reading ability, and other cognitive skills -- to the three
groups. According to preliminary data that he has presented at conferences,
church members show no deficits compared with sober nonmembers and score
significantly better than the former alcoholics. Church members also report
no flashbacks. With his coauthor Pope, Halpern plans to publish his full
results in a peer-reviewed journal this summer, after presenting them to
church leaders and Navajo health officials.

Halpern is already anticipating objections to his research -- for example,
that its significance applies only to one substance used by one ethnic
group. "You could in one sense say mescaline is not the same as all these
other compounds," he says. His study nonetheless indicates that psychedelics
as a class may not "burn out" the brain. "If we find this group of people
that, with these special conditions, aren't having problems, that does have
some relevance for the population at large."

Halpern also realizes that he may be accused of going native, of becoming so
close to his subjects that his objectivity has been compromised. To reduce
the risk of bias, he and Pope designed the study to be blind; those who
scored the tests given to the Navajo did not know to which group each
subject belonged. Moreover, Halpern did not participate in peyote ceremonies
with any of his research subjects.

Perhaps the biggest weakness of his and Pope's research, Halpern
acknowledges, is that its design precluded testing to see whether peyote
reduces the risk of alcoholism. Halpern would like to see that issue
addressed in a follow-up study. An ideal partner for a trial could be the
Na'nizhoozhi Center, a substance-abuse clinic in Gallup whose clientele is
almost entirely Native American. The center, founded a decade ago, offers
conventional therapies and self-help programs, such as Alcoholics Anonymous,
as well as various traditional Indian healing ceremonies. These take place
in a yard behind the clinic that is large enough for several of the
octagonal log cabins known as hogans, sweat lodges, and a tepee for Native
American Church sessions. Although peyote is not given to patients during
on-site church sessions, staff members encourage some clients to participate
in regular peyote ceremonies once they leave the clinic.

The clinic's records indicate that those who participate in Indian healing
ceremonies fare better than those who have participated in Alcoholics
Anonymous. Halpern hopes that someday the clinic, perhaps with his help,
will rigorously compare the relapse rates of patients who participate in
peyote ceremonies versus other treatments. Ideally, to distinguish the
effects of peyote per se from those of the ceremony and of church
membership, one group of alcoholics could receive peyote in a non-religious
setting; another group could receive a placebo.

Halpern would never recommend such a protocol, however, because it would
violate precepts of the Native American Church. "Peyote taken the wrong way,
they believe, is harmful," he explains. Out of respect for the church,
Halpern would never advocate testing peyote's effects on non-Indians,
either. In this respect, he acknowledges, his affection for church members
does influence his role as a researcher.

But there are many other compounds that can be explored as potential
treatments for non-Indians. In a 1996 paper, Halpern reviewed scores of
studies of the treatment of substance abuse with psychedelics and found
tentative evidence that they reduce addicts' craving during a post-trip
"afterglow" lasting a month or two. This effect might be at least partially
biochemical; LSD, mescaline, and psilocybin are known to modulate
neurotransmitters such as serotonin and dopamine, which play a crucial role
in the regulation of pleasure.

One possible candidate for psychedelic therapy would be dimethyltryptamine,
or DMT, the only psychedelic known to occur naturally in trace amounts in
human blood and brain tissue. DMT is the primary active ingredient of
ayahuasca, a tea made from two Amazonian plants. Like peyote, ayahuasca has
been used for centuries by Indians and now serves as a legal sacrament for
several Brazilian churches. Recent studies of Brazilian ayahuasca drinkers
by Charles Grob, a psychiatrist at the Harbor-UCLA Medical Center, and
others suggest that ayahuasca has no adverse neurocognitive effects. An
advantage of DMT, Halpern says, is that when injected its effects last less
than an hour, and so it could be incorporated into relatively short
therapeutic sessions.

Halpern already has research experience with DMT. In 1994 he spent six weeks
helping Rick Strassman, a psychiatrist at the University of New Mexico,
inject DMT into volunteers to measure the drug's physiological effects. That
study showed that DMT is not necessarily benign. Twenty-five of Strassman's
60 subjects underwent what Strassman defined as "adverse effects," ranging
from hallucinations of terrifying "aliens" to, in one case, a dangerous
spike in blood pressure. Strassman's concerns about these reactions
contributed to his decision to end his study early.

An even more controversial candidate for clinical testing is
3,4-methylenedioxymethamphetamine, more commonly known as MDMA or Ecstasy.
MDMA is sometimes called an empathogen rather than a psychedelic, because
its most striking effects are amplified feelings of empathy and diminished
anxiety. Advocates contend that MDMA has therapeutic potential, and several
researchers around the world are now administering the drug to patients with
post-traumatic stress and other disorders.

Critics point out that MDMA has rapidly become a drug of abuse, with almost
800,000 Americans believed to be users. The drugs has been linked to fatal
overdoses and brain damage; just last fall, a paper in Science reported that
only a few doses of MDMA caused neuropathy in monkeys. To help resolve
questions about MDMA's safety, Halpern and Pope have begun a study of young
Midwesterners who claim to take MDMA while shunning other drugs and alcohol.

All drugs pose certain risks, Halpern says. The question is whether the
risks are outweighed by the potential benefits for a population. For
example, the benefits of giving MDMA to terminal cancer patients to help
them cope with their anxiety might outweigh the risks posed to their health.
In the same way, DMT or some other psychedelic might be worth giving to
alcoholics and addicts who have failed to respond to other treatments.

Halpern also hopes to conduct a brain-imaging study to test his hypothesis
that psychedelics reduce craving in addicts by affecting their serotonin and
dopamine systems. "It sounds reductionistic," he says, "but a picture can be
worth a thousand words." An ideal collaborator would be Franz Vollenweider,
a psychiatrist at the University of Zurich, who with positron-emission
tomography has measured neural changes induced in healthy volunteers by
psilocybin and MDMA.

Some psychedelic effects have already been explained in relatively
straightforward neural terms. For example, human brain-imaging tests and
experiments on animals have shown that mescaline, LSD, and other
psychedelics boost the random discharge of neurons in the visual cortex.
This neural excitation is thought to induce form constants, the dynamic
patterns I saw when I closed my eyes under the influence of peyote, which
are also generated by migraines, epileptic seizures, and other brain
disorders. But the effects of hallucinogens will never be reducible to
neurochemistry alone, Halpern emphasizes. Decades of research have confirmed
the importance of "set and setting" -- the prior expectations of users and
the context of their experience. The same compound can evoke psychotic
paranoia, psychological insight, or blissful communion, depending on whether
it is consumed as a party drug in a nightclub, a medicine in a
psychiatrist's office, or a sacrament in a tepee. In the same way,
psychedelic treatments may produce different outcomes depending on the
setting.

The long-term challenge for researchers, Halpern says, is to determine which
settings can exploit the therapeutic potential of hallucinogens while
reducing the risk of adverse reactions. In the 1950s and the 1960s,
psychedelic therapy usually involved a single patient and therapist. In many
cases, Halpern believes, psychedelic therapy might work best for couples,
families, and friends. "If you take it be yourself, you may have important
insights," he says, "but you've lost this other opportunity to learn and
grow."

People might also respond to settings and rituals designed to evoke
religious sentiments. Recently various scientists, notably Harold Koenig at
Duke University, have reported finding correlations between religiosity --
as reflected by church attendance and other measures -- and resistance to
depression. Ideally, Halpern says, therapists should be able to choose among
many different settings to best serve a patient's needs. One of his favorite
proverbs is, "Many paths, one mountain."

Halpern believes he has benefited from his peyote sessions, albeit in ways
difficult to quantify or even describe. Borrowing the term for a compound
that boosts the effect of a neurotransmitter, he speculates that peyote
serves as a "humility agonist," counteracting his arrogance by instilling
awe and reverence in him. He acknowledges, however, that these emotions
might be less a function of the peyote than of the ceremony of the Native
American Church.

Reverence is certainly evident in Halpern's bearing throughout the session
we attend together. Although plagued by chronic back pain, he sits
straight-backed for hour after hour on the $5 cushion he purchased earlier
that day at Wal-Mart. He intently watches every ritual, listens to every
song. When the roadman asks everyone to pray for the husband and wife who
are the meeting's focus, Halpern chimes in loudly.

Especially early on, the ceremony seems impenetrably foreign, but its
meaning becomes more apparent as the night progresses. At one point the
roadman, after offering a long prayer in Dine, turns to the husband and wife
and says in English: "You must make more time in your lives for those who
care about you." The rituals, I realize, are just expressions of gratitude
for earth, fire, food, and other primordial elements of existence. After
each of us sips from a bowl of water passed around the tepee, the roadman
carefully pours some water on the dirt floor. Halpern says in my ear, "Think
what water means to these desert people."

As dawn approaches, the mood throughout the tepee brightens. Everyone smiles
as the husband and wife embrace and as their two children, who have been
sleeping since midnight, wake up blinking and yawning. The wife, coming back
into the tepee after fetching a platter of sweet rolls, jokes and laughs
with a friend. As we drink coffee and eat the rolls, she thanks us for
having sat through this long night with her and her family. "Thank you for
letting us join you," Halpern replies, beaming at her, "and may you and your
family enjoy good health."

Driving out of the Navajo Nation that afternoon, Halpern seems exhilarated,
although he has not slept for 36 hours. He howls along with a CD of Native
American Church chants and does imitations of Bill Clinton and several Star
Trek characters. Outside Shiprock, New Mexico, his expression turns grim as
we pass a policeman giving a sobriety test to a wobbly young man. Neither
peyote nor any other medicine, Halpern realizes, can cure all those
afflicted with alcoholism or addiction. "We don't have magic pills," he says
dryly. If his research on psychedelics yields therapies that can benefit
just 10 or 15 percent of the millions struggling with these disorders, he
will be more than satisfied. "I'm trying very slowly," he says, "to put all
the pieces in place."

Sidebars And Captions:

1) Peyote is a hallucinogen considered sacred medicine by members of the
Native American Church. It was formally legalized for church members in 1994
as an amendment to the American Indian Religious Freedom Act. Buttons
harvested from peyote cacti are purchased from licensed dealers in southern
Texas.

2) Experiments With People -- John Halpern's peyote study is part of a
revival of psychedelic research. At least a half dozen prominent researchers
are exploring the potential of using hallucinogens, including:

* -- Francisco Moreno, a psychiatrist at the University of Arizona College
of Medicine in Tucson, administers psilocybin, the primary active ingredient
of hallucinogenic mushrooms such as Psilocybe semilanceata, to 10 patients
as an experimental treatment for obsessive-compulsive disorder.

* -- Pedro Sopelana Rodriguez, a psychiatrist at the Psychiatric Hospital of
Madrid in Spain, gives MDMA, or Ecstasy, to 29 women suffering from
post-traumatic stress disorder caused by sexual abuse.

* -- Evgeny Krupitsky, a psychiatrist at the St. Petersburg Scientific
Research Center of Addictions and Psychopharmacology in Russia, treats
alcoholics and heroin addicts with ketamine, an anesthetic that at
sub-anesthetic doses produces out-of-body experiences. Krupitsky has
reported positive results in his clinic and at the Yale/West Haven VA
Medical Center in Connecticut.

* -- Deborah Mash, a neurologist at the University of Miami School of
Medicine who also works at a clinic in St. Kitts, West Indies, treats opiate
and cocaine addicts with ibogaine, an extract of the West African shrub
Tabernanthe iboga.

* -- Charles Grob, a psychiatrist at the Harbor-UCLA Medical Center In
Torrance, California, plans to offer psilocybin to late-stage cancer
patients as an experimental treatment for pain, anxiety, and depression.

3) Mushrooms such as Psilocybe semilanceata reportedly ease symptoms of
obsessive-compulsive disorder.

4) John Halpern, a research psychiatrist at Harvard, says he suspects that
psychedelic compounds such as LSD, psilocybin, and mescaline stimulate "a
center in the brain that is involved in spirituality."

5) Peyote ceremonies on Navajo Nation lands typically take place in a tepee
on a Saturday night and are followed by a communal morning feast.