Janeen Delany describes herself as an "old hippie" who's smoked plenty of marijuana. But she never really dabbled in hallucinogens -- until two years ago, at the age of 59.
A diagnosis of incurable leukemia had knocked the optimism out of the retired plant nurserywoman living in Phoenix. So she signed up for a clinical trial to test whether psilocybin -- the active ingredient in "magic mushrooms" -- could help with depression or anxiety following a grim diagnosis.
Delaney swallowed a blue capsule of psilocybin in a cozy office at Johns Hopkins University in Baltimore. She donned a blindfold, a blood pressure cuff and a headset playing classical music. With two researchers at her side, she embarked on a six-hour journey into altered consciousness that she calls "the single most life-changing experience I've ever had."
What a long, strange trip it's been. In the 1960s and '70s, a rebellious generation embraced hallucinogens and a wide array of street drugs to "turn on, tune in and drop out." Almost half a century later, magic mushrooms, LSD, Ecstasy and ketamine are being studied for legitimate therapeutic uses. Scientists believe these agents have the potential to help patients with post-traumatic stress disorder, drug or alcohol addiction, unremitting pain or depression and the existential anxiety of terminal illness.
"Scientifically, these compounds are way too important not to study," said Johns Hopkins psychopharmacologist Roland Griffiths, who conducted the psilocybin trial.
In their next incarnation, these drugs may help the psychologically wounded tune in to their darkest feelings and memories and turn therapy sessions into heightened opportunities to learn and heal.
"We're trying to break a social mind-set saying these are strictly drugs of abuse," said Rick Doblin, a public policy expert who founded the Multidisciplinary Assn. for Psychedelic Studies in 1986 to encourage research on therapeutic uses for medical marijuana and hallucinogens. "It's not the drug but how the drug is used that matters."
Regulators and medical researchers remain wary. But among at least some experts at the National Institutes of Health and the Food and Drug Administration, the shift in attitude "has been dramatic," Doblin said.
Researchers explored the usefulness of hallucinogenic agents as an adjunct to psychotherapy in the 1950s and '60s. But allegations that hallucinogens were used in government-funded "mind control" efforts, freewheeling experimentation by proponents like Dr. Timothy Leary, and the drugs' appeal to a generation in revolt quashed legitimate research for decades.
The thaw has been slow in coming. In 2008, Griffiths co-wrote a report in the Journal of Psychopharmacology comparing psilocybin with a placebo for people dealing with incurable diseases. Psilocybin resulted in "mystical experiences having substantial and sustained personal meaning and spiritual significance," according to the study, the first since 1972 to explore a hallucinogen's therapeutic value.
In January, a team led by UCLA psychiatrist Charles Grob reported in Archives of General Psychiatry that psilocybin improved the mood of patients with "existential anxiety" related to advanced-stage cancer. The benefits lasted at least three months.
Janeen Delany is a typical case: The insights she gleaned during her encounter with psilocybin continue to shape her attitudes toward life and death.
Delany said her "trip" awakened a deep and reassuring sense of "knowing." She came to see the universe and everything in it as interconnected. As the music in her headphones reached a crescendo, she held her breath and realized it would OK -- no, really easy -- not to breathe anymore. She sensed there was nothing more she needed to know and therefore nothing she needed to fear about dying.
And that, paradoxically, has allowed her to live.
"When you take the veil of fear away from your life, you can see and experience everything in such a present way," she said. "I don't have to know what the future is. Every day is the day of days."
Such mystical insights are central in another potential use for psilocybin -- as an addiction treatment. Griffiths is conducting a pilot study combining psilocybin with cognitive behavioral therapy to help smokers quit. Four people have completed the program, and so far none has returned to smoking, Griffiths says.
At the University of Arizona in Tucson, addiction specialist Dr. Michael P. Bogenschutz has proposed a clinical trial to test whether psilocybin can help ease alcohol dependence. If the NIH agrees to fund the study, it would be the first instance in decades of government financial support for a trial involving any drug of abuse.
Psilocybin's effect on the brain can be described, if not explained. It increases the activity of serotonin, a chemical that affects mood. Brain networks associated with emotions are highly active in the presence of psilocybin, as are structures involved in higher reasoning and judgment, MRI scans show.
Griffiths says that subjects routinely describe their psilocybin experience as one that "helps reorganize their thinking." For those facing death, that can bring new perspective on loved ones, on life and on what lies beyond; for those stymied by addiction, it can cut the addictive substance down to size. "Their enslavement to cigarette smoking will be almost funny," Griffiths said.
Psilocybin isn't the only drug on the cusp of a medical renaissance. Ketamine, best known as "Special K," has shown promise as a fast-acting antidepressant. It induces euphoria, hallucinations and "out of body" experiences when smoked or snorted. When administered intravenously at low doses, it can lift symptoms of deep depression in a matter of hours.
Ketamine's use in anesthesia has made it easier for researchers to study. They suspected its influence on a neurochemical called NMDA would make it a good antidepressant, since NMDA's activity is altered in people with depression.
In case reports, severely depressed patients who got ketamine in preparation for electroconvulsive shock therapy showed improvements in mood (even when the shock therapy failed), and several small clinical trials have demonstrated its fast-acting abilities. The findings indicate that for suicidal patients who can't afford to wait weeks or months for a standard antidepressant to take effect, ketamine could be a valuable rescue drug.
LSD may also be on the road to legitimacy. A 2006 study in Neurology surveyed people who used the drug to cope with persistent cluster headaches and found that it cleared them up and made them less frequent in most cases.
The results prompted Dr. John Halpern of Harvard Medical School's McLean Hospital to test a nonhallucinogenic LSD analog from the vaults of pharmaceutical giant Sandoz. At a research meeting in June, Halpern reported that 2-Bromo-LSD reduced the number of daily cluster headaches in six sufferers who participated in a pilot study.
War has also created openings for the rehabilitation of some of these drugs. Ecstasy is a case in point.
The drug -- whose chemical name is methylene dioxy methamphetamine, or MDMA -- was patented in 1912 by Merck & Co. Its psychoactive properties prompted doctors to prescribe it for their patients; one pharmacologist called it "penicillin for the soul." But in 1988, the Drug Enforcement Agency declared MDMA a Schedule 1 controlled substance with high potential for abuse. Psychotherapists stopped prescribing it or continued to do so furtively.
On the street, Ecstasy has a reputation for dissolving anxiety and fear, suppressing social inhibition and enhancing one's willingness to trust others. PTSD sufferers avoid reminders of their pain or shut down at the prospect of facing it. A dose of Ecstasy appears to help these patients revisit their traumas and reflect on them without fear.
"It can connect people more with their emotions without them feeling they'll be overwhelmed by them," said psychiatrist Michael Mithoefer of Charleston, S.C., a clinical investigator for the Multidisciplinary Assn. for Psychedelic Studies.
Mithoefer has received FDA permission to test whether Ecstasy can help Iraq and Afghanistan veterans overcome their PTSD when used during psychotherapy sessions; six veterans have enrolled in the study. In an earlier clinical trial, Ecstasy helped 10 of 12 women recover from PTSD stemming from child sexual trauma. Only 2 out of 8 women who took a placebo had similar results, Mithoefer reported last year in the Journal of Psychopharmacology.
Ecstasy's reputation for enhancing trust has clear roots in its biological effect. Using brain scans, Columbia University psychologist Gillinder Bedi found that subjects who took MDMA showed heightened activity in a brain region associated with processing rewards and depressed activity in the amygdala -- a source of fear reactions. In animals, MDMA boosts the hormone oxytocin, which promotes trust, sociability and interpersonal attachment.
A drug can't be dismissed because of a dangerous reputation or colorful history, Bedi said, if trials demonstrate that it is safe and can benefit patients.
Janeen Delany said her psilocybin experience had added life to her years -- and perhaps years to her life.
Every three months, she gets her white blood cells checked. With her form of leukemia, those counts are expected to rise steadily as the disease progresses. But in June 2009, four months after her psilocybin session, they went down. Every three months since, they have retreated further, leading two of her three doctors to declare her in remission.
Delany said her psychological improvement may have helped reverse her fortunes. Her lead oncologist is skeptical, but her neurologist is not so quick to dismiss the link. One should never underestimate "the healing power of the psyche," he told her.
Whatever, Delany said. Remission is beside the point.
"The fear is gone. It's all about living," she said. "The big stuff? Sheeesh -- it's handled."