• Psychedelic Medicine

KETAMINE | +50 articles


Ketamine-Assisted Psychotherapy for frontline workers

by Ritika Dubey | truffle report | 15 Jul 2021

Truffle Report Connects with Dr. Reid Robison of Novamind to discuss treating the pandemic’s other casualties.

The COVID-19 pandemic has been long and exhausting, and frontline workers have had to witness the worst of things since the onset. As cases skyrocketed, so did the pressure. As they continued to risk their lives and health, their psychological well-being also deteriorated drastically.

The Psychedelic Renaissance — the reemergence of psychedelics for their therapeutic benefits — is intervening in mainstream mental healthcare at a crucial time, when many of us are struggling with heightened anxiety, depression, and substance use arising from living through COVID-19. In an attempt to provide novel treatment protocols to frontline workers, one mental healthcare company has launched a psychedelic therapy pilot with ketamine.

Novamind, a mental healthcare organization working to ensure access to psychedelic medicine through a network of clinics, retreats, and clinical research sites, is providing free-of-cost ketamine-assisted therapy to frontline workers in Utah and Colorado.

“We really paid attention to the trauma, stress and burnout experienced by frontline workers,” shares Dr. Reid Robison, Chief Medical Officer of Novamind. “There’s a significant risk of burnout among healthcare workers, worsening during the pandemic.”

Explaining the common symptoms of psychological distress, Dr. Robison says, “Healthcare workers helping others experience fatigue, burnout, or exhaustion spilling into everyday life. Along those lines, there’s ‘compassion fatigue’ that can happen by giving so much of yourself and not recharging your own batteries, which is hard to do in times of crisis like the peak of a pandemic. The last thing would be trauma. Vicarious trauma is sometimes brought on by helping others who have been through difficult things and taking that on as an empathetic professional in the healing arts.”

A survey published by The Lancet in May 2021 revealed that 61 percent of U.S. healthcare professionals reported fear of exposure transmission, 38 percent reported anxiety, and 43 percent experienced work overload while 49 percent had burnout. The survey polled over 20,000 healthcare professionals representing 42 organizations.

Frontline ketamine-assisted psychotherapy, or ‘Frontline KAP’, is a first-of-its-kind program designed to treat frontline workers with ketamine as their work-related stress and trauma continue to grow.

Ketamine has moved from being a party drug to a medicalized substance for treating symptoms of depression and trauma. Since Spravato’s (esketamine) approval by the U.S . Food and Drug Administration (FDA), healthcare professionals have been using a combination of therapy and ketamine — ketamine-assisted psychotherapy— for mood disorders and suicidal ideation.

Dr. Robison shared that the protocol for frontline workers differs from the regular intake for patients seeking relief through ketamine-assisted psychotherapy.

Delivering the substance through six treatment sessions, the therapy will be conducted in small group settings. "Group therapy in particular is expected to play a strong role in the healing process among these individuals," Dr. Robison said.

“The Frontline KAP project in a group setting is to not only provide ketamine as a medicine for depression and trauma that acts quickly, but to offer a group therapy session where individuals can see they’re not alone in this,” he told Truffle. “The individuals can open up safely and work through things to get back and thrive more in their lives and their jobs.”

As a part of the protocol, the first session is dedicated to preparation, with participants hearing each other’s stories, building relationships and focusing on set and setting. The following session is to consume low doses of ketamine.

“This is a low dose where there’s interaction but more openness and to help build trust and ease defenses. You might call this a psychoanalytic dosing, or greasing the wheels of therapy. After each dosing session, the next group will be able to make sense of those experiences, draw wisdom from them into everyday life,” Dr. Robison shares.

Medium doses are about exploring personal experiences, with the final dosing session involving injections rather than oral doses. Dr. Robinson adds, “We’re still in a group setting, but the individuals have eyeshades, headphones and music. They’re supported by at least two therapists and other support as needed to help sit for the person, and guide them through anything difficult.”

The sessions are then followed by integration where individuals process their experiences as a group.

“The last step is to take these insights we’ve had collectively and manifest them in their fullest expression. With a fresh perspective, where cups are filled up from focusing on our mental health, we can go forward with a follow-up plan to do whatever we can to sustain these positive changes,” Dr. Robison explains.

Through this, he adds, “We set up the path in a sustainable way so people can get back to the profession they love without it being overwhelming or all-consuming.”

The pilot program began with a screening process, collecting information from the frontline healthcare workers through a questionnaire designed around areas of burnout, compassion, fatigue, and trauma. This was then followed by a one-to-one video chat to get familiar with the two facilitators. Since ketamine is a controlled substance in the U.S., the organization is required to maintain records of diagnosis.

“We’re all about accessibility, and treating or helping groups who might be traditionally overlooked. This clinical pilot program will help us inform whether or not we can or should offer it more broadly at our clinics, or even in our hybrid clinic/retreat model,” Dr. Robison says.

He adds that if the program stands as a success, Novamind would attempt to get the clinical treatment covered by either employers of the frontline workers, or by insurance providers.


Ketamine may combat depression in teens

by Jon Kelvey | LUCID| 30 Jul 2021

Evidence of ketamine’s power to alleviate treatment resistant depression in adults continues to mount, with clinical studies showing the drug’s efficacy even as Janssen’s FDA-approved ketamine-based nasal spray Spravato enters the market. But surprising findings in a new study suggest the common anesthetic and sometimes club drug may help adolescents with depression too, and might even make teens more resilient to stress-induced depression after treatment.

The results are preclinical and require further study, but it’s a first step toward determining whether ketamine could be an appropriate and effective treatment for adolescent depression. “One of the striking things about adolescent depression is that they tend to be treatment resistant,” said Eric Parise, a postdoctoral fellow in the Nestler lab at the Icahn School of Medicine and first author on the study that was published in the journal Biological Psychiatry.

Parise and his fellow researchers administered 10 milligrams of ketamine per kilogram of bodyweight — a dose that approximates that used in human treatments for depression — to adolescent mice every day for 15 days, and then allowed a week for any ketamine in their systems to wash out. Control mice were given saline injections over the same time period.

Both the saline controls and ketamine-treated mice were then subjected to “chronic social defeat stress,” where they were placed in a cage with a larger, more aggressive mouse that would dominate them for 10 minutes a day, for 10 days. Researchers intervened to prevent any injuries, but Parise notes that this kind of social stress is more relevant and a better model for human depression, as such interactions are natural in rodent societies. “Rodents fight,” he said, “and they develop social hierarchies based on who is victorious in these fights.”

After allowing 24 hours to pass after the last social defeat stressor, researchers assessed the mice using a social interaction test, a measure of how much the rodents interact with each other, and the forced swim test, which is a standard rodent model for measuring the antidepressant effects of interventions. In each test, the control mice showed signs of depression, while the ketamine-treated mice did not. Importantly, the ketamine-treated mice showed resilience to stress without any ketamine in their systems, recapitulating a sometimes naturally occurring “stress-resistant phenotype” in mice.

“There’s a subset of those mice that do not succumb to that stress after 10 days,” Parise said. “In that case, you would sort of expect that when you look at them from a molecular standpoint, that they would almost be identical to a control animal who has not received any exposure to stress. But it turns out that’s not true.”

Resistance to stress-induced depression, the researchers found, is instead an active process depending on molecular and DNA transcriptional changes that occur naturally in some mice, and are induced by repeated ketamine exposure in others.

The result was surprising, Parise said because typically adolescent drug exposure leads to negative outcomes in older animals. “We tested a lot of other drugs over the years and they almost overwhelmingly did not result in positive findings,” Parise said. "In tests of adolescent rodent exposure to nicotine, methamphetamine, cocaine and Ritalin, all of them produced stress-sensitive phenotypes in adulthood. These animals would be hypersensitive to the effects of anxiety and stress in general.”

Their results are not the first to show ketamine protects against social defeat stress in rodents, Parise said, but they are the first to show this effect extends to adolescents. So the effect appears robust, but more work is required to ensure against any risks specific to human adolescents. “I think the next steps need to be our sort of ironing out what are the true addictive liability aspects of [ketamine] exposure during adolescence.”

"At the same time," Parise said, "there is always a trade-off between risks and benefits in medicine, noting that Ritalin is still widely prescribed to children despite evidence it can make them more prone to abuse stimulants as adults. In cases of treatment-resistant depression with suicidal ideation, the risks of ketamine may be outweighed by the positives. Technically speaking, it is FDA-approved and can be prescribed off-label, so there’s no rule stating that a psychiatrist can’t administer it to an adolescent,” Parise said. “You just have to find one who’s willing to put themselves out there and do it.”

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A randomized placebo-controlled PET study of ketamine´s effect on serotonin1B
receptor binding in patients with SSRI-resistant depression.

Ketamine uses serotonin receptors to relieve depression

by Dr. Liji Thomas, MD | News Medical | 31 May 2020

Ketamine is a drug used to induce general anesthesia. It has also been found to act rapidly to relieve depression that has failed to respond to two other rounds of medication. A new study published in the journal Translational Psychiatry in May 2020 reports the mechanism of action of the drug, which was hitherto unknown. This could help find new ways to treat this debilitating and sometimes fatal condition.

The study comes from Sweden, where depression affects 10% of men and 20% of women. This makes it the most frequently diagnosed mental disorder in this country. The treatment of this condition fails after two rounds or more in about 15-30% of patients. At this point, the depression is termed difficult-to-treat.

Ketamine and depression

Ketamine is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist. It is a dissociative drug, meaning it disrupts the user's relationship with sensory perceptions.

Higher doses can cause breathing to slow dangerously, produce muscle spasms, dizziness, loss of balance, and slurring, with severe confusion. Hallucinations described as "out of body" experiences occur when emerging from the drug, which can be very distressing.

Treatment-resistant depression that has been found to respond quickly to ketamine at low doses. This has led to the approval of a nasal ketamine-containing spray in the USA and EU for this condition. Despite this knowledge, little has been known about how it acts.

Earlier research, in which Tiger and his team had collaborated, shows that the brains of people with depression presented low levels of these receptors.

In the first step, the researchers performed a randomized double-blinded controlled study on 30 patients with treatment-resistant depression. They divided them at random into two groups. One group of 20 received ketamine infusions. The other group of 10 received only saline infusions.

Neither the doctor treating them nor the patients knew who was getting what. Both before and after infusions, the patients underwent brain imaging using the PET cameras. This was repeated after 24-72 hours after the completion of the procedure.

The second part of the study involved voluntary participation. This phase included 29 individuals who got ketamine infusions twice weekly for two weeks.

Ketamine acts by bosting Serotonin 1B receptors

When the results were assessed, the doctors found that more than 70% of the patients who had received ketamine experienced relief of depressive symptoms, as recorded using a rating scale for depression.

The researchers found that the therapeutic effects of ketamine were due to inhibition of serotonin action. Serotonin is a neurochemical which acts like a brain hormone, in part. It is best known for its significant contribution to triggering depression. Low levels of this hormone are thought to be associated with more severe depression.

Neurons have 14 serotonin receptor subtypes on their cell surfaces. However, in the current study, the researchers used a more specific molecule, a radioactive substance that binds only to serotonin 1B receptors. They thus discovered a novel mechanism of action for ketamine.

The binding of the serotonin 1B receptor causes serotonin levels to go down, while another neurochemical called dopamine, which also transmits nerve signals, is increased. Dopamine is a neurotransmitter related to the reward circuits of the brain, which means its levels cause more positive feelings or mood elevation. This feature is highly desirable in depression.

So how does ketamine do what it does? Apparently, it increases the number of serotonin 1B receptors. This is the first time this effect has been observed, and it explains the quick and favorable action of ketamine.

This discovery could trigger more research on whether the serotonin 1B receptor offers a target for newer drugs that may avoid ketamine's adverse effects even while maintaining its rapid mood-lifting capability.Another researcher, Johan Lundberg, says, "Ketamine has the advantage of being very rapid-acting, but at the same time it is a narcotic-classed drug that can lead to addiction."

The Ketamine study: What was done?

In the current study, researchers used positron emission tomography (PET) to image the brains of depression patients on ketamine treatment. Calling it "the largest PET study of its kind in the world," researcher Mikael Tiger says their "focus was on finding how much of an effect ketamine has on depression, as well as trying to identify the role of serotonin 1B receptors."


How much does a Ketamine Infusion cost?

by Sam Woolfe | HEALING MAPS | 11 Aug 2021

If you are considering getting a ketamine infusion, then you will want to know how much this treatment will cost you. In this post, we outline the average price of a ketamine infusion, explain why it costs what it does, and then underscore some key factors that can influence changes in price. Understanding this information is essential before deciding if ketamine treatment is the right choice for you.

The cost of a Ketamine Infusion

A ketamine infusion in the United States costs between $400-$800 per infusion. Some providers may charge more, such as $1,000 per infusion, but this price is not common.

Bear in mind that there will be an initial fee for your consultation and assessment (which will cost around $350). This initial consultation is critical, as the psychiatrist carrying it out will inform you whether any medications you take — or health conditions you have — may interfere with the ketamine treatment. If you have a problem with addiction, this also needs to be discussed during the consultation. Be aware that it may make you unsuitable for treatment.

In other words, you should consider the consultation fee as a given. So, if you signed up for just a single ketamine infusion, the overall cost will then be about $750-$1,150. Of course, if you opt for ketamine treatment, you should know that treatment plans typically involve a round of infusions, not just one. Multiple infusions can help to enhance the efficacy of the treatment.

The total cost of ketamine treatment, then, will depend on how many infusions you get. These details will be sorted out during your consultation. A trained psychiatrist at the ketamine clinic can figure out how many infusions will be ideal. Note, however, that many clinics often offer patients six rounds of infusions (two per week). This treatment plan is based on clinical studies that investigate the effects of six infusions, finding this to be effective in alleviating depression.

It’s important to remember that the actual cost of ketamine treatment will be more than that of a single infusion. You can expect to pay $2750-$5,150 for ketamine treatment involving six infusions and an initial assessment.

Why a Ketamine Infusion costs what it does

You may think that a ketamine infusion is expensive, especially when you work out the cost of multiple infusions. However, ketamine treatment is on par with other procedures that require an intravenous (IV) drip.

The ketamine itself costs around $10. So the bulk of the price really comes down to the other factors involved in treatment, not the drug itself. The price factors in the qualified staff working at the ketamine clinic, the equipment, and the kind of facility needed to administer the drug. All of these aspects are expensive and so they translate into the $400-$800 that a single infusion costs.

Factors that influence the cost of Ketamine Infusion

As we can see, the cost of a ketamine infusion can differ significantly. If you pay $400 per infusion, your overall treatment will be much more affordable than committing to $800 per infusion.

Let’s examine some of the factors that influence these differences in price. Likewise, we’ll show you how to potentially reduce the cost through a health insurance plan.

The reputation of the clinic

If a particular ketamine clinic has a strong reputation for delivering a high level of care, consideration, and efficacy, then they may understandably charge a higher fee for this service. Differences in cost do not always reflect differences in quality, but sometimes they do. Be sure to take this into account when deciding whether to pay more to receive a ketamine infusion at a particular clinic.

The reputation of the staff

Administering a ketamine infusion requires the expertise of psychiatrists, nurses, anesthesiologists, and psychotherapists (if the clinic offers on-site psychotherapy alongside ketamine infusions). The more skilled and reputable the staff at a clinic are, the more this provider may charge per ketamine infusion. This applies to any other medical treatment you might pay for.

If you want the best specialists for your plan, the cost of the ketamine infusion will reflect that. This also includes the initial consultation and any follow-up assessments.

The cost of running the clinic

Not all ketamine clinics cost the same to run. Factors that can influence the cost of maintaining a ketamine clinic include the following:​
  • Size and quality of the facility​
  • Quantity and quality of equipment​
  • Number of staff members (e.g. psychiatrists, psychotherapists, anesthesiologists, nurses, admin)​
If a provider includes the above factors, then this will reasonably be reflected in the cost of treatment.

A ketamine provider has a relatively low cost based on the above factors. However, this does not necessarily mean they are sacrificing quality or safety. For example, they might simply have a smaller facility and fewer employees working there. Smaller ketamine clinics can still offer a high degree of care, attention, and safety.

Health insurance

Health insurance companies don’t cover ketamine treatments for the following reasons.​
  • Unawareness of ketamine as a treatment. Many insurance companies simply do not know that ketamine is being used to treat depression and other mental health conditions in outpatient clinics. They might only be aware of it as a recreational drug or veterinary medication. This is due to a lack of education.​
  • Ketamine is not an FDA-approved treatment for mental health conditions. The drug is only approved by the FDA as an anesthetic and analgesic in operating rooms and emergency departments. The FDA has not (yet) approved outpatient ketamine for depression, PTSD, anxiety, OCD, and bipolar disorder. The FDA approval process is very costly and there is little incentive for pharmaceutical companies to fund the research needed for approval since ketamine is an old, generic medication.​
  • Ketamine is considered an experimental drug. The specific use of ketamine for the treatment of depression and other disorders is relatively new, with studies on the treatment being small scale with a limited number of participants. Although the evidence so far reveals that ketamine is highly effective in the treatment of depression, there is still not enough research in the eyes of the insurance companies.​
While an insurance company probably won’t cover the entire cost of ketamine infusion, part of the treatment may get coverage. Each insurance company will cover different amounts, and different patients will often see varying results — even from the same insurer.

In some cases, insurance companies will offer reimbursement

Nonetheless, some patients are able to get certain aspects of ketamine treatment covered, such as the consultation fee. There are some patients who are reimbursed by their insurance for the total cost of their treatments. But this is rare.

While you may be able to collect some money from your insurance company, it can take a lot of work.

The cost of ketamine infusion can be pricey, but there are some options. Most ketamine treatment providers accept credit cards and may offer financing options. Another option is to enroll in a clinical trial. This carries its own risk, but the benefits may outweigh those risks. This is especially true if other treatments aren’t offering the relief you need.

It is possible to receive a single ketamine infusion, in which case, you can see if this will be sufficient. You may notice some relief from a single infusion, which may lead you to accepting the cost of further infusions. For many patients, a single ketamine infusion is enough to reduce depressive symptoms, allowing them to function and feel well.


Ketamine has an "unbelievable" effect in treating severe depression

BEC Crew | Science Alert

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

Its probably not the first place you'd go to find relief from severe clinical depression, but the psychedelic 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. Its really obvious if its 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 drugs 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 this new treatment option for depression so exciting? Put simply, for many people with severe depression, and 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 re-absorption of serotonin into the brains pre-synaptic cell, and this readjustment of serotonin levels appears to help the brain cells send and receive chemical messages more effectively, which can boost a persons mood.

But every SSRI has a different chemical make-up, and it is 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.

Medical centers across the US are now increasingly opting to treat their patients with Ketamine, including Yale University, the University of California at San Diego, and 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 have 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 dont respond to antidepressants, and weve 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 arent 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 behavioral 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 its 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 isnt 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 note: 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 told ScienceAlert. "Very few have 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 that patients with few alternatives have benefited from it, and research institutions are investing a lot of time and money into figuring out its potential, and we will update you with more information as it's made known.


I use Ketamine for Depression – Here’s how it works

by Doug Dais | Freethink

Ketamine’s reputation is moving away from “party drug” and into one of the newest and most effective forms of depression treatment.

When first manufactured as an anesthetic for humans and animals in 1962, doctors certainly had no intention of prescribing ketamine for depression. Nor did they intend for its psychoactive effects to boost its popularity among festival-goers and galaxy explorers.

The surprising and powerful effect that ketamine has proven to have on the brain’s neurons though, has led doctors to explore its medical potential and begin to strip away the stigma that decades of recreational abuse have given to a potentially life-saving treatment.

From party drug to life-saving treatment

Ketamine has gained notoriety over the past few decades as a mind-altering drug capable of both anesthetizing horses and sending party-goers into hallucinogenic bliss. The drug has a long and storied history in the club scene and due to its abuse in this scene, it became discredited and stigmatized.

Once drugs are scandalized to this extent it’s difficult to highlight the positive neurological and psychoactive effects of which they’re capable. But doctors such as Dr. Dennis Charney, of the Icahn School of Medicine at Mount Sinai, are finding that ketamine has incredible potential when used as a means of treating various forms of mental illness.

Dr. Charney recognized an alternate potential for ketamine and created an entirely new field of science called suicide biology. He jumped on the opportunity to harness the drug’s effects to address the country’s rapidly growing issues of depression and suicide.

Because of the research of Dr. Charney and others, ketamine’s reputation is now moving away from that of a party drug and into one of the newest and most effective forms of medication to treat severe depression.

Ketamine for depression: How it works

What differentiates ketamine from other antidepressants is how it works to affect the brain. Antidepressants typically focus on increasing chemicals in the brain such as serotonin and dopamine.

Using ketamine for depression, however, can actually assist in repairing neuron synapses that typically don’t function properly in the brains of depressed patients. Ketamine provokes a response in the brain, and it’s the adaptation to that provocation- the regrowth of synaptic connections- that is responsible for the rapid improvement in the mood it creates.

The need for an alternative treatment

Depression is an ever-growing epidemic in America and it’s one that requires outside-of-the box thinking, such as the introduction of ketamine therapy. An NBC article reports that since 2013, diagnoses of major depression have risen by 33%, including a 47% increase in those ages 18 to 34.

The exponential growth of this affliction, despite the large number of chemical antidepressants currently available, indicates that there is an enormous need and opportunity for alternative treatments like using ketamine for depression.

"I was suicidal with a plan, and ketamine stopped that in it's tracks. After the 3rd infusion I was getting in tickle fights with my husband. I can't believe how fast I've been getting better and happy and thinking about goals." -Sheen Hunter

One of the major issues with today’s well known and more socially-accepted forms of antidepressants is their ineffectiveness on a growing number of individuals. Around five million people in the U.S. with depression don’t respond to commonly prescribed or recommended treatments.

This condition is known as Treatment-Resistant Depression. The hopeless feeling that these individuals experience is compounded by the bombardment of prescribed but ineffective treatments. The crushing weight of doom they carry is further impacted by the feeling that nothing is going to be able to help them unload this burden.

It’s no wonder then that, as Bloomberg Businessweek reports, the rate of suicides in our country rose by 30% between 1999 to 2016 alone. Additionally, suicide is now the second-leading cause of death for Americans ages 10 to 34.

Ketamine infusion and nasal sprays

Ketamine infusion therapy is one of the newest and most effective ways that doctors are able to provide relief for individuals with severe depression. Infusion centers are beginning to pop up all over the country, which is making the treatment more accepted and accessible.

Patients interested in trying ketamine for depression can visit these centers once every one to six months depending on the severity of their condition. Within several hours of treatment many patients begin to feel better, and within 24 hours some feel nearly or completely better.

People with Treatment-Resistant Depression who start taking prescription antidepressants typically have between a 10 and 20 percent chance of a positive response. Those being treated with ketamine infusions have a positive response rate between 50 and 80 percent.
Ketamine can actually assist in repairing neuron synapses that don’t function properly in depressed patients.

These staggering and positive results have been known to the scientific and medical communities for many years, but ketamine’s “party drug” stigma hindered further research and adoption. The good news is that now, attitudes toward the drug are finally starting to change and with the changes, access to ketamine as a medication is becoming more readily available.

As both society and the medical community begin to gain a different perspective on ketamine, new research findings continue to expand the drug’s possibilities. The FDA approved a nasal spray form of the drug last year which can be used in addition to ketamine infusion.

The spray allows users to get relief in minutes or hours, rather than weeks or months like typical antidepressants. Providing those with severe depression fast-acting, at-home relief is incredibly important as the country fights to reverse high suicide rates.

New promise for ketamine and depression

The recent growth of research has also expanded the scope of ketamine’s potential for those dealing with PTSD, severe anxiety, chronic pain, OCD, and bipolar disorder, offering new hope for individuals who have felt hopeless for too long.

Like with any drug, ketamine’s effects can be dangerous and abused if it’s used improperly and for non-medical purposes. It’s equally important though to weigh the exponential impact that ketamine could have for those who suffer from mental illness, and it would be negligent to not continue the expansion of research of this drug.

Time is rarely on the side of those suffering with a severe mental illness, but the fast-acting potential of ketamine might just be able to reverse the clock on depression rates and erase the drug’s negative stigma.

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Ketamine a breakthrough treatment for suicidal children

by Jack Turban | July 18, 2017

Initial research finds fast, dramatic benefits for a vulnerable population.

Fourteen-year-old Nicole, whose name I changed for her privacy, told her mother every day for years that she wanted to end her own life. Between suicide attempts were more psychiatric hospital visits than she or her mother could count. She refused to get out of bed, shower, or go to school, missing sixty school days in a single year. In one visit with her therapist, she admitted to praying every night that she would not wake up the next morning. After countless psychiatrists and psychotherapists were unable to improve her depression, her mother converted a bathroom cabinet into a locked safe, containing all of the sharp objects and pills in the house. Her parents were certain it was only a matter of time until Nicole killed herself.

Today, a now seventeen-year-old Nicole greets me with a big smile. Her blonde hair is pulled back into a ponytail to reveal her bright blue eyes. She tells me she hasn’t missed a day of school and is preparing for college. Blushing, she lets me know that her first date is coming up, a prom date to be precise. For the first time in years, she is happy and wants to live.

What happened to cause this dramatic change? In December, Nicole started infusions of a psychedelic drug called ketamine. Though she had failed to respond to endless medication trials for her depression (selective serotonin reuptake inhibitors, mirtazapine, topiramate, antipsychotics, and lithium to name just a few), ketamine cleared her depression within hours. The effect lasts about two weeks before she needs a new infusion.

Ketamine is a drug with many identities. For anesthesiologists, it’s a sedative for painful procedures. For partiers, it’s a fun way to hallucinate and have an out-of-body experience. For critics, it’s a dangerous addictive drug that can cause memory problems, bladder disease, and psychosis when abused. In the past few years, it has taken on a new identity: miracle psychiatric drug that works within hours. Its use as a psychiatric medication is relatively new, and it’s possible that regular infusions could cause significant long-term side effects. We currently lack the long-term data to know. Still, the National Institute of Mental Health has called it “the most important breakthrough in antidepressant treatment in decades.”

The ketamine for mental health story goes back as far as the 1980s, when neuroscientists examined the brains of people who had committed suicide. They found that suicide victims had structural abnormalities in a protein called NMDAR, a neurotransmitter receptor that is sprinkled throughout the brain. It also happens to be the receptor to which ketamine binds. Though some animal models suggested that ketamine improved depression in mice, it wasn’t until 2000 that researchers tried giving the drug to adults with depression. Surprisingly, many patients’ depression completely resolved within hours. The quick and dramatic result was unprecedented for an anti-depressant medication.

Since then, physicians have given the drug to thousands of depressed adults, including patients in eight successful clinical trials. But fewer have been willing to infuse the drug into the veins of minors. Yale School of Medicine is an exception, and I recently watched a few adolescents receive the infusions with Yale’s clinical trial team. It was less dramatic to watch than I expected, but the kids were definitely high. There was a lot of giggling involved, and they often said that they felt like time was changing and that their bodies felt ‘funny’ and sometimes numb. Nicole admitted, “I’m not gonna lie. I like the feeling of it.”

Perhaps more dramatic than the trips themselves, which happened in a carefully controlled procedure room with a psychiatrist and anesthesiologist ready to intervene if needed, were the interviews that came after. I could see the weight of depression lifted from these patients within hours. Adolescents who were previously ready to end their own lives became bright and hopeful. Psychiatry has never seen a drug intervention so powerful and fast acting. While most anti-depressants take weeks to work and offer modest improvement, ketamine offers dramatic improvement in less than a day.

Because of early success in adult patients, there has been explosion of ketamine clinical trails for adolescents. Frustrated by a lack of effective treatments for children experiencing severe, debilitating, psychiatric disease, doctors have new clinical trials underway for adolescents with depression, anxiety, obsessive-compulsive disorder, and even a rare autism-like condition called Rett’s syndrome. Dr. Gerard Sanacora at Yale School of Medicine explained it like this: “We know high blood pressure causes all kinds of things: heart attacks, strokes, vision problems, and kidney diseases. We treat all of those with blood pressure pills. Ketamine may be the blood pressure pill of psychiatry — altering basic physiology [of neuronal connections] and having a wide range of beneficial effects.”

But there is also reason to be concerned. Before now, ketamine has only been used as a one-time injection for anesthesia. The FDA approved the drug based on trials where the drug was given just once. For depression, however, it is given every few weeks with an unclear end point. Will repeated administration reveal new risks? Studies in adolescent mice show that ketamine can cause long-term cognitive problems. Ketamine-treated mice can also develop a schizophrenia-like illness, with a pattern of neuron loss in the brain that is similar to schizophrenia. However, it’s important to note that the majority of these studies use mice given ketamine doses equivalent to 10 times that which is given to patients.

Dr. Michael Bloch, Yale child psychiatrist and principal investigator of several controlled trials for ketamine for adolescents, points out that the drug is only used for select patients who have severe mental health problems that have not responded to other medications. The infusions are provided in a clinical trial setting, where doctors collect efficacy data and carefully watch for side effects. For each of his patients, the theoretical risks of ketamine are carefully weighed against the risk of suicide. For Nicole, who seemed likely to die from suicide, the calculus was not difficult.

Though Dwyer and Bloch stress that doctors need to be careful, they are also quick to point out the potential promise of this research. Dr. Bloch explains, “Suicide is the second leading cause of death in adolescents. 40% of depressed adolescents don’t respond to first-line treatments. Another half of those don’t respond to multiple trials of medication paired with psychotherapy. Other than electroconvulsive therapy, which carries its own risk of memory problems, doctors have almost no other choice.” Suicidal patients are also at a high risk for suicide after leaving the hospital. Existing anti-depressants like Prozac take weeks to work, while ketamine can take effect in less than 24 hours. This could decrease deaths from suicide after patients leave the hospital.

For Nicole, one of those suicidal teens, everyone involved seems convinced that ketamine saved her life. According to her, her family, and her doctors, the theoretical risk of long-term side effects was less frightening than what might happen in the face of chronic hopelessness and suicidality.


How does Ketamine combat Depression?

McGill University | Neuroscience News | 16 Dec 2020

E-BPs proteins are key to unlocking ketamine’s antidepressant effects. When 4E-BPs are absent in neurons, ketamine can not produce its antidepressant effect.

A group of proteins called 4E-BPs, involved in memory formation, is the key to unlocking the antidepressant effect of ketamine in the brain, according to researchers from three Canadian universities. The discovery could lead to better and safer treatments for certain patients suffering from major depression.

Because more than 30% of patients are resistant to selective serotonin reuptake inhibitors (SSRI), the most commonly-prescribed antidepressants, finding an effective treatment for major depressive disorder is challenging.

Initially, ketamine was approved for anesthesia and pain relief. Since its discovery, researchers have been studying new uses for this drug, and ketamine was approved last year for patients with major depression who are treatment-resistant. Unlike standard antidepressants, which can take several weeks to have an effect, ketamine works within hours. Until now, little was known about the molecular mechanism that triggers the antidepressant effect of ketamine on the brain.

In the study published in Nature, researchers from McGill University, Université de Montréal, and Carleton University investigated the effect of ketamine on behaviour and neuronal activity in mice. Using genetic tools to remove proteins from specific brain cells, the team found that when 4E-BPs are absent in the brain, specifically in neurons, ketamine cannot produce its antidepressant effect. 4E-BPs act as a switch to turn on or off the process of protein synthesis – an essential component of memory formation.

“This is yet another prime example of how basic research, in this case the control of protein synthesis, leads to major discoveries in understanding disease, and the hope of curing it,” says co-author Nahum Sonenberg, a professor at the Department of Biochemistry at McGill University.

The researchers examined the role of 4E-BPs on ketamine’s effect in two major types of neurons: excitatory neurons, which make up most of the neurons in certain parts of the brain, and inhibitory neurons, which control excitatory neurons and have important effects on behaviour.

“We were expecting that 4E-BPs would only be important in excitatory cells, but surprisingly, removing 4E-BPs from inhibitory cells was sufficient to block the effect of ketamine,” says co-author Jean-Claude Lacaille, a professor at the Department of Neurosciences at Université de Montréal.

Medicine is not one size fits all

The discovery and approval of ketamine for treatment-resistant patients was considered a major advance in modern psychiatry. Despite its promise, ketamine remains a less-than-perfect therapy because it can be addictive. The researchers hope that their findings will pave the way for better and safer antidepressant therapies for patients with major depressive disorder.

“Too many decisions continue to be made by a trial-and-error approach that can prolong the suffering of patients and affect their quality of life,” says co-author Aguilar-Valles, a former research associate at McGill University and now an assistant professor at Carleton University. “Our discovery has the potential to bring us closer to find a safer alternative to ketamine, and ultimately to a personalized medicine approach, where medical treatments are tailored to the individual characteristics of each patient.”

The study also involved a clinician-researcher, Dr. Gabriella Gobbi, from the Department of Psychiatry at McGill University, who works with individuals affected with depression and other psychiatric illnesses.

As next steps, the researchers will examine whether males and females have different responses to ketamine. This could have important implications for treatment for people with depressive disorders, among which women are significantly overrepresented.


Columbia University Medical Center

Ketamine 'rapid and effective' for reducing suicidal thoughts

by Honor Whitema | Medical News Today

According to a new study by researchers from Columbia University Medical Center, Ketamine — a medication primarily used as an anesthetic — may offer a fast and effective way to reduce suicidal thoughts among individuals with depression.

Depression is by far the most common disorder underlying a suicide attempt; around 30–70 percent of those who attempt suicide have major depression or bipolar disorder.

But how can you tell if a friend or loved one with depression is having suicidal thoughts? Verbal threats of suicide or being a burden to others, an increase in the use of drugs or alcohol, and changes in mood can all be warning signs.

Of course, it is not possible to predict whether a person will attempt suicide, which highlights the need for speedy treatments that can reduce suicidal thoughts.

"There is a critical window in which depressed patients who are suicidal need rapid relief to prevent self-harm," explains study leader Dr. Michael Grunebaum, a research psychiatrist at Columbia University Medical Center.

"Currently available antidepressants can be effective in reducing suicidal thoughts in patients with depression," he adds, "but they can take weeks to have an effect."

Dr. Grunebaum explains, "Suicidal, depressed patients need treatments that are rapidly effective in reducing suicidal thoughts when they are at highest risk. Currently, there is no such treatment for rapid relief of suicidal thoughts in depressed patients."

Previous research, however, has pointed to ketamine as a potential candidate, after finding that low doses of the drug may help to reduce suicidal ideation in people with depression.

Dr. Grunebaum and colleagues set out to investigate this association further with their new study. Specifically, they investigated whether or not ketamine could reduce suicidal thoughts within 24 hours of administration.

The findings were recently published in The American Journal of Psychiatry.

Ketamine quickly halved suicidal thoughts

The research included 80 adults who had major depression. All participants had suicidal thoughts, as determined by their scores on the Scale for Suicidal Ideation (SSI).

The participants were randomized to one of two treatment groups. One group received a low-dose of ketamine, while the other group received a low-dose of midazolam, a sedative.

Using the SSI, the researchers assessed the presence of suicidal thoughts at 24 hours after each drug was administered.

While both groups saw a clinically significant reduction in suicidal thoughts, this reduction was greater for subjects who received ketamine: 55 percent of the ketamine group experienced a 50 percent or higher reduction in suicidal thoughts, compared with 30 percent of the midazolam group.

Ketamine's effects on suicidal thoughts remained for up to 6 weeks, the team reports. Furthermore, those who received ketamine experienced greater improvements in mood, depression, and fatigue, compared with those who received midazolam.

The team notes the effects of ketamine on depression accounted for around a third of the drug's effects on SSI scores, which suggests that ketamine can directly target suicidal thoughts.

The most common side effects of ketamine were dissociation and an increase in blood pressure upon administration. However, the team notes that these side effects soon subsided.

Overall, the researchers say that their findings show that "ketamine offers promise as a rapidly acting treatment for reducing suicidal thoughts in patients with depression."

"Additional research to evaluate ketamine's antidepressant and anti-suicidal effects may pave the way for the development of new antidepressant medications that are faster-acting and have the potential to help individuals who do not respond to currently available treatments."
- Dr. Michael Grunebaum


Why Ketamine is such a Powerful Antidepressant*

by Carly Cassella | Science Alert | 13 Aug 2021

Oral ketamine, known both as an anesthetic and a recreational drug, has recently emerged as a highly promising, rapid treatment for severe depression.

Within hours, a single dose of the psychedelic substance has been shown to curb suicidal intent, and recent clinical trials suggest these effects work on two thirds of patients, lasting for up to several weeks before fading away.

Given the promising early results and the limits of currently available antidepressants, oral ketamine is now available as a nasal spray in the United States for those with intractable depression and chronic suicidal thoughts.

Yet despite the drug's growing use nationwide, we still don't really know the full extent of its antidepressant activity. Ketamine interacts with a range of receptors in the brain, but which are the ones that lead to anti-depressant effects?

Some scientists think ketamine's therapeutic power relies on its influence over glutamate, a neurotransmitter that is secreted by the ends of certain neurons in the brain. But while ketamine appears to increase glutamate release in some parts of the brain in both mice and humans, in other parts of the mammalian brain, the drug seems to decrease this release.

"Elevated glutamate release has been linked to stress, depression and other mood disorders, so lowered glutamate levels may explain some of the effects of ketamine," explains neuroscientist Per Svenningsson from the Karolinska Institutet in Sweden.

Now, new results from experiments on mice and their neurons further support that hypothesis - at least for the prefrontal cortex, which is connected to complex cognitive behavior and the modulation of emotion.

Measuring glutamate levels among free-moving and anesthetized mice, Svenningsson and colleagues have found ketamine reduces the persistent release of this neurotransmitter almost immediately.

When researchers injected ketamine into the prefrontal cortex of a mouse's brain, they noticed a reduction in extracellular glutamate levels within 30 minutes. What's more, the authors saw similar effects for both normal mice and mice that showed depression-like symptoms.

"These effects could contribute to the efficacy of ketamine to instantly alleviate depressive symptoms and suicidal ideation, taking into account that excessive glutamate levels have been linked to MDD and other mood disorders," the authors write.

Further analysis under the microscope suggests ketamine acts on the neurons that usually receive glutamate, causing these cells to release more of a neurotransmitter called adenosine.

Adenosine then enters the space between neurons, known as the synapse, to tell the presynaptic neurons to stop producing so much glutamate.

When researchers blocked ketamine receptors on the postsynaptic neuron to test its role, they were able to completely prevent the decrease in glutamate from the presynaptic neuron.

"This suggests that the antidepressant action of ketamine can be regulated by a feedback mechanism," says Svenningsson

"It is new knowledge that can explain some of the rapid effects of ketamine."

The fast inhibitory action could be part of why ketamine is so successful at treating depressive symptoms. Some cells in the cerebrospinal fluid that help control glutamate levels, for instance, have recently been linked to stress-induced depression and anxiety-like behaviors in mouse models.

Today, while oral ketamine has provided much-needed relief for many patients with severe depression resistant to other antidepressants, its use is limited by its side effects.

Ketamine is a psychoactive drug that can cause feelings of fatigue, restlessness, anxiety, dizziness and hallucinations - all of which make it a tricky treatment to control clinically.

Some scientists are therefore exploring whether they can isolate the parts of ketamine that rapidly treat depression without having to include the parts that drive unwanted side effects.

But maybe it's the hallucinogenic parts that make the medicine work. We still don't really know, which is why we need to learn more about what makes ketamine such a powerful antidepressant.

If drug engineers can one day mimic the most important antidepressant effects of glutamate, they could potentially produce an alternative that comes with far fewer side effects but still works just as rapidly and aggressively as ketamine itself

So far, scientists have only engineered two non-hallucinogenic drugs that show clinical benefits similar to ketamine, neither of which specifically targets glutamate production, and these drugs have only been tested on mice. That said, the drugs did appear to show rapid anti-depressant effects without any of the usual head twitches that ketamine can cause.

The research to date is still being conducted on animal models, but if the findings prove promising enough, clinical trials among humans could be just around the corner.

The study was published in Molecular Psychiatry.

*From the article here :

Ketamine Treatment Guide for Mental Health*

Ketamine treatment is now available to improve mental health. Ketamine therapy helps to reduce depression and other psychiatric symptoms.

by Psychedelic.Support | 25 Aug 2021

Ketamine has been around for decades but only in recent years has it found applications in mental health. Ketamine treatments are available in two main frameworks, either with a course of psychotherapy or as a standalone medication. Read this guide to learn more about how ketamine treatment works and how it is used in therapy.

Discovered in 1962 and patented in 1963, racemic ketamine is an arylcyclohexylamine used as a rapid-acting general anesthetic agent in human and veterinary medicine. Following FDA approval in 1970 as an anesthetic drug, ketamine is now legally prescribed off-label for a growing list of indications.

Ketamine is a non-competitive NMDA antagonist and interacts with a number of other receptor targets that contribute to its effects. Beyond its primary application for anesthesia, it is used as an analgesic, anti-obsessional, and antidepressant compound, and may possess neuroprotective and neuroplastic properties.

The effects of ketamine are highly dependent on the bioavailable dose by way of the route of administration, ranging from slight perceptual disruptions to paralysis and full dissociation to sedation. In medical settings, ketamine is considered relatively safe because it has less circulatory and respiratory depression compared to other anesthetic agents. Long-term use and high doses of ketamine are associated with greater incidence of adverse effects and increased risk of dependence.

From the streets to psychotherapy offices

What is ketamine treatment originally for? Ketamine is an anesthetic. It was discovered in 1962. However, since then, ketamine has been on an odd journey. Due to this, ketamine is widely misunderstood. Here’s why.

There are 2 main ways the vast majority of Americans have come to know ketamine.

Hearing it referred to as “horse tranquilizer.” And/or, hearing it referred to as its slang name among the electronic dance music and rave scene – “Special K.”

The mass media sensationalized these two soundbites over recent decades in order to bypass a nuanced conversation while pandering to the status quo’s anti-drug hysteria.

Although, to be fair, both of these misrepresentations have a bit of truth to them.

After its discovery, ketamine was later used widely in the Vietnam war, thanks to its pain killing effects that don’t inhibit respiratory functioning like other anesthetics. Ketamine can be preferable to other drugs and treatments due to its lower physically addictive quality. A dose used in this way induces a dissociative state providing pain relief, sedation and amnesia.

Over the years, ketamine was also used for anesthesia in animals. Unfortunately the mass media exploited a possible urban legend that quantities of ketamine were being stolen from veterinary clinics. Since it was used as a horse tranquilizer at veterinary clinics, the mass media latched onto this. The mass media made ketamine bigger, scarier and spookier. In reality, ketamine has been used on a wide range of animals, besides just horses. For example ketamine is used with: elephants, camels, gorillas, pigs, sheep, goats, dogs, cats, rabbits, snakes, guinea pigs, birds, gerbils and mice.

So ketamine isn’t just a horse tranquilizer, it’s also a wide ranging mammal tranquilizer, and this includes humans as well. But what about “Special K”?

This made for another sensational headline to connect “stolen horse tranquilizer” to raves and electronic dance music festivals. Parents were stricken with fear of simply letting their kids go out at night, lest they end up being knocked out like a horse. Of course this type of dose is much too large for a human. However, when used at higher levels, ketamine becomes a powerful hallucinogen. At high doses of this type, ketamine’s dissociative state leads to visual and/or auditory hallucinations.

Ketamine has taken an odd journey from the battlefield, to raves, and now to depression and PTSD treatment. Despite the circuitous route, ketamine always maintained its medical usefulness. Thus ketamine never strayed far from further research and studies.

Even though ketamine was always approved for anesthetic use by the FDA, it wasn’t used for mental health treatments until recently. After many years of use as an anesthetic, human studies for other applications and treatments began in the 1990s. Some of these new territories of ketamine explored schizophrenia.

During the 1990s Yale researchers “…started giving ketamine to healthy individuals to produce transient symptoms of schizophrenia with the idea that they could then study these individuals.” Since ketamine mimics schizophrenia symptoms (known as psychotomimetic effects), the researchers could “…study their brain activity to gain a better understanding of the condition.” A few years later, ketamine had a serendipitous moment. It was unintentionally found to be successful in treating depression.


Discovering ketamine’s rapid antidepressant effect led to an insight. Since ketamine works on a different neurotransmitter, compared to selective serotonin reuptake inhibitors (SSRIs), it stimulates BDNF production. BDNF stands for brain derived neurotrophic factor. Some people think of BDNF like it’s Miracle Gro. Rupert McShane says “You can think of BDNF as a “fertilizer” for the brain.” McShane is an associate professor in the Department of Psychiatry at the University of Oxford. He continues saying that BDNF boosts results in “…neurogenesis, the growth of new brain cells, and synaptogenesis, the formation of new connections between brain cells.” After that, ketamine never looked back.

What is Ketamine-Assisted Therapy (KAP)?

The use of ketamine for mental health symptoms falls into two broad frameworks – a pharmaceutical/biochemical framework and ketamine-assisted psychotherapy (KAP). Ketamine itself has physiological effects that appear important for antidepressant and other therapeutic effects.

The pharmaceutical/biochemical framework has a neurobiological approach that often employs intravenous dosing by an anesthesiologist with no therapy. Some doctors will administer ketamine, typically through IV infusions or lozenges, to relieve psychiatric symptoms.


In this methodology, the drug itself acts through neurobiological mechanisms and the symptom relief is dependent on repeated administrations because the therapeutic effects last for days or up to two weeks. Patients are offered minimal support and no talk therapy which may lead to a dependence on ketamine to achieve symptom reduction. The contents of the experience or talking about interpersonal issues aren’t the focus of the treatment. Long-term use of ketamine is associated with negative side effects, namely kidney and bladder toxicity and ketamine tolerance and dependence.

Because symptom reductions usually only last for up to 7 days, repeated administrations of ketamine are necessary to achieve therapeutic benefits. If a patient takes ketamine long-term, they are at greater risk for negative side effects. These effects can be severe and cause toxicity to the bladder and kidney. Tolerance and dependence to ketamine can develop over time which can make medication cessation psychologically difficult.

Ketamine-assisted psychotherapy (KAP) is a method where low to moderate doses of ketamine are delivered with the intention of altering consciousness to facilitate psychotherapy. A therapist sits and talks with a client as they experience ketamines, and after the effects wear off.


Alternatively, KAP may also employ high doses of ketamine. High ketamine doses are used to induce a non-ordinary state of consciousness, provoking a person to experience major shifts of perceptions in many ways similar to classical psychedelics. Mystical-type experiences and feelings of ego dissolution are common for high dose sessions. These effects can be extremely negative if a person is not well prepared and supported during and afterwards.

Either immediately after the effects of ketamine dissipate, and/or in the days to weeks to follow, a person undergoes a course of counseling or psychotherapy to examine the experience and emotions within the framework of their personal goals. The psychotherapeutic process aims to stabilize positive behavioral changes, consolidate psychological material, resolve psychological issues, improve relationships, catalyze new insights, and enhance self-awareness.

While still under-researched, ketamine-assisted psychotherapy is presumed to amplify the neurobiological properties of ketamine by addressing underlying psychological issues and bolstering transformational healing.

For a robust explanation between the 3 ketamine therapy types (pharmaceutical/biochemical, low dose KAP, and high dose KAP) we strongly encourage you to follow the work of Dr. Raquel Bennett.

Raquel Bennett, PsyD is a psychologist and ketamine specialist from Berkeley, CA. She has been studying the therapeutic properties of ketamine since 2002. Dr. Bennett is the founder of KRIYA Institute and the organizer of KRIYA Conference, which is an international event devoted to the use of ketamine in psychiatry and psychotherapy. Dr. Bennett has a long-standing interest in the relationship between mood modulation and psychedelic experience.

Bennett has written much on the subject of ketamine, as well as the 3 different types of treatment methods over her 19 years of study. She sums up the subject best by saying:

So which of these treatment paradigms works the best? In other words, what is the “right” way to use ketamine therapeutically? The answer is that all of the paradigms are useful. In my 17 years of experience to date, it is clear that different things work well for different people: Some patients are excellent candidates for a series of low-dose ketamine infusions or nasal spray; some patients are tied up in emotional knots on the inside and truly benefit from ketamine-facilitated psychotherapy; and a tiny fraction of clinical patients are actually good candidates for a full psychedelic ketamine journey. Learning how to distinguish which patients are likely to benefit from each strategy is beyond the scope of this article and the subject of much active debate in the clinical ketamine community.

Similar to other classical psychedelics, not everyone is the right fit for ketamine, especially at higher doses. Screening for contraindicated medical and mental health conditions is essential as is a proper setting for psychological safety. Research dating back to the 1950s and current day psychedelic-assisted clinical trials are elucidating how psychedelic experiences can be beneficial for therapeutic applications, and what parameters are necessary to support a person undergoing these experiences.

What does ketamine do to my brain (pharmacologically)?

PubChem describes the basic pharmacology of ketamine hydrochloride, by stating:

Although its mechanism of action is not well understood, ketamine appears to non-competitively block N-methyl-D-aspartate (NMDA) receptors and may interact with opioid mu receptors and sigma receptors, thereby reducing pain perception, inducing sedation, and producing dissociative anesthesia.

This explanation concurs with why ketamine is often referred to as a “pharmacologist’s nightmare.” Ketamine has earned this nickname given its diverse array of effects at numerous receptors in preclinical research.

Indeed, there are (often conflicting) studies demonstrating effects on opioid, sigma, cholinergic, dopamine, serotonin, and adenosine systems, amongst others.

These additional properties aside, the best understood mechanism of action is via noncompetitive antagonism of N-methyl-D-aspartate (NMDA) receptors, first demonstrated in 1983.

NMDA receptors are ionotropic glutamate receptors found extensively in the central nervous system, and to a lesser extent peripherally. When NMDA receptors are activated by glutamate binding, ion channels are opened allowing for various positive charged ions to flow through them into cells, triggering membrane depolarization and modulating signal transmission. Ketamine blocks the flow of ions.

Ketamine Positive Effects

The subjective effects of ketamine are highly dependent on the dose administered. The environment where ketamine is taken, as well as the type of support or adjunctive therapies, strongly impact the drug effects and the subjective interpretations.

Here is a list of possible effects: drowsiness, dissociation (body dissociates from the mind), out-of-body experiences or illusions, changes in perception or cognition or emotion, vivid imagery, visual hallucinations or distortions, altered auditory perception and proprioception, mood enhancement, ego dissolution, transcendence of space and time, mystical experiences, experiences of death and rebirth, muscle relaxation, pain relief, feeling of awe and wonder.


Ketamine Negative Effects

Ketamine can also induce undesirable or negative effects. The risk for some of these effects are associated with the context where ketamine is taken. For example, unsupervised use of ketamine carries a greater risk of accidents, such as falling or car crashes. Prolonged use of ketamine is associated with different negative effects, often more severe, than the acute side effects.

Here is a list of possible acute negative effects: anxiety, nausea, vomiting, dizziness, paranoia, dysphoria, distorted perceptions of body and self, loss of coordination, disorientation, confusion, double or blurred vision, blunted affect or emotional withdrawal, increased blood pressure and heart rate, increased intraocular eye pressure, muscle trembles or jerks, decreased concentration, recall, recognition, and mental sharpness, psychological distress, accidents (falling, car, etc), decreased conscious breathing (though unconscious respiratory drive is preserved), or laryngospasm (an involuntary contraction of the vocal folds that can impair speech and breathing.


Here is a list of possible negative effects associated with prolonged use: kidney and bladder (cystitis) toxicity, urinary tract dysfunction, psychological dependence, misuse, tolerance, and addiction, psychological withdrawal syndromes, flashbacks, memory-related deficits, and decreased sociability.

In 2020, new safety information for chronic use was added to ketamine products marketed in Canada. Liver enzyme elevations, biliary ductal dilatations, and hepatic fibrosis were added to the section on warnings and adverse reactions.


Ketamine Contraindicated Medications and Conditions

Several medical conditions are contraindicated for ketamine use or may increase the risk of side effects. Individuals with pre-existing conditions where elevated blood pressure would increase the risk for complications should avoid or be extremely cautious with ketamine.

Here is a list of contraindicated conditions: hypertension, preeclampsia or eclampsia, severe cardiac disease, stroke, raised intracranial pressure, acute porphyria, epilepsy, schizophrenia, alcoholism, and children under the age of 3. Patients with epilepsy are sometimes administered ketamine but with extra caution and medical oversight.


Unlike the classical psychedelics and MDMA, ketamine is considered safe and effective in combination with multiple classes of psychiatric and non-psychiatric medications. It is often given in addition to a wide range of antidepressants. However, medications that modulate glutamate and GABA may have strong influences, for example benzodiazepines and lamotrigine.

Ketamine History and Law

Ketamine’s discovery can be traced to phencyclidine (PCP). PCP was developed for anesthesia and was first tested on humans in 1958 under the name Sernyl. It was found to produce a “centrally mediated sensory deprivation syndrome” with a neural signature distinct from any other sedative or states like sleep.

Though PCP proved to be a potent anesthetic, a significant number of patients experienced “excitation” or “psychotic reactions” that could last for more than 12 hours after the anesthetic effects of a single dose wore off. These states went on to be referred to as “emergence reactions”, or delirium, and limited any further medical development.

Ketamine, originally called Cl-581, was synthesized as a derivative of PCP in 1962 in order to address this issue. Ketamine produced the same sort of “sensory deprivation syndrome” as PCP, but its development was pursued because it was metabolised much faster and therefore caused less “emergence reaction” as its effects wore off.

The scientists that synthesized ketamine initially proposed describing its unique effects as “dreaming”, in reference to the feelings of “floating” and markedly decreased sensation it induced. This term foreshadowed many of the future studies in anesthesia describing patient reports of vivid “ketamine dreams,” as well as the influential 2004 book “Ketamine: Dreams and Realities” by Karl Jansen.

Instead, the term “dissociation” was selected as a more marketable descriptor of ketamine’s effects. This term was suggested by Antoinette Domino, the wife of the primary investigating chemist Ed Domino, based on his descriptions of how patients seemed to be disconnected from their surroundings. This term stuck and ketamine has largely been unknown as a “dissociative anesthetic”, at least in the realm of medicine.

Use in Medicine

Ketamine’s anesthetic properties differed dramatically from the existing anesthetic agents of the day — and still do. This novelty led to inappropriate early uses and suboptimal dosing regimens, which resulted in disruptive and distressing emergence reactions, poor quality sedation, and unpleasant hallucinations. Ketamine thus gained more initial interest as an anesthetic agent for animals, for which it is still used (earning its nickname as a “horse tranquilizer”).

In the late 1960s and 1970s, ketamine found a niche as a combat anesthetic in the Vietnam War, where it was prized for its potent anti-pain effects without risk of respiratory depression. It became the US’s most widely-used battlefield anesthetic and earned the name “Buddy Drug” in reference to its ease of use: many soldiers with little training or specialized equipment carried stocks of ketamine to administer to injured comrades.

From here, ketamine continued to attract interest in anesthesia, particularly in developing countries due to its unrivalled ease of use and for its safety. For this reason, it has been found on the WHO Essential Medicine list since 1985.

Further medical uses (with varying levels of evidence) include treating opioid-induced hyperalgesia, chronic pain, refractory status epilepticus, severe headache, and alcohol detoxification.

Appearance in Psychiatry

Most modern works trace ketamine’s use in psychiatry to the first randomized controlled trial in depression, published in the year 2000.

However, the first works describing the use of ketamine in psychiatry date to at least the early 1970s by authors in Mexico, Argentina, Iran, and the former Soviet Union. These works all posited psychological (or psychedelic) mechanisms of action, rather than purely biological effects. Much like other psychedelic treatments, and unlike almost all psychiatric medications, these early protocols featured time-limited treatments rather than long term regular dosing. Also like other psychedelics, ketamine was initially combined with a variety of diverse psychotherapeutic approaches, including a form of psychoanalysis incorporating shamanic elements and a therapy described as “death and rebirth.”

Notable other early works documenting psychedelic uses of ketamine include two books: John C Lilly’s memoir “The Scientist” and “Journeys Into the Bright World” by Marcia Moore and her husband. Both works were published in 1978 and described psychedelic experiences from self-experimentation with ketamine.

These early forays into psychedelic uses of ketamine were largely ignored by mainstream psychiatry. This reflects the general movement away from psychedelic-assisted psychotherapy, as well as psychiatrists wanting to distance themselves from public figures like Marcia Moore, who died following self-experimentation with ketamine. Shortly after her book was published in 1978, she disappeared. Two years later, her body was found in the woods near her Washington home. It is believed that she self-administered ketamine alone and subsequently died of exposure.

These publications did, however, contribute to growing recreational use. Owing to such use, particularly low-doses as part of dance culture, ketamine was scheduled by the DEA in 1999 as a drug with significant abuse potential (but confirmed medical utility as a Schedule III compound).

Modern Uses of Ketamine Treatments in Psychiatry

As described above, the first appearance of the modern intravenous ketamine protocol was a small randomized controlled trial in the year 2000, which tested a 40-minute infusion of 0.5 mg ketamine per kg of body weight in 7 depressed patients in a double-blind fashion. A rapid, dramatic improvement in depressive symptoms was shown.

This experiment and its dosing was based on the authors’ years of research on the use of ketamine as a tool to model psychosis. In this framework, the subjective effects of ketamine are described as psychotomimetic — that is, mimics of psychosis — rather than psychedelic.

These promising results were confirmed by dozens of subsequent randomized controlled trials, reigniting interest in psychiatric uses of ketamine. In the past several years, public interest has also exploded, resulting in ketamine appearing on the cover of Time Magazine in 2017 as a breakthrough treatment of depression. Michael Pollan’s 2018 international bestseller “How to Change Your Mind” also largely reignited public interest in psychedelics.

Extensive investments in research and development also recently led to the first FDA approval for ketamine for a psychiatric indication in 2019 with the approval of an intranasal formulation of the s-enantiomer of ketamine, Spravato™. Spravato has been approved for treatment-resistant depression in conjunction with a regular oral antidepressant. As with the intravenous protocol, the psychoactive effects of Spavato™ are typically framed as unwanted treatment side-effects that mimic psychosis.

Research on the psychedelic use of ketamine has also continued throughout the United States and abroad, though at a much smaller scale than the biomedical research. As discussed later, this paradigm differs significantly from the biomedical body of research in several ways.

The psychoactive effects of ketamine are seen as potentially therapeutic, not treatment side effects.

Dosages and routes of administration, including subcutaneous injections and sublingual lozenges, differ significantly from the model of Spravato and typical intravenous ketamine protocols. They are typically tailored to individual patients to a much higher degree than the biomedical model.

The psychedelic model aims typically to create lasting change with brief treatment courses in conjunction with psychotherapy, rather than with long-term repeated dosing of ketamine.

Doctors are prescribing ketamine for the treatment of depression and other conditions. You can learn more from the Ketamine Advocacy Network and The Brain-Mind Institute of New England.

Psychotherapeutic Applications for Ketamine Treatment

Ketamine has a wide variety of treatment possibilities that are being explored in scientific trials. Ketamine sees potential benefits in treatment for: severe and refractory (treatment-resistant) depression, bipolar depression, ruminative suicidal ideation, obsessive-compulsive disorder (OCD), pain with depression, post-traumatic stress disorder (PTSD), substance use disorders (cocaine, opioids, alcohol), anxiety associated with death, anorexia, and chronic relational problems (personality disorders).


Ethical Guidelines for Ketamine Clinicians

Therapeutic use of ketamine has grown exponentially over recent years, thus creating a lot of gray areas in the mental health field. Dr. Bennett of the Kriya Institute has addressed the ethics of ketamine therapy and administration.

Clinical Trials now enrolling participants for Ketamine Treatment

Ketamine clinical trials might be some of the most common, psychedelic clinical trials found worldwide. As a result, there are too many to list here. However, we can point you in the right direction.

The best place to start is right here in our searchable trial directory. Clicking through will bring you to a compilation of 800+ ketamine studies around the world that are either recruiting, not yet recruiting, or completed.

Some clinical trial participants have volunteered to go public with their journey and talk about how ketamine-assisted psychotherapy helped them heal. The best way to learn about the potential of ketamine as medicine are the people who’ve used it to heal.

Ketamine Treatment Testimonials from Patients

  • “Recently I have had to face a very painful and difficult life experience and since my ketamine session a week and a half ago, I have felt significant emotional relief. It’s as if my mind and heart simply can’t go back to that old painful place. As a psychologist, meditator, and healer myself, I am familiar with many healing ways and to help myself through this challenge I have tried, psychotherapy, shamanic work, the medicine of friendship, mindfulness, and more, and nothing has been nearly as helpful nor as potent as my ketamine session.”
  • “I’m finally present for my family. I’m enjoying real quality time with them. Both at home and out on the town. It means everything to me to be with my family. Both physically & mentally. Especially when my ptsd often took me out of the room even if I was still there physically. In many cases I was just going through the motions. No longer.”
  • “If you suffer from PTSD and want to feel like yourself again? If you can’t remember what normal reactions to triggers felt like? If you’re paralyzed in any aspect of your life? Going out? Being social? Relationships, friendships or work environments? I’m writing this review today to tell you that you CAN feel normal again. No matter how impossible that seems based on years of nothing working for you. I’m living proof that being at home in your own skin is possible again.”
  • “It’s just been transformative,” Lynn told me. She calls Wolfson and Andries “miracle workers.” Michael is not, by his own admission, cured. He still has bad days, and he still needs occasional ketamine “booster” sessions to keep his mood up. But he credits ketamine with bringing him back to life and, ultimately, with saving his relationship with his wife. “It’s probably the only reason I’m still married,” he says.​
  • “It was indeed transformational,” Mathis said. “Nothing less than transformational."
  • Mathis described the experience as taking him out of his own ego, a “tilt(ing) of the prism on how I see things. It allowed me to have a detached, philosophical view on all things — me, my place in the world, my relationships.” This helps him make sense of his emotions “in a way that can be extremely difficult and sometimes even impossible to do when I am inside of myself,” referring to his default, day-to-day mental state.​

“First let me say that I have tried over 10 different SSRI/NDRI’s over the last 20+ years, talk therapy, cognitive therapy, hypnotherapy, acupuncture, wellness centers, etc. Nothing has helped me get my severe “treatment resistant” depression in check. NOTHING. I was so exhausted from trying something new and it not working. I had pretty much given up any hope that I’d be able to lead a “normal” life. Then a dear friend of mine told me that she had done ketamine infusion therapy and that it changed her life. She is in the same boat as me, except she also suffers from anxiety. I do not. I knew that this type of therapy was going to be expensive as insurance does not cover it. But I knew that it could be the most important investment I would make in my life. And it WAS. These infusions changed my life! They legit SAVED my life. I honestly had very little hope going into this, but I came out a changed person who got her life back. I now know what it feels like to live a normal life. I am super happy, the dark cloud that had been following me around is gone, the sky is bluer, the grass is greener and I have so much gratitude now. I have gone from a negative Nancy to a positive, grateful, blessed person. I was shocked at how quickly this treatment worked. It did take me until around my 4th infusion to finally feel the effects, so I extended my treatment by 3 more sessions. So glad I did. This has literally been the best thing I could have ever done for myself…”

Psychotherapy Testimonials from Therapists

So what do therapists have to say? The picture wouldn’t be complete without hearing from a therapist’s perspective, especially in regards to a not yet legal treatment.​

  • “Many clients find that ketamine experiences, delivered within a psychotherapeutic setting, foster greater insights into themselves and their interpersonal relationships, and enhance their overall sense of well-being.”- Polaris Co-Founders​
“Recent data suggest that ketamine, given intravenously, might be the most important breakthrough in antidepressant treatment in decades. First and most important, several studies demonstrate that ketamine reduces depression within six hours, with effects that are equal to or greater than the effects of six weeks of treatment with other antidepressant medications. Second, ketamine’s effects have been noted in people with treatment-resistant depression. This promises a new option for people with some of the most disabling and chronic forms of depression, whether classified as major depressive disorder or bipolar depression. Third, it appears that one of the earliest effects of the drug is a profound reduction in suicidal thoughts.”- Tom Insel, MD, former Provost of Harvard University.

Ketamine-Assisted Psychotherapy Training Opportunities

Want to get more familiar with ketamine, and ketamine psychotherapy? We’re offering our FREE “Little Book of Psychedelic Substances” that includes ketamine and esketamine information. The book also includes a wide array of other psychedelics currently being vetted for psychotherapeutic use.

If you are a clinician and would like training to offer ketamine in your practice, take one of our foundational courses or clinician training programs from leading ketamine experts.​

Published by Psychedelic.Support

Psychedelic.Support offers evidence-based information to promote psychedelic education and safety. The content is developed by health professionals and researchers, and peer reviewed for accuracy by members of the Psychedelic Support Network and Allison Feduccia, PhD.

*From the article (including linked sources) here :
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Navigating New York City’s Ketamine Clinics

by Sophie Saint Thomas | LUCID NEWS | 24 Nov 2021

Walking into Nushama, a new psychedelic wellness center in Manhattan, feels like entering a boutique hotel. There’s calming pastel art by Navina Khatib on the walls, murals and silk flowers, and at the recent opening of its new office, a harpist plays. The treatment rooms have pristine white zero-gravity chairs. Copies of books such as How to Change Your Mind by Michael Pollan sit on chic minimalist bookshelves.

At first glance, one wouldn’t think people coping with debilitating conditions such as treatment-resistant depression and eating disorders are here for therapy. But not just any therapy ⁠— ketamine-assisted psychotherapy, one of the few legal psychedelic medicines currently available and sanctioned by medical institutions.

Ketamine is FDA-approved in the form of the nasal spray Spravato (esketamine), for treatment-resistant depression. While generic, or “racemic” ketamine – the form that is used for intravenous infusions – is a mixture of two mirror-image molecules, “R” and “S” ketamine, the FDA-approved nasal spray, Spravato (esketamine) only contains the “S” molecule.

Most of the research on ketamine in clinical trials for mental health is done using off-label ketamine infusions, which tend to occur at ketamine clinics. As a result, clinics, which look like everything from a med spa to an art gallery, are cropping up all over the country, including progressive and wealthy cities such as New York.

Ketamine’s backstory is wild enough for a Hollywood thriller. It first gained fame on the battlefields of Vietnam, where it proved a safe and effective anesthetic. Ketamine is not considered a classic psychedelic, but rather a dissociative and is still regularly used in anesthesia. If you’ve had surgery recently, there’s a good chance that you’ve had ketamine.

Any therapeutic use besides the nasal spray is done off-label, meaning that it’s prescribed for mental health conditions outside of FDA-approved anesthetic purposes. This approach gives doctors the discretion to treat patients who may not meet DSM criteria, as stated in the diagnostic tool published by the American Psychiatric Association, as well as to work with their in-house psychiatrists. But it also means that the therapeutic approach the doctors take is determined by the clinics offering the ketamine.

“There’s a lot of places out there that look only at the medical sliver of it, which is they give you your ketamine, and you’re on your way. We believe that people need to be supported in the preparation, during their infusion, and after with integration,” says Jay Godfrey, co-founder of Nushama.

Increasingly, clinics seek to provide the experience of a wellness center, and that’s how they want to be addressed. “We provide an experience including preparation for one’s journey,” says Godfrey. “That includes intention setting, breathwork, and helping the participant become at ease in an environment that feels like a dreamscape itself.”

Nushama is even shying away from medical terminology, including the label “patient.”

Godfrey says, “We don’t want people to feel like patients, and we don’t want them to feel sick. We don’t even want to call them patients. We want to call them participants or journeyers.”

Nushama provides both intravenous infusions as intramuscular ketamine injections. Field Trip, another New York City-based provider of therapeutic ketamine, only does intramuscular injections, which they say allows for a more psychedelic experience.

“We do ketamine intramuscularly as opposed to IV, and that’s important because we want people to have a psychedelic experience,” says executive chairman and co-founder of Field Trip, Ronan Levy. “We want people to be able to have the visions and revisit past traumas, past experiences, whatever the case may be. So that’s why we use intramuscular because it’s a more immediate onset to a more intense experience, which we want to encourage.”

The Field Trip location might as well be a secret ski lodge, covered in lush murals and greenery. Field Trip offers one introductory session for $750, followed by additional infusions for $750 and an integration session for $250. Six treatments cost $4,500, or $6,000 when included with integration sessions, a common price range for the high end treatment centers

It’s hard to get insurance to reimburse for the cost of these treatments. For instance, according to Nushama, insurance can cover infusions if there’s a dual diagnosis that includes a pain condition. However, insurance will not cover if a diagnosis is only for a mood disorder like depression, PTSD, or addiction on its own. In these scenarios, six ketamine infusions cost $4,000 and include a seventh booster session which is usually administered as needed.

Mindbloom, another increasingly popular New York clinic, takes a different approach that is meant to tackle the affordability issue. They only provide service through oral ketamine tablets that are taken at home. “Mindbloom’s ketamine treatment is convenient, affordable, and accessible, all from the comfort of your own home. We’ve helped reduce the cost of this treatment by 75% over in-person clinic experiences,” says board-certified psychiatrist and addiction psychiatrist Dr. Leonardo Vando of Mindbloom.

While taking ketamine at home removes the benefit of having a medical practitioner supervising the experience, the cost is significantly lower: at $1,068 for six sessions that take place over the course of three months. Each session at New York Ketamine Infusions, which does not include psychological support services, is also therefore less expensive, costing $475, bringing an initial six sessions to $2,850.

Not long after Vietnam, people began to figure out that taking ketamine is fun, and by the 90s its reputation shifted to that of a club drug taken by bright-haired party animals at raves. While popular as a recreational drug in some circles, ketamine’s burgeoning reputation as a mental health treatment is giving it a much-needed makeover. Side effects of ketamine include euphoria, dissociation, and other psychedelic experiences. While high doses of ketamine bring on these states, some doctors say that these outcomes are unnecessary side effects, and that the benefits of the medicine actually begin only after the infusion is finished.

“It’s not about the infusion, it’s not about the ketamine experience,” says Dr. Glen Brooks, founder of New York Ketamine Infusions. “What ketamine is doing is growing dendrites and synapses, which is totally independent of what goes on in the infusion, and doesn’t even begin for ten to twelve hours after the infusion.”

New York Ketamine Infusions has private patient rooms and friendly nurses on staff, but looks much more like a medical center than a spa. Patients who choose to include therapy as part of their treatment will work with their own outside therapist, rather than do integration with mental health therapists on site.

Since the emergence of ketamine as a mental health treatment, providers have been divided on best methods of administration. Some insist that the safest way to treat mental health with ketamine is to provide psychological or psychiatric care alongside the treatments, while others have made the case for administering the drug without trained mental health specialists on the treatment team. Providing onsite support from mental health specialists during the infusions and integration services afterwards increases the cost of these services, which is why some providers do not offer it.

Dr. Brooks of New York Ketamine Infusions says his center does not provide onsite integration services from mental health professionals because he believes that ketamine’s benefits come from its physiological rather than its psychological effects. He believes that it is also not necessary to have a psychedelic experience to find healing with ketamine.

“It’s not necessary for someone to go into a hallucinogenic experience to achieve [the results]. It can be very dangerous pushing some people into these dissociative or flashback experiences,” says Brooks. “Ketamine grows dendrites and synapses. It restores communication between mood center neurons.”

The ketamine therapy centers interviewed for this article describe an intake process that includes mental and physical exams to ensure that a patient doesn’t have any contraindications to the treatment. To ensure that patients have a positive experience, some providers offer check-ins and integration work to maintain safety and help patients chart their psychological process.

"For Nushama, that means taking inspiration from practices developed by psychedelic therapists both underground and by participating in clinical trials," says Nushama’s Jay Godfrey.

“The treatment itself is about an hour. But we have about 15 to 20 minutes prior for intention setting, then 15 or 20 minutes after of just coming back to our consciousness. Then after that, another 15 minutes of integration talk therapy,” says Godfrey “If they’re still not ready to go on the subway, which, I don’t blame them, they can hang out and have a cup of tea, have some snacks, sit in our chill-out lounge and spend the day.”

Field Trip also takes this approach, providing a therapist in the room for the duration of a patient’s ketamine experience. At New York Ketamine Infusions, however, while nurses check in, the patient has much less direct support.

The missions of the major players in the New York ketamine scene are the same — to help people function and feel better. But with no standard guidelines it’s up to each provider to determine best practices and ethics of care and up to the patients (or journeyers) to do their research and determine what’s right for them.

“I think we’re all part of a broader solution. Mental health is broken, and I think we’re all brothers and sisters in this fight,” Godfrey says.

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Ketamine may relieve depression by repairing damaged brain circuits

by Jon Hamilton | NPR | April 11, 2019

The anesthetic ketamine can relieve depression in hours and keep it at bay for a week or more. Now scientists have found hints about how ketamine works in the brain.

In mice, the drug appears to quickly improve the functioning of certain brain circuits involved in mood. Then, hours later, it begins to restore faulty connections between cells in these circuits.

The finding comes after the Food and Drug Administration in March approved Spravato, a nasal spray that is the first antidepressant based on ketamine.

The anesthetic version of ketamine has already been used to treat thousands of people with depression. But scientists have known relatively little about how ketamine and similar drugs affect brain circuits.

The study offers "a substantial breakthrough" in scientists' understanding, says Anna Beyeler, a neuroscientist at INSERM, the French equivalent of the National Institutes of Health, who wasn't involved in the research. But there are still many remaining questions, she says.

Research has found evidence that ketamine was creating new synapses, the connections between brain cells. But the new study appears to add important details about how and when these new synapses affect brain circuits, says Ronald Duman, a professor of psychiatry and neuroscience at Yale University.

Studying ketamine's antidepressant effects in mice presented a challenge. "There's probably no such thing as a depressed mouse," says Dr. Conor Liston, a neuroscientist and psychiatrist at Weill Cornell Medicine in New York and an author of the Science paper.

Liston and his team of scientists gave mice a stress hormone that caused them to act depressed. For example, the animals lost interest in favorite activities like eating sugar and exploring a maze.

Then the team used a special laser microscope to study the animals' brains. The researchers were looking for changes to synapses.

"Stress is associated with a loss of synapses in this region of the brain that we think is important in depression," Liston says. "And sure enough, the stressed-out mice lost a lot of synapses."

Next, the scientists gave the animals a dose of ketamine. And Liston says that's when they noticed something surprising. "Ketamine was actually restoring many of the exact same synapses in their exact same configuration that existed before the animal was exposed to chronic stress," he says.

In other words, the drug seemed to be repairing brain circuits that had been damaged by stress.

That finding suggested one way that ketamine could be relieving depression in people. But it didn't explain how ketamine could work so quickly.

Was the drug really creating all these new synapses in just a couple of hours?

To find out, the team used a technology that makes living brain cells glow under a microscope. "You can kind of imagine Van Gogh's Starry Night," Liston says. "The brain cells light up when they become active and become dimmer when they become inactive."

That allowed the team to identify brain circuits by looking for groups of brain cells that lit up together.

And that's when the scientists got another surprise.

After the mice got ketamine, it took less than six hours for the brain circuits damaged by stress to begin working better. The mice also stopped acting depressed in this time period.

But both of these changes took place long before the drug was able to restore many synapses.

"It wasn't until 12 hours after ketamine treatment that we really saw a big increase in the formation of new connections between neurons," Liston says.

The research suggests that ketamine triggers a two-step process that relieves depression.

First, the drug somehow coaxes faulty brain circuits to function better temporarily. Then it provides a longer-term fix by restoring the synaptic connections between cells in a circuit.

"One possibility is that the synapses are restored spontaneously once the cells in a circuit begin firing in a synchronized fashion," says INSERM'S Beyeler, who wrote a commentary accompanying the study.

"The new study suggests not only how ketamine works but also why its effects typically wear off after a few days or weeks", she says. "What we can imagine is that ketamine always has this short-term antidepressant effect, but then if the synaptic changes are not maintained, you will have relapse, and if that's true," she says, "scientists' next challenge is to find a way to maintain the brain circuits that ketamine has restored."


For individuals with substance use disorders, ketamine treatment led to short-term reductions in
craving, consumption and withdrawal symptoms.

Ketamine Therapy swiftly reduces depression, suicidal thoughts

University of Exeter | Neuroscience News | 24 Dec 2021

Ketamine reduces symptoms of depression and suicidal thoughts within four hours of a single treatment, and the effects last for up to two weeks. Additional treatments may prolong the effects, researchers say.

Ketamine therapy has a swift short-term effect on reducing symptoms of depression and suicidal thoughts, according to a review of all the available evidence.

A systematic review led by the University of Exeter and funded by the Medical Research Council analyzed evidence from 83 published research papers. The strongest evidence emerged around the use of ketamine to treat both major depression and bipolar depression. Symptoms were reduced as swiftly as one to four hours after a single treatment, and lasted up to two weeks. Some evidence suggested that repeated treatment may prolong the effects, however more high-quality research is needed to determine by how long.

Similarly, single or multiple doses of ketamine resulted in moderate to large reductions in suicidal thoughts. This improvement was seen as early as four hours following ketamine treatment and lasted on average three days, and up to a week.

Lead author Merve Mollaahmetoglu, of the University of Exeter, said: “Our research is the most comprehensive review of the growing body of evidence on the therapeutic effects of ketamine to date. Our findings suggest that ketamine may be useful in providing rapid relief from depression and suicidal thoughts, creating a window of opportunity for further therapeutic interventions to be effective. It’s important to note that this review examined ketamine administration in carefully controlled clinical settings where any risks of ketamine can be safely managed."

For other psychiatric disorders, including anxiety disorders, post-traumatic stress disorders and obsessive-compulsive disorders, there is early evidence to suggest the potential benefit of ketamine treatment. Moreover, for individuals with substance use disorders, ketamine treatment led to short-term reductions in craving, consumption and withdrawal symptoms.

Published in the British Journal of Psychiatry Open, the review synthesizes the evidence from a growing field of research into the potential benefits of ketamine for conditions for which there are limited effective treatments. The review included 33 systematic reviews, 29 randomized control trials, and 21 observational studies.

Ketamine’s effects on depressive symptoms and suicidal thoughts are supported by numerous systematic reviews and meta-analyses, which provide an exhaustive overview of research in a given topic. These are considered to have the highest strength of evidence compared to other types of studies, increasing confidence in the evidence for ketamine’s antidepressant and anti-suicidal effects.

However, ketamine’s therapeutic effects for psychiatric conditions other than depression and suicidal thoughts are based on small number of studies that did not randomize people into different treatment arms. These effects require replication in larger randomized placebo-controlled trials, which are considered as gold standard.

The authors noted a number of difficulties in the research field, which they recommend that future studies should seek to address. One factor is the bias created because participants realize they have been given ketamine, rather than a saline solution. Senior author Professor Celia Morgan, of the University of Exeter, said:

“We’re finding that ketamine may have promising benefits for conditions that are notoriously hard to treat in clinic. We now need bigger and better-designed trials to test these benefits. For example, due to ketamine’s unique subjective effects participants may be able to tell whether they have been given ketamine or a saline solution as the placebo, potentially creating an expectation about the effects of the drug. This effect may be better controlled by having active placebo-controlled trials, where the control group receives another drug with psychoactive properties.”

A number of questions remain unanswered in the research field, including the optimal dose, route of administration and number of doses of ketamine treatment. There is also a need for further research on the added and interactive benefit of psychotherapy alongside ketamine treatment.

Additionally, the importance of ketamine’s acute subjective effects in its therapeutic benefits has not been fully explored. More research is also needed on how to optimize participants’ preparation for ketamine treatment and the setting in which ketamine treatment is delivered.

The research involved collaboration with the University of British Columbia, and received support from the Society for the Study of Addiction.​

About this psychopharmacology and depression research news

Author: Press Office
Source: University of Exeter

Original Research: Open access.
Ketamine for the treatment of mental health and substance use disorders: a comprehensive systematic review” by Celia Morgan et al. British Journal of Psychiatry

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Ketamine Therapy is going mainstream. Are we ready?

The mind-altering drug has been shown to help people suffering from anxiety and depression. But how it helps, who it will serve, and who will profit are open questions.

by Emily Witt | The New Yorker | 29 Dec 2021

In the fall of 1972, a psychiatrist named Salvador Roquet travelled from his home in Mexico City to the Maryland Psychiatric Research Center, an institution largely funded by the United States government, to give a presentation on an ongoing experiment. For several years, Roquet had been running a series of group-therapy sessions: over the course of eight or nine hours, his staff would administer psilocybin mushrooms, morning-glory seeds, peyote cacti, and the herb datura to small groups of patients. He would then orchestrate what he called a “sensory overload show,” with lights, sounds, and images from violent or erotic movies. The idea was to push the patients through an extreme experience to a psycho-spiritual rebirth. One of the participants, an American psychology professor, described the session as a “descent into hell.” But Roquet wanted to give his patients smooth landings, and so, eventually, he added a common hospital anesthetic called ketamine hydrochloride. He found that, given as the other drugs were wearing off, it alleviated the anxiety brought on by these punishing ordeals.

Clinicians at the Maryland Psychiatric Research Center had been studying LSD and other psychedelics since the early nineteen-fifties, beginning at a related institution, the Spring Grove Hospital Center. But ketamine was new: it was first synthesized in 1962, by a researcher named Calvin Stevens, who did consulting work for the pharmaceutical company Parke-Davis. (Stevens had been looking for a less volatile alternative to phencyclidine, better known as PCP.) Two years later, a doctor named Edward Domino conducted the first human trials of ketamine, with men incarcerated at Jackson State Prison, in Michigan, serving as his subjects. At higher doses, Domino noticed, ketamine knocked people out, but at lower ones it produced odd psychoactive effects on otherwise lucid patients. Parke-Davis wanted to avoid characterizing the drug as psychedelic, and Domino’s wife suggested the term “dissociative anesthetic” to describe the way it seemed to separate the mind from the body even as the mind retained consciousness. The F.D.A. approved ketamine as an anesthetic in 1970, and Parke-Davis began marketing it under the brand name Ketalar. It was widely used by the U.S. military during the Vietnam War, and remains a standard anesthetic in emergency rooms around the world.

Roquet found other uses for it. After his lecture in Maryland, he offered experiential training to the clinicians there. “I was introduced to the strangest psychoactive substance I have ever experienced in the 50 years of my consciousness research,” the psychiatrist Stanislav Grof recalls in “The Ketamine Papers,” a book edited by the psychiatrist Phil Wolfson and the researcher Glenn Hartelius. Grof subsequently experimented with ketamine personally, and found himself inhabiting the perspectives of a wet towel hanging on a railing overlooking the ocean, petroleum filling the cavities of the earth, and the prisms of a diamond. “In one of my ketamine sessions, I became a tadpole undergoing a metamorphosis into a frog, and in another one, a giant silverback gorilla claiming his territory,” Grof writes.

When the training took place, psychedelic research was already coming under legal threat. In 1968, the U.S. government outlawed possession of LSD; Richard Nixon announced a war on drugs three years later. In 1974, Roquet was jailed for several months in Mexico, and subsequently cut back on his group sessions. (He died in 1995.) The Maryland Psychiatric Research Center ended its psychedelic research in the mid-seventies, amid broader upheaval at the center.

But ketamine remained medically legal, and countercultural psychiatrists continued to experiment with it. In the eighties, the drug’s best-known enthusiast was John C. Lilly, a doctor and psychoanalyst perhaps most famous for using sensory-deprivation tanks and dabbling in human-dolphin communication. Lilly became addicted to ketamine: a researcher who crossed paths with him at the Esalen Institute, a retreat in Northern California, recalled Lilly spending most of his time in his Volkswagen minibus, where he was evidently injecting himself multiple times a day. (Lilly said that he stopped using the drug in his early sixties, on the orders of extraterrestrials, but he resumed taking it later in life. He died in 2001, at eighty-six.) During these years, ketamine also became a popular dance-floor drug. Partyers generally snorted it, at lower doses, for a less drastic and more interactive high, experiencing distortions of perception that have been described as “scenery slicing” and “environmental cubism.” Among clubgoers, taking so much that you became unaware of your surroundings—experiencing a “K-hole”—was typically considered a scary mistake. The drug became especially fashionable among ravers in the nineties, and, at the end of that decade, the U.S. government made ketamine a Schedule III substance, putting it on the same regulatory footing as steroids and Tylenol with codeine.

Meanwhile, clinicians at Yale, who were using the drug to mimic the symptoms of schizophrenia, noticed that ketamine improved people’s moods. Researchers began studying it as a treatment for depression, and, in 2006, the National Institute of Mental Health concluded that a single intravenous dose of ketamine had rapid antidepressant effects. Around three hundred clinical trials have since been held; the broad consensus is that ketamine relieves symptoms of depression for a period that can last days or weeks, during which time talk therapy often proves more effective than normal. Ketamine is what’s called a “dirty drug,” meaning that it acts on different parts of the brain at once, and there are several theories about how it works against depression, but most focus on its effects on certain receptors in the brain, and on the neurotransmitter glutamate. (One theory holds that ketamine modulates levels of a protein that can generate new neurons.) By 2010, doctors were recommending its off-label use to acutely suicidal patients, and ketamine clinics began opening around the country. These days, the research and debate surrounding ketamine are less concerned with whether it can treat depression than with how it works, which delivery method makes it most effective, and how drug companies and health-care providers might best profit off a substance whose patent expired in the nineteen-eighties.

One of the first clinics, New York Ketamine Infusions, was opened by Glen Brooks, a Harvard-trained anesthesiologist, in 2012. Brooks sometimes wears a white lab coat, and practices in an ordinary-looking doctor’s office, where he keeps jars of FireBall candies on his desk. (He used to sublet space from a podiatrist.) He’d been a physician for more than thirty years when a relative’s drug problems prompted him to pursue addiction medicine. After just a few months, he concluded that the field was hopeless when it came to addressing the childhood traumas that lead people to self-medicate. He read the early research on ketamine as a treatment for mood disorders and saw not only reason for optimism but a business opportunity.

Brooks administers ketamine by I.V., at subanesthetic doses, and only some of his patients have dissociative experiences. “There’s nothing therapeutic going on when they’re here,” he told me, when I visited him at his clinic on a rainy Sunday this past spring. Patients hooked up to I.V. drips were undergoing treatment in dimly lit rooms. “We’re growing dendrites and synapses,” he said. Brooks encourages his patients to bring a friend or listen to a podcast to distract themselves from ketamine’s psychoactive effects. He said that what patients happen to think about during their sessions doesn’t really matter.

This approach, which is typical of the early ketamine clinics, contrasts with the countercultural attitude that prevailed among the drug’s advocates in the seventies and in a new tide of startups. Beginning roughly with the publication of “How to Change Your Mind,” a best-selling book by Michael Pollan, in 2018, psychedelic treatments for mental health have gone mainstream. Publicly traded companies, such as Compass Pathways and MindMed, have begun patenting variations on psychedelic treatments. Last fall, Peter Thiel was among the investors in a hundred-and-twenty-five-million-dollar round of funding for the biotech company atai Life Sciences, which principally focuses on the use of psychedelics in the treatment of mental illness; in June, the company went public, and was valued at more than three billion dollars.

In recent years, I have watched many people in my life quit antidepressants and start microdosing LSD and mushrooms, informed by exuberant news reports and the encouraging but not yet conclusive data documented in Pollan’s book and elsewhere. Most of these people are skeptical of the pharmaceutical industry and desperate to find more pleasure in life; for some, coding substance use as an antidepressant routine, and ingesting very tiny doses, seems to suit a sense of middle-class propriety and upwardly mobile productivity. (The doctors I spoke with by and large agreed that ketamine—which a number of outlets have proclaimed the “It Drug” of personal use during the pandemic—does not have the same clinically proven antidepressant effects when snorted.)

It is also, unlike LSD and mushrooms, legal for medical use throughout the U.S., and so provides the only avenue for American medical providers to generate revenue with psychedelic substances. (In 2019, the F.D.A. approved Spravato, from Johnson & Johnson, which contains one of the two molecules in the original ketamine formulation, and which will allow the company to sell a more profitable, if not necessarily more effective, version of the drug.) Today, a self-referring depressive with several hundred dollars on hand who is not in the throes of active mania or psychosis can seek out a wide array of clinical treatments with the drug: a titrated dose given intravenously by an anesthesiologist at a retail clinic, a shot in the arm from a psychiatrist in private practice, an oral lozenge sent in the mail by a startup taking advantage of pandemic-era changes to the regulation of remote prescriptions. If you can get to the right city, and have sufficient funds, you can easily secure a legal, therapist-guided, mind-expanding trip at a clinic that advertises on Facebook and is funded by venture capital.

The New York office of Field Trip Health, which opened in August, 2020, is situated in the Kips Bay neighborhood of Manhattan. It occupies the entire eleventh floor of a building next to Baruch College, and has big windows and a wraparound terrace. The decorative touches are spa-like: white rugs, fiddle-leaf figs, electric candles inside glass-paned lanterns. The aesthetic seems based on the assumption that, when a company hopes to take a formerly taboo practice mainstream, a West Elm interior can go a long way.

When I visited, this past spring, Matt Emmer, Field Trip’s vice president of health-care practice, showed me around—he was wearing a floral button-down of the sort that I associate with tech-company business casual. Field Trip was founded, in April, 2019, by five Canadian entrepreneurs, four of whom previously founded a chain of cannabis-dispensing medical clinics. The company now operates ten ketamine clinics in Canada and the U.S., with plans to open several more in the near future. (Field Trip recently opened a clinic in Amsterdam that offers patients guided-therapy sessions with magic mushrooms.) The company has a research and development wing, Field Trip Discovery, which is devoted to the cultivation of psilocybin mushrooms and the development of psychedelic-inspired medicines; this work is being done at a laboratory at the University of the West Indies, in Mona, Jamaica, where the drug laws are relatively forgiving. Field Trip recently filed a patent for a molecule called FT-104, which, according to preclinical experiments, targets the same serotonin receptor as psilocybin, but has much briefer effects. A drug trip that lasts two hours offers a far more viable business model than one that lasts five or six.

Emmer walked me down a hallway where the sound of water burbled from a white-noise machine, and he told me that he took interior-design cues from nature (“something that’s universal”). In the reception area, I saw copies of “How to Change Your Mind” for sale alongside “Be Here Now,” by the psychedelic guru Ram Dass. But, for the most part, signs of the counterculture were muted. Emmer led me into a windowless room. On one wall was a mural of spider monkeys peeking through palm fronds. In a corner, there was a large, white leather, zero-gravity chair. I sat down, and, at Emmer’s invitation, pressed a button on a remote. The chair made a soothing hum and slowly tipped backward, ready to carry me across the threshold of consciousness in its arms. “It makes you feel as weightless as possible without going into space,” Emmer said.

Sitting where the therapist normally would, Emmer explained the process. A patient arrives and selects from a menu of guided meditations and light therapy as a way of easing in before her trip. Ketamine is then administered with one or two intramuscular shots—the mind-altering equivalent of a rocket launch. The patient puts on noise-cancelling headphones, a weighted blanket, and an eye mask, and turns inward, listening to a soundtrack of nonverbal music. (One playlist is mostly classical and another is electronic; the music is intentionally obscure, to avoid provoking personal associations.)

I pressed another button on the remote, and Emmer waited as my chair slowly returned to its upright position. After the ketamine subsides, he explained, the patient sits for a session of talk therapy. The entire round of treatment lasts between two and three hours. A lounge stocked with mandala coloring books and watercolors offers a restful place to come back to earth before going home. Like most ketamine clinics, Field Trip encourages an initial set of four to six infusions spaced out across two to four weeks, with boosters available on an as-needed basis thereafter. The first session costs seven hundred and fifty dollars and subsequent treatments cost a thousand. The patient is paying for the therapy more than the drug, which costs as little as seven dollars a dose.

Earlier this year, a thirty-five-year-old filmmaker I know signed up for ketamine-assisted therapy at Field Trip. She had been reading about psychedelics during the pandemic. She read the Pollan book and a memoir called “The Wild Kindness: A Psilocybin Odyssey.” She listened to a lot of podcasts. She had tried LSD and mushrooms before. On those trips, she felt expansive and connected to the cosmos; she looked at the clouds, which seemed to be moving backward, and at the moon, which appeared more three-dimensional than usual. She wanted to undergo other shifts in her perspective. She was experiencing a degree of anxiety and obsessive thinking—she takes antidepressants and has more than a decade of therapy in her past—but she did not believe that she had any urgent mental-health issues. “I’m actually in a good place in my life right now,” she told me, “and it’s more about wanting to take it to the next level.” She contacted an underground therapist about a supervised mushroom trip, but the waitlist was two years long. “This was the path of least resistance,” she explained to me, of Field Trip. “I literally typed something into Google.” She underwent two screenings with the clinic, the first of which focussed on what ketamine is and what it can offer, and the second of which, she told me, was “about making sure you’re not crazy or you’re not going to kill yourself afterward.”

Her first session was scheduled for June. I spoke to her later that week. The experience had been more intense than what she was expecting. Her intake sessions were conducted virtually, so the day of her trip was her first visit to the office. An employee showed her a chair with a kind of helmet that descends upon the sitter’s head and provides a choice of colored lights to set the mood for meditation. She saw a glass table with a tray underneath it, in which a self-propelled metal ball traced patterns in sand. “I felt like I was already tripping when I went in there,” she told me. She found the burbling water sounds from the white-noise machine unnerving.

They put her in a room with a jungle-themed mural at the end of a long hall. She lay down in the anti-gravity chair and waited for its slow, dental-office recline. A nurse took her blood pressure and then presented a syringe of ketamine in a bronze Tibetan bowl. “I had to stop myself from cracking up,” she said, “because I didn’t want to be laughing at them, but there was something about it that was so absurd.” After the shot, she put on her eye mask and waited. She thought of her poodle at home and told the therapist that she was worried about her, but she calmed down after remembering that her partner was coming home early from work that day and would take care of the dog. She was given a second shot, and images began rushing through her mind: indecipherable hieroglyphics, ancient calligraphy. She saw herself onstage at a Q. & A. for one of her films. She experienced a kind of consciousness without identity. She felt as if she were inside a cardboard box with only a small hole of light and she was tearing at the aperture to widen it. She lifted her eye mask and looked down at her hands, and thought, Oh, wow, I’m a human. But she couldn’t remember where or who she was. Then she was overwhelmed with nausea, which happens to a modest subset of people who inject ketamine. She cancelled her second session immediately afterward. “I still feel so out of sorts,” she told me.

But, a few weeks later, she was ready to return. At her second session, she received a lower dose, and the effects of the drug were milder. She saw a sea of waving Japanese maneki-neko cat figurines and tried to find her mother’s face among them. A day or two later, she began to have a recurring feeling that seemed new. “This new feeling was, What if it works out?” she told me. It was a hopeful, expansive feeling. Then, one day, it was gone. “I guess it’s worn off or something?” she said. “It’s funny how it’s something you can’t talk yourself into feeling.”

For the countercultural therapists who have been administering ketamine to their patients for years, the current boom is seen with bemusement and not a small amount of worry. Phil Wolfson, who co-edited “The Ketamine Papers,” first took ketamine in 1990, and began giving it to select patients twenty years later. (Prior to that, he had used MDMA in therapy, but stopped when the drug became a Schedule I substance, in 1985.) Now in his seventies, he has trained many psychotherapists in the use of ketamine, including several at Field Trip Health. In his own practice, he offers both psychotherapy with lozenges and more intense guided trips with intramuscular injections. He is fluent in the neuroscientific theories about how ketamine works but regards them as reductionist. “Everything causes neuroplasticity,” he told me. “Having great love, or climbing a mountain, or having a terrible tragedy—it all creates movement of dendrites”—the branched tips where neurons form pathways—“because movement of dendrites is an essential adaptive function. We change because of experience.” We were speaking on the day after the anniversary of Wolfson’s son’s death, more than thirty years ago, from leukemia, at the age of sixteen, which Wolfson honors each year with a memorial.

Wolfson, who has a corona of silver hair and whose New York accent has resisted decades of living in California, is not eager to categorize ketamine as an antidepressant. Change is not merely a chemical by-product, he told me, and diagnostic categories help only up to a point. He believes that ketamine’s particular power is in the way that it offers a “subjective time-out.” Unlike ayahuasca or mushrooms, which often produce visions that coalesce into narratives, ketamine usually gives a brief experience of the void. “Ketamine really makes no sense,” he said. “It’s not attached to subjective experiences—themes don’t occur, or, if they do, they might not be particularly psychological in nature. I’m not reformed by neuroplasticity; I’m reformed by having had a break from the obsessions of my mind.”

The most striking results from ketamine therapy do not involve people like my filmmaker friend, who has manageable anxiety, but those who are experiencing chronic, treatment-resistant depression. Zachary Rice, a twenty-eight-year-old TV writer, has seen a therapist since he was ten. At sixteen, he was diagnosed with clinical depression, and in his early twenties he was diagnosed with acute post-traumatic stress disorder and obsessive-compulsive disorder. He began taking antidepressants at eighteen; since then, he has been prescribed thirteen different medications and has attempted suicide. In March, 2020, as the pandemic started to spread, he became suicidal again. He spoke with his therapist and psychiatrist on the phone. Concerned that more medication wouldn’t help him quickly enough, they gave him two options: hospitalization or ketamine. “I basically only knew it as a gay party drug or a horse tranquilizer,” he said.

That call was on a Friday. The following Monday, Rice went to a clinic in Brooklyn Heights called Ember Health. Ember was started by an emergency-medicine physician named Nico Grundmann and his wife, Tiffany Franke, a strategy consultant, in 2018. Ember makes no reference to psychedelic experiences in its marketing materials, and, in conversation, Grundmann seemed wary of the term “psychedelic,” saying that it could scare some patients away. But the altered state of mind produced by ketamine is a fundamental aspect of the company’s approach to treatment, he said. The company’s office has rugs and sofas and herbal teas—“like a well-appointed home,” he told me. He said that Ember tries to take the most evidence-based approach, which is to administer ketamine by I.V. infusion, not intramuscular injection, at a dose of 0.5 to one milligram per kilogram of a patient’s weight. Ember does not offer psychotherapy in-house, but the company only accepts clients who are actively being treated by mental-health professionals.

Rice had never taken psychedelic drugs before—he’d always worried about how they would interact with his medications. On the intake questionnaire, he got a perfect score: severe depression. He recalls thinking, “If this doesn’t work, at least I get to try a cool drug and I know I won’t die, because I’m in a doctor’s office.”

Rice put on an eye mask and a pair of headphones and was hooked to an I.V. drip and a cardiac monitor. He was encouraged to think about a happy moment, so he thought of standing on the outer rim of Yosemite Valley and watching the sunset with his friends. “Then it was as if the lights dimmed in a movie theatre and reality went away,” he recalled. “I flew across the valley at five thousand miles an hour and smashed into Half Dome, then Half Dome exploded into the universe and I was floating in space.” A narrator coalesced, a kind of entity or guide, with a commanding yet comforting voice. (He sounded like Danny Glover, Rice said.) He asked Rice if he wanted to take a tour of his own brain. Rice proceeded to greet all the people who work in his brain, and then the tour moved on to the formative experiences in his life, including deeply traumatic ones that he considers the roots of his mental illness. He saw a mosaic of every person who loves him and has been important to him. “You don’t have to scare them anymore,” the narrator said. “You can be alive and it’s O.K. and it’s good.” It was the first time in twenty years, Rice said, that he’d had anything like a positive internal monologue. The tour concluded with an “interdimensional safari” where he watched elephants twirl until the safari car folded back onto itself and his brain merged with the driver’s. When Rice regained normal consciousness, he was laughing and crying.

He was given tea and wrote down what he’d seen. Then he took the elevator back down to the streets of Brooklyn. Outside, everyone was wearing masks, and a pigeon pooped on him. He walked into a park and looked at the birds, crying at their beauty. He went home and did chores he had put off for years. “It was literally like entering life for the first time,” he told me, comparing it to the process of color correction when making a film. “Ketamine color-corrected for my existence. I saw the world as it was, without this heavy gray mass.”

Rice did four sessions across ten days, and he has done monthly sessions ever since. Each session is distinct: sometimes, he gets no visions at all, and sometimes he feels like he is in a Windows 95 screensaver. “I’ve died in ketamine sessions,” he said. “I’ve met what I was meant to understand was God.” The sessions are five hundred dollars each, but sixty per cent of the cost is covered by his insurance. He can tell that the effect of a session is wearing off when daily tasks start to feel insurmountable, he said. “It’s not hyperbolic to say that ketamine saved my life,” he said. “That hour session was more transformative for my mental health than anything I’ve done in my twenty-plus years of therapy and medication.”

Field Trip, in contrast to Ember Health and New York Ketamine Infusions, seems to be interested in a broader customer base than those who are treatment-resistant. Ben Medrano, the New York clinic’s medical director, told me that he first tried ketamine and other psychedelic drugs as a raver in the nineteen-nineties, and that the spiritual benefits of such experiences should be extended to people who are uncomfortable sourcing drugs illicitly but could use a break from their ordinary mind. These benefits will never be easily verifiable in a laboratory or a double-blind study, he told me. “These are healing tools that access the potential of consciousness,” he said. “And, at the end of the day, we, as scientists, can’t talk about that much, because what do we say? We don’t even know where consciousness resides.”

If going to the doctor for a guided trip becomes as routine, for some, as getting Botox, there will surely be a bifurcated clinical scene: one for people who like hippie stuff and one for people who want nothing to do with it. In late June, I drove to the Catskills to watch a group of people receive training in ketamine-assisted psychotherapy at the Menla Institute, a Buddhist retreat center. There were a number of psychotherapists, but the group also included an E.R. physician, a military veteran who works to bring psychedelic-assisted therapy to fellow-veterans who have P.T.S.D., and an executive with a Miami-based startup called Nue Life.

Also in attendance was the psychiatrist Bessel van der Kolk, whose book “The Body Keeps the Score,” first published in 2014, frequently ranks among the ten best-selling books on Amazon. Van der Kolk told me about his experience working on the first studies of Prozac and Zoloft as treatments for P.T.S.D. “They weren’t bad,” he said, but they didn’t cure anyone, he noted, adding, “All you get now is drugs that by and large don’t work.” Van der Kolk had received an injection of ketamine from Wolfson a few years before. “I was blown into the universe,” he told me. “I had no mental experience—I lost my body, I lost my mind.” He emerged from his trip skeptical that ketamine could do anything, but his wife and collaborator, Licia Sky, noticed changes in him afterward. “Before, there was like this undercurrent of impatience, like this readiness to be agitated,” Sky, who was also at the training, told me. “That agitation got very quiet, but your power stayed,” she went on, turning to her husband. “That doesn’t mean that we don’t disagree about things. It means that there’s a level of urgency that’s gone.”

It was an exquisite day in Ulster County. The sky was a bright blue and the mountains were a lush and vivid green. The trainees gathered in a large, wood-beamed room, at the front of which stood a shimmering gong, flanked by a trio of Tibetan wall hangings. Wolfson had set up a small altar to one side, with a framed photograph of his son. It was the fourth day of the training. Half the workshop’s participants would be receiving injections, and the other half would watch over them. On the walls, large pieces of paper bore descriptions of the previous day’s trips. Among the phrases people had written down were “breath of God” and “saw ancestral stuff.” In a corner of the room, a woman prepared for her journey with some yoga asanas. Others filtered in from a vegetarian breakfast in the retreat center’s dining hall and settled onto mats and pillows laid out on the floor.

The session began with an invocation and the recitation of a poem by Rumi. An assistant brought out paper coffee cups labelled with the participants’ names: each contained a syringe with a dose of ketamine. For the next hour, I watched the therapists undergo their training. The trip sitters monitored them closely, occasionally taking notes or mirroring their movements. A sort of drumming-and-didgeridoo song played over speakers, followed by a track that prominently featured a rainstick. The woman who had been doing yoga flung her arms out wide and moved her body ecstatically. Toward the back of the room, a man began to sob, and an assistant came to Wolfson for advice. “We need to help him listen to the music,” Wolfson whispered.

After an hour, the group began to emerge from their trips. Wolfson took the microphone. “Relax into your being,” he said. “Find great peace, find your heart for yourself, find great compassion.” Assistants circulated with a tray of orange slices and the group began sharing what they had experienced. It was “not so much a seeing journey as a feeling journey,” one said. Another said that his experience in a prior session, with a lower dosage of orally ingested ketamine, had felt more beneficial—on the higher, intramuscular dose, he had gone to “fractal land, to the matrix, and being that far out you don’t do the work,” he said. A third person said, “Our inner children who are bereft long to be safe with their tears.” Van der Kolk, who had taken a moderate dose, of sixty milligrams, had been enamored with the soundtrack. “Every sound becomes a vision, every sound becomes a shape,” he said. Someone else said, “Well, what this weekend has done has given me a real appreciation of trance music.” The trainees then had lunch and attended a seminar about attachment theory.

I like hippie stuff, so when I decided to take a guided ketamine trip, I did so with Wolfson. Prior to my appointment, I completed questionnaires that evaluated my family history and whether I had experienced violence, trauma, or depression. In mid-June, I went to the lower Manhattan office of Gita Vaid, a psychiatrist and psychoanalyst in private practice who had also been at the training in the Catskills. There, Wolfson, Vaid, and I talked for an hour. I told them that I was struggling to recover from a bad experience the year before. I had taken some time off work, gone to therapy, and gone back on antidepressants for the first time in almost a decade, but I seemed unable to regain stability, or the sense of belonging that had once held me in the world. Then, Wolfson, drawing on our conversation, recited a personalized invocation to send me on my way. I lay down on a couch and Vaid put an injection in my arm.

My mind dissolved into a muted silence, as though I were in a warm, carpeted soundbooth. I had taken an initial dose of thirty-five milligrams, and no specific visions coalesced, but the soundbooth walls began to collapse, like the C.G.I. sand in “The Mummy,” and swirled into shifting shapes, blown around by gusts of a mysterious wind. It was like being immersed in a world of iron filings, drawn into patterns by a magnet in a dimly lit forge. Twelve minutes after the first shot, I was asked if I wanted the second injection, also of thirty-five milligrams. The question seemed to come from very far away, and I was surprised that I could articulate a response. Vaid lifted my sleeve and gave me another shot. Now, I was in a velvet painting; I was sinking into the carpet; I was under the canopy of a primeval forest, on its mossy floor, hidden under ferns. I wanted to sink deeper into the primordial nothing, but, in time, I became aware of my body again. Before taking the shot, I had been sad and worried. I emerged feeling calm and soothed. As psychoactive experiences go, it was five stars, truly enjoyable. All I could repeat, stupidly, as I regained awareness of my surroundings, was how “cool” it had been.

I’d done ketamine at parties before, and liked how it fragmented sensory input and seemed to dilate time; the experience of injecting it was far more intense. It was as if I had taken a different drug altogether. During the previous year, I had become increasingly skeptical of the enthusiasm for psychedelic drugs as a revolution for mental health. This may have involved some mild hypocrisy, since I have done psychedelics and have found that, in addition to being fun, they sometimes helped me gain perspective and process difficult experiences. I was uneasy about pinning messianic potential on any particular mind-altering thing, and I felt aware of the limits of what such substances could do. I also feared the warping effects of the profit motive. As I researched this article, I began getting Facebook ads for a controversial company called Mindbloom, which sends ketamine lozenges in the mail to be taken between scheduled video sessions with a trained guide. The ads include a quote from someone saying, of ketamine treatment, “Before I started, I felt like I had run up against a wall in therapy.”

Wolfson, the first time we spoke, told me, “There’s this huge population of chronically depressed people in a chronically depressing world that’s making more chronic depression.” In other words, the way we live is making us sick. The suicide rate in the U.S. has increased by nearly thirty per cent since 1999; from April 2020 to April 2021, a hundred thousand Americans have died of drug overdoses, many of them presumably medicating themselves out of the difficulties of ordinary consciousness. In “The Ketamine Papers,” Wolfson offers “a very partial list of antidepressants.” On his list: “anticonvulsants, stimulants, marijuana, exercise, meditation, hedonism, temporary satisfaction of cravings, elimination of cravings, oxytocin, sexuality, spiritual practice, money, love, children, activism, justice, a good job, respect, friendship, education, a good book, a bad book, and so on.”

Ketamine is generally considered safe when used at sufficient intervals, but, when snorted or injected daily for long periods of time, it can cause increased tolerance, cravings, withdrawal, and permanent urinary-tract and kidney damage. It may also affect long- and short-term memory. “You do see these sort of unique personalities that are inclined to it,” Ben Medrano, of Field Trip Health, told me, of the risks of ketamine addiction. “Like, John C. Lilly was an astrophysicist who studied dolphins.” But Medrano was insistent that it’s only “a subset of people who are prone to it.” The government classifies ketamine’s abuse potential as moderate to low. Still, the risk of overuse has long been acknowledged in underground circles. In “The Essential Psychedelic Guide,” published in 1994, the researcher D. M. Turner writes, “A fairly large percentage of those who try Ketamine will consume it non-stop until their supply is exhausted. I’ve seen this in friends I’ve known for many years who are regular psychedelic users and have never before had problems controlling their drug consumption.” Turner died in a bathtub on New Year’s Eve in 1996, apparently having drowned after injecting himself with ketamine.

Multiple doctors who conduct ketamine therapy assured me that they do not accept patients who are exhibiting drug-seeking behavior, and also told me that, at the pace of treatment practiced by responsible clinicians, there is minimal risk of dependency or of the urinary-tract infection known as ulcerative cystitis. But the pandemic had brought home to me some indelible lessons about the fragility of the mind. Wolfson was more willing than most of the physicians I met to acknowledge this fragility. “Anyone doing this work as a therapist will come across those folks who become too attached to a drug or drugs, who make broad mistakes, lose their relationships, even themselves,” he once wrote, in a consideration of Lilly, the ketamine user who lost his way. The best-known risk for people who dabble with psychedelic states is still, as Wolfson puts it, “the loss of the monitor that overrides and guides us through the labyrinth of life, as best as it can.”

Wolfson and Vaid told me that I could recover in the waiting room for as long as I needed, but I was impatient to return to the world. I stepped out onto the street into the late afternoon with a wobbliness familiar from years of leaving nightclubs after daybreak, my arms sore as if I had just gotten two COVID vaccines at once. The apartment buildings along University Place were vaguely changing sizes, so I walked across the street to a nail salon and used a pedicure as an excuse to sit in a chair for forty minutes and let my gaze go out of focus. By the time the polish was dry, I had returned to baseline. I had skipped lunch to avoid getting nauseated, so I found a place where I could eat dumplings. Then I met up with friends in the East Village, where the Friday-evening atmosphere in the streets had the uncorked chaos of a belated spring break.

The next day, I felt different. I did some things I had put off for a long time, and stopped obsessing over other things that had monopolized my thoughts for weeks or months. Perhaps I had been primed to feel this way by the research I had read, but my state of mind seemed only indirectly related to anything I’d seen on my ketamine trip, and entirely unrelated to any kind of therapy. It seemed physical in nature. My mind was working the way I often wish it did. I had, in the past, tried to achieve this state of mind through drinking caffeine, through not drinking caffeine, through exercise, sleep, meditation, antidepressants, healthy eating, Vitamin B12, magnesium, amphetamines, yoga. My mind had always seemed resistant to on-demand engineering. This new feeling was neither an afterglow nor a state of stimulation. It felt like stability. I didn’t want to drink alcohol, or even coffee, out of a fear that the feeling would abandon me; I dreaded being thrown back into my ordinary mind. The feeling lasted a little more than two weeks, and then it went away. The memory of what it had felt like lingered a bit longer, and then it went away, too.

Emily Witt is a staff writer at The New Yorker and the author of “Future Sex” and “Nollywood: The Making of a Film Empire.”

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Ketamine shots are powerful medicine for depression, doctor says

by Jimmy McCloskey | METRO | 9 Jan 2018

A doctor says she was astonished by how well ketamine helps patients suffering from depression.

Dr Kathleen Wong, who runs a clinic in Fayetteville, Ak, said business has absolutely exploded since she began prescribing ketamine to patients in June 2017. Dr Wong told the Springfield News-Leader:

"I'm floored by how powerful an agent it seems to be. After a few treatments, people transformed. People's symptoms get resolved, particularly suicidal ideation (ideas). They need less psychiatric medication, and their psychotherapy sessions become more productive."

While FDA-approved drugs for depression have a success rate of up to 40 percent, ketamine has succeeded on 70 per cent of her patients. "It begins working within minutes of being administered intravenously, and has a more potent effect each time it is given to a patient," Dr Wong said.

The drug, which is not FDA-approved for the treatment of mental disorders, works on patients who have exhausted traditional routes of treatment, including electric shock therapy.

Patients who take it are given a test dosage, over the course of a week, then several more infusions the following week if successful. After that, patients can generally go several months before requiring a further treatment. It is not available on insurance, meaning patients must pay for the treatments.

One of Dr Wong's patients, Gabrielle Idlet, said ketamine treatment transformed her life. She said the treatment left her able to complete simple tasks like holding a conversation or doing the housework for the first time in years. She described it as a pleasant, fascinating experience that allowed her to focus and feel energized and unusually stable. She was able to engage in conversations and navigate situations, unlike before.

Ketamine is a powerful anaesthetic most commonly used by veterinarians. It can also be used for surgery on humans, with dosages used for depression around one tenth to one twentieth the size of those given in the operating theater.


Could Ketamine help tackle Gambling Addiction?

by Alexander Beadle | Technology Networks | 6 Oct 2021

Recruitment is now underway for a first-of-its-kind study investigating the potential of ketamine to fight gambling addiction.

The new research will look to explore whether ketamine’s effect on human memory might be leveraged to break down the “superstitious thinking” that is common in gambling addiction, as well as lessen the general habit or compulsive urge to gamble.

Conducted by the biotechnology company Awakn Life Sciences, the study will be led by the internationally respected ketamine researcher Celia Morgan, a professor of psychopharmacology at the University of Exeter and Awakn’s head of ketamine-assisted psychotherapy for addiction.

The difference between behavioral addictions and drug addiction

While substance addiction and behavioral addictions may appear to be two sides of the same coin, each comes with its own set of complications that can complicate treatment.

“We know that the dopaminergic system is involved in both and we get the same kind of changes, but there’s not the effects of these substances on the brain as well [with behavioral addiction],” Morgan explained. “Drugs and alcohol actually change your brain function by the chemicals themselves. That doesn’t happen with behavioral addictions, but we do get similar brain changes in things like dopamine transmission.”

Perhaps because of the highly stigmatized nature of substance addictions in society, behavioral addictions such as gambling addiction have largely flown under the radar. Sex addiction and food addiction are not yet recognized by World Health Organization diagnostic criteria, and so they can be very difficult to recognize and treat. The prevalence of food, sex, and money at a societal level can also massively complicate the road to abstinence.

To add to this, gambling addiction specifically comes with its own set of behaviors that can be challenging to treat with psychotherapy alone.

“Something that we’re really interested in tackling in gambling addiction is a kind of superstitious thinking which we particularly think ketamine might work on, which is where gamblers come to associate certain cues and they’ve got to overlearn the association between a cue and winning. They enter into very superstitious behaviors, which is quite unique to gambling,” said Morgan.

First study examining ketamine for gambling addiction now recruiting

Ketamine’s effect on memory has already shown promise as a potential treatment avenue in tackling alcohol use disorder, with one study suggesting that ketamine may result in a meaningful reduction in drinking by rewriting the maladaptive reward memories that contribute to substance misuse and addiction. In a similar vein, the new Awakn study will look to see whether ketamine’s effects on memory might also benefit people with gambling addictions by altering how the brain handles the reward memories associated with past gambling.

“We are using one of the capacities of the ketamine which is to block a process of re-stabilization of memory. In the study that we’re doing, we’re going to reactivate gambling memories. We’ll be showing people, depending on what their modality of gambling is, a roulette wheel or slot machines or horses, and this reactivates the memory,” Morgan explained.

“Normally in memory, this means that this memory becomes active and you’re able to update it. Then it’s re-stabilized – saved again, in computer terms – and is laid down more strongly. If you give ketamine during this time of reactivation, what’s been found particularly in animals is that this can weaken the memory trace. That’s what we’re looking at in this study.”

The Awakn study has received approval from the relevant ethics committee and is now actively recruiting participants. Those taking part in the trial will have the strength of their maladaptive reward memories measured before undergoing a supervised ketamine infusion session. Importantly, the ketamine infusion session will not be accompanied by any kind of directed psychotherapy, so that the fundamental drug effects of the ketamine remain the central focus of the study. The strength of these reward memories will then be reassessed after the session, with additional follow-up assessments one week and one month after treatment to examine any longer-term changes that might occur.

“This isn’t a treatment study, that’s important to emphasize,” said Morgan. “This is just a study looking at mechanistic action. That is a subtle distinction, but it means it’s not a clinical trial.”

Changing how we think about addiction

Previously, to be considered as having an addiction, a patient would need to show prominent physical withdrawal symptoms such as shivering, vomiting, or insomnia. With substance addictions this was relatively straightforward, as the biological withdrawal symptoms associated with the lack of substance in a person’s system would normally produce some visible physical side effects. But now this school of thought is on the way out, and scientists tend to focus more on the impact a certain behavior may have on a person’s quality of life to determine whether they might have an addiction.

“Now we very much think what constitutes an addiction is the impacts, the use of something, whatever it is, be it a behavior or a drug has on your life and your relationships and your ability to function. That’s somewhat of a paradigm shift in the way we think about addiction and that has allowed people to start recognizing these addictions,” said Morgan.

Psychological therapy is not an effective treatment for all people struggling with addiction, but there are no pharmacological therapies approved for treating gambling addiction – a fact that is perhaps unsurprising given the past lack of recognition for this type of addiction. This new study is just one aspect of a wider research strategy from Awakn that aims to develop and deliver new proprietary therapeutics for both substance and behavioral addictions using psychedelic medicine.

“Hopefully, increasingly as we acknowledge the distress and the huge impact this has on people’s relationships, their work, their daily functioning, we will start to recognize these [behavioral addictions] as disorders that are worthy of treatment and healthcare. There’s a lot of stigma around them as well – particularly sex and food addiction,” Morgan said.

“I’m hopeful that we’ll be able to find some new treatments. I’m very pleased that Awakn has backed this approach.”


Alexander Beadle


New program brings ketamine-assisted psychotherapy to Canadian vets

by Justin Hampton | LUCID News | 9 Nov 2020

For many veterans of war, the battle continues even after they’ve returned home from combat. The Veterans Affairs Canada website estimates that up to 10% of their warzone veterans will suffer from PTSD or another mental health affliction, and are 14-19% more likely than the general Canadian population to commit suicide, according to their 2019 Veteran Sucide Report. While both medications and therapeutic interventions are available for this condition, they haven’t proven very effective.

To address this, the Canadian-based psychedelic mental health provider Field Trip Health Ltd. announced a partnership with Heroic Hearts, a nonprofit which pairs veterans with psychedelic therapy. Under the partnership, Heroic Hearts will educate veterans about the benefits of ketamine-assisted psychotherapy, and recommend them towards the ketamine treatments of Field Trip Basecamp, a Field Trip offshoot which delivers KAP+, or Ketamine-Assisted Psychotherapy-plus, to veterans and first responders.

Heroic Hearts founder and president Jessie Gould says the nonprofit’s mission is to “highlight the responsible players in this rapidly expanding field of psychedelic health and ensure all veterans are supported when they decide to participate in something like ketamine assisted therapy.” He praised Field Trip for having “made great efforts to work with us in supporting the veteran community in both Canada and the US.”

Much of the activity around psychedelic medicine and PTSD centers on MDMA, which is currently undergoing Phase III clinical trials in America through the Multidisciplinary Association of Psychedelic Studies. However, Field Trip Basecamp Director Adam Wright points to off-label studies of Ketamine for PTSD as well as treatment-resistant depression and major depressive disorder, and maintains that it can be just as helpful.

“With the promising results in PTSD, as well as the highly comorbid nature of PTSD and depression, we have developed a treatment stream that will specifically target military veterans,” says Wright.

People with PTSD often dissociate as a defense mechanism against dealing with overwhelming emotion or horrific memories, says Dr. Jessica Katzman, a psychologist and cofounder of Healing Realms, a ketamine-assisted psychotherapy practice in San Francisco.

“Ketamine can potentially reduce anxiety and hypervigilance, the driving forces behind dissociation, and may allow the individual to step back and explore what’s under the defensive layer,” says Katzman.

For now, Basecamp will offer this treatment exclusively to Canadian soldiers at their Field Trip Toronto facility, and assist in insurance and reimbursement options with participants.

In spite of the ketamine derivative Spravato’s availability in the US, the partnership cannot offer treatment or reimbursement for KAP+ treatment through the Veteran/s Administration health program at this time, says Gould.

“For many veterans, ketamine therapy can be cost-prohibitive without some form of subsidy. Unfortunately, the US Veterans Affairs has faltered on its promise to increase veteran access to ketamine options,” Gould says. “Since the Canadian VA has been more willing, we hope to use the Canadian model to guide and put more pressure on the US to adopt similar practices.”

Field Trip has already expressed its intention to open up psilocybin treatment clinics in Oregon following the passage of Proposition 109, which legalized licensed psilocybin-assisted therapy in that state. Field Trip currently runs clinics in New York, Chicago and Santa Monica.


We visited a clinic that offers 45-minute ketamine infusions for depression

by Erin Brodwin | Business Insider | 8 Nov 2017

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

XYZ Neurotherapies 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."

As with any treatment approach, 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."

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 psilocybin, which 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 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. "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. 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 UC 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 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."


Maximizing Ketamine's healing effects in treating depression*

by Erica Zelfand | Psychedelic Support | Aug 14 2019

Although the ideal way to use ketamine likely entails receiving the treatment in a safe and comfortable setting, in an unrushed atmosphere, with a supportive psychotherapist or counselor nearby (or just a phone call away), this is not always the experience that the ever-growing number of ketamine treatment facilities offer their patients.

Even when many of the therapeutic elements are stripped away, however, the drug can in and of itself still offer individuals significant relief from the symptoms of depression – including severe, debilitating, and otherwise treatment-resistant types of depression. And thankfully, there are some simple things that patients can do to empower themselves, return the center of healing into their own realms, and enhance the success of the ketamine treatments they receive – no matter what kind of doctor they see or what kind of facility they visit.

Here are some simple ways to get the most out of each and every ketamine treatment:

{1} Trust in the journey. As with any psychedelic-inducing experience, it’s important to let go, let the journey take you, and try to learn something from the experience. As a dissociative drug, furthermore, ketamine might help you feel like your problems are smaller, more manageable, or not as suffocating as they might feel otherwise. Whether you experience a full-blown mystical journey or just a welcomed feeling of distance between yourself and the depression, enjoy this opportunity to consider your life and its challenges from a new angle. Notice what it’s like not to feel engulfed by your problems. Appreciate the newfound space you feel that separates your core Self from the pain of your human existence. See what wisdom and lessons you might be able to glean.

Enjoy this opportunity to consider your life and its challenges from a new angle.

{2} Listen to music. Music is a powerful tool for enhancing relaxation and supporting the inward journey. Check out these wonderful playlists and download them onto your phone (or MP3 player, if you still have one). Wearing headphones will also help minimize the distractions you may hear from doors slamming elsewhere in the clinic, nurses talking in the hallway, or the buzzing sound coming from the medical machinery in the treatment room.

{3} Ignore your phone. Put your phone on airplane mode, turn off notifications, and minimize distractions. Futzing with a phone while on ketamine will not only pull you out of your healing journey, but it’s also likely to be outrageously annoying to try and operate an electronic device when you’re clumsy, confused, seeing double, and/or feeling that you’re floating in space above your own body! Trying to navigate the three-dimensional world while on ketamine is not only vexing, but it can also make some people feel anxious.

Many ketamine treatment clinics are located in medical office buildings with harsh fluorescent tube lights – the antithesis of a healing, relaxing, or journey-supportive environment.

{4} Bring an eye mask. Many ketamine treatment clinics are located in medical office buildings with harsh fluorescent tube lights – the antithesis of a healing, relaxing, or journey-supportive environment. An eye mask worn during sessions can help support your inward journey and make the treatment a restful, restorative experience.

{5} Wear layers or bring a blanket. Medical offices tend to be overly air conditioned, which can make for a chilly session. Keep in mind that you will be laying still for at least an hour during your infusion, so pack accordingly. Bringing cozy socks, a shawl, or even a blanket with you can help keep you comfortable during your infusions. Also keep in mind that when our temperature is regulated we tend to feel safer and more relaxed, factors that can only help enhance the treatment.

{6} Bring a friend. Ketamine is a powerful, dissociative drug. This means that as the ketamine levels build up in your bloodstream, you’ll likely feel disconnected from your body. It may be annoying to move, your coordination and reaction times may diminish, you might feel confused, and it could be difficult to communicate. It’s sadly for these reasons that ketamine is sometimes abused as a date-rape drug: the person under the influence of ketamine cannot sufficiently spring to action (or even awareness) to protect him- or herself. For this reason I recommend bringing a trusted friend or family member to each and every appointment and asking them to come into the room with you – but not to talk to you or otherwise distract you. If you want to be alone for the infusion, you could also have your chaperone sit in a spot where they can see the door of your treatment room and pop in every time the doctor or nurse enters your room. By having a trusted person watch over your body while you receive the treatment, you may be able to relax more fully into the experience. Having somebody in the room can also be handy for things like bundling you up with an extra blanket, turning off the lights, or holding your hand if you feel overwhelmed.

{7} Arrange for a ride home. Going to the toilet on your own may be enough of a challenge right after a ketamine infusion; driving or operating heavy machinery is an absolutely dangerous idea. Likewise, taking public transportation, especially if traveling alone, might be very overwhelming, and walking even a couple of blocks might be challenging and exhausting. This is where having that friend/chaperone can come in handy; you may want to ask them ahead of time to double as your chauffeur and ask them to see you all the way into your home. If you’re traveling solo, then a medical transportation company is likely the safest way to go.

{8} Take the rest of the day off. Most people feel out of it for the remainder of the day after a ketamine infusion and might even experience a worsening of their depressive symptoms. Give yourself a break and don’t schedule any obligations – even fun, social engagements – for the remainder of the day post infusion. Stocking the fridge ahead of time with ready-made meals, packets of instant miso soup, and other easy to prepare, nourishing foods is likewise a good idea, as is ignoring your e-mail inbox.

{9} You may feel worse before you feel better. Ketamine is often presented in a rosy light as a miracle switch in the brain that gets flipped and makes depression and anxiety go away. But some people find that their suicidal ideation and hopelessness actually worsen in the hours post infusion. If this happens to you, don’t despair; it will likely pass within a day. If you’re worried about hurting yourself, ask a friend, family member, or other trustworthy person to stay with you after your infusions.

Having a therapy session during, immediately following, or shortly after a ketamine infusion may lead to therapeutic breakthroughs that might otherwise never happen.

{10} Connect with a counselor in person or online. As explained above, the dissociative state created by ketamine offers a unique window of opportunity to dig into psychological traumas and emotional pains that might otherwise be too guarded or too painful to penetrate in normal, baseline consciousness. Having a therapy session during, immediately following, or shortly after a ketamine infusion may lead to therapeutic breakthroughs that might otherwise never happen [5]. Don’t have a therapist or integration counselor? An entire directory of providers who work in person and online can be found here.

{11} Keep taking your mood-supporting medications and supplements. An advantage ketamine has over other psychotropic medicines is that it tends to play quite well with most other medications and supplements. Whereas patients typically have to taper down off of antidepressants before they can participate in MDMA- or psilocybin-assisted psychotherapy, those undergoing ketamine treatments can typically continue taking their prescription drugs, mood-enhancing herbal formulas, and nutraceutical supplements as usual. Continuing with your daily medication/supplement regimen might also help stretch out the intervals between infusions, furthermore.

When meaningful psychedelic journeys and dissociated states are properly processed and integrated, however, they can stay with us for weeks, months, years, and even decades.

{12} Skip the –epams and –zolams (benzodiazepines). As calming as they can be, benzodiazepine drugs like alprazolam (Xanax), lorazepam (Ativan), and diazepam (Valium) can actually dampen the anti-depressive effects of ketamine. In other words: ketamine works better when taken away from these other drugs.

Natural anxiolytics like L-theanine, passionflower, kava kava, and Rescue Remedy, however, can typically be used without issue in conjunction with ketamine infusions. If you’re feeling anxious about your next infusion, talk to your naturopathic physician or other functional medicine provider about taking a supplemental dose of an anti-anxiety supplement in the days before or even the day of your ketamine treatment. (After all, having a panic attack on your way to a ketamine infusion somewhat defeats the purpose of getting the infusion.)

{13} Integrate. There are various theories on how ketamine helps with depression, most of which center around various receptor sites in the brain. Unfortunately, any such changes to brain chemistry are likely to be merely transient. When meaningful psychedelic journeys and dissociated states are properly processed and integrated, however, they can stay with us for weeks, months, years, and even decades. So take the time to integrate and honor what came up during your infusion. Journal about it, record yourself talking about it, make artwork, talk to a friend, join a psychedelic integration circle, connect with a therapist or integration counselor, and do what you feel will help you weave the healing parts of your journey into your day-to-day life.

Remember: the drug is but a part of the medicine.

*From the article here :