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**Sherman Peabody** · 09-25-2017, 07:21 PM

Can LSD treat depression?

By Rachel Nania

When routine therapies and medications failed to help Ayelet Waldman overcome intense mood swings and a deep depression, she turned to something that is generally associated with harm, not health: LSD. Waldman makes it clear that she is the last person in the world who, under normal circumstances, would be associated with drugs. Prior to her experiment, living in Berkeley, California — a town synonymous with hippie culture — was her closest tie to a tab of acid.

“I’m like the lady in yoga pants with the skinny vanilla latte standing in front of you at Starbucks,” said Waldman, a Harvard Law School graduate and former corporate lawyer. But the mom of four was desperate. Her mood disorder was destroying her life and threatening her relationship with her family. At her lowest point, she was suicidal. “That’s when I realized I needed to try something drastic,” she said.

Waldman heard about microdosing, or taking tiny doses of drugs, thanks to its growing presence in the media. Researchers at Johns Hopkins and New York universities have studied the impact of psychedelic drugs on cancer patients for anxiety, and the FDA recently approved large-scale trials to test the effect of ecstasy on post-traumatic stress disorder in combat veterans.

After reading up on microdosing, Waldman didn’t need much convincing. Procuring the illegal substance, however, wasn’t so easy. Waldman, who is married to Pulitzer Prize-winning novelist Michael Chabon, started asking friends, neighbors — anyone she knew — if they had any idea where she could get LSD. “And everybody looked at me like I was completely crazy,” she said. Finally, someone told her about an old professor who had been microdosing for years. Soon after, she found a small envelope in her mailbox with the name “Lewis Carroll” on the return address. Inside the envelope was a small blue bottle of LSD diluted in distilled water. (Waldman said she ordered an LSD drug kit on Amazon to be sure.)

Not knowing what to expect, Waldman told a friend she was taking a new medication for the first time and asked her to come over in case there were any side effects. There were no voices, no flashing colors and no groovy trips. Just a return to her normal. “About 90 minutes later, I looked out my window and my dogwood tree was in bloom. And I thought, ‘Oh, the tree looks so beautiful today.’ And that was the first time anything had looked beautiful in a really, really long time,” Waldman said about her experience with microdosing.

“I just felt like the fog — the ugly, miserable fog of depression — was gone. And at the end of the day, I thought to myself, ‘Wow. That was a really good day.’” Waldman details her experience with microdosing in her new book, “A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life.”

Her blue bottle of LSD is now empty, but her hope for a future open to alternative drug therapies is not. “We should be studying these drugs because we have an epidemic of depression … people are suffering, people are in pain,” she said.

Right now, Waldman has to work really hard to maintain equilibrium. She receives therapy, is on a hormone patch and “does a lot of different things.” She wishes she could still microdose LSD and knows it’s always a possibility if her really good days turn really bad.

“I also know that if I become suicidal again, and I feel like I’m facing a choice between breaking the law or killing myself, I will once again choose to break the law,” she said.

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One-time party drug hailed as miracle for treating severe depression

By Sara Solovitch

It was November 2012 when Dennis Hartman, a Seattle business executive, managed to pull himself out of bed, force himself to shower for the first time in days and board a plane that would carry him across the country to a clinical trial at the National Institute of Mental Health (NIMH) in Bethesda.

After a lifetime of profound depression, 25 years of therapy and cycling through 18 antidepressants and mood stabilizers, Hartman, then 46, had settled on a date and a plan to end it all. The clinical trial would be his last attempt at salvation.

For 40 minutes, he sat in a hospital room as an IV drip delivered ketamine through his system. Several more hours passed before it occurred to him that all his thoughts of suicide had evaporated.

“My life will always be divided into the time before that first infusion and the time after,” Hartman says today. “That sense of suffering and pain draining away. I was bewildered by the absence of pain.”

Ketamine, popularly known as the psychedelic club drug Special K, has been around since the early 1960s. It is a staple anesthetic in emergency rooms, regularly used for children when they come in with broken bones and dislocated shoulders. It’s an important tool in burn centers and veterinary medicine, as well as a notorious date-**** drug, known for its power to quickly numb and render someone immobile.

Since 2006, dozens of studies have reported that it can also reverse the kind of severe depression that traditional antidepressants often don’t touch. The momentum behind the drug has now reached the American Psychiatric Association, which, according to members of a ketamine task force, seems headed toward a tacit endorsement of the drug for treatment-resistant depression.

Experts are calling it the most significant advance in mental health in more than half a century. They point to studies showing ketamine not only produces a rapid and robust antidepressant effect; it also puts a quick end to suicidal thinking.

Traditional antidepressants and mood stabilizers, by comparison, can take weeks or months to work. In 2010, a major study published in JAMA, the journal of the American Medical Association, reported that drugs in a leading class of antidepressants were no better than placebos for most depression.

A growing number of academic medical centers, including Yale University, the University of California at San Diego, the Mayo Clinic and the Cleveland Clinic, have begun offering ketamine treatments off-label for severe depression, as has Kaiser Permanente in Northern California.

The ‘next big thing’

“This is the next big thing in psychiatry,” says L. Alison McInnes, a San Francisco psychiatrist who over the past year has enrolled 58 severely depressed patients in Kaiser’s San Francisco clinic. She says her long-term success rate of 60 percent for people with treatment-resistant depression who try the drug has persuaded Kaiser to expand treatment to two other clinics in the Bay Area. The excitement stems from the fact that it’s working for patients who have spent years cycling through antidepressants, mood stabilizers and various therapies.

“Psychiatry has run out of gas in trying to help depressed patients for whom nothing has worked," she says. “There is a significant number of people who don’t respond to antidepressants, and we’ve had nothing to offer them other than cognitive behavior therapy, electroshock therapy and transcranial stimulation.”

McInnes is a member of the APA’s ketamine task force, assigned to codify the protocol for how and when the drug will be given. She says she expects the APA to support the use of ketamine treatment early this year.

The guidelines, which follow the protocol used in the NIMH clinical trial involving Hartman, call for six IV drips over a two-week period. The dosage is very low, about 1/10 of the amount used in anesthesia. And when it works, it does so within minutes or hours.

“It’s not subtle,” says Enrique Abreu, a Portland, Ore., anesthesiologist who began treating depressed patients with it in 2012. “It’s really obvious if it’s going to be effective. And the response rate is unbelievable. This drug is 75 percent effective, which means that three-quarters of my patients do well. Nothing in medicine has those kind of numbers.”

So far, there is no evidence of addiction at the low dose in which infusions are delivered. Ketamine does, however, have one major limitation: Its relief is temporary. Clinical trials at NIMH have found that relapse usually occurs about a week after a single infusion.

Ketamine works differently from traditional antidepressants, which target the brain’s serotonin and noradrenalin systems. It blocks N-methyl-D-aspartate (NMDA), a receptor in the brain that is activated by glutamate, a neurotransmitter.

In excessive quantities, glutamate becomes an excitotoxin, meaning that it overstimulates brain cells.

“Ketamine almost certainly modifies the function of synapses and circuits, turning certain circuits on and off,” explains Carlos Zarate Jr., NIMH’s chief of neurobiology and treatment of mood disorders, who has led the research on ketamine. “The result is a rapid antidepressant effect.”

Rapid effect

A study published in the journal Science in 2010 suggested that ketamine restores brain function through a process called synaptogenesis. Scientists at Yale University found that ketamine not only improved depression-like behavior in rats but also promoted the growth of new synaptic connections between neurons in the brain.

Even a low-dose infusion can cause intense hallucinations. Patients often describe a kind of lucid dreaming or dissociative state in which they lose track of time and feel separated from their bodies. Many enjoy it; some don’t. But studies at NIMH and elsewhere suggest that the psychedelic experience may play a small but significant role in the drug’s efficacy.

“It’s one of the things that’s really striking,” says Steven Levine, a Princeton, N.J., psychiatrist who estimates that he has treated 500 patients with ketamine since 2011. “With depression, people often feel very isolated and disconnected. Ketamine seems to leave something indelible behind. People use remarkably similar language to describe their experience: ‘a sense of connection to other people,’ ‘a greater sense of connection to the universe.’ ”

Although bladder problems and cognitive deficits have been reported among long-term ketamine abusers, none of these effects have been observed in low-dose clinical trials. In addition to depression, the drug is being studied for its effectiveness in treating obsessive-compulsive disorder, post-traumatic stress disorder, extreme anxiety and Rett syndrome, a rare developmental disorder on the autism spectrum.

Booster treatments

The drug’s fleeting remission effect has led many patients to seek booster infusions. Hartman, for one, began his search before he even left his hospital room in Bethesda.

Four years ago, he couldn’t find a doctor in the Pacific Northwest willing to administer ketamine. “At the time, psychiatrists hovered between willful ignorance and outright opposition to it,” says Hartman, whose depression began creeping back a few weeks after his return to Seattle.

It took nine months before he found an anesthesiologist in New York who was treating patients with ketamine. Soon, he was flying back and forth across the country for bimonthly infusions.

Upon his request, he received the same dosage and routine he’d received in Bethesda: six infusions over two weeks. And with each return to New York, his relief seemed to last a little longer. These days, he says that his periods of remission between infusions often stretch to six months. He says he no longer takes any medication for depression besides ketamine.

“I don’t consider myself permanently cured, but now it’s something I can manage,” Hartman says, “like diabetes or arthritis. Before, it was completely unmanageable. It dominated my life and prevented me from functioning.”

In 2012 he helped found the Ketamine Advocacy Network, a group that vets ketamine clinics, advocates for insurance coverage and spreads the word about the drug.

And word has indeed spread. Ketamine clinics, typically operated by psychiatrists or anesthesiologists, are popping up in major cities around the country.

Levine, for one, is about to expand from New Jersey to Denver and Baltimore. Portland’s Abreu recently opened a second clinic in Seattle.

Depression is big business. An estimated 15.7 million adults in the United States experienced at least one major depressive episode in 2014, according to the NIMH.

“There’s a great unmet need in depression,” says Gerard Sanacora, director of the Yale Depression Research Program. “We think this is an extremely important treatment. The concern comes if people start using ketamine before CBT [cognitive behavioral therapy] or Prozac. Maybe someday it will be a first-line treatment. But we’re not there yet.”

Many unknowns

Sanacora says a lot more research is required. “It’s a medication that can have big changes in heart rate and blood pressure. There are so many unknowns, I’m not sure it should be used more widely till we understand its long-term benefits and risks.”

While a single dose of ketamine is cheaper than a $2 bottle of water, the cost to the consumer varies wildly, anywhere from $500-$1,500 per treatment. The drug is easily available in any pharmacy, and doctors are free to prescribe it — as with any medication approved by the Food and Drug Administration — for off-label use. Practitioners attribute the expense to medical monitoring of patients and IV equipment required during an infusion.

There is no registry for tracking the number of patients being treated with ketamine for depression, the frequency of those treatments, dosage levels, follow-up care and adverse effects.

“We clearly need more standardization in its use,” Zarate says. “We still don’t know what the proper dose should be. We need to do more studies. It still, in my opinion, should be used predominantly in a research setting or highly specialized clinic.”

As a drug once known almost exclusively to anesthesiologists, ketamine now falls into a gray zone.

“Most anesthesiologists don’t do mental health, and there’s no way a psychiatrist feels comfortable putting an IV in someone’s arm,” Abreu says.

It’s a drug, in other words, that practically demands collaboration. Instead, it has set off a turf war. As the use of ketamine looks likely to grow, many psychiatrists say that use of ketamine for depression should be left to them.

“The bottom line is you’re treating depression,” says psychiatrist David Feifel, director of the Center for Advanced Treatment of Mood and Anxiety Disorders at the University of California at San Diego. “And this isn’t garden-variety depression. The people coming in for ketamine are people who have the toughest, potentially most dangerous depressions. I think it’s a disaster if anesthesiologists feel competent to monitor these patients. Many of them have bipolar disorder and are in danger of becoming manic.”

But ketamine has flourished from the ground up and with little or no advertising. The demand has come primarily from patients and their families; Zarate, for instance, says he receives “at least 100 emails a day” from patients. "Nearly every one of them wants to know where they can get it."

**Sherman Peabody** · 10-06-2017, 02:33 AM

Parent's fight to set up the largest ever magic mushroom trial for depression is nearly over

By Martha Henriques of IBT
September 15, 2017

When Ekaterina Malievskaia and George Jay Goldsmith's son started university in New York, he developed severe depression. Standard antidepressants and other therapies didn't do any good. As with parents, Malievskaia and Goldsmith started to think hard about what they could do to help improve their son's mental health.

Malievskaia is a doctor working in internal medicine and public health, and Goldsmith is an entrepreneur. They began drilling down into the science to understand treatment-resistant depression, and see if there was anything they could do to help their son and others with a similar condition.

"We found out that research on one compound in particular – psilocybin – had been carried out for nearly 50 years, with positive results in treating depression and anxiety. Psilocybin has been known to psychiatrists and neuroscientists for a very long time for this link to mental health," Malievskaia told IBTimes UK.

Psilocybin is best known as the psychoactive component of magic mushrooms. Taking it recreationally – which is illegal in many countries – can lead to feelings of euphoria, a distorted sense of time and hallucinations.

Many small studies have linked psilocybin to improvements in mental health, for example reducing anxiety and depression among cancer patients. But larger-scale clinical trials have been lacking. Without these, the journey towards medical use of psilocybin to treat depression has more or less ground to a halt.

"It was interesting science, but there was no pathway for patients," Malievskaia said.

Malievskaia used her medical expertise and Goldsmith his experience in multi-stakeholder collaborations to set up Compass Pathways, a healthcare company aimed at speeding up patient access to new, evidence-based mental health treatments.

"We came at this not from a position of favouring the legalisation of psychedelics. We came from a perspective of creating another option for patients who have exhausted all the others."

"In terms of the science, psilocybin has been known and used for thousands of years," Malievskaia points out. "There is a great deal of ethnographic observational data and small-scale experimental data. What has been lacking is the large-scale trial data of the effects of psilocybin that would be necessary to develop it for therapeutic use."

"We got to the point when the signals were too strong to ignore. The need was too great. So we decided to put our skills together to accelerate patient access to psilocybin."

"Compass Pathways isn't arguing for legalisation of psilocybin or magic mushrooms for recreational purposes," Malievskaia emphasized.

"We are substance-agnostic. It just happened to be that psilocybin is a psychedelic."

The company is now working towards running the largest trial of psilocybin for treatment-resistant depression to date, aiming to recruit a total of 400 patients. The next largest trial done so far was on about 50 people.

Discussions with regulators such as the European Medicines Agency have been positive, Malievskaia said, with a protocol for the trial now confirmed. Next up is holding talks with regulators in the individual countries where the research would be carried out. Seven European countries are contenders, where Compass Pathways would work with academic institutions to run the trial.

As for the mechanism by which psilocybin appears to influence mental health, the jury is still out.

"We have a number of hypotheses, but none of them are confirmed. At this point it's really hard to say anything definitive," Malievskaia noted.

"Research shows it might be due to an increased sense of connection in the brain. It could be something about the nature of the experience, and the effect it has on the personal narrative. It could be the ability to have a different vantage option on your life situation."

If the trial does indeed go ahead in Europe, it may have the potential to reopen this avenue of research in the potential therapeutic effects of psychedelics for mental health, which has been largely dormant since the 1960s.

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**Sherman Peabody** · 10-09-2017, 09:03 PM

Psychedelic therapy for severe depression

Jackson Lavell-Lee
October 2, 2017

Researchers from UCLA, Johns Hopkins University and NYU are currently conducting phase 2 pharmaceutical trials on Psilocybin, the main ingredient in magic mushrooms,
for the treatment of severe depression.

Other research is underway at the Multidisciplinary Association for Psychedelic Studies (MAPS), a Californian based membership organization raising awareness and understanding of psychotropic substances.

MAPS was founded by Dr Rick Doblin in 1986. He lobbied for 14 years before obtaining sufficient financial and political support to have psychedelic research approved in the USA. MAPS
is now conducting phase III trails on MDMA-assisted psychotherapy for PTSD that is non-responsive to conventional treatment.

The Australian version of MAPS is called Psychedelic Research in Science and Medicine (PRISM). It has been attempting to establish an Australian version of MAPS’ MDMA clinical trial.

Speaking about the psilcybin research, President of PRISM, Dr Martin Williams said that he would advocate and consider both himself and loved ones taking psilocybin, if the case of
severe depression arose, due to encouraging evidence in the American trials.

“In America, they are working on the dosage of 20-40mg for a 70kg person,” Dr Williams said. “It’s a very safe drug, there is no documented case of long time psychosis. With anti-depressants, there can be problems with tapering up the dose on initial administration. As the person’s immediate increase in serotonin sharpens, suicide ideation can increase.

"It can take some time before serotonin reaches a steady state in the blood stream so there is an initial at-risk period. I suspect the mechanism in how Psilocybin works is more of a psychological manner rather than a neuro-pharmacological response. What tends to happen with people who have done the trials is their whole perspective of life and place in the
universe is somewhat changed,”[/I] he said.

Families and friends have said loved ones experiencing cancer and other terminal illnesses such as AIDS, heart failure and kidney disease have made remarkable psychological recoveries from severe depression and accepted their fate to enjoy their final days.

In a time when youth suicide in WA is at a record high – the latest WA Ombudsman’s report shows that 42 per cent of all sudden deaths of 13 to 17-year-olds between 2009 and 2017 were a result of suicide – more research should be conducted into alternative therapies that have a potentially higher success rate.

Suicide is the number one killer of youth, more than car crashes (29 per cent), illness or medical conditions (13 per cent), other accidents (6 per cent), alleged homicides (4 per cent)
and drowning (2 per cent).

Past severe depression sufferer, Toby Prunty said the anti-depressants he was first prescribed made him feel more suicidal and some people didn’t get a second chance.

“I think the clinical testing is interesting because I always found CBT (Cognitive Behavioural Therapy) to be the most effective. I always found it hard to talk to people about certain issues so if a substance helps those that have suffered from traumatic depression open about their experiences then that’s a positive,” he said.

“Obviously there is a stigma against all illicit drugs. However, I think in certain aspects that is changing for the next generation. People are more open minded and those who are interested in fighting the battle against mental illness and pharmacologists alike are more outspoken,” he said.

Australian universities and hospitals have rejected the study of psychedelics due to apparent negative standing in the community and the suspected ‘high risk’ of adverse effects after ingestion.

However, senior lecturer of addiction at Edith Cowan University, Dr Stephen Bright, said there had never been a documented case of over-dose from psilocybin, yet there have been several cases of overdose and attempted suicide on anti-depressants.

“The psychedelic renaissance really excites me as a clinically trained psychologist because mounting evidence suggests that psychedelic assisted psychotherapies are effective in the treatment for people who don’t respond to therapies in a range of mental health conditions,” he said.

[I]“We used to think psychedelics turned on parts of the mind. We’ve now learned that what it actually does is turn off a part of the brain called the default mode network. The default mode network is a series of neural pathways that connect certain areas of the brain together while preventing other parts of the brain cross-talking. It becomes hyperactive when people experience depression,”[I] he said.

It has been hypothesized that this is the reason why people have spiritual experiences and heightened creativity when taking psychedelics. This increased connectivity in the brain and could help treat people who are resistant to therapy, experiencing severe depression, end-of-life anxiety, addiction and Post Traumatic Stress Disorder.

Unfortunately, pharmaceutical companies are unlikely to support MAPS testing due to the ease of reproduction of the drug. Lack of complexity means the drug could be sold cheaply, limiting potential profits.

Research efforts into affordable ways to reduce youth suicide and other effects of depression would therefore need to be led by universities, hospitals and philanthropically-funded research centres.

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**Sherman Peabody** · 10-10-2017, 01:45 PM

I am someone who has suffered from severe depression since childhood. I've tried prescription anti-depressants, therapy, exercise, and sleep. I'm a proactive and intelligent person
who has never taken recreational drugs and tries not to abuse alcohol. A very good friend told me about psilocybins and said they might help, and although deeply skeptical, I felt like
it was worth a shot and took them in a safe, controlled environment.

The difference has been enormous. It's not permanent (I'll have to repeat every 4-6 months), but it's like having the volume turned down on part of my brain that seizes onto negativity
or procrastinates, and it's like waking up the next day and feeling optimistic about the future for the first time. If nothing else it's given me the opportunity and relief to be able to put in place structures that will hopefully help me maintain a drug-free long-term mental health that would otherwise be impossible.

Prescription drugs just made me near-catatonic and incredibly detached from the world, which for someone struggling to feel integrated or part of the world already, is incredibly unhelpful. I was incredibly skeptical before trying it myself, but please don't espouse a full-on refusal to consider the possibility that they might actually work.

-FreshFlesh

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I had depression/anxiety for about 11 years. I booked a hotel room in Amsterdam, took some mushrooms and found some revelations. You realise that the mind is conditioned, and that
the capacity for imagination is infinite. These personal revelations made me realise the importance of making certain changes in my life, which I have done. As a result I am happier, and
on a more meaningful path, or rather the only real path for me.

ID7034232

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I had a history of bipolar disorder throughout my teens and twenties. I started regularly using LSD, mushrooms and MDMA in my 30s. It helped me enormously, and for the first time in my life, I really came to terms with who I am and my place in the world. I am in my mid-40s now and I only indulge occasionally. I have enjoyed very good mental health for the past decade, a happy state I honestly put down to the above.

-campesque

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I've only done mushrooms once, about a month ago. Before I did them, I was very depressed and was considering suicide. I've been chronicly depressed for as long as I can remember,
but I've never been to see a doctor about it or taken anti depressants. I didn't intend to take mushrooms so I didn't do any preparation beforehand.

I took 3 in 30min increments and was moderately drinking. I didn't experience anything profound, but the week after I felt amazing! Calm and in control of my emotions. I felt happy, and negative emotions had no weight to them.

Even now that the afterglow has worn off, I still feel better. Life still gets on top of me some days, but it was like it reset my mood and I can cope easier. I haven't had the urge to drink like I did either, which was a big thing before I took them.

-salt_licker_210 (Bluelight)

**Sherman Peabody** · 10-17-2017, 02:30 PM

Study: Psilocybin helps depressed patients ‘re-connect’ to the world

Eric Dolan
August 2, 2017

New research sheds light on how psilocybin could help people overcome depressive symptoms. The psychedelic drug appears to promote a change from disconnection to connection and a change from avoidance to acceptance.

Psilocybin is the primary mind-altering substance in psychedelic “magic” mushrooms. The drug can profoundly alter the way a person experiences the world by producing changes in mood, sensory perception, time perception, and sense of self.

Scientists have recently starting re-examining at whether psilocybin can be used in the treatment of mental illnesses — and the initial results are promising.

“Although many of us think of psychedelics as dangerous drugs, it’s time for a rethink,” explained the study’s corresponding author, Rosalind Watts of Imperial College London. “When used carefully in clinical research settings, psychedelics have been reported to have a profoundly beneficial effect on many people’s lives. They are non-toxic, non-addictive, have very few side effects, and could potentially offer relief for people suffering from a range of psychological difficulties.”

In the current qualitative study, which was published in the Journal of Humanistic Psychology, researchers interviewed patients from a clinical trial of psilocybin for treatment-resistant depression. (The initial results of the clinical trial were published in The Lancet.)

“Working in a community mental health team, I realised that conventional mental health treatments (antidepressants, CBT) were not working for many people. I also watched my best friend struggle with depression for many years,” Watts told PsyPost.

“When she told me she was going to do an ayahuasca ceremony in Peru, I knew nothing about psychedelic therapy research, and thought it was a terrible idea. But she came back home with a sparkle in her eye that I hadn’t seen for years, and told me that the depression had finally lifted. So I thought to myself ‘this looks promising, let’s find out more.'”

A number of themes emerged after the researchers questioned 6 women and 13 men who had undergone psychedelic therapy 6 months prior.

First, the participants described depression as a state of disconnection, which was reversed with psilocybin. Secondly, the psychedelic treatment helped them confront, process, and accept painful memories and thoughts. Thirdly, they described previous depression treatments as reinforcing the disconnection and avoidance they felt — while psilocybin worked in the opposite way.

“The reset switch had been pressed so everything could run properly, thoughts could run more freely, all these networks could work again. It unlocked certain parts which were restricted before,” one participant explained.

“I got a wider perspective, I stepped back. It helped me appreciate that the world is a big place that there’s a lot more going on than just the minor things that were going on in my head,” another participant told the researchers.

A third remarked: “My previous treatments, talking therapy and meds, were next to useless, utterly useless. My experience of psilocybin has been very positive. I believe there is an unknown physiological and neurochemical change in me, I am absolutely convinced of that.”

Or as another participante summed it up: “Now there’s a greater sense of ‘we’re all in the same boat’; less unease.”

There were no serious adverse events reported during the psilocybin sessions. But a few participants had troubling psychological experiences which resolved themselves before the session was over. A few participants also wished they had received more psychotherapy following the drug session.

“The psychedelic experience is not to be taken lightly,” Watts explained. “Participants in our study found psilocybin therapy to be preferable to other treatments they had tried, but that does not mean it was easy. Many of them had experiences of deep grief, sadness and fear, and relied upon the support of their ‘guides’ to enable them to fully accept and process these emotions.”

“It’s very early days: the sample sizes are small, and we need to determine the role of placebo effects. Randomized control trials in the United States (John Hopkins, NYU) have started to address the question about placebo effects with similar promising findings. Upcoming randomized control trials in Europe will continue to investigate.”

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**Sherman Peabody** · 10-28-2017, 09:43 AM

Ketamine found to have an "unbelievable" effect in treating severe depression

"The most significant advance in mental health in more than half a century."

It’s probably not the first place you’d go to find relief from severe clinical depression, but the psychedelic party drug ketamine has revealed itself to be something of a 'miracle drug', performing far more quickly and effectively than traditional antidepressants and mood stabilisers.

Where current treatments take weeks to work - and then might not work at all, depending on the patient - ketamine has been shown to treat the symptoms of depression within hours.

"It’s not subtle. It’s really obvious if it’s going to be effective," Enrique Abreu, a Portland-based doctor who began treating depressed patients with ketamine in 2012, told The Washington Post. "And the response rate is unbelievable. This drug is 75 percent effective, which means that three-quarters of my patients do well. Nothing in medicine has those kind of numbers."

Over the past decade, the drug’s enormous potential in the treatment of mental health issues has become a focus for researchers and psychiatrists trying to come up with a solution to severe depression where currently available medications have failed.

"Since 2006, dozens of studies have reported that it can also reverse the kind of severe depression that traditional antidepressants often don’t touch," Sara Solovitch reports for The Washington Post. "Experts are calling it the most significant advance in mental health in more than half a century."

Why is a new treatment option for depression so exciting? Put simply, for many people with severe depression, the drugs available to them - known as selective serotonin reuptake inhibitors (SSRIs) - are terrible. Not only do they take three to eight weeks to actually have an effect, but once you make it through those months of waiting, there’s no guarantee they’ll actually work for you.

As we reported back in July, SSRIs are believed to work by limiting the reabsorption of serotonin into the brain’s presynaptic cell, and this readjustment of serotonin levels appears to help the brain cells send and receive chemical messages more effectively, which can boost a person’s mood.

But every SSRI has a different chemical make-up, and it’s basically a case of trial-and-error to see which ones will benefit or mess with your unique brain chemistry. And on top of not being super effective for many people, SSRIs are also known to cause a range of negative side effects, such as nausea, dizziness, drowsiness, insomnia, weight gain, and reduced sexual desire or erectile dysfunction.

Clearly, there has to be a better way.

Academic medical centres across the US are now increasingly opting to treat their patients with ketamine, including Yale University, the University of California at San Diego, the Mayo Clinic, and the Cleveland Clinic. The drug is administered by a single intravenous infusion at doses less than those used in anaesthesia, which is thought to prevent addictions from developing.

Patients who’ve had no choice but to keep trawling through the various types of SSRIs for years to see if one fits - while having to deal with the debilitating effects of having untreated depression - are finally seeing results, sometimes as quickly as within 2 hours of taking the drug.

"There is a significant number of people who don’t respond to antidepressants, and we’ve had nothing to offer them other than cognitive behaviour therapy, electroshock therapy and transcranial stimulation," L. Alison McInnes, a psychiatrist from the Kaiser Permanente clinic in California, told Solovitch.

Just yesterday, researchers from Vanderbilt University Medical Centre published the results of a study where mice with alcoholism had their depressive-like withdrawal symptoms reversed when treated with ketamine.

So why does ketamine work so well? Scientists aren’t actually sure, but a 2010 study published in Science suggests that by blocking proteins called NMDA receptors, the drug prompts the brain to increase the production of synaptic signalling proteins in the prefrontal cortex - a region thought to regulate complex cognitive, emotional, and behavioural functioning.

In doing this, it appears to be not only promoting the growth of new synapses, which leads to greater connectivity in the brain, but it’s also switching certain connections on and off, and for whatever reason, this has a rapid anti-depressive effect. SSRIs, on the other hand, target the serotonin and noradrenalin systems in the brain.

The drug isn’t perfect by any means - some patients find the hallucinations it causes to be uncomfortable, and the cost isn’t regulated, which means it can get very expensive depending on where you get it. It's also not a 'cure' - time between doses varies between person to person, but in order to treat the symptoms of severe depression, you need to keep taking it, just like traditional anti-depressants.

That said, the fact that it's bringing relief to many people who are resistant to SSRIs is really exciting, and with so much support for the drug as a mental health aid in the medical community right now, we're only going to get a better understanding of its potential.

Editors’s note: It has been brought to our attention that despite many positive first-hand accounts from treatment-resistant depression patients, and the researchers and doctors who work with them, some researchers are in opposition of ketamine being touted as a treatment for depression.

While there have been many studies conducted on the antidepressant effects of ketamine, and positive accounts from patients who have found no success from traditional drugs, criticism has been squared at the limited sample sizes of these studies and the strength of the evidence - most notably, this 2015 review.

"Nearly all ketamine studies had short-term follow-ups," Keith Harris from the University of Queensland, Australia told ScienceAlert. "Very few tested even modestly long-term affects on substance abuse and other possible effects."

As with many experimental drug treatments with conflicting statements for and against their merits, it will take many years to figure out the true value of ketamine in this space.

What we do know is patients with few alternatives have benefitted from it, and research institutions are investing a lot of time and money into figuring out its potential, and we'll update you with more information as it's made known.

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**Sherman Peabody** · 11-15-2017, 01:31 PM

Can Psilocybin treat severe depression?

Barbara Geller, MD
2017 Oct 13

Neuroimaging findings predicted response with this hallucinogen at post-treatment week 5 and correlated with decreased depressive symptoms and heightened “mystic feelings.”

In 1970, the FDA categorized psilocybin as a Schedule 1 drug, largely because of its recreational uses, which include inducing spirituality and synesthesias (e.g., seeing music, hearing art). More recently, several trials of this serotonin 2A agonist have supported further research into its use for treatment-resistant major depressive disorder (MDD; NEJM JW Psychiatry Jul 2017 and Neuropsychopharmacology 2017; 42:2105). The current researchers administered psilocybin to 19 medication-free participants with MDD (mean age, 42; 21% women).

Two-time dosing was once at 10 mg, followed 1 week later with 25 mg. Functional magnetic resonance imaging (fMRI)occurred at baseline and post-treatment at 1 day after the 25-mg dose — to capture “afterglow” phenomena, which are characterized by elevated mood and lower stress.

Significant decreases in depression occurred post-treatment; 47% of participants met response criteria at 5-week follow-up. On fMRI, blood flow decreased from baseline in temporal (including amygdala) and parietal areas, similar to previous reports. Decreased amygdala activity significantly correlated with improved depression scores and increased feelings of a “mystic experience.” On resting-state fMRI, connectivity between several cortical areas increased post-treatment, contrary to findings elsewhere. Treatment response at 5 weeks was predicted by increased connectivity post-treatment between the ventromedial prefrontal cortex and inferior parietal cortex and by decreased parahippocampal-prefrontal connectivity.
Comment

Both the increased connectivity on post-treatment resting-state fMRI and its predictive value were similar to findings for electroconvulsive therapy, supporting the current study's validity. Experimental options for treatment-resistant MDD include invasive procedures like deep brain stimulation, which requires implanting brain devices with possible long-term adverse effects. Thus, clinicians can tell patients with access to federally funded psilocybin trials that this is a reasonable, noninvasive approach. Further, patients need to know that psilocybin must be taken only in closely supervised research settings because of its capacity to induce unusual psychic experiences.

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**Sherman Peabody** · 11-15-2017, 02:04 PM

We visited a clinic that delivers 45-minute ketamine infusions for depression – here’s what it was like

Erin Brodwin
Nov. 8, 2017

Ketamine is emerging as a potential new treatment for some types of depression.

Researchers have called it "the most important discovery in half a century."

We visited a ketamine clinic that offers 45-minute infusions of the therapy in San Francisco.

After a 45-minute infusion of ketamine, clients at a clinic in San Francisco's Nob Hill neighborhood are not partying.

Instead, they're in a state of quiet contemplation — reclining on cushioned chairs, listening to music, or occasionally striking a tranquil yoga pose.

These clients are patients at one of ten ketamine clinics operated by XYZ Neurotherapies, a network that offers the treatments to people diagnosed with severe forms of anxiety and depression. Ketamine is best known for its illegal recreational uses — it is a powerful dissociative that can induce feelings of being separated from one's own body. But it is also one of
the safest and most widely used legal anesthetics. And ketamine's utility as an antidepressant has recently started to gain attention.

A spate of studies over the past several years suggests ketamine may provide swift and powerful relief to people suffering from some of the hardest-to-treat forms of depression — an illness that is the leading disability worldwide. Those findings have been so promising, in fact, that some researchers are calling it “the most important discovery in half a century." However, the US Food and Drug Administration has not yet approved ketamine for the treatment of anxiety or depression.

XYZ Neurotherapies' San Francisco facility is currently offering treatments to thousands of patients anyway, and is one of an estimated 50 to 100 such clinics operating across the US. Here's what it's like.

Inside a ketamine clinic

Like XYZ Neurotherapies' other nine locations, the San Francisco office is a cross between clinical and therapeutic. In each treatment room, a reclining clinical chair sits facing a large window. In the corner is a chair decorated with a colorful crocheted blanket.

"We're striking a balance between a clinical setting and a home setting," Steve Levine, a psychiatrist and the CEO of XYZ Neurotherapies, told Business Insider.

Each two-hour visit includes 45 minutes of ketamine infusion, 45 minutes of a saline drip, and a consultation with Alison McInnes, a physician who founded a regional ketamine therapy program with Kaiser Permanente.

"Therapy and ketamine go together like peanut butter and chocolate," Levine said. "And with our approach, you have someone with an extensive background in mental health and therapy always present, and talk therapy happens before and after the infusion."

At XYZ, most patients receive 10 infusions over the course of 10 weeks — three in the first week, two in the second, and one infusion in the third, fourth, and fifth weeks. The last two infusions are spread between weeks seven and 10. Doctors who track patient progress, and people to fill out a standard depression and anxiety questionnaire before each treatment and the following day.

A single infusion costs $650, and insurance doesn't officially cover any of that, but Levine said his team can typically get providers to reimburse "a lot of it."

However, as with any treatment approach — especially one involving drugs — there are drawbacks. Most studies on ketamine use in people with depression have been limited to about two weeks, so it remains unclear how long the benefits last. And not all clinics offering ketamine infusions are like Levine's network, which always has a psychiatrist or mental health professional on staff. Furthermore, such treatments often range from $400 to $1,000 per infusion around the US, a price tag that can leave vulnerable patients paying out of pocket and not getting reimbursed at all. Plus there's the fact that the FDA has only approved ketamine for use as an anesthetic.

Existing treatments for depression are very limited, however.

'Why the heck aren't we using this?'

Levine said that when he first saw a study about ketamine's impact on people with severe depression, it "spun his head around."

Other treatments for depression, like talk therapy and antidepressants, mostly haven't improved since they were introduced in the 1950s. Decades of research suggest that those existing treatments don't work that well for everyone, and may not work at all for some. Yet physicians and psychiatrists have been doling out the same medications to clients for 70 years.

Some scientists seeking a new approach have looked to psychedelics like ayahuasca and magic mushrooms, which appear to reduce depressive symptoms by increasing the connectivity between certain parts of the brain. So it's not a complete surprise that they're also exploring the depression-reducing qualities of ketamine, Levine said.

But research has suggested that ketamine might stand out as conferring seemingly fast, widespread benefits to people with the condition. A 2012 review of four preliminary studies in patients with severe depression concluded that approximately 65-70% of patients responded well to ketamine. The other 35-30% either did not have a significant response, or their relief from depression was only short-lived.

"The findings were unanticipated, especially the robustness and rapidity of benefit," the authors wrote in their review. "Ketamine appeared to directly target core depressive symptoms such as sad mood, suicidality, helplessness and worthlessness, rather than inducing a nonspecific mood-elevating effect."

Levine read everything he could on the treatment while maintaining his private psychiatry practice.

"Here's an incredibly safe medicine that works within hours," he said. "So my immediate question was, 'Why the heck aren't we using this?'"

He eventually decided to start his own clinics — the first treatment center opened in 2011 in Princeton, New Jersey, and the other nine followed between 2015 and 2017.

New findings on ketamine

A study published in the journal Scientific Reports in May was the first large, non-preliminary study to show that ketamine appears to provide significant relief to people suffering from some of the hardest-to-treat forms of depression. The finding did not go unnoticed amongst pharmaceutical companies — Johnson and Johnson is developing a form of ketamine that could be better tolerated and would be marketed as an antidepressant; Allergan is in the last phase of clinical trials with a drug that acts on the same receptor as ketamine.

For the most recent study, researchers at the University of California in San Diego turned to an FDA database with records from more than 8 million patients. Using this data, the researchers homed in on patients who'd been given ketamine as a treatment for their chronic pain. Then they looked at how their depression symptoms compared to the depression symptoms in people who received other pain medications.

The findings were striking. The patients who took ketamine reported symptoms of depression 50% less frequently than patients who were given any other combination of drugs for pain.

"This reduction in depression is specific to ketamine and is known to be much more rapid than current antidepressants," the researchers wrote in their paper, adding that their observations were "very promising" for people with serious depression or thoughts of suicide.

"These patients cannot afford to wait up to six weeks for reductions in their depressive symptoms," they wrote.

Beyond a reduction in their symptoms of depression, the patients on ketamine also reported significantly less pain than those given the other drugs. They were also less likely to experience the unpleasant side-effects that frequently come with other pain medications like constipation, vomiting, and nausea.

Still, the ketamine had its own negative side effects, including kidney failure and low blood pressure.

For Levine, however, those negatives pale in comparison to the host of downsides that can accompany most treatments for depression.

"When you're treating very very ill people, you will have side effects. That's a reality," Levine said, adding, "these are people who've been sick for decades and heard from multiple doctors that there's nothing else they can do. We're enabling them to get back to their normal lives."

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**Sherman Peabody** · 11-20-2017, 02:25 PM

Microdosing LSD safer than antidepressants, says neurobiologist

By Jacqueline Ronson

When Ayelet Waldman embarked on an experiment to relieve her dark moods with the help of tiny doses of LSD, she was understandably hesitant. Trendy though LSD microdosing may be, the drug is Schedule 1 — deemed highly dangerous and of no medical value.

But Waldman got some surprisingly reassuring advice from David Presti, a professor of neurobiology and expert on the effects of drugs on the brain at the University of California, Berkeley. “I really think there’s something going on with microdosing,” Presti told her. “I think when people do get around to researching it, it’s going to be relatively easy to demonstrate positive effects that are better than conventional antidepressants, which are awful.”

Is microdosing LSD really as safe as, or perhaps even safer than, taking anti-depressants? “Oh absolutely,” Presti said.

Waldman recounts the conversation in her book, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life, published January 2017 by Penguin Random House.

The problem with prescription antidepressants is “they have all kinds of side effects, and we have no idea, really, what they’re doing,” Presti said. “They cost a lot of money and they’re marketed with all kinds of flimflam.”

What these drugs have on their side that LSD doesn’t are controlled, clinical trials that demonstrate safety and efficacy of the drugs. And yet, the evidence is still quite mixed. Selective serotonin reuptake inhibitors, or SSRIs, simply don’t work for a lot of people with depression, and most users experience negative side effects, some of which can be quite nasty.

Meanwhile, psychedelic drugs are quite safe. We actually don’t know how much LSD it would take to kill a person since no one’s ever taken enough to find out. Bad trips happen — and they can lead to people making dangerous decisions — but they end when the drug’s effects wear off, and the drug itself appears to cause no lasting harm to the mind or body. And the tiny amounts used in microdosing, which are supposedly too small to cause hallucinations or even make you feel high, the risk of negative outcomes might be almost inconsequential.

But do they work? No government-approved study has looked at the effects of microdosing on depression, procrastination, low energy, or any of the other ills it is purported to relieve. And yet, the volume of anecdotal evidence is substantial. James Fadiman and Sophia Korb, researchers with Sofia University, have collected thousands of reports from people who microdose, and they are overwhelmingly positive. A few people have reported to him that they tried it, and it didn’t work or they didn’t like it, and they stopped. But the vast majority report benefits, including surprising and unexpected things, like relief from chronic pain or the physical and emotional symptoms associated with the menstrual cycle.

The largest barrier to research is money. Pharmaceutical companies won’t pay to research drugs they can’t patent, and governments are wary of investing in science on illegal and controversial drugs. Philanthropy and crowdfunding are beginning to step up to fill the gap. A group called Fundamental is currently raising money for several research projects relating to psychedelic medicine, including one led by Amanda Feilding and the Beckley/Imperial Research Programme that might become the first to demonstrate in a controlled way the effects of LSD microdosing on mood and cognition.

Clinical research is expensive and time consuming, but if the early results are even close to as encouraging as the anecdotal reports, momentum will surely build. In the meantime, those curious or desperate enough will continue to find a way to experiment on themselves, Schedule 1 contraband or not.

---

MRI scans reveal differences in brains of people with anxiety and depression

by Sarah Sloat

In the U.S., 16 million adults are diagnosed with major depression disorder, and 15 million have Social Anxiety Disorder. While the disorders are different — people with depression often feel persistent sadness and lose interest in things they once cared about, and those with anxiety have an intense fear of being watched and judged — some of the most debilitating clinical symptoms of depression and anxiety overlap.

New research, which will be presented next week at the annual meeting of the Radiological Society of North America, is the first evidence that this overlap may be caused by similar structural abnormalities people with depression and social anxiety have in their brains. While the paper is not published yet, the abstract is available online.

A team of doctors from Sichuan University in Chendgu, China discovered that patients with depression and anxiety both have abnormalities in the grey matter of their brains’ salience and dorsal attention networks. The salience network determines what stimuli catch the attention of the brain, and the dorsal attention network drives focus and attention.

“These consistent structural differences in the two patient groups may contribute to the broad spectrum of emotional, cognitive, and behavioral disturbances observed in MD [major depression] and SAD [social anxiety disorder] patients,” the doctors write. “These findings provide new evidence of shared and specific neuropathological mechanisms underlying MDD [major depressive disorder] and SAD.”

In the study, which uncovered the first preliminary evidence of the gray matter changes in the brains of MDD and SAD patients, the researchers used magnetic resonance imaging (MRI) to evaluate the brains of 37 MDD patients, 24 SAD patients, and 41 healthy control individuals.

Compared to the control participants, MDD and SAD patients showed a cortical thickening in the brain’s insular cortex, which influences perceptions of empathy, self-awareness, and interpersonal experiences. "This thickening," study co-author Youjin Zhao, M.D., Ph.D., explains in a statement, "may be a result of inflammation and could “be the result of both the continuous coping efforts and emotion regulation attempts of MDD and SAD patients.”

The researchers found differences between the brains of people with MDD and SAD, too. Brains of patients with depression showed alterations in the regions of the brain that control emotional facial processing, while brains of patients with anxiety had “disorder-specific involvement” in the regions associated with processing fear.

"What the exact relationship between these disorders and the cortical thickening of the brain, particularly in the anterior cingulate cortex, remains to be understood. More studies with larger sample sizes that use machine learning analysis, are needed," says Zhao "— but there may be a future where MRIs can help aid the diagnosis of these widespread, debilitating conditions."

^^
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