Medical Possibilities for Psychedelic Drugs

Scientists at the Orenda Institute in Baltimore are taking a novel approach to treating drug addiction: They plan to give patients LSD.

That's lysergic acid diethylamide, or "acid" for short, one of several psychedelic drugs that were placed under the U.S. Controlled Substances Act in 1970. They're Schedule I drugs, which means they're considered to have a high potential for abuse, present an unacceptable safety risk, and have no acceptable medical use.

However, in recent years, the Food and Drug Administration has sought ways to allow human studies to test LSD and other Schedule I psychedelic drugs to see if they have any medical usefulness. The National Institute on Drug Abuse funds some of these studies.

In the Baltimore study, scientists are examining LSD as a possible treatment for addiction to heroin, opium, alcohol, and sedative hypnotics. University of Miami researchers are studying the psychedelic drug ibogaine to treat cocaine addiction. Other scientists are focusing their psychedelic research on learning more about the human brain, discovering antidotes to drug overdoses, and relieving pain in cancer patients.

It's still too early to say whether the drugs have medicinal uses or not, according to government scientists. "These are all very small studies, mostly with fewer than 10 patients," said Curtis Wright, M.D., a medical officer with the addiction medicine staff in FDA's Center for Drug Evaluation and Research. "It's far too early to tell whether these drugs work or not or provide any therapeutic benefit."

Drugs of Abuse

The drugs are known more for their abuse potential. They include, in addition to LSD and ibogaine, mescaline, MDMA (3-4-methylenedioxymethamphetamine--commonly called "Ecstasy"), DMT (dimethyltryptamine--known on the street as "Businessman's Special"), PCP ("Angel Dust"), N,N-diethyltryptamine (DET), psilocybin, psilocin, and alpha-ethyltryptamine (alpha-ET--also known on the street as "Trip" and "ET").

Some of the drugs occur naturally, such as ibogaine, which comes from the root of a rain forest shrub. Others, such as MDMA, are synthesized, mostly illegally, in clandestine laboratories.

As a group, the drugs are often referred to as psychedelic (meaning mind-altering) or hallucinogenic because they cause people to have hallucinations; that is, to imagine they see and hear things.

Each drug has its own unique properties, though. "There are differences, big pharmacological and psychopharmacological differences," said Frank Vocci, Ph.D., deputy director for the medications development branch of the National Institute on Drug Abuse (NIDA). "The drugs are alike only in that they share a common ability to alter perceptions or result in some type of hallucinatory experience."

Street users call these experiences "trips," which can be extremely pleasant or highly unpleasant and frightening.

Hallucinogens' Hazards

The drugs can cause other adverse reactions, too. LSD, for example, can dilate pupils; increase body temperature, heart rate, blood pressure, and sweating; and cause loss of appetite, sleeplessness, dry mouth, and tremors. Also, many LSD users experience flashbacks, spontaneous recurrences of certain aspects of the person's "trip" (without the user having taken the drug again). Long-term LSD users may develop psychoses, such as schizophrenia and severe depression.

MDMA users also may suffer from psychological difficulties, including confusion, depression, sleep problems, drug craving, severe anxiety, and paranoia--during and sometimes weeks after taking the drug. Physical symptoms of MDMA use include muscle tension, nausea, blurred vision, rapid eye movements, faintness, chills or sweating, and increased heart rate and blood pressure--a special risk for people with heart disease.

Overuse of some pyschedelic drugs is associated with death. The pyschedelic drug alpha-ET, which was sold legally under the trade name Monase in the early 1960s for depression, was taken off the market after only one year because three illnesses and four deaths in patients taking the drug were documented. The drug was associated with a significant decrease in certain body cells.

Ibogaine as well has been linked to at least three deaths overseas.

"We have to realize that there are problems with these drugs," said Michael Klein, Ph.D., a senior interdisciplinary scientist on FDA's pilot drug evaluation staff. "We don't want to make it sound as though these drugs offer exciting possibilities, when we really don't know for sure. Each drug has to be weighed on its own merits."

Hallucinogen History

Scientific interest in these drugs is not new. Information about the effects of ibogaine, which West Africans use as a stimulant and aphrodisiac and in religious rituals, began appearing in the medical literature in the early 1900s. Mescaline, from the peyote cactus and used in Native American religious rituals, was studied in the 1920s.

LSD, perhaps the most popular of the psychedelic drugs, was first synthesized in 1938. It is made from lysergic acid, which is found in ergot, a fungus that grows on rye and other grains and has been known throughout history as a source of various types of medications. Its psychedelic effects were discovered in 1943.

During the 20 years following World War II, LSD was used to study brain chemistry and to determine its effects in patients with schizophrenia and other mental disorders. It also was studied for use in conjunction with psychotherapy--with, for example, alcoholics and cancer patients.

Due to concern about possible unpredictable side effects and abuse, LSD research came to a virtual halt by the mid-1970s. Unsupervised use of these drugs by millions of young adults in the 1960s made use and abuse of psychedelic drugs a major public health concern.

According to FDA's Klein, the Controlled Substances Act was an attempt to control the use of these drugs so that they would be used only for scientific reasons. "The purpose of the act was not to hinder or stop research," he said, "but to ensure that as the research proceeded, proper controls were in place to prevent abuse and misuse of the drugs."

However, by the 1970s, psychedelic drugs were not only viewed as a public health problem but also carried a social implication. Psychedelic drugs were associated with "hippies," a counterculture of mostly young people who felt alienated from the mainstream American society and grew, in part, out of the anti-Vietnam war sentiment of the time.

"There seemed to be an increasing hysteria about hallucinogenic drugs in the 1960s that essentially shut down the research," NIDA's Vocci said. "It became socially unacceptable to do this kind of work."

Promising Potential

Early research suggested medical promise for psychedelic drugs. According to a 1992 report by Richard Yensen, Ph.D., and Donna Dryer, M.D., director and medical director at the Orenda Institute, a 1960s' study of 135 alcoholics found that six months after treatment with LSD, 53 percent of a high-dose group reported abstinence compared with 33 percent of a low-dose group. Alcoholics receiving conventional therapy had a 12 percent improvement rate.

In a study of 31 cancer patients suffering from anxiety, depression and uncontrollable pain, 71 percent showed improvement in their physical and emotional status after each LSD session.

According to Yensen, researchers also observed that many cancer patients receiving LSD reported that their desire for addictive pain medicines, such as morphine, had diminished or vanished, along with the pain.

An article in the winter 1995 edition of MAPS, published by the Multidisciplinary Association for Psychedelic Studies, reports success with another hallucinogen, ibogaine, in the treatment of chemical dependencies. The article's author, Howard Lotsof, founder of NDA International Inc.--a private organization based in Staten Island, N.Y., that treats drug addicts overseas--discusses several treatment successes, including a medical doctor whose addiction to a pain medication vanished after receiving four doses of ibogaine. Lotsof reported in the article that "29 of 35 patients successfully treated with ibogaine had numerous unsuccessful experiences with other treatment modalities."

Lotsof's studies are not sanctioned by FDA, and he is not authorized to treat patients in the United States.

Members of FDA's pilot drug evaluation staff advise caution in interpreting the results of these early studies and observations. "We have to wonder: What was the quality of the drugs?" FDA's Klein said. "What other factors were involved? Were the doses adhered to? What was the outcome measured? These are the kinds of questions we need to go back and look at objectively."

Research Renewed

The current round of research activity got under way in the late 1980s, bolstered in large part by advances in the understanding of brain chemistry.

FDA has granted IND status to several psychedelic drugs in recent years. The IND status means the drugs have been studied in the laboratory for their major physical and chemical properties and tested in laboratory animals for their pharmacologic and toxic effects.

In granting IND status, FDA carefully monitors study protocols to ensure that they meet FDA's safety and scientific standards. "The studies have to be safe and conducted under controlled conditions," Klein said. "Otherwise, the research may offer questionable or, at best, minimal returns."

Because the drugs are controlled substances, scientists must apply to the Drug Enforcement Administration for a Schedule I permit in conjunction with filing an IND application with FDA. And, to receive IND approval, researchers must document that they have a suitable drug source whose manufacturing capabilities meet the agency's good manufacturing procedures. That presents a challenge because few reputable U.S. drug manufacturers make these drugs.

To get high-quality drugs, psychedelic researchers rely on European manufacturers, hospital pharmacies, and university chemistry labs.

Recruiting subjects can be a challenge, too, because in many cases, experienced psychedelic users are preferred, and their identities need to be protected for most studies.

"They're less likely to panic," said Rick Strassman, M.D., associate professor of psychiatry at the University of New Mexico. "It can happen that people get frightened."

For that reason, in these studies, subjects are closely monitored in the clinical setting by one or more health professionals. Drugs, such as Valium (diazepam), are on hand to reduce the effects of bad reactions.

The researchers foresee various uses for their research. At the University of New Mexico, where scientists are studying the effects of DMT and psilocybin in humans, lead investigator Strassman believes his work may enable scientists to develop treatments for drug overdoses.

"People on the street take these drugs," he said. "If we determine how these drugs work, perhaps we would be able to treat those who come into the emergency room because of a bad trip or panic reaction."

Other scientists say psychedelic research may serve as a way to learn more about the human brain. Writing in a 1994 National Institute on Drug Abuse report, Stephen Sz‡ra, M.D., D.Sc., former chief of the institute's biomedical research branch, said, "Recent advances in the neurosciences and cognitive sciences have created opportunities for using hallucinogens as tools in attacking the supreme mystery: How does the brain work?"

NIDA's Vocci believes that this time around, scientists may have a better chance to find the answer to this and other psychedelic research questions.

"The investigators are very serious, dedicated professionals," he said. "They're truly interested in trying to evaluate what these drugs can do."

Paula Kurtzweil is a member of FDA's public affairs staff.