Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

This study was approved by the National Research Ethics Service (NRES) committee London – West London and was conducted in accordance with the revised declaration of Helsinki (2000), the International Committee on Harmonisation Good Clinical Practice (GCP) guidelines and National Health Service (NHS) Research Governance Framework. Imperial College London sponsored the research which was conducted under a Home Office license for research with schedule 1 drugs. The Medicines and Healthcare products Regulatory Agency (MHRA) approved the study. All patients gave written informed consent, consistent with GCP.

Imaging vs clinical outcomes

To explore relationships between significant imaging outcomes and the main clinical outcomes, we chose to focus on changes in depressive symptoms from: 1) pre-Treatment to scan 2 (i.e. one-day post-treatment), and 2) pre-Treatment to 5 weeks post-Treatment. The primary clinical outcome measure, the 16-item Quick Inventory of Depressive Symptoms (QIDS-SR16) was chosen for this purpose. Relationships between imaging outcomes and contemporaneous decreases in depressive symptoms were calculated using a standard Pearson’s r, and relationships with the longer-term (i.e. at 5 weeks post-treatment) changes in depressive symptoms were calculated by splitting the sample into responders (>50% reduction in QIDS-SR16 scores) and non-responders at this time-point, and then performing a one-tailed t-test on the relevant imaging outcomes (one-tailed as directionality was unequivocally implied by the direction of the significant imaging outcome). We used a revised version of the QIDS-SR16 for 24-hour measurement for the post-treatment scan in order to get a contemporaneous, state-related index of depressive symptoms at this time-point.

Anatomical Scans

Imaging was performed on a 3 T Siemens Tim Trio using a 12-channel head coil at Imanova, London, UK. Anatomical images were acquired using the ADNI-GO (Alzheimer’s Disease Neuroimaging Initiative, Grand Opportunity52) recommended MPRAGE parameters (1 mm isotropic voxels, TR = 2300 ms, TE = 2.98 ms, 160 sagittal slices, 256 × 256 in-plane FOV, flip angle = 9 degrees, bandwidth = 240 Hz/pixel, GRAPPA acceleration = 2).

 

Source: Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms | Scientific Reports

Can magic mushrooms treat depression? – New Scientist Live 2017

Could psychedelic drugs make the world a better place?

In this talk, Robin Carhart-Harris will describe the rationale behind conducting the first ever clinical trial of psilocybin (magic mushrooms) as a treatment for depression – and share his results.

Robin will describe how psilocybin works in the brain to have its antidepressant effects and discuss the psychology of the drug experience and after-effects of the treatment.

Could psychedelic drugs like psilocybin revolutionise psychology and psychiatry?

Source: Can magic mushrooms treat depression? – New Scientist Live 2017

David Nutt – The Psychedelic Crusader

 

David Nutt
The Psychedelic Crusader

In a society where almost all drugs have negative associations, it’s hard to have an open and rational discussion about their potential miraculous effects.

So you used to work as a government adviser. What did that life teach you about how the government approaches drugs, as opposed to what you’re doing now? There must be a huge gap.

Yes, there is an enormous gap. That was the great dissolution and that’s why I got sacked. I spent nine years chairing a committee that did the most systematic analysis of drug harms that has ever been done. It developed new methodologies, published papers, and that was enormously fruitful. I believe that’s what governments should do if they want to make good laws. But it gradually became clear to me during that decade that I was working there that they weren’t interested in the facts. They were very happy with the facts that justified their preconceptions, but the facts that conflicted with their preconceptions they tried to dismiss, or hide, or ignore. In the end it became too oppressive. I suddenly discovered one day, during an interview with one of the BBC home affairs correspondents that I was actually speaking like them. I suddenly thought – who is saying these things? This is not me.  I had to stop the interview and say, no we can’t go on. Then I started telling the truth and within six months I was sacked.

You are very enthusiastic about green-lighting trials in this area and understandably so. We’re talking about people suffering from anxiety and depression. The Default Mode Network is generally overactive in people with those disorders and Psilocybin has been shown to turn off the DMN and allow the brain to behave in ways never seen before. But we still know very little for certain. Isn’t that terrifying?

The point is we don’t know about it because no one has done it before. It’s quite fascinating. Getting some of this stuff published has been quite difficult. A lot of scientists would prefer if this whole thing went away. It raises challenges to philosophies and theories of science. It is like Einstein. We had a nice theory of physics and then suddenly relativity comes along and we have a different theory. Similarly we had a nice theory of consciousness but then our work comes along and says actually there’s another kind of psychedelic consciousness and that’s associated with very different brain activity. All the scientists working in the area of consciousness are saying, “Hey, get out of here. You’re a fucking psychiatrist.” But the truth is we’ve challenged things and shaken things up.

 

“I’m sure that within ten years psilocybin will be an accepted alternative treatment for depression.”

Full Article – 

Source: David Nutt – The Psychedelic Crusader

2016’s best bits: breakthroughs in science

 

Powered by Guardian.co.ukThis article titled “2016’s best bits: breakthroughs in science” was written by Ian Sample, for The Guardian on Saturday 24th December 2016 09.00 UTC

It came from beyond the Large Magellanic Cloud. The signal, a mere 20 milliseconds long, captured the moment when two black holes slammed together – a cataclysm that sent ripples through spacetime and onwards to Earth, where they made instruments chirp and scientists cheer. “We have detected gravitational waves,” said David Reitze of the Laser Interferometer Gravitational-Wave Observatory (Ligo). “We did it.”

The announcement ranked as the physics discovery of the year, confirming Einstein’s century-old theory of gravity and putting the Ligo team on course for a Nobel. But the real excitement is yet to come. For the first quarter of a million years, the cosmos was hidden from astronomers. Now scientists can build gravitational wave observatories and, with them, look back to the birth of the universe. We can study the moment of creation.

It wasn’t the only time astronomers celebrated in 2016. In August, the European Southern Observatory in the Chilean desert saw changes in the light coming from Proxima Centauri, the star nearest to the sun. An Earth-sized planet was pulling the red dwarf around. What thrilled astronomers was that the newly discovered world lay in the star’s habitable zone, that Goldilocks region of space where the temperature is right for liquid water, and along with water, perhaps life. The discovery brought the question, “Are we alone?” to our cosmic doorstep – and with it the realisation that such planets are not rare.

Stephen Hawking is convinced that aliens are out there, but he’s wary of inviting them over. In his 2016 film, Stephen Hawking’s Favourite Places, he warned that meeting up with a technologically advanced bunch of cosmic hooligans might do for humanity what Christopher Columbus did for the Native Americans.

Hawking is equally suspicious of artificial intelligence. Yes, superintelligent machines might solve our greatest challenges, but not if they wipe us out instead. Fortunately, that threat remains a distant one.

Magic mushrooms
Magic mushrooms, or medicine? Photograph: Martin Bond/Science Photo Library

For some people, merging with robots makes sense. Nathan Copeland, a 28-year-old who broke his neck in a car crash, had a robot arm wired directly into his brain. He could move it by thinking, and through signals passed back to his brain, experience a sense of touch. By providing sensory feedback, researchers are edging towards their ultimate goal: robotic limbs that move and feel like real ones.

More than 25 US states have now legalised marijuana for medical uses, but could magic mushrooms be next? A handful of small studies found that psilocybin (the ingredient that made for happy hippies in the 1970s) could lift severe depression in one group of volunteers, and reduce anxiety and depression in cancer patients. For Stephen Ross, director of addiction psychiatry at NYU Langone Medical Center, the latter results were unprecedented. “We don’t have anything like it,” he said.

Goodnews list

“More work needed” was the take home from another trial in 2016; this time for a male contraceptive. At last it seemed that men could shoulder the responsibility for birth control, and all it required was, well, a little prick. The bimonthly hormone jab was nearly as effective as the female pill, but the trial was halted after 20 men dropped out. Some suffered from depression and acne; others had to contend with soaring libidos.

Of the 130 million or so babies born this year, one that arrived in April marked a scientific first. A Jordanian boy was created with DNA from three people (his parents, plus a healthy donor) to prevent him from inheriting a serious genetic disease. The US team who performed the treatment in Mexico say the boy is healthy, but such diseases can take hold later in life. In December, the fertility regulator in the UK gave clinics the green light to apply for a licence to offer the procedure, known as mitochondrial replacement therapy, paving the way for similar births in Britain.

Every year has its own advances, but all tell the story of science. Great ideas work or fail. Achievements are lauded, but make us think twice. With each, we understand that little bit more about ourselves and the universe. And if none of it makes much sense yet? Well, we can always ask the aliens.

• Where did it all go right? For a more positive view of the world in 2017, follow the Guardian’s Half Full online series, with reports on innovative ideas and solutions to the challenges of the day. Wishing you all a happier new year.

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Power of psychedelic drugs to lift mental distress shown in trials

 

Powered by Guardian.co.ukThis article titled “Power of psychedelic drugs to lift mental distress shown in trials” was written by Sarah Boseley Health editor, for The Guardian on Friday 2nd December 2016 17.37 UTC

When Aldous Huxley was dying in 1963, he asked his wife to inject him with LSD, and he passed away, she wrote afterwards, without any of the pain and distress that cancer can cause in the final hours.

“All five people in the room said that this was the most serene, the most beautiful death,” Laura Huxley, a psychotherapist, wrote to other members of his family.

Huxley, who wrote his 1954 essay The Doors of Perception about his experience of taking the psychedelic drug mescaline, anticipated just such a death in his last novel, Island. At the time, many in the psychiatric field thought psychedelic drugs such as psilocybin, the active ingredient of magic mushrooms, and LSD held huge promise to alleviate all kinds of severe mental distress. There were experiments, funded by the United States government, into the use of LSD at the end of life.

But the doors clanged shut in 1970, when the US government classified the drugs in schedule 1, which meant they had no medical use.

Nearly half a century later, two trials in the US may have proven that wrong. One, conducted at Johns Hopkins University and the other, at New York University, gave a single high dose of psilocybin, along with psychotherapy, to 80 people with advanced cancer who were experiencing depression and anxiety.

The results published this week were remarkable, prompting 10 eminent figures in the psychiatric world in the US and Europe to contribute commentaries to the Journal of Psychopharmacology, where the trial outcomes were published, calling for more research. In 80% of cases, patients’ distress was lifted and remained so for six to eight months.

In the same week, the Food and Drug Administration in the US gave the green light to a phase 3 trial of MDMA, or ecstasy, for post-traumatic stress disorder (PTSD). This will be a large-scale trial, following several small and successful trials, capable of producing the evidence needed for the FDA to approve MDMA as a licensed medication.

It’s a watershed. Years of hard work by those convinced that mind-altering drugs have a place in medicine have led up to it, overcoming legal and financial obstacles to trials as well as social and political hostility. The multidisciplinary association for psychedelic studies (Maps), which has fought for this and other trials since 1986, believes ecstasy will be a licensed medicine within four years.

“We’re not counter-cultural in any sense,” says Brad Burge of California-based Maps, which will raise $20m to fund the final trials. “We are trying to develop a legitimate treatment option for people with PTSD and other illnesses.”

What has shifted over the decades is gradual recognition of the vast amount of untreated need. “There is a great deal more awareness than there used to be of PTSD as an epidemic worldwide,” says Burge.

The conventional treatments for PTSD such as anti-depressants and anti-anxiety pills do not work for most people, any more than they do for the sort of distress around life-threatening cancer that makes some sufferers have suicidal thoughts. Psychotherapy can help, but the psychiatric community is astounded by the lasting effect of a dose of MDMA on a war veteran who cannot leave his home for fear of reliving the horrors he has seen.

Prof David Nutt from Imperial College in London, editor of the journal that ran the psilocybin trials this week and involved in a smaller study that reported in May on the use of psilocybin in other sorts of depression, says MDMA works in a very different way from magic mushrooms.

“MDMA in PTSD is not a psychedelic,” he says. “I’m not sure psychedelics would work in PTSD. They might make it worse.

“What MDMA does is dampen down the brain circuit which is overactive in PTSD and that allows people to engage in the psychotherapy in a more efficient way. I’ve treated patients with PTSD and as soon as you say, look I want you to start thinking about the trauma, they faint. You can’t engage with them. The traumatic memories are so overwhelming.”

Psilocybin is different. Like LSD, it can produce a mystical experience. Scientists do not yet know if that is why it has a profound effect on depression. “That’s one of the key research questions,” says Nutt. “Do you need a mystical experience? Do you need to meet some greater being?”

Back before the US blanket ban in 1970, scientists trialled LSD as a treatment for alcoholism. The co-founder of Alcoholics Anonymous, Bill Wilson, credited mystical experiences on the drug for his own recovery. “His belief was that you had to find a higher power so that you could look down on this rather petty affection people have for alcohol,” said Nutt.

In his own depression study, he said, some people did have mystical experiences. Others had powerful emotional experiences. When it comes to using psychedelics at the end of life, which was very much of interest to scientists in the 1940s and 1950s, a mystical experience may be key.

“When you see that you are more than your current self and you have experiences as our patients do, feeling you are taken outside of your body and floating off into space and into other worlds, then you see the bigger picture. You realise you don’t ever die. No one ever dies. You stop breathing. You stop thinking. But the atoms are still there,” said Nutt.

“There used to be this wonderful little quiz question they set for scientists doing the Cambridge entrance exam. How many O2 molecules of Socrates’ last breath do you inhale every time you breathe? The answer is about 26 because those atoms, those molecules, are still around. We are just a rather complicated form of life but our matter doesn’t disappear – it’s just the way it’s organised that does.”

Whether such a mind-expanding experience can ever become part of mainstream psychotherapy is no longer just a rhetorical question.

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Magic mushrooms lift severe depression in clinical trial


Powered by Guardian.co.ukThis article titled “Magic mushrooms lift severe depression in clinical trial” was written by Sarah Boseley Health editor, for theguardian.com on Tuesday 17th May 2016 09.15 UTC

Magic mushrooms have lifted severe depression in a dozen volunteers in a clinical trial, raising scientists’ hopes that the psychedelic experiences beloved of the Aztecs and the hippy counter-culture of the 1970s could one day become mainstream medicine.

A clinical trial, which took years and significant money to complete due to the stringent regulatory restrictions imposed around the class 1 drug, has found that two doses of psilocybin, the active substance in the mushrooms, was sufficient to lift resistant depression in all 12 volunteers for three weeks, and to keep it away in five of them for three months.

The size of the trial and the absence of any placebo means the research, funded by the Medical Research Council and published in the Lancet Psychiatry journal (pdf), is a proof of principle only.

The scientists, from Imperial College London, said they hoped the results would encourage the MRC or other funders to put up the money needed for a full trial. However, the use of a placebo control, comparing those who use the drug with those who do not, will always be difficult, because it will be obvious who is having a psychedelic experience.

In spite of the outcome, the researchers urged people not to try magic mushrooms themselves.

The lead author, Dr Robin Carhart-Harris, said: “Psychedelic drugs have potent psychological effects and are only given in our research when appropriate safeguards are in place, such as careful screening and professional therapeutic support.

“I wouldn’t want members of the public thinking they can treat their own depressions by picking their own magic mushrooms. That kind of approach could be risky.”

The senior author, Prof David Nutt, said it was justified for researchers to explore the medical use of banned recreational drugs.

“It is important that academic research groups try to develop possible new treatments for depression as the pharmaceutical industry is pulling out of this field‎. Our study has shown psilocybin is safe and fast acting so may, if administered carefully, have value for these patients.”

All the volunteers had severe depression and had failed to improve on at least two standard antidepressants. They were initially given a low dose of psilocybin to ensure they had no adverse reactions (none did) and then a higher dose a week later. They were treated in a specially prepared room, with music playing and in the presence of two psychiatrists who talked with them throughout. The psychedelic experience lasted up to five hours.

One of the volunteers, Kirk Rutter, from London, described himself as being heartbroken by the death of his mother and unable to come to terms with it in spite of counselling and medication. He said he was nervous about taking part and had never taken magic mushrooms, but said the friendly staff, the room layout and the music had relaxed him by the time he came to swallow the capsules.

“Both times I experienced something called ‘psychedelic turbulence’. This is the transition period to the psychedelic state, and caused me to feel cold and anxious,” the 45-year-old said. “However this soon passed, and I had a mostly pleasant – and sometimes beautiful – experience.

“There were certainly some challenging moments during the sessions, for instance when I experienced being in hospital with my mother when she was very ill. And during the high-dose session I visualised my grief as an ulcer that I was preventing from healing so that I could stay connected to my mother. However, by going through memories, and feeling the love in our relationship, I saw that letting go of the grief was not letting go of her memory.”

He said it was not a quick fix and he needed to keep working at feeling positive, but he was still “doing great”.

Nutt said major hurdles had to be overcome to carry out the research. It took a year to get ethical approval and there was a six-month safety study, but the hardest part was getting through the red tape.

It took 30 months to get the drug, which had to be specially packaged into capsules for the trial by a company which was required to get a licence to do so. All the regulatory approvals took 32 months, Nutt said. “It cost £1,500 to dose each person, when in a sane world it might cost £30.”

The researchers said they did not know whether the effect of the drug was caused by chemical changes in the brain or whether the psychedelic experience, which people describe as spiritual or mystical, gives them a new perspective. Either way, they said psilocybin offered hope for those who had been depressed for an average of 18 years – the majority of the volunteers had been depressed most of their lives.

The study was part of a research collaboration between Imperial and the Beckley Foundation, a thinktank that focuses on drugs policy.

Amanda Feilding, founder of Beckley and co-director of the trial programme with Nutt, said: “The results from our research are helping is to understand how psychedelics change consciousness, and how this information can be used to find breakthrough treatments for many of humanity’s most intractable psychiatric disorders, such as depression, addiction and obsessive compulsive disorder.”

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