Is the most effective antidepressant illegal?

If the volume of prescriptions written are any guide to the prevalence of medically diagnosed disorders, then depression is the greatest single medical problem in the United States.

As CNN reported on in 2007 about a just-published survey:

According to a government study, antidepressants have become the most commonly prescribed drugs in the United States. They’re prescribed more than drugs to treat high blood pressure, high cholesterol, asthma, or headaches. . .

In its study, the U.S. Centers for Disease Control and Prevention looked at 2.4 billion drugs prescribed in visits to doctors and hospitals in 2005. Of those, 118 million were for antidepressants.

High blood pressure drugs were the next most-common with 113 million prescriptions.

The use of antidepressants and other psychotropic drugs — those that affect brain chemistry — has skyrocketed over the last decade.

Adult use of antidepressants almost tripled between the periods 1988-1994 and 1999-2000.

Between 1995 and 2002, the most recent year for which statistics are available, the use of these drugs rose 48 percent, the CDC reported.

Now it’s certainly arguable that depression may be overdiagnosed, and there are real questions about the diagnosis of discontent and malaise as a “disease” rather than a rational reaction to increasingly depressing conditions in the wider world itself, conditions which are a central focus of this blog.

We would also note that antidepressants, once the preserve of the psychiatric profession, are now handed out by general practitioners, in part because health insurers have radically curtailed extended psychiatric sessions as part of their overall cost-cutting strategy.

Besides, the drugs do make one group of people very, very happy: The executives and shareholders of Big Pharma, who sold us $11 billion worth of the drugs in 2008.

That said, there are real questions about the effectiveness of any of the current antidepressants.

To quote from Wikipedia:

A review of all studies ever submitted to the U.S. Food and Drug Administration (FDA) of 12 anti-depressants, published and unpublished, was submitted to the FDA in 2004. In the published literature, anti-depressants had 94% success in treating depression. In the withheld literature, they had below 50% success. Combined, all studies showed 51% efficacy – only two points better than that of placebo. This increased the apparent efficacy of different anti-depressants from between 11% to 69% over placebo. Possible exceptions are mirtazapine – a norepinephrine and serotonin antagonist – and venlafaxine, an SNRI with substantial similarity in chemical structure to the opioid derivative tramadol. A separate study concluded that the difference in effect between active placebos and several anti-depressants appeared small and strongly affected by publication bias.

We would even argue that of those antidepressants which appear to show some small impacts that a study in which a placebo that had some physiological effect [caffeine, say] might negate whatever positive impacts were shown for the prescription drug. We hope some researcher follows up.

But prescription antidepressants generate huge profits for Big Pharma, and they spend large fortunes trying to persuade us of the efficacy of their latest molecular tweaks.

One drug that does exhibit real promise

There is a drug that does show real promise in clinical studies.

But there are three problems. First, it’s illegal, second, it occurs in nature and is readily cultivated, and third, the synthesized form was created so long ago that it’s out of patent.

The drug is psilocin, the active agent in the very illegal and very psychedelic Psilocybin mushroom [or ‘shrooms in street argot].

And unlike conventional antidepressants, researchers actually know how psilocin works to produce its effects.

And yes, you read that correctly. Scientists can’t even say how conventional antidepressants work to produce what little impacts they may have on depressed people!

Enhancing neuroplasticity in the brain

The latest findings on the pscychedelic ‘shroom are reported by the fortuitously named Arran Frood in New Scientist:

Psychedelic drug users throughout the ages have described their experiences as mind-expanding. They might be surprised, therefore, to hear that psilocybin – the active ingredient in magic mushrooms – actually decreases blood flow as well as connectivity between important areas of the brain that control perception and cognition.

The same areas can be overactive in people who suffer from depression, making the drug a potential treatment option for the condition.

The study is the first time that psilocybin’s effects have been measured with fMRI, and the first experiment involving a hallucinogenic drug and human participants in the UK for decades.

Robin Carhart-Harris at Imperial College London and colleagues recruited 30 volunteers who agreed to be injected with psilocybin and have their brain scanned using two types of fMRI.

fMRI, or functional Magnetic Resonance Imaging, affords an indirect measure of neural activity within the brain by the monitoring changes in blood flow that accompany increases and decreases in nerve cell activity.

What the researchers found was not an increase in blood flow, but declines in specific regions of the brain:

Less blood flow was seen in the brain regions known as the thalamus, the posterior cingulate and the medial prefrontal cortex. “Seeing a decrease was surprising. We thought profound experience equalled more activity, but this formula is clearly too simplistic,” says Carhart-Harris. “We didn’t see an increase in any regions,” he says.

Decreases in connectivity were also observed, such as between the hippocampus and the posterior cingulate and medial prefrontal cortex.

But the real news in Frood’s story was contained in his penultimate paragraph:

Franz Vollenweider, who works in a similar field at the Psychiatric University Hospital Zurich, Switzerland, says that the immediate effects of psilocybin are not as important for clinical benefit as the longer-term effects. That’s because psilocybin increases the expression of genes and signalling proteins associated with nerve growth and connectivity, he says: “We think that the antidepressant effects of psilocybin may be due to a possible increase of factors that activate long-term neuroplasticity.”

In other words, psilocybin helps the brain rewire itself, which is probably the factor that produces long-term antidepressant effects noted in several other studies now underway.

The most potent antidepressant?

Because Uncle Sam places the drug in the same category as heroin, researchers have had a hard time conducting studies of its efficacy, and most of the work underway in the United States focuses on the treatment of patients with severe forms of cancer.

Thomas H. Maugh II reported for the Los Angeles Times last 7 September on one such research program in Southern California:

The psychedelic drug psilocybin, the active ingredient in “magic mushrooms,” can improve mood and reduce anxiety and depression in terminal cancer patients, Los Angeles researchers reported Monday.

A single modest dose of the hallucinogen, whose reputation was severely tarnished by widespread nonmedical use in the psychedelic ‘60s and ethical lapses by researchers such as Timothy Leary, can improve patients’ functioning for as long as six months, allowing them to spend their last days with more peace, researchers said.

>snip<

The patients were given a relatively low dose of psilocybin, 0.2 milligram per kilogram of body weight. Nonetheless, the team reported in the Archives of General Psychiatry, all patients reported a significant improvement in mood for at least two weeks after the psilocybin treatment and up to a six-month improvement on a scale that measures depression and anxiety. Most also reported a decreased need for narcotic pain relievers. No adverse reactions were observed.

These types of patients normally do not respond well to psychological therapy, Grob said, but his study showed that the drug has “great promise for alleviating anxiety and other psychiatric symptoms.”

Read the rest.

Other studies are  currently underway at Johns Hopkins medical school, the subject of an 11 April 2010 New York Times report by John Tierney, who recounted the experiences one subject, retired clinical psychologist Clark Martin, who had been laboring under the burden of cancer and a severe, long-term depression:

After taking the hallucinogen, Dr. Martin put on an eye mask and headphones, and lay on a couch listening to classical music as he contemplated the universe.

“All of a sudden, everything familiar started evaporating,” he recalled. “Imagine you fall off a boat out in the open ocean, and you turn around, and the boat is gone. And then the water’s gone. And then you’re gone.”

Today, more than a year later, Dr. Martin credits that six-hour experience with helping him overcome his depression and profoundly transforming his relationships with his daughter and friends. He ranks it among the most meaningful events of his life, which makes him a fairly typical member of a growing club of experimental subjects.

Roland Griffiths, the behavioral biologist who is the principal researcher on the project, told Tierney that “Dr. Martin’s experience is fairly typical. . .an improved outlook on life after an experience in which the boundaries between the self and others disappear.”

According to an abstract of one of their projects published in the Journal of Psychopharmacology

At the 14-month follow-up, 58% and 67%, respectively, of volunteers rated the psilocybin-occasioned experience as being among the five most personally meaningful and among the five most spiritually significant experiences of their lives; 64% indicated that the experience increased well-being or life satisfaction; 58% met criteria for having had a ‘complete’ mystical experience. Correlation and regression analyses indicated a central role of the mystical experience assessed on the session day in the high ratings of personal meaning and spiritual significance at follow-up. Of the measures of personality, affect, quality of life and spirituality assessed across the study, only a scale measuring mystical experience showed a difference from screening. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-month follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.

And it’s just not depression

A very preliminary study conducted in England indicated the same drug may provide at least temporary relief for victims of another severely disabling malady, obsessive-compulsive disorder [OCD].

A second study, conducted by Francisco Moreno of the University of Arizona, found significant relief for several OCD patients. To quote from the summary of the abstract in the Journal of Clinical Psychiatry:

In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.

Another study, reported in the journal Neurology, recounts the findings of a study by Harvard Medical School researcher R. Andrew Sewell and colleagues conducted at McLean Hospital of the effectiveness of psilocybin and LSD on cluster headaches:

Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. Research on the effects of psilocybin and LSD on cluster headache may be warranted.

So what’s next?

At this point, and in the interests of journalistic objectivity, we feel obligated to report that esnl has thrice ingested the fungus in question, the last time quite legally in Amsterdam in 2006, before sale of the drug was banned.

We also have suffered from ongoing depression, which hasn’t responded to any of the current antidepressants but which was relieved for about a year after our experience. But then the experiential joy of our first ever-trip to Europe surely played a part as well, so our own report is of little value, even as anecdotal evidence.

That said, we sure enjoyed the experience.

With that out of the way, the new medical findings and the revelation that psilocin may facilitate greater neuroplasticity should, in any rational world, trigger a new wave of research into psilocybin and other “scheduled” drugs.

If the neopuritans have their way, however, that won’t be happening — and that would really be depressing.