Pubdate: Mon, 13 Feb 2017
Source: New York Times (NY)
Copyright: 2017 The New York Times Company
Author: Richard Friedman


Psychedelics, the fabled enlightenment drugs of the '60s, are making a
comeback - this time as medical treatment.

A recent study claimed that psilocybin, a mushroom-derived
hallucinogenic, relieves anxiety and depression in people with
life-threatening cancer. Anecdotal reports have said similar things
about so-called microdoses of LSD.

The allure is understandable, given the limits of our treatments for
depression and anxiety. About a third of patients with major
depression don't get better, even after several trials of different
antidepressants. But I fear that in our desire to combat suffering, we
will ignore the potential risks of these drugs, or be seduced by
preliminary research that seems promising.

This appears to be the case with the new psilocybin study, which has
some serious design flaws that cast doubt on the results (and which
the authors mention briefly). The study, done at New York University
School of Medicine, examined a very small number of people with cancer
in a "crossover" design in which each subject served as her own
control, sequentially receiving doses of psilocybin and the control
drug niacin, in random order. (Another recent study of psilocybin,
done at Johns Hopkins University, used a similar crossover design.)

Psilocybin, being a hallucinogen, has immediately recognizable mental
effects, so subjects would almost certainly know when they were
getting it compared with niacin, a vitamin that causes flushing but
has no discernible effect on mood or thinking. This makes it hard to
know if subjects got better because of the psilocybin, or because of a
placebo effect.

The design also means that subjects who got psilocybin first could
have had a "carry-over effect" from the drug when they received
niacin. In other words, they might still have been under the
influence, contaminating the control condition.

The fad of LSD microdosing - typified by Ayelet Waldman's new memoir, "A 
Really Good Day: How Microdosing Made a Mega Difference in My Mood, My 
Marriage and My Life" - is far more worrisome. LSD is an unregulated and 
superpotent drug; users cannot be sure what or how much they are 
actually taking.

Proponents point out that there is little evidence that these drugs
are habit forming or harmful, especially not in low doses. This
assertion seems to rest on short-term clinical studies that found no
adverse effects (but which could miss problems that occur over longer
periods) and on a study of data drawn from the National Survey on Drug
Use and Health, which found no significant associations between
hallucinogen use and mental illness (but it relied on retrospective
self-reporting, which often involves memory lapses and

There is little question from clinical experience that psychedelics
can be behaviorally toxic, even if they are not addicting in the way
cocaine or alcohol are. Bad trips and flashbacks occur with some
frequency in recreational users - and sometimes hallucinogens can
unleash a psychotic disorder in those who are genetically at risk.
Microdoses are supposedly too small to cause those effects, but again,
it could be easy to take more by accident.

The bottom line is that we don't know how safe or effective
psychedelics are because most of the data have been anecdotal or from
small trials. Part of the reason is that hallucinogens have been
classified as Schedule I drugs, the most restrictive category,
reserved for drugs considered to have no legitimate medical use and to
have a high abuse potential. This makes it somewhat difficult for
researchers to conduct large studies, but it is by no means an
absolute bar; there are many trials of Schedule I drugs like THC and
cannabinol, active molecules in marijuana.

I am anxious that we do not repeat the mistake that we made with
cocaine. Aside from Freud's glowing 1884 monograph on cocaine, "Uber
Coca," in which he described his research on cocaine - and his
addiction to it - there was little modern research on the drug. In the
'70s and '80s, people assumed that the absence of data that cocaine
was addictive meant that it was safe and dismissed concerns as
hysterical moralizing. An epidemic followed.

Psychedelic drugs don't come close to the toxicity or abuse potential
of cocaine. But we can't assume they are perfectly safe just because
we don't yet have serious evidence of harm.

Psychedelics might turn out to have real promise, but that needs to be
proven through large, rigorous, placebo-controlled trials. We're not
there yet.

In the end, I suspect they may prove more interesting as probes of
brain function - perhaps illuminating the neural basis of
extraordinary mental states, like our experiences of mysticism - than
as therapeutic agents. What they tell us about our brain is probably
more valuable than what they can do for us.

Richard A. Friedman is a professor of clinical psychiatry and the
director of the psychopharmacology clinic at the Weill Cornell Medical
College, and a contributing opinion writer.
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