[THS] The Lancet: Research on psychedelics moves into the mainstream

[Peter Webster]

The Lancet 3 May 2008; 371:1491-1492

World Report

Research on psychedelics moves into the mainstream

Kelly Morris

The backlash against the recreational use of psychedelic drugs in the 1960s
had a negative effect on research into their potential therapeutic benefit.
But now attitudes are changing and work in this area is being revitalised,
with several early-stage trials underway. Kelly Morris reports.

Some 50 years ago, substances called psychedelics were hailed as the new
tools of psychiatry. After their use in diverse clinical contexts, not always
with rigorous methods, and following widespread non-medical use,
“research was quashed for misguided but understandable reasons”,
explains Rick Doblin, president of the US Multidisciplinary Association for
Psychedelic Studies (MAPS). Now, that scenario is rapidly changing, with
several phase II trials underway worldwide, and many more studies
ongoing or planned. “It's amazing how much is going on”, Doblin told The
Lancet after the World Psychedelic Forum that took place in
<?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-
com:office:smarttags" />Basel, Switzerland at the end of March.

Part of this resurgence, say experts, is down to a more measured attitude of
researchers towards the risks and the benefits of drugs like lysergide (LSD),
psilocybin, and methylenedioxymethamfetamine (MDMA). “What we see
now is the [US] FDA (Food and Drug Administration) making decisions
based on data rather than politics, and major universities involved in
research”, notes Tom Roberts, a professor of educational psychology from
Northern Illinois University, IL, USA, and co-editor of the book Psychedelic
Medicine. Clinical studies are the most appropriate context to start re-
exploring the use of psychedelics, says Roberts, because of rigorous review
processes and the step-by-step development of studies. The “Timothy Leary
era” of informal or illegal explorations “caused a lot of problems”, he notes.
Ben Sessa, a consultant psychiatrist based in the UK, agrees. “At the end of
the 1960s these drugs were labelled as dangerous drugs of abuse in the
wake of the explosion of recreational use by the general public. The
resulting war on drugs has been only minimally effective at tackling
recreational use but has been extremely damaging for any genuine medical
research”, he says.

What the experience of the 1960s has shown is pointers to many possible
therapeutic and non-medical uses. “The evidence so far suggests that the
anxiety (neurotic) disorders tend to do well with psychedelics—that includes
anxiety, post-traumatic stress disorder, and obsessive-compulsive disorder.
This is because these drugs are particularly good at allowing the user to
access otherwise repressed and painful memories and do some meaningful
psychotherapeutic work under the influence of the drug”, says Sessa.
Previous clinical experience, plus more recent informal use, has indicated
other potential therapeutic uses for cluster headaches and addictions,
among other conditions.


The therapeutic benefit of MDMA is being tested in pilot studies for post-
traumatic stress disorder
Science Photo Library

Some of the first clinical trials have focused on MDMA, which is not a classic
hallucinogen. Doblin was keen to develop protocols for formal phase II
studies given the drug's reported capacity “to enhance people's ability to
feel, accept, and integrate difficult emotions” within a psychotherapeutic
context. Of MAPS' three pilot studies for post-traumatic stress disorder
worldwide, the US study ends first, in July. Three further phase II studies
are in planning. “What we need to do is to replicate the US findings”, says
Doblin, who th en hopes to see the development of phase III trials in
Europe and the USA, which, if positive, could pave the way for MDMA to be
available as a prescription medicine.

“We have shown that LSD [historically] and MDMA given in a
psychotherapeutic context can be safe”, notes Doblin, but he emphasises
that the therapeutic outcome seems highly dependent on the therapeutic
context. Thus, as Roberts explains, “in psychotherapeutic sessions,
psychedelics are best thought of as adjuncts to psychotherapy, not as
whole treatments themselves”. Doblin concurs: “We are talking about
reversing a lifetime of patterns, in some cases, so the magic bullet or single-
dose miracle cure theory is out the window. Multiple doses are needed in
the context of long-term psychotherapy.”


Psychedelics might be of benefit in the treatment of cluster headaches
Photolibrary

Now, the first clinical trial of psilocybin in terminal cancer patients led by
Charles Grob at the University of California is nearing completion, and
others are recruiting or about to start further investigating psilocybin,
MDMA, or LSD in similar situations. For example, a study led by Stephen
Ross and Anthony Bossis from the New York University School of Medicine,
NY, USA, is about to commence using psilocybin with psychological support,
with endpoints that include reductions in anxiety, depression, pain, and
increased acceptance of death. “I am interested in novel ways to relieve
suffering for end-of-life cancer patients”, says Bossis. “We are looking to
determine whether a mystical state can alleviate the psychosocial and
existential anxiety associat ed with the end of life.” Roland Griffiths from
Johns Hopkins University School of Medicine, Baltimore, MD, USA, is also
researching the effect of psilocybin on anxiety surrounding cancer
diagnosis; this trial is unique in that patients with and without disease
progression will be eligible.

Amanda Neidpath, director of the UK Beckley Foundation, has been working
for years to initiate new research on LSD, by collaborating with various
groups worldwide. In addition to therapeutic research, she believes “we
need to understand the mechanisms by which we get these changes of
perception that may be beneficial
how these substances work, how they
are helpful, and for whom”. Also, since psychedelics would not be
efficacious in everyone, an understanding of mechanisms may point to non-
psychedelic means to achieve the same therapeutic effects. Research on
mechanisms might also help explore other potential uses for psychedelics.
One such study about to commence will investigate the effects of LSD on
brain connectivity and sensory processing, which might clarify previous
suggestions about how psychedelics might enhance cognition and crea
tivity.

“As our view of the human mind and nervous system expands, it is being
recognised that different mind-body states, different from our waking state,
are also useful”, says Roberts. One such state, which has been anecdotally
linked with enhanced wellbeing and anti-addictive properties, is the group
use of ayahuasca. This ancient compound is not pure, but a mixture of
plants used mainly by indigenous and spiritual groups. Traditional mixtures
vary, but all contain a source of the psychedelic dimethyltryptamine plus a
compound to prevent its gastrointestinal breakdown.

Jordi Riba and a team led by Manel Barbanoj from the Hospital de Sant Pau
in Barcelona, Spain have been studying ayahuasca in healthy volunteers for
about 10 years. Using a freeze-dried preparation, administered at standard
doses of the active alkaloids, the team have done tolerability and
pharmacokinetic studies in addition to collecting data on neuroendocrine,
immune, and subjective parameters. “During the acute phase [3–4 h],
volunteers reported having gone through a deeply introspective and
emotional experience with thoughts usually revolving around personal
concerns”, notes Riba. “Most participants found this interesting and useful,
and it is in this remarkable characteristic of ayahuasca where the potentia l
for modifying self-destructive behaviours, such as drug abuse, could
reside”, he speculates. EEG and SPECT studies have confirmed changes in
brain electrical activity and blood flow consistent with these subjective
effects, and now the team plans to assess the effect on long-term healthy
users.

In learning lessons from the 1950s and 1960s, researchers in general
remain cautious about the potential for psychedelics and how they are
investigated. Roberts notes that except for a study on cluster headaches
(which reviewed informal use), all studies presented at the recent Basel
forum specify that psychedelics are taken in the presence of a trained
professional, and programmes for educating and training professionals are
starting to be developed. MAPS is planning to seek FDA approval for a
training programme for psychotherapists or nurses to become psychedelic
psychotherapists. Ross, with Jeffrey Guss, has developed a course on
psychedelic medicine, taught earlier this year to a group including medical
students, psychiatry residents, and post-doctoral addiction fellows at
Bellevue Hospital department of psychiatry in New York, USA. The course
focuses on use of psychedelics for addiction.

The development of education in parallel with research is essential to
ensure an academic focus towards psychedelic medicine, Ross and others
believe. “Often people hold very passionate and pseudo-scientific opinions
about these drugs on both sides of the debate. As clinicians, we need to
remain dispassionate and hold true to the principles of evidence-based
medicine
we owe it to those patients who may benefit from this
approach”, says Sessa.