Recreational Drugs Go Straight

Catherine Lange, New Scientist Magazine

With a handful of trials showing positive results, from the treatment of cancer to alcohol addiction, could illegal drugs enter mainstream medicine?

From the relaxing effects of cannabis to the highs of LSD and ecstasy, illegal drugs are not generally associated with the lab bench. Now, for the first time in decades, that's starting to change.

For almost 40 years, mainstream research has shied away from investigating the therapeutic benefits of drugs whose recreational use is prohibited by law. But a better understanding of how these drugs work in animal studies, and the advancement of brain-imaging techniques, has sparked a swathe of new research.

What's more, clinical trials of MDMA (ecstasy), LSD and other psychoactive drugs are starting to yield some positive results. This could lead to a call for governments to take a new approach to the funding and regulation of research into the potential benefits of such chemicals.

LSD was developed in the 1940s, but by the 1970s it and many other drugs became classed as schedule 1 in many countries -- described as "abuse" drugs with no accepted medical use.

"Research on psychedelics was severely restricted and interest in the therapeutic use of these drugs faded," says Franz Vollenweider of the neuropsychopharmacology and brain-imaging unit at the Zurich University Hospital of Psychiatry, Switzerland.

The classification of LSD as schedule 1 was a mistake born of "ignorance and taboo," says Amanda Feilding (cq), director of the Beckley Foundation, a charitable trust that promotes investigation into consciousness and its modulation, based in Oxford, England.

These kinds of decisions are political not scientific, says Michael Mithoefer, a psychiatrist in Mount Pleasant, California.

"When the U.S. Drug Enforcement Agency held hearings about MDMA, the judge ruled it did not meet criteria for schedule 1 and should be schedule 3, so it could be used by physicians but not sold in bars. The DEA administrator put it in schedule 1 despite it not meeting the criteria."

Despite these hurdles, a number of trials are now under way in the U.S. and Switzerland to investigate the potential of LSD and psilocybin -- the psychoactive component of magic mushrooms -- in helping terminal cancer patients deal with anxiety and depression.

Feilding is also working with David Nutt of Imperial College London on the first UK study using psychedelics for 40 years. Among other things, they are researching how psilocybin can help in recalling distant memories, which they say could help with psychotherapy following trauma.

Meanwhile, in a study at Johns Hopkins University, Baltimore, Maryland, funded by the Beckley Foundation, Roland Griffiths and colleagues have seen positive results in their study into the use of psilocybin as an aid to psychotherapy to treat tobacco addiction. At Hanover Medical School in Germany, a team led by Matthias Karst has been investigating whether bromo-LSD -- a non-psychoactive form of the drug -- can be used to treat painful cluster headaches.

Cannabis is already known to have a soothing effect on the symptoms of multiple sclerosis. Canada recently approved the use of Sativex -- derived from cannabis plant extracts -- for relief of spasticity in adults with MS. September saw the publication of the first study suggesting that smoking cannabis can also reduce neuropathic pain, caused by damage to the nervous system.

Mark Ware and colleagues at McGill University in Montreal, Canada, gave patients suffering from chronic pain one of three different doses of cannabis, or a placebo. On average, patients reported lower pain intensity and a better quality of sleep when they smoked the highest dose of cannabis compared with the placebo, and the reported side effects were minimal (Canadian Medical Association Journal)

"Previous studies have looked at cannabis and pain, but this is the first one I've seen looking at smoked cannabis," says Tony Dickinson, a pharmacologist at University College London. Although there were only 21 participants, and smoking of course raises health issues, the study is nevertheless important, Dickinson says, because neuropathic pain is notoriously resistant to other forms of treatment.

While many drugs could have medical uses, don't their psychoactive effects limit their use? Feilding doesn't think so. LSD, psilocybin and MDMA are neither addictive nor dangerous in controlled doses, she argues. Others disagree.

"The psychiatric risks of these substances are well known," says Ken Checinski, who studies addictive behavior at St. George's, University of London. "There may be a narrow therapeutic window between potential benefits and significant adverse events."

However, this problem isn't unique to psychoactive drugs.

"We use many things in medicine that can be misused and be very dangerous in the wrong doses," says Mithoefer. Feilding thinks governments need to see past the stigma of schedule 1 drugs and fund medical research that could be "very valuable."

Some funding organizations already exist, including the Beckley Foundation, and the Multidisciplinary Association for Psychedelic Studies in the U.S. Their funds are limited, though.

"As research progresses, larger studies will get more expensive and it would be most helpful to have government funding," Mithoefer says.

His latest study investigated whether MDMA could help people suffering from post-traumatic stress disorder (PTSD). MDMA decreases the fear response, so he reasoned it might help people undergo therapy "without being overwhelmed by anxiety while revisiting traumatic experiences."

Of the 12 patients who received the drug, 10 saw such an improvement in their symptoms that they were no longer categorized as suffering from PTSD, compared with two out of the eight patients who received a placebo (Journal of Psychopharmacology).

Government funding may still be some way off, though. For one thing, it's hard to design an effective double-blind trial when the secondary effects of the drug are so well known, says Dickinson. In Mithoefer's study, for example, all but one of the patients correctly guessed whether they were receiving the placebo or MDMA.

"There is much to be learned and we're still in the early stages," Mithoefer says, "but it's important that the research moves forward so we can establish whether or not (psychoactive drugs) can be safe and effective therapeutic tools."

THE HIGHS AND LOWS OF LSD

By Helen Thompson

"With a remarkable restlessness and slight dizziness, I sank into a not unpleasant intoxicated-like condition. In a dreamlike state, I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic colors."

This is the description of the first LSD trip taken by Albert Hofmann, the inventor of the drug, in 1943.

He initially developed LSD in 1938 on the premise that it may act as a circulatory and respiratory stimulant. Working as a chemist at Sandoz Laboratories (now Novartis) in Basel, Switzerland, Hofmann shelved the compound -- known as LSD25 -- after it had no obvious effects in mice. Five years later, while re-synthesizing the drug, he was interrupted by the unusual activity described above.

Realizing the symptoms must have occurred from inhalation or absorption of LSD-25, Hofmann took an oral dose of the chemical, estimating that 250 micrograms would be the threshold at which effects would occur. In reality, the threshold is closer to 20 micrograms. After 6 hours of positive and negative experiences, which involved thinking his neighbor was "an insidious witch," the effects subsided.

"I was aware that LSD, with such properties, would be of use in pharmacology, in neurology, and especially in psychiatry," Hofmann wrote in his biography.

Over the next 20 years, thousands of papers were published on the drug's effects, including treatment for alcohol addiction and psychosis. Several positive outcomes were also reported for the treatment of autism, such as an increase in social behaviors manifested by increased eye-to-face contact (Behavioral Neuropsychiatry).

Unfortunately, many of the studies lacked proper experimental controls and presented largely descriptive data. The lack of long-term follow-up studies and a realistic placebo have been major limitations of the work to date.

The drug quickly leaked into the general population, which led to an investigation by the U.S. Food and Drug Administration, and in 1970, LSD was classified as a drug of abuse with no medical value. Research into any therapeutic effects stopped.

Today, many researchers believe that LSD poses no risk to health when administered in a controlled environment and that the case for medicinal LSD should be reopened (see main story).

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