A new dawn for psychedelics? - Ukraine Russia War News

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Psychedelic drugs are getting a new lease on life.

These molecules are steeped in ancient ritualistic history. They found the masses in the summer of love. They felt the wrath of governments who were threatened by their effects. And have since found their way into scientists’ laboratories.

Now, after decades of research, they’re proving their value as potentially promising medicines that could hold the key to tackling some of the most stubbornly treatment-resistant mental health disorders.

Among the market leaders are, deep breath, methylenedioxymethamphetamine — commonly known as MDMA or ecstasy — and psilocybin, or magic mushrooms. Others in development include lysergic acid diethylamide (LSD, or acid) and N, N-Dimethyltryptamine (DMT).

Clinical trial data is amassing, compelling progress toward regulatory submissions — possibly even next year in some countries, including in the EU. But probably not in the U.K. due to its “medieval” approach to mental health, according to David Nutt, a neuropsychopharmacologist at Imperial College London.

MDMA is a Schedule 1 drug that is likely to be the first one on the market | Alberto Valdes/EPA-EFE

Nutt’s fascination with these molecules spearheaded some of the first clinical trials that subsequently spawned a now-booming psychedelics industry with dozens of players and hopeful investors.

With the sector growing rapidly, he’s helped form the Psychedelic Access and Research European Alliance, PAREA, which he chairs and officially launched recently. POLITICO caught up with professor Nutt to talk psychedelic science, research hurdles, highs and lows.

It feels like there’s been a shift in attitude toward these types of therapies, with a big Psych Summit in London recently and the launch of PAREA now. Is that right and if so, why now?

Yes. There were no companies in the psychedelic space five years ago, and now there’s probably 50 — it’s definitely a sea change. It’s been driven by research by the team at Imperial and the American universities. We’ve shown two things: First, that we know how these drugs work. We did imaging studies and it turns out that psilocybin and LSD — and almost certainly DMT —turn off the parts of the brain which we know are involved in depression. Our first trial in resistant depression showed a single dose of psilocybin was the most powerful single intervention ever in resistant depression. And that spawned the companies. Compass Pathways have replicated our study across 11 countries. It seems pretty clear that psilocybin does work in depression, particularly people where the drugs haven’t worked, and that’s very exciting.

When Compass Pathways replicated that study, what was the patent situation at that point? Was it a patented product, given it’s a mushroom that anyone could pick?

I don’t think you can patent mushrooms, but I think they tried. They are trying to patent the polymorph — the form that they’ve made — but there’s a huge controversy over that. It’s being debated by patent experts across the globe. But on the other hand, they do provide a therapy and they will at least be the first in the market, so that can still be quite valuable for them.

Some of the small companies that are working in this field are hugely valued. What are the incentives here if patenting things like magic mushrooms is so hard?

A lot of money has come from the cannabis industry. People believe that the psychedelic industry is a natural follow-on and there’s quite a lot of spare cash there. There are three ways you can gain any kind of IP. One is to make a formulation of psilocybin. That’s contested but it’s plausible. Other companies are modifying the molecule by changing the hydrogen — but regulators might question any claim of novelty. And the third way is to change the molecules by adding bits and seeing if we get a novel compound which has the same effects. Quite a few companies are working with analogs of psilocybin.

One of the things these drugs do quite reliably is to increase the production of synapses — they seem to increase connectivity in the brain in an enduring way — called neuroplasticity. There are companies that have made compounds that do that which are not psychedelic, in animals, but they need to be tested in humans.

Where do you think the lowest-hanging fruit is across all of the different therapies in development in this field?

MDMA is most ahead. It’s not really a psychedelic, but it’s an illegal drug with serotonergic activity. It’s a Schedule 1 drug that is likely to be the first one on the market. It’s in a second Phase 3 study with MAPS, a public benefit corporation. It’s taken them 30 years to raise the money to do these trials. It’s almost certain that the first Phase 3 trial is very positive, and if the second one looks good as well, then they will get licensed to use MDMA for post-traumatic stress disorder (PTSD). And that could happen by the end of next year.

What formulation is it and how is it administered?

It’s a capsule. They don’t have a patent, I don’t think, but what they do have is data. They’ve done the safety studies we need for licensing a medicine in the Western world. They’ve shown it’s not toxic. That’s a million dollars’ worth of research investment.

And would the first license be in the U.S.?

I think so. But the European regulators are pretty open. PTSD is an enormous challenge, so I think it’ll get a license in Europe. I don’t think the Europeans are going to require more data than the Americans.

What effect does the illegality of these drugs have on their medical development?

It adds huge cost. That’s one of the reasons it’s taken 30 years for MAPS to get to where they are because they have to get licenses for every place they do any research.

In the U.K., my research requires a license to hold the drug, a license to supply the drug to patients, and then if you’re doing a multicenter trial, every pharmacy and every hospital has to have its own licenses. It can take up to a year to get a schedule license because the Home Office is overwhelmed and they cost about £5,000, so for academics and universities it’s a deterrent to research.

But they have to have a license because the United Nations says so. Everything clamped down in 1971 with the U.N. Convention on Psychotropics. It’s a 50-year anomaly in terms of thinking about the science.

There’s a real pressure now to try to accelerate this research by de-scheduling these drugs — getting them out of Schedule 1 and putting them into Schedule 2. If that happened in Western countries that would greatly facilitate research.

Where do things stand currently to review that U.N. convention?

There’s an international campaign to try to get the World Health Organization to accept that psilocybin is a medicine. It was licensed and sold as a medicine in the 1950s and ’60s by Sandoz as psilocybin.

There are two stages to getting it changed. First, the WHO has to concede it does have medical value. And I think it will be very hard for them to say it doesn’t. The problem with the WHO, you can’t force them to review the drug; you have to ask them to get their expert committees to review it.

The same thing happened with medical cannabis. The WHO hadn’t reviewed medical cannabis in 84 years, but eventually in 2018 we pressured them to review it and they came to the conclusion it was a medicine.

The second stage is to get the U.N. to reschedule. Although, the U.N. still hasn’t accepted medical cannabis — it’s kind of under the control of Russia and China. It’s still blocked at the U.N. Office on Drugs and Crime, which controls drugs.

There’s an international campaign to try to get the WHO to accept that psilocybin is a medicine | Fabrice Coffrini/AFP via Getty Images

But I think if the WHO accepts psilocybin, then Britain would too. The reason Britain allowed medical cannabis was because WHO said it’s a medicine. So you can basically ignore the U.N. if you have to, and I think a lot of countries would want to if they change their stance on psilocybin.

Have you had any correspondence back from the WHO on this? Have they indicated that psilocybin is likely to get reviewed?

We haven’t made a formal application yet. We’re still in the process of preparing the groundwork.

Compared with the existing medicines we have to treat mental health conditions, what are the biggest benefits of these new types of therapies?

First, they work in people in whom other medicines haven’t worked. And that’s really helpful because we know with current medicines — particularly for depression, anxiety, PTSD, OCD, anorexia, addictions — success rates are barely 50 percent, sometimes less.

Secondly, they work in a different way and that’s important. The more approaches you can take to a disorder, the better the overall outcomes. We’ve got six or seven different approaches in hypertension. When you’ve got different targets, you’ve got the opportunity of combining medicine to get better outcomes, as well as finding medicines which are particularly suited to one kind of disorder.

And third, they work fast. People have a trip and most of the effect is as big at day one as it is over the next four-to-eight weeks. So you can rapidly get people well, which conventional treatments in psychiatry rarely, if ever, do. That’s appealing because it means you haven’t got to take a pill every day, so there’s no enduring side effects.

What’s the process of taking these therapies, and to what extent is psychotherapy a part of it?

With psychedelics — psilocybin, DMT — there are three phases: There’s the preparation the day before. People are told what might happen, how to deal with the experiences, how strange they might be, and they get reassured. It’s important that people go into this experience with a knowledge that whatever happens they will be looked after. We know one thing does tends to predict a less good outcome is being anxious about the experience. It’s not something you can force on people to do; they’ve got to want it.

During the session, we encourage people to explore this new experience and go to where it takes them. Often they go back to places which are harrowing and challenging, see the origins of a trauma which led to their depression or their PTSD. And we ask them to see if there’s anything in there that they can bring out that is positive. They usually have eye masks, music if they want. They very rarely talk and occasionally they might ask for someone to hold their hand.

The day after and subsequently we do psychotherapy sessions, to make sense of it. A lot of people have fascinating insights, although challenging. They often come out and have understood why they’re depressed and they want to talk that through.

The fact that you get this period of neuroplasticity with psychedelics which may last several weeks gives the psychotherapy even more oomph. Your brain is more flexible so you can really engage better with the psychotherapists. That goes on for as long as we can afford it, in trials. Quite often, patients set up their own support groups afterwards.

MDMA therapy isn’t the same; it doesn’t disrupt the consciousness so much and usually you talk about the trauma during the session. It’s normally two or three sessions over the course of about 12 weeks. In those sessions, people relive the trauma and then try to extinguish the emotions which come bubbling out when they talk about it. The MDMA helps them contain the emotion.

DMT is very short acting, it lasts about 10 minutes. There’s a sense in which being in the therapeutic state for longer may actually be better, but we can’t prove that yet. However, LSD lasts too long, it’s 12 hours. One company is working with LSD plus a blocker, so this could stop the effects say after five hours. There’s a lot of creativity going on.

We can already use ketamine today to treat depression and addiction, we’ve got nice data on that. Ketamine is a kind of psychedelic and there are ketamine clinics now in the NHS and privately. It introduces this period of increased cognitive flexibility where you can improve psychotherapy. It’s quite hard to do because it’s Schedule 2 drug but it’s also a medicine and has been for 30 years so it’s got all the safety data, and doctors are allowed to use it off-license if they’ve got good reason.

And where do you sit with short-term investors jumping on the bandwagon?

I obviously prefer long-term investors. But without money, we can’t do anything. What’s really disappointing is that the British government isn’t investing. That’s one of the reasons we set up PAREA. We were leading the field, we did the first study, we got 40 companies doing psilocybin research based on our trial, and the government’s invested nothing. It’s turned down five of our grants, it’s totally appalling. They seem to have buried their head in the sand.

With the Horizon program, there’s a real opportunity for European researchers and potentially, depending on whether we stay part of Horizon or not, for us to engage in and access bigger European funds. Europeans are much more rational about trying to develop new treatments for mental health. I think in Britain, there’s still a lot of stigma. We have a very primitive, medieval view of mental illness, whereas in Europe, I think they’re more open-minded. I’m hoping that PAREA will begin to develop a dialogue with European funders and we could potentially get a whole Horizon program on the utility of psychedelics.

You were infamously sacked by the government after claiming that ecstasy and LSD were less dangerous than alcohol. Do you still hold that view?

Even more so. Because that analysis didn’t take into account the benefits. And when you add benefits to the equation, unquestionably that’s true. The fact that these drugs are now going through trials and we’re collecting safety data, we are being reassured that our analysis of safety was correct.

What’s the risk to the U.K. if it doesn’t change its attitude? We’re seeing the U.S. pulling away and Europe is more open to discussing the benefits of these types of treatments. Is there a risk that the U.K. will see a brain drain of expertise to other countries?

My star pupil Robin Carhartt Harris, who I trained up from a Ph.D. student to take the lead in the psychedelic center, he’s now in university in San Francisco. His applications for research fellowships in Britain were turned down by the Wellcome Trust, the MRC. We have only got one grant ever from normal British funders, and that was in 2012 to do the resistant depression study, which should transform the world. They’ve turned down everything subsequently. I don’t know why.

We’re already losing our potential. We were massively ahead of the game. We’ll just sink further to become a kind of weird, second division, scientific and clinical nation. It’s a great worry.

What is the MHRA’s response to these types of treatments?

Up to now they’ve been interested and positive. We’ve got the permission to do all the things we’ve done. I think that they’re open-minded. There’s still quite a lot of learning to happen. The biggest issue will come when the companies present their data. I just hope that they are prepared to accept the point it might not conform to the traditional approach.