March 13, 2001
Scientists Test Hallucinogens for Mental Ills
By SANDRA BLAKESLEE
Hallucinogenic drugs like LSD and peyote ^ derided as toys of the
hippie generation ^ are increasingly drawing the interest of
neurologists and psychiatrists who want to test the idea that
they may be valuable tools in treating a range of mental
Although there are anecdotal reports that psychedelic drugs can
help some people with mental illness, the idea has never been
substantiated by mainstream psychiatry and remains highly
controversial ^ some would say outlandish.
And even the researchers involved in the new work are not
suggesting that people start medicating themselves with
But researchers like Dr. David E. Nichols, a professor of
pharmacology and medicinal chemistry at Purdue, believe the
drugs' potential should be investigated.
For example, Dr. Nichols, an expert on hallucinogenic drugs, said
there were reports that symptoms of obsessive compulsive
disorder, like washing one's hands dozens of times a day, subside
under the influence of psilocybin, a hallucinogen derived from
Dying patients given LSD have reported less pain and less fear,
he said. Ayahuasca (a Brazilian plant extract) and peyote
(derived from cactus) have reportedly helped alcoholics stay
"We now know a lot about how they work in the brain, but we have
not begun to investigate their potential for treating brain
disorders," he said.
Dr. Nichols is the founder of the Heffter Research Institute,
begun in 1993 and named for Arthur Heffter, a 19th-century
chemist who was the first person to identify a hallucinogenic
molecule, mescaline, which he extracted from peyote. Backed by
private donors like Laurence S. Rockefeller and Bob Wallace, a
Microsoft millionaire, the institute is financing clinical trials
with LSD, psilocybin and other hallucinogens to treat phobias,
depression, obsessive compulsive disorders and substance abuse,
said James Thornton, its executive director.
Dr. Nichols said trials were under way or planned in Switzerland,
Russia and the United States. Most of the work is being done
overseas, he said.
Dr. Janet Woodcock, director of the Center for Drug Evaluation
and Research at the Food and Drug Administration, said that any
proposal to study the medical use of a hallucinogen must meet the
same rigorous medical and scientific standards used to evaluate
any other unapproved drug.
Furthermore, because hallucinogens are controlled substances, the
investigator will need a license from the Drug Enforcement Agency
to use such a substance in a clinical trial.
The D.E.A. classifies hallucinogens as drugs with no known
medical value ^ purely "drugs of abuse." But if a valid medical
use is found for hallucinogens, Dr. Woodcock said, the F.D.A. has
safeguards to prevent the drugs from being diverted and used for
Separating a drug's beneficial effects from the harm it can cause
is possible, said Dr. Alan Leshner, director of the National
Institute on Drug Abuse. "Morphine works for pain, but it's
horrendous when used in an addictive way," he said. "The same may
or may not be true for hallucinogens. It's a mistake to confuse
the two issues."
Much has changed in the half-century since LSD was first used by
psychiatrists and then found widespread recreational use in the
1960's and 70's. Modern psychiatry has embraced drugs that affect
the same brain molecules that are tweaked by hallucinogens. Tools
for studying the brain's neurochemistry and response to drugs
like LSD are far more advanced than they were in the 1960's and
Moreover, many of the people who hold political and scientific
power today came of age during the 1960's, and they, unlike their
parents, are not as afraid of hallucinogens, Dr. Nichols said.
By definition, hallucinogens are drugs that produce bizarre
sights, sounds and feelings that appear to have no basis in
reality. All work by changing levels of a brain chemical called
serotonin, a substance involved in the modulation of many brain
states, including depression, euphoria and appetite.
While antidepressants like Prozac work by making the
neurotransmitter serotonin linger in the gaps between brain
cells, hallucinogens have a different mechanism of action. They
are what are called serotonin agonists ^ molecules that are very
similar to the body's natural serotonin and, when taken in large
doses, push the serotonin system into overdrive, making many
brain systems more sensitive, Dr. Nichols said. "It's like
turning up the volume on your radio. Suddenly you can hear very
Thus, for example, hallucinogens amplify signals in the visual
system to produce distortions of form and size. Instead of seeing
one object, a person sees many copies of that object, he said.
Perceived motion is similarly distorted. People begin to "hear"
colors and "see" sounds or have out-of-body experiences. Some are
so disoriented they experience a terrifying "bad trip."
But very little is known about how hallucinogens can be used
therapeutically, Dr. Nichols said. "The first thing we want to
know is, Are they safe?"
Dr. John H. Halpern, a psychiatrist at McLeans Hospital in
Boston, is looking at this question in a study financed by the
Heffter Research Institute and the National Institute on Drug
Abuse. The study will involve members the Native American Church
who, as part of their religious rituals, take peyote in a group
setting but use no other drugs, not even alcohol.
Using a battery of tests for mental and social health, three
groups of Native Americans ^ 70 church members, 70 alcoholics and
70 people from local communities in the Southwest ^ are being
followed and compared for two to three years. The goal is to see
whether peyote users are healthier or less healthy than the
Similar studies in Brazil showed that violent alcoholics who took
hallucinogens in a ritualistic context often stopped drinking and
had higher blood levels of serotonin, said Dr. Dennis McKenna,
Heffter's director of ethnopharmacology.
Those changes may reflect an increase in their brain levels of
serotonin, added Dr. McKenna, who is also a lecturer at the
University of Minnesota Center for Spirituality and Healing,
which seeks to integrate cultural and spiritual aspects of care
with the biomedical aspects.
Dr. Francisco Moreno, a psychiatrist at the University of
Arizona, and his colleagues there have permission from their
hospital review board and expect final approval from the F.D.A.
soon to carry out a study on obsessive compulsive disorder and
"We want to know if psilocybin can reduce symptoms, and if so,
how much do you need to take?" Dr. Moreno said. Subjects will be
closely supervised while under the influence of the drug and kept
in the hospital overnight as a precaution.
At the University of Zurich in Switzerland, Dr. Franz
Vollenweider has permission from his government to explore
hallucinogens in treating depression and schizophrenia. "We are
interested in the nature of the human experience, of the
subjective me-ness or self that guides our behavior," Dr.
He wonders whether a medically facilitated experience in which
the self temporarily "dissolves" might reduce the symptoms of a
With money from the Heffter Institute, Dr. Vollenweider and his
colleagues are conducting a three-year study of 64 depressed
patients treated with psilocybin.
In related research, Dr. Vollenweider plans to continue brain
imaging studies of healthy volunteers who have taken psilocybin
"We can tease out specific brain regions responsible for
hallucinations and ego boundaries," he said in a telephone
At Harvard, Dr. Harrison Pope, a professor of psychiatry, is
planning to carry out a study to see whether LSD can alleviate
fear and anxiety in dying patients. Studies in the 1960's
suggested that the drug reduced pain and improved mood, he said,
but they were not done under rigorous standards.
Eighty patients would be given an "active placebo," a drug that
has physiological effects but is not hallucinogenic, or LSD under
close supervision of a psychiatrist or trained mental health
worker, Dr. Pope said.
And in St. Petersburg, Russia, Dr. Evgeny Krupitsky, chief of the
research laboratory at the Leningrad Regional Center of
Addictions, is administering ketamine, an anesthetic with strong
hallucinogenic properties, to alcoholics and heroin addicts, as
they are treated with talk therapy.
One day, advocates of this research say, their results will be
"If hallucinogens ever find their way into mainstream medicine ^
and I am convinced they will ^ they will never be handed out like
Prozac," said Dr. George Greer, Heffter's medical director and a
psychiatrist in private practice in Santa Fe, N.M. "People will
need guidance. These are not drugs you administer every day."
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