SCIENTISTS TEST HALLUCINOGENS FOR MENTAL ILLS

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 disorders.

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 hallucinogens.

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 mushrooms.

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 sober.

"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 unapproved purposes.

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 70's.

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 weak stations."

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 others.

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 psilocybin.

"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. Vollenweider said.

He wonders whether a medically facilitated experience in which the self
temporarily "dissolves" might reduce the symptoms of a clinical
depression.

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 and LSD.

"We can tease out specific brain regions responsible for hallucinations
and ego boundaries," he said in a telephone interview.

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 valuable.

"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."