Tom Parkhill interviews former ECNP President, Professor Guy Goodwin (University of Oxford, UK), who will be talking on the clinical use of psychedelic drugs at the 33rd ECNP Congress in September.

“If the doors of perception were cleansed everything would appear to man as it is: Infinite”.
William Blake, adapted by Aldous Huxley in his description of his use of peyote, The Doors of Perception.

Professor Goodwin, which drugs are we talking about?
In this presentation we are talking specifically about psilocybin, which is the psychedelic drug closest to getting regulatory approval. The psilocybin drug itself was synthesised a long time ago, actually by Albert Hoffman who also synthesised LSD. It’s predominantly a 5HT 2A agonist, so it shares this feature with LSD, with mescaline (from the peyote cactus), and with a few others such as the drug commonly known as toad (5-methoxy-N,N-dimethyltryptamine). All these drugs can at the right dose produce a dramatic change in consciousness, which initially starts as visual distortions and elaborations, and then morphs into a much greater breakdown of one’s sense of self. One may lose the distinction between the universe and one’s individual identity, and people often describe this in quite mystical terms. There are a lot of these drugs in nature: psilocybin is found in mushrooms, peyote in cactus, and toad is actually found in toads. There’s also the potential for novel psychedelic compounds.

These are some differences in potency between the various psychedelic drugs, but from the clinical point of view one of the most important factors is the duration of the effect. A drug like LSD can have a psychedelic effect for around 12 hours, whereas psilocybin last around 6 hours, which makes it much more manageable within the working day of a clinic. The effects of toad lasts only around 20 minutes, so that also has some clinical potential, but that’s still a long way off.

So psilocybin is in development?
Yes. The drug itself is not directly under any patent, and there are different routes to bringing it to the market. The Usona charity in the US is looking to develop the drug on a charitable basis, and some companies are looking at more conventional pharmacological routes, perhaps by adapting the formulation. Compass Pathways for example is doing trials in treatment-resistant depression (I have consulted for Compass Pathways) and we will be discussing their experience in the brainstorming session.

Taking a psychedelic like psilocybin won’t be like taking an SSRI. How is this managed?
All the studies are currently designed to work with a single dose. The history of psychedelics shows that the set and setting are important: how and where the drug is taken. Patients also have to discontinue other antidepressants before treatment, which can be inconvenient. There is a fairly intensive clinical contact with the patient before the session of several hours to prepare the patient for the psychedelic experience. They take the drug first thing in the morning, with the experience lasting most of the day. They are continually supervised, although mostly there’s not much direct communication, taking a psychedelic tends to be an inward-looking experience. The supervisors are trained on how to help patients overcome any bad periods in the experience. They are encouraged to treat the experience as a journey, like a trip down a river; you may run into rapids but it will pass. The drugs themselves are physically very safe. What seems to be beneficial is that the patient returns the next day and talks through the experience.

Do we know how long the improvements last?
Most patients seem to maintain an improvement for up to 12 weeks, with a big average reduction in symptoms. Some patients continue to show an improvement after a year or two; this may not be a ‘cure’ but remember that these can be difficult patients to treat, so it’s progress. The patients often emphasise the experience of taking the drug, the trip. The breakthrough that they feel when taking the drugs echoes many of the descriptions of the psychedelic experiences in the past. This experience itself is believed to be the treatment, although we can’t yet exclude more pharmacological explanations. It gives a sort of reset of how you see the world, one looks at the world in a more informed and enlightened way, similar to the experiences some people get with Eastern religions or enlightenment. I’ve met a couple of patients who give a very convincing account of how their life has turned around immediately – on a dime – based on the experience. This is the current explanation of how the treatment works.

So it’s not just a treatment for depression, it may change your whole personality.
It may, and it is usually assumed for the better! We want to be cautious on the ethical aspects, however. The documentation on long-term outcomes is not complete. By and large, we have not seen much in the way of really negative outcomes. There are occasional bad trips and perhaps 10% of patients have marked increases in anxiety at some point in the drug experience, but people appear to recover fairly quickly. I believe that the key ethical issue is informed consent: people need to understand in advance what they should expect and that means updating on the basis of clinical experience in controlled studies.
I think that we also need a bigger emphasis on objective outcomes. This is an issue in depression trials generally. We need objective evidence; is it enough that people say that they feel better? I’d like to see something more measurable, for example objective proof that someone has gone back to work, or is more economically active. But perhaps that’s a more general issue.

So what are the practical problems of dealing with controlled substances, and with convincing people that taking a controlled substance might help them?
The fact that they are controlled substances – and have been since the early 1970s – has severely limited the amount and type of research that has been carried out. The reasons behind the ban were political, stemming largely from the crisis in US politics – specifically over the Vietnam war. The issue then was the perception that anti-war people were pro-drugs, and psychedelic use was seen as an assault on the values of the time. Of course, there were also some good reasons to be concerned; the scale of drug use at the time had escalated very quickly, and people were taking the drugs without much consideration of the “set and setting”, and so it could be dangerous. The drugs disappeared entirely from human research and practice after the United Nations ban in 1971, although of course they were available outside the law. The drugs had been used in psychiatry before the UN ban, for example there was a provincial hospital in England where thousands of people were treated with LSD, but the methodology for analysing the results wasn’t good, and interpretation was also coloured by the psychoanalytical paradigms of the day. This was an in-patient population, with a poor prognosis, so it’s difficult to interpret and to put into the context of today’s more objective clinical trials environment. The staff were careful, and knew what they were doing, but this was over 50 years ago.

But it will be interesting to see how patients react, and I’m very much looking forward to hearing Metten Somers’ talk (which follows mine) on the practicalities of giving psychedelics to patients.

Brainstorming Session
BS.07 – Can we successfully re-medicalise the psychedelics?
Tuesday, 15 September, 13:00-13:30

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