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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Supper with the Psychedelic Society – tales of therapy, poetry and ayahuasca


Powered by Guardian.co.ukThis article titled “Supper with the Psychedelic Society – tales of therapy, poetry and ayahuasca” was written by Damien Gayle, for theguardian.com on Monday 19th October 2015 06.00 UTC

Amid an abundance of food and drink, flickering candles and a heady air of altered states,100 or so people in north London’s New Unity church watched John, a mop-haired Irishman in his late 20s, tell the story of how he learned to love through therapy, poetry and ayahuasca.

“I arrived at Cuzco and, sure God, how do you find an ayahuasca ceremony?” he said from a stage adorned with a creeping, twisting vine of fairy lights. “Well you Google it obviously, and you go on to TripAdvisor.” That bizarre mix of the hi-tech and the traditional, the western world and the south, sums up the Psychedelic Society, which held its first “psychedelic supper” on Sunday.

The event – a bring-and-share meal with speakers – comes amid a renaissance in the use of psychedelics. In two years, the number of young people reporting using LSD has almost tripled; the number reporting use of psychedelic drugs more broadly is up 88%.

This rise has come alongside a resurgence of research into the use of psychedelic drugs for mental health. Decades-old reports that claim LSD may profoundly help addicts are being revisited. Recent studies have found that psilocybin – found in magic mushrooms – may have lasting benefits for people suffering from depression.

Psilocybin is found in certain kinds of mushrooms.
Psilocybin is found in certain kinds of mushrooms. Photograph: Peter Dejong/AP

At the dinner, Maria, 30, said her interest in psychedelics began after volunteering for a UK study earlier this year that tried to replicate those effects. She had already undergone conventional treatment for depression, using two different medications, without success.

Psilocybin offered an alternative path, forcing her to explore her “madness”, she said. “It was a bit [psychologically] painful, but it was beneficial because it helped you realise the patterns, and how to break them. I wouldn’t say it was a cure, but it was a catalyst for asking about the self. It was wonderful – for two months afterwards I was depression-free.”

The problem is that psilocybin and LSD are schedule 1, class A illegal drugs, neither regarded officially as having a medical use. They are more tightly restricted than heroin and cocaine, which mean massive costs to any researcher who wants to work with them. Scientists like Dr David Nutt, the former government drugs adviser, have heavily criticised the law, and proposals for a tighter ban on psychoactives.

No suspicious mushroom risottos were being passed around at the dinner on Friday night – the society says it does not engage in illegal activity during events. However, attendees discussed the darknet’s anonymous drug marketplaces, as well as mushroom picking (the psychoactive liberty cap is in season in Britain). There are also legal and semi-legal alternatives, the society points out.

A change in the law on psychedelic drugs is its key aim, and not merely for their reputed therapeutic purposes. Society at large can benefit from psychedelic drugs, it says. “The current legal context does not reflect our massively rich history of using psychedelic drugs,” said Nadia, organiser of the Psychedelic Society in London. “Nationally and globally, we have indigenous roots where people have taken psychedelics as part of their attempts to understand their existence and the nature of reality. Many cultures have shamans. Psychedelics are considered powerful deconditioning agents, so that’s very transformative and revolutionary to our consciousness.

“One experience of psychedelics has apparently changed attitudes towards nature and the earth, which is so important right now. It has a big effect of dissolving our ego, or at least reducing it, helping us to interconnect.”

Back on stage, a third speaker, Dan, spoke about the origins of acid house and ecstasy in the Thatcher era, and how this changed the people who experienced it. “Look at the politics of being in a field with 10,000 people,” he said, “and almost every conversation starts with things like: ‘I’ve never told anyone this in my life, man, but …’”

Tying rave culture to the eco-warrior and anti-globalisation protest movements, he added: “It’s our minds that are our last chances. You can spend all your life doing demos and dropping banners … we end up on page three of the Guardian. If there’s cops, it will be on page two – and that’s not going to do anything. It’s actually ideas that are going to change the world. It’s totally changing the way we answer that question, which is: what the fuck did we come here for?”

John’s journey through psychedelics had led him to look deep inside himself, to dispense with his impulse to judge, and to realise his love for a close friend. He said: “For me, if I look back a year ago, I really thought that I might never fall in love. And now I am. And so, I was thinking about psychedelics being mind-manifesting, but I really feel they’re heart-manifesting. They give the heart a place to hear its voice.”

The names of interviewees have been changed at their request.

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Depressed? Your doctor might soon prescribe ketamine


Powered by Guardian.co.ukThis article titled “Depressed? Your doctor might soon prescribe ketamine” was written by Olga Oksman, for theguardian.com on Thursday 3rd March 2016 16.29 UTC

New Jersey psychiatrist Steven Levine first thought of using ketamine in his practice when a patient came in whose depression could not be lifted by any commercially available antidepressants. After talking to Levine for a while, the patient confessed she felt better when she self medicated with cough syrup. When Levine looked up the active ingredient in the cough syrups the patient used, it was dextromethorphan, which, like ketamine, can induce a dissociative state or a detachment from reality.

You have to be looking in order to find something, says Levine, who is now one of a few practitioners who administer ketamine for depression, along with a few research centers. When he started out, dosing his first patient in 2011, he was as far as he knows the first to offer it outside a research setting. Levine was tired of the available drugs for depression, which have a high side effect profile and are ineffective for some patients.

Only around 45% of patients respond to traditional antidepressants, leaving a huge population that continues to suffer.

Levine was seeing patients who had failed on every class of antidepressants, who had submitted to dramatic last line treatments, like electroconvulsive therapy and transcranial stimulation, and were still depressed.

Unlike with traditional antidepressants, which can take weeks to show any impact, within a few hours, when Levine administered ketamine, it was obvious if it had worked or not. Patients “don’t wake up with a blue bird on their finger”, says Levine, but they do get better.

Since 2011, he has given ketamine to 600 patients. When he administered it only to patients for whom no other treatment had worked, Levine found that 70% got better using ketamine. For the past year he has also been treating patients who have not had any success on two types of antidepressants, and with the addition of that patient population, his success rate is now closer to 80-85%.

While ketamine is not indicated for depression, doctors can prescribe medications off-label at their discretion. Unlike other psychedelic drugs that have also been investigated for their ability to help treat mental illness, like MDMA, ketamine is a legal, widely available and easy to procure medication, says Levine.

Ketamine’s ability to lift people out of severe depression, replicated over and over in research studies, has not gone unnoticed. Unlike in 2011, when Levine first started using it, there are now hundreds of medical studies on ketamine. The American Psychiatric Association (APA) is working on creating official guidelines for administering the drug, which are expected out this year.

Ketamine is administered intravenously to patients. If a patient responds positively to ketamine, they are given a series of doses close together over a couple weeks, followed by spread out maintenance doses. Therapy is recommended in conjunction, to help patients rebuild their lives after depression and maintain their improved state.

Levine is hopeful that after the APA issues its guidelines, insurance coverage will soon follow. He has been speaking with insurance companies, and they have said they would be open to covering the drug when there is an official protocol from the APA.

Ketamine, which has been on the market as an anesthetic for many years, is a generic, inexpensive medication, though its intravenous administration, done at the doctor’s office, does add treatment costs.

Pharmaceutical companies, never one to let a lucrative opportunity pass them by, are attempting to develop easier to administer version of ketamine that have fewer psychedelic effects, as well as exploring other drugs that target the same neurotransmitters and receptors. Johnson & Johnson, which is developing an inhaled version of ketamine, may be the first to reach the market, says Levine.

Ketamine has several mechanisms of action. It promotes neuroplasticity, new learning and has anti-inflammatory properties, explains Levine. But interestingly, the psychedelic impact of the drug may also be part of the reason it works. Attempting to remove it to make a more traditional depression drug may create a diluted, less effective version, he cautions.

Liz Lehmann, one of Levine’s patients, is quick to admit that the dissociative effect of the drug is wonderful. She describes it like being a lava lamp: flowing, warm, tingly, relaxed but energized at the same time. When she is getting a dose she feels like she can breathe easily, she tells me.

Before starting treatment with ketamine, Lehmann says she had trouble getting out of bed and wanted to hide all the time. She was textbook depressed, barely functioning, she explains. She had been in countless hours of therapy and tried a laundry list of medications to treat her depression.

When nothing helped, her psychiatrist at the time recommended she see Levine. Levine tried a few more conventional depression drugs but nothing really made a huge impact in treating Lehmann’s depression. That was when he suggested she try ketamine.

She was taken aback at first. She knew the drug primarily from its reputation as a common animal tranquilizer and a party drug. But after doing some research on it, she decided to give it a try.

The difference in her life before and after the ketamine treatments is striking, she says. Where she stayed in bed and “did the bare minimum” before, she is now learning the guitar and spending time with friends. She recently took the polar bear plunge with her son. She says ketamine gave her back “an interest in life”. When she talks about the difference the treatments made in her life, her voice – already cheerful – becomes boisterous. She jokingly says her family describes her visits to get maintenance doses as “Liz going into the K-hole”, a slang drug term for the dissociative state brought on by ketamine.

Like Levine, Mason Turner, chief of psychiatry at Kaiser Permanente San Francisco Medical Center and assistant regional director of mental health for Kaiser Permanente in Northern California, also sees the dissociative effects of ketamine as integral to its ability to treat depression. The dissociation experienced by the patients on ketamine has something to do with activating the neurotransmitter system and is part of the action of the drug, says Turner. Ketamine clears away the negative thinking of patients with depression and allows them to see life in a more positive way, promoting new learning. “We can reverse years of negative thinking about oneself after one treatment,” he tells me.

He cautions, however, that the medication does not work for everyone. Kaiser has been offering the treatment for a little over a year and has found that about 75% of patients with treatment-resistant depression respond to ketamine, results similar to Levine’s patients.

Ketamine is not the only psychedelic treatment that has a positive impact on depression. There are also studies looking at using psilocybin, the active ingredient in hallucinogenic mushrooms, as a treatment for anxiety and depression. With psilocybin, which is in earlier stages of research than ketamine, the psychedelic experience also seems to have an impact in alleviating depression.

“In general, there is a correlation with patients having a subjective peak experience and reduction in symptoms,” says George Greer, co-founder and medical director of the Heffter Research Institute, who has researched the use of psilocybin in alleviating anxiety in advanced cancer patients. The Heffter Research Institute funds scientific studies using hallucinogens and psychedelics. “Probably both neurobiological effects and subjective experiences are involved in the reduction of depressive symptoms,” says Greer.

It may take some time to get the general public used to the idea of treating mental illness with drugs many associate with destructive behavior and hard partying. The main roadblocks to wider adoption are the necessity of having office-based administration of the drug, says Levine, instead of the convenience of taking a pill at home.

There are also misconceptions around its abuse potential, says Levine. Ketamine is a schedule III drug, along with other drugs like Tylenol with codeine and anabolic steroids. While ketamine is abused as a recreational drug, the doses given to patients for depression are low and in a controlled environment. The intention of a ketamine dose matters, says Levine, adding that he sees no abuse potential when it is administered in a medical setting with no easy access to the drug.

With all the renewed interest in psychedelics, widespread acceptance may not be too far behind. The Heffter Research Institute is planning to support a phase III study needed to get FDA approval for using psilocybin to treat depression and anxiety in cancer patients, says Greer. It is his hope that 20 years from now psilocybin will be commonly used in psychiatric practice. Levine estimates that the first branded version of ketamine for treating depression could be available as soon as 2019.

Turner says it has been gratifying as a psychiatrist to be able to offer a medication that works so well. “We feel like we have saved some people’s lives with this treatment,” he says, referring to ketamine.

Now researchers and doctors have to figure out when to give patients the drug. Is it after they have failed other antidepressant medications and treatments? After patients failed to improve after trying five or 10 or 15 treatments? Or should something this powerful be offered as a first line treatment?

The answer is one that that many sufferers of depression and their families will be anxiously awaiting in the years to come.

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LSD’s impact on the brain revealed in groundbreaking images


Powered by Guardian.co.ukThis article titled “LSD’s impact on the brain revealed in groundbreaking images” was written by Ian Sample Science editor, for The Guardian on Monday 11th April 2016 18.09 UTC

The profound impact of LSD on the brain has been laid bare by the first modern scans of people high on the drug.

The images, taken from volunteers who agreed to take a trip in the name of science, have given researchers an unprecedented insight into the neural basis for effects produced by one of the most powerful drugs ever created.

A dose of the psychedelic substance – injected rather than dropped – unleashed a wave of changes that altered activity and connectivity across the brain. This has led scientists to new theories of visual hallucinations and the sense of oneness with the universe some users report.

The brain scans revealed that trippers experienced images through information drawn from many parts of their brains, and not just the visual cortex at the back of the head that normally processes visual information. Under the drug, regions once segregated spoke to one another.

Further images showed that other brain regions that usually form a network became more separated in a change that accompanied users’ feelings of oneness with the world, a loss of personal identity called “ego dissolution”.

David Nutt, the government’s former drugs advisor, professor of neuropsychopharmacology at Imperial College London, and senior researcher on the study, said neuroscientists had waited 50 years for this moment. “This is to neuroscience what the Higgs boson was to particle physics,” he said. “We didn’t know how these profound effects were produced. It was too difficult to do. Scientists were either scared or couldn’t be bothered to overcome the enormous hurdles to get this done.”

LSD, or lysergic acid diethylamide, was first synthesised in 1938 but its extraordinary psychological properties did not become clear until 1943. Throughout the 1950s and 60s the drug had a major impact on psychology and psychiatric research, but its adoption as a recreational drug and its influence on youth culture led to it being banned in the 1960s.

The outlawing of LSD had an immediate effect on scientific research and studies into its effects on the brain and its potential therapeutic uses have been hampered ever since. The latest study was made possible through a crowdfunding campaign and The Beckley Foundation, which researches psychoactive substances.

With his colleague Robin Carhart-Harris, Nutt invited 20 physically and mentally healthy volunteers to attend a clinic on two separate days. One day they received an injection of 75mcg of LSD and on the other they received a placebo instead.

Using three different brain imaging techniques, named arterial spin labelling, resting state MRI and magnetoencephalography, the scientists measured blood flow, functional connections within and between brain networks, and brainwaves in the volunteers on and off the drug.

Carhart-Harris said that on LSD, scans suggested volunteers were “seeing with their eyes shut”, though the images they reported were from their imaginations rather than the world outside. “We saw many more areas of the brain than normal were contributing to visual processing under LSD, even though volunteers’ eyes were closed,” he said. The more prominent the effect, the more intense people rated their dreamlike visions.

Under the influence, brain networks that deal with vision, attention, movement and hearing became far more connected, leading to what looked like a “more unified brain”, he said. But at the same time, other networks broke down. Scans revealed a loss of connections between part of the brain called the parahippocampus and another region known as the retrosplenial cortex.

LSD brain scan
A second image shows different sections of the brain, either on placebo, or under the influence of LSD (lots of orange). Photograph: Imperial/Beckley Foundation

The effect could underpin the altered state of consciousness long linked to LSD, and the sense of the self-disintegrating and being replaced with a sense of oneness with others and nature. “This experience is sometimes framed in a religious or spiritual way, and seems to be associated with improvements in wellbeing after the drug’s effects have subsided,” Carhart-Harris said.

The drug can be seen as reversing the more restricted thinking we develop from infancy to adulthood, said Nutt, whose study appears in the journal Proceedings of the National Academy of Sciences.

The study could pave the way for LSD or related chemicals to be used to treat psychiatric disorders. Nutt said the drug could pull the brain out of thought patterns seen in depression and addiction through its effects on brain networks.

Amanda Feilding, director of the Beckley Foundation, said: “We are finally unveiling the brain mechanisms underlying the potential of LSD, not only to heal, but also to deepen our understanding of consciousness itself.”

  • This article was amended on 11 April 2016 to give the correct amount (75mcg) of LSD administered to each volunteer.

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