Blog

Why Psychedelic Psychotherapy?

It provides a new experience of yourself and enables you to revise your view of yourself, your relationships and your world view.

It tends to create connection by reducing self-involvement and leads to time-outs from usual concerns and obsessions.

It makes for a larger, more spacious sense of who you are and your place in the world; towards equanimity and letting go.

It is entertaining, unusual and an out of time/space experience, facilitating your world view of this precious life and how you wish to lead it with awareness of impermanence.

It exposes you to new concepts of personal form and energy and your relationship to nature and beings

-Phil Wolfson, MD

Written by: the Editors of goop

 Updated: August 1, 2019

 Reviewed by: Will Siu, MD

KAP: Ketamine-Facilitated Psychotherapy for Trauma, Anxiety and Depression

Drugs are powerful. This is one reason we, as a culture, like to place each drug into a specific category: healing or harming, licit or illicit, medicine or poison.

But the reality is often much messier than those simple dichotomies. It’s challenging to hold one substance in both realms at once, to acknowledge that, depending on dose and context, one person’s cure is another’s sickness.

Of course, that’s why good doctors are critical. A psychedelic drug like ketamine is a perfect illustration of these conflicts: When abused, it can be a source of great harm. In hospitals, it is an anesthetic (the original use of ketamine) and a necessary salve for incredible pain. And increasingly, in therapeutic contexts, ketamine is considered a promising treatment for depression, anxiety, PTSD, and trauma.

In his New York City practice, Harvard-trained psychiatrist Will Siu has found that low doses of ketamine administered in conjunction with psychotherapy are effective. He walks us through what ketamine is, what a ketamine-facilitated therapy session is like, and why he thinks his patients have had success with it.

(To hear more from Siu, listen to him on The goop Podcast talking about trauma, loneliness, and paths toward healing and connection. And to learn more about ketamine infusions, listen to the episode with psychiatrist Steven Levine.)

What is Ketamine?

Ketamine is a synthetic compound that modulates a neurotransmitter called glutamate. It has long been used in clinical settings as an anesthetic and analgesic. And it’s a psychedelic: In the right dose, it acts, as psychiatrist Stanislav Grof put it, as “a nonspecific amplifier of the unconscious process.” Ketamine hasn’t been getting as much attention as other high-profile psychedelic drugs, like MDMA and psilocybin, but psychiatrists have been using it safely as an adjunct to psychotherapy for nearly twenty years.

Its effect is dependent on how you’re using it: Dosage matters, as does whether it’s injected in the vein or in the muscle, taken by mouth, or taken intranasally.

Although it’s legal in therapeutic contexts, ketamine has a somewhat negative reputation: There are serious problems with people becoming addicted to intranasal ketamine and abusing it for nontherapeutic purposes. Some refer to it as the heroin of psychedelics. But at the right dose, it can have a pretty significant clinical impact. I find in my practice that ketamine can act as a jump start for a lot of emotional material that would otherwise take months to work through.

Why do you do ketamine-facilitated therapy in your psychotherapy practice?

Ketamine-facilitated therapy is a process that allows us to gain access to the unconscious. At low doses, ketamine produces a hypnotic or dreamlike state. During normal waking life, we have barriers and defense mechanisms that serve to push away unpleasant or intolerable memories, emotions, and phobias—feelings that we repress and store in our unconscious, where we can’t readily access them. Ketamine can break down those barriers and open up a filter to the unconscious. At higher doses, ketamine can be dissociative and produce deep, meaningful transpersonal experiences.

The rate at which someone can reach a breakthrough and come to terms with negative emotions is far quicker. A specific patient of mine blew me away with her ability to open up during ketamine-facilitated therapy after three or four weeks. It’s likely we could have reached that point of emotional release with just talk therapy, but it would have likely taken significantly more time.

Essentially, ketamine helps bring deep-rooted emotions to the surface, giving us a glimpse into the unconscious mind. The talk therapy helps us work through and examine those emotions in a safe and freeing environment.

What happens in a session of ketamine-facilitated therapy?

It’s a two-hour experience. When a new patient expresses interest in ketamine-facilitated therapy, I take a few regular psychotherapy sessions to get to know them before we start working with ketamine. In the first session I’ll go over medical and psychiatric histories, in addition to what medications they’re on. Ketamine is typically a very safe drug with few complications, so as long as there isn’t anything glaringly problematic, we can proceed.

That process of getting to know that patient goes on for a few more weekly hour-long sessions of therapy. After those initial three to four weeks of getting to know a patient, we’ll have a ketamine-facilitated session. Patients will lie down and take a prescribed dose of about 150 milligrams of ketamine in the form of a lozenge that goes under the tongue; it takes around ten minutes to dissolve. At the end of those ten minutes, most people will experience a body-tingling sensation and overall relaxation. I try to keep the environment in my office as conducive to that mental state as possible: My patients will use an eye mask, and I’ll have calming music on. There is a significant amount of dissociation during the experience—feeling like you’re not present in your own body, as if it’s difficult to move. It’s akin to being in a trance state, where you’ll access some old memories and things will just come to mind, especially if the music correlates to some of the emotions you might be feeling while you explore your unconscious state of mind.

Patients stay in a lying position for about an hour. Following that, the ketamine experience ends, and we discuss what came up for about a half hour or so.

Then there is the integration work. After the initial ketamine experience, we’ll meet weekly and talk about the experience—what emotions arose, what those mean to the patient, what they saw, and how they felt after the experience. We explore what was seen and felt in a way that allows for personal discovery you wouldn’t otherwise get in therapy that doesn’t incorporate ketamine.

Can patients expect an epiphany or a breakthrough?

In order for someone to have catharsis, they need access to both the intellectual memory and the emotional memory of what happened. That isn’t something that’s easy to access. We could tell a story of a car accident that happened ten years ago, but we’re not experiencing the fear that we had when it was happening. Getting that combination of intellectual awareness and emotional memory is a task in and of itself, but MDMA and ketamine can help in doing that. The third piece we need for catharsis is an empathic environment. We need to feel safe, and we need to feel like the person in front of us understands our experience.

What are the risks of taking ketamine?

Medically, the risks are extremely low. In every hospital in the country, ketamine is used as an analgesic for pain on a daily basis and for surgical procedures at a much higher dose.

I haven’t run into any negative consequences using ketamine myself or with my patients. The risks are similar to those of any consciousness-altering substance: If you bring up old trauma or old emotions or old memories in a setting where you’re not met with empathy, it can lead to you feeling worse than you did to begin with, until it’s worked through.

Most people who receive ketamine therapy are doing it via ketamine infusions. IV therapy has more risk involved, because you’re using much higher doses, and at most centers that provide this treatment there typically isn’t any psychological-support component to help you process the emotions or the trauma that might arise.

We see more risk with other psychedelics, like MDMA and psilocybin, just because they tend to be a really powerful experience even at low doses. Ketamine is much more subtle. With MDMA, people describe a rolling experience, where you get this flood of emotion and memories, and then you come down, and then you come back up, and down again, etc. But one ketamine session is like a single roll of MDMA—you typically get one transpersonal experience, and then you come down, and it’s quite subtle for the rest of the session. Overall, it’s just much less intense.

What can ketamine-facilitated therapy help treat?

Most of my patients suffer from anxiety, PTSD, depression, or bipolar disorder. Ketamine infusions can be immediately helpful with depression, in extreme cases where a patient presents with suicidal ideation. Studies have shown it acts in a similar manner to that of drugs like Prozac; monthly infusions are needed, or the depression comes back.

People who are experiencing physical symptoms from anxiety or chronic pain can potentially benefit from ketamine-facilitated therapy because of the psychological component of those issues.

We typically think of dissociation of the mind from the body as being a negative thing, especially as it relates to trauma and PTSD. Why is it helpful in this context?

Dissociation is a psychological defense mechanism the mind has, like the classic ones that you hear about—like using humor or projection. Dissociation is when you separate yourself from the reality of what’s happening right now.

We all do this. People who have trauma, usually as kids, often learn to cope with stress through dissociation. That tends to be very difficult for them because if you’re at work or with a lover or with friends and you dissociate, it can get in the way of your life. It’s really an unpleasant symptom or defense mechanism to have. But it’s not uncommon for people with PTSD or borderline personality or victims of sexual abuse to have dissociative symptoms.

Ketamine is a dissociative drug, especially at higher doses. Not a lot of research has been published, but those of us who have been using it with people with PTSD who dissociate are finding pretty good results with it. It’s different, though, because it’s a controlled dissociation; you’re with a practitioner whom you trust and you’re able to undergo a process of working through those traumas.

We don’t know how it works. One hypothesis I have is that our feelings come from our body: We know we’re anxious or we know we’re sad or we feel ashamed because our body sends us signals. They’re usually unpleasant, and that’s when we go to alcohol or some other behavior to dull the negative sensations and feel better in the short term.

Ketamine, however, dissociates the mind from the body. All of a sudden you can work through a problem—you can really look at yourself—without having all the negative feedback from your body. You’re looking at a situation or a memory without your body giving you unpleasant feedback that you’re ashamed, scared, or sad. But in your mind, you’re fully aware, you’re conscious, you’re present. You’re almost able to make changes to how you think and the way you look at the world while you’re in that state. As the ketamine comes down, people often feel differently—better—about a situation that’s been bothering them for a long time. The memory of the trauma is still there—it always will be—but the context has shifted.

Will Siu, MD, DPhil, completed medical and graduate school at UCLA and Oxford University, respectively, before training as a psychiatrist at Harvard Medical School. He was on the faculty at Harvard for two years prior to moving to New York City to further pursue his interests in psychedelic medicine as a practitioner and a public advocate. Siu has been trained by MAPS to provide MDMA-assisted therapy and has a private practice in Manhattan where he provides individual psychotherapy and ketamine-facilitated psychotherapy. He is also on the faculty at Columbia University where he conducts research using IV ketamine to treat heroin and cocaine additions.

How Ketamine Helps Alleviate Depression

By Brianna RandallOct 14, 2021 6:00 AM

Inside the Big Sky Ketamine Care clinic in Missoula, Montana, a woman relaxes in a leather recliner as soothing classical music pipes through the speakers. She watches nature scenes flicker across a TV screen as a low dose of ketamine drips into her arm for 40 minutes. A nurse monitors vitals and sits beside the woman as her mind drifts — and hopefully heals.

The Montana business is just one example of the recent boom in ketamine treatment, which uses a sedative also known as an animal tranquilizer or a club drug nicknamed “Special K.”

This alternative therapy option for treating mood disorders has grown in popularity as patients and medical providers look to fast-acting options for the 264 million people worldwide who suffer from depression.

It’s the only legal psychedelic currently available in the U.S., though psilocybin was recently legalized for therapy in Oregon. Providers and many researchers say ketamine can alleviate anxiety or depression symptoms, including suicidality, in a matter of hours; commonly prescribed oral antidepressants, like Zoloft or Prozac, on the other hand, often take weeks before they kick-in.

Still, along with its promise in psychiatric treatment, ketamine faces cultural distrust and lingering questions, especially surrounding its main side effect: feeling high, or a dissociated sense that you are separate from your mind, body and surroundings. Scientists still don’t know the exact pathways by which ketamine alleviates mood disorders, but recent research about how ketamine works in the brain — as well as how best to use it in clinical settings — may help overcome some of the distrust.

Growing New Synapses

Ketamine was first synthesized as an anesthetic in the 1950s and originally used to sedate wounded soldiers. About 20 years ago, researchers discovered that a low dose of ketamine (about one-tenth the amount used for anesthesia) worked as a fast-acting antidepressant. In 2019, the FDA approved the medication Spravato for treatment-resistant depression. The nasal spray contains esketamine, one of the two mirror-image molecules in ketamine. Now, a flurry of research is investigating how sub-anesthetic ketamine works on the brain. 

For the past 60 years, medical professionals’ main theory about the chemical source of depression has been a lack of serotonin in the brain — a messenger neurotransmitter or hormone that impacts everything from emotions to motor skills. The most common oral antidepressants are selective serotonin reuptake inhibitors (SSRIs), which block the reabsorption of serotonin into neurons. It takes several weeks for serotonin levels to plateau once patients start taking daily pills like Zoloft or Prozac. Plus, only one-third of patients successfully overcome depression after trying an oral antidepressant, and about half of people find success after trying two brands of antidepressants, according to a comprehensive 2008 study on major depressive order in the Cleveland Clinic Journal of Medicine. 

Ketamine, on the other hand, works on glutamate, the most common chemical messenger that regulates much of the nervous system and also plays an important role in the brain’s response to experiences. Neuroimaging studies have shown that ketamine increases glutamate release in the prefrontal cortex, a surge that is likely associated with its rapid antidepressant effects as well as its dissociative side effects. But scientists still don’t know exactly what initiates the glutamate release, or whether it’s even the main driver behind the relief of depression and anxiety.

“We believe that this rapid burst of glutamate activates downstream receptors, which can trigger new synapses to grow,” says Lace M. Riggs, a neuroscience Ph.D. candidate at the University of Maryland School of Medicine who co-authored a recent review of ketamine’s use as an antidepressant. “While we’ve made a lot of progress to understand this process, it probably only scratches the surface of ketamine’s full mechanism of action as an antidepressant.”

Brain Connections in Minutes

Ketamine, like oral antidepressants, also promotes neuroplasticity, which is the brain’s ability to create new connections and pathways. 

“We assumed that antidepressants were just inherently slow in developing neuroplasticity,” says Eero Castrén at the University of Helsinki’s Neuroscience Center in Finland. “So when ketamine came out and acted really quickly, we were all shocked.”

The big question may not necessarily be why ketamine acts so quickly, says Castrén, but rather why traditional antidepressants act so slowly. “We don’t expect aspirin to take three weeks to get rid of a headache. An hour should suffice for most drugs to take effect.”

New research by Castrén and his colleagues explain part of the delay: They found that both ketamine and three types of commonly prescribed oral antidepressants bind directly to a receptor for the brain derived neurotrophic factor (BDNF), a protein that encourages growth and differentiation of new nerve cells. Ketamine, however, binds to the BDNF receptors within minutes instead of days, which may be why patients experience relief immediately.

As for increasing the brain’s plasticity, Castrén says, this is not in and of itself a good thing, but rather a neutral process. If someone experiences stressful situations during a period of increased neuroplasticity, it could translate into negative emotions.

Pairing Ketamine With Therapy

Since ketamine increases neuroplasticity and can temporarily induce an altered state of consciousness, some practitioners believe that it’s critical to administer the medicine in a safe, supportive setting. Julane Andries, a psychotherapist in San Anselmo, Calif., says that breakthroughs come more quickly when ketamine is paired with therapy.

“It helps to have a therapist process the experience with you and integrate any insights from ketamine treatment into your daily life,” Andries says. “That’s how people can make lasting changes in how they react to depression triggers in the future.”

Andries has helped train over 400 practitioners around the world in ketamine-assisted psychotherapy (KAP). The KAP model includes calming practices for patients during treatment, like wearing an eye mask, focusing on breathing and listening to specific music.

Andries also co-authored a 2019 article in the Journal of Psychoactive Drugs that analyzed the self-reported depression and anxiety scores of 235 patients who received ketamine (via an injection or an oral lozenge) paired with therapy. Participant average scores for both depression and anxiety decreased significantly. Those with the most severe symptoms, including suicidality, showed the greatest improvement post-KAP treatment. Additionally, the older the age of the participant, the greater the improvement in their depression score.

In comparison, a a study of 22 patients who received a series of oral ketamine treatments with no accompanying therapy found only modest gains in mental health: 30 percent reported some benefit while nearly 70 percent said they felt no benefit or felt worse.

Concerns About Misuse

Ketamine clinics like the one in Montana are popping up nationwide, touting off-label ketamine as a treatment for everything from depression to nicotine addiction. Most clinics administer ketamine as an intravenous drip, and begin with six treatments over two weeks. Because it’s not approved specifically for psychiatric disorders (like Spravato is), off-label ketamine is not covered by insurance and can cost anywhere from $300–$800 per visit. And since it’s a treatment, not a cure, most people need booster doses every few weeks or months, perhaps indefinitely.

Some physicians are worried that providers at these ketamine clinics are not required to go through any training or certification to administer the drug.

“Ketamine is a valuable, life-saving treatment that’s very much needed in the field. But it has the potential to be misused, which makes the treatment vulnerable,” says Sandhya Prashad, a psychiatrist based in Houston who is also president and co-founder of the American Society of Ketamine Physicians, Psychotherapists and Practitioners.

Prashad says that some clinics don’t screen patients appropriately for contra-indications, such as heart conditions or active use of addictive substances. Others vary the dosages from the recommended standards, which can exacerbate ketamine’s short-term side effects: dissociation, nausea, agitation and temporarily elevated blood pressure and heart rate.

At present, the jury is still out regarding long-term effects of ketamine on the body and brain.

“Even though ketamine has been around for 50 years, we don’t know that repeat dosing is safe,” Prashad says. She points out that one reason the FDA hasn’t approved off-label ketamine as a treatment for depression is because of a lack of long-term, formal data that proves it’s safe. But since ketamine is already widely available, there’s less incentive for pharmaceutical companies to fund testing that provides that data.

Scientists are trying to design new rapid-acting antidepressant drugs that act like ketamine without its stigma, potential of abuse or dissociative side effects. Riggs, for instance, works in a lab focused on investigating whether the metabolites of ketamine could be a safer, therapeutic alternative — and perhaps, someday, taken as a pill at home instead of in a clinical setting.

But our incomplete understanding of how ketamine works in the brain has made it especially challenging to find or design drugs that mimic its antidepressant actions. “Many drugs that are structurally or pharmacologically similar to ketamine do not exhibit its amazing antidepressant effects,” Riggs says. 

For now, there are often as many questions as answers when it comes to how and when to use ketamine to treat mood disorders. But one thing seems certain: ketamine is here to stay as a tool for relieving depression.

It’s the only legal psychedelic currently available in the U.S., though psilocybin was recently legalized for therapy in Oregon. Providers and many researchers say ketamine can alleviate anxiety or depression symptoms, including suicidality, in a matter of hours; commonly prescribed oral antidepressants, like Zoloft or Prozac, on the other hand, often take weeks before they kick-in.

Still, along with its promise in psychiatric treatment, ketamine faces cultural distrust and lingering questions, especially surrounding its main side effect: feeling high, or a dissociated sense that you are separate from your mind, body and surroundings. Scientists still don’t know the exact pathways by which ketamine alleviates mood disorders, but recent research about how ketamine works in the brain — as well as how best to use it in clinical settings — may help overcome some of the distrust.

Growing New Synapses

Ketamine was first synthesized as an anesthetic in the 1950s and originally used to sedate wounded soldiers. About 20 years ago, researchers discovered that a low dose of ketamine (about one-tenth the amount used for anesthesia) worked as a fast-acting antidepressant. In 2019, the FDA approved the medication Spravato for treatment-resistant depression. The nasal spray contains esketamine, one of the two mirror-image molecules in ketamine. Now, a flurry of research is investigating how sub-anesthetic ketamine works on the brain. 

For the past 60 years, medical professionals’ main theory about the chemical source of depression has been a lack of serotonin in the brain — a messenger neurotransmitter or hormone that impacts everything from emotions to motor skills. The most common oral antidepressants are selective serotonin reuptake inhibitors (SSRIs), which block the reabsorption of serotonin into neurons. It takes several weeks for serotonin levels to plateau once patients start taking daily pills like Zoloft or Prozac. Plus, only one-third of patients successfully overcome depression after trying an oral antidepressant, and about half of people find success after trying two brands of antidepressants, according to a comprehensive 2008 study on major depressive order in the Cleveland Clinic Journal of Medicine. 

Ketamine, on the other hand, works on glutamate, the most common chemical messenger that regulates much of the nervous system and also plays an important role in the brain’s response to experiences. Neuroimaging studies have shown that ketamine increases glutamate release in the prefrontal cortex, a surge that is likely associated with its rapid antidepressant effects as well as its dissociative side effects. But scientists still don’t know exactly what initiates the glutamate release, or whether it’s even the main driver behind the relief of depression and anxiety.

“We believe that this rapid burst of glutamate activates downstream receptors, which can trigger new synapses to grow,” says Lace M. Riggs, a neuroscience Ph.D. candidate at the University of Maryland School of Medicine who co-authored a recent review of ketamine’s use as an antidepressant. “While we’ve made a lot of progress to understand this process, it probably only scratches the surface of ketamine’s full mechanism of action as an antidepressant.”

Brain Connections in Minutes

Ketamine, like oral antidepressants, also promotes neuroplasticity, which is the brain’s ability to create new connections and pathways. 

“We assumed that antidepressants were just inherently slow in developing neuroplasticity,” says Eero Castrén at the University of Helsinki’s Neuroscience Center in Finland. “So when ketamine came out and acted really quickly, we were all shocked.”

The big question may not necessarily be why ketamine acts so quickly, says Castrén, but rather why traditional antidepressants act so slowly. “We don’t expect aspirin to take three weeks to get rid of a headache. An hour should suffice for most drugs to take effect.”

New research by Castrén and his colleagues explain part of the delay: They found that both ketamine and three types of commonly prescribed oral antidepressants bind directly to a receptor for the brain derived neurotrophic factor (BDNF), a protein that encourages growth and differentiation of new nerve cells. Ketamine, however, binds to the BDNF receptors within minutes instead of days, which may be why patients experience relief immediately.

As for increasing the brain’s plasticity, Castrén says, this is not in and of itself a good thing, but rather a neutral process. If someone experiences stressful situations during a period of increased neuroplasticity, it could translate into negative emotions.

Pairing Ketamine With Therapy

Since ketamine increases neuroplasticity and can temporarily induce an altered state of consciousness, some practitioners believe that it’s critical to administer the medicine in a safe, supportive setting. Julane Andries, a psychotherapist in San Anselmo, Calif., says that breakthroughs come more quickly when ketamine is paired with therapy.

“It helps to have a therapist process the experience with you and integrate any insights from ketamine treatment into your daily life,” Andries says. “That’s how people can make lasting changes in how they react to depression triggers in the future.”

Andries has helped train over 400 practitioners around the world in ketamine-assisted psychotherapy (KAP). The KAP model includes calming practices for patients during treatment, like wearing an eye mask, focusing on breathing and listening to specific music.

Andries also co-authored a 2019 article in the Journal of Psychoactive Drugs that analyzed the self-reported depression and anxiety scores of 235 patients who received ketamine (via an injection or an oral lozenge) paired with therapy. Participant average scores for both depression and anxiety decreased significantly. Those with the most severe symptoms, including suicidality, showed the greatest improvement post-KAP treatment. Additionally, the older the age of the participant, the greater the improvement in their depression score.

In comparison, a a study of 22 patients who received a series of oral ketamine treatments with no accompanying therapy found only modest gains in mental health: 30 percent reported some benefit while nearly 70 percent said they felt no benefit or felt worse.

Concerns About Misuse

Ketamine clinics like the one in Montana are popping up nationwide, touting off-label ketamine as a treatment for everything from depression to nicotine addiction. Most clinics administer ketamine as an intravenous drip, and begin with six treatments over two weeks. Because it’s not approved specifically for psychiatric disorders (like Spravato is), off-label ketamine is not covered by insurance and can cost anywhere from $300–$800 per visit. And since it’s a treatment, not a cure, most people need booster doses every few weeks or months, perhaps indefinitely.

Some physicians are worried that providers at these ketamine clinics are not required to go through any training or certification to administer the drug.

“Ketamine is a valuable, life-saving treatment that’s very much needed in the field. But it has the potential to be misused, which makes the treatment vulnerable,” says Sandhya Prashad, a psychiatrist based in Houston who is also president and co-founder of the American Society of Ketamine Physicians, Psychotherapists and Practitioners.

Prashad says that some clinics don’t screen patients appropriately for contra-indications, such as heart conditions or active use of addictive substances. Others vary the dosages from the recommended standards, which can exacerbate ketamine’s short-term side effects: dissociation, nausea, agitation and temporarily elevated blood pressure and heart rate.

At present, the jury is still out regarding long-term effects of ketamine on the body and brain.

“Even though ketamine has been around for 50 years, we don’t know that repeat dosing is safe,” Prashad says. She points out that one reason the FDA hasn’t approved off-label ketamine as a treatment for depression is because of a lack of long-term, formal data that proves it’s safe. But since ketamine is already widely available, there’s less incentive for pharmaceutical companies to fund testing that provides that data.

Scientists are trying to design new rapid-acting antidepressant drugs that act like ketamine without its stigma, potential of abuse or dissociative side effects. Riggs, for instance, works in a lab focused on investigating whether the metabolites of ketamine could be a safer, therapeutic alternative — and perhaps, someday, taken as a pill at home instead of in a clinical setting.

But our incomplete understanding of how ketamine works in the brain has made it especially challenging to find or design drugs that mimic its antidepressant actions. “Many drugs that are structurally or pharmacologically similar to ketamine do not exhibit its amazing antidepressant effects,” Riggs says. 

For now, there are often as many questions as answers when it comes to how and when to use ketamine to treat mood disorders. But one thing seems certain: ketamine is here to stay as a tool for relieving depression.

The Default Mode Network (DMT)

The default mode network is a group of brain regions that seem to show lower levels of activity when we are engaged in a particular task like paying attention, but higher levels of activity when we are awake and not involved in any specific mental exercise.

It is during these times that we might be daydreaming, recalling memories, envisioning the future, monitoring the environment, thinking about the intentions of others, ruminating on our performance or actions. All the things that we often do when we find ourselves just “thinking” without any explicit goal of thinking in mind.

Additionally, recent research has begun to detect links between activity in the default mode network and mental disorders like depression, anxiety, and schizophrenia. Furthermore, therapies like meditation have received attention for influencing activity in the default mode network, suggesting this may be part of their mechanism for improving well-being.

(https://www.neuroscientificallychallenged.com/blog/know-your-brain-default-mode-network)

How the Default Mode Network operates:

The default mode network, discovered by neurologist Marcus Raichle, spans a number of brain regions, incorporating parts of the prefrontal, parietal, and temporal cortices that show joint activation, or deactivation, in connection with particular mental functions.

 Evolutionarily speaking, the DMN is the most recent part of the brain, and it’s closely connected to the brain regions responsible for memories and emotions (Michael Pollan quote, you can read more here: (https://www.vox.com/science-and-health/2018/5/21/17339488/psychedelics-mental-health-michael-pollan-lsd-psilocybin)

A lot of commentary exists regarding the DMN and that it is essentially ones Ego, the decision-making component of personality. Your ego’s job is to feel important. Its survival depends on it. Unfortunately, this translates to your ego needing to fight and defend itself. It seems counterintuitive, but the ego needs negative situations to arise so it can have something to do, something to worry about, or something to change. So, if you’re happy, and everything is perfect, your ego will already be looking for an issue to cling to or a drama to create.

The ego does not live in the present. While it is a fact that only the present moment exists, and the past and future exist only in the mind, your ego wants you to be thinking about the past and future. This means thinking about things that have gone wrong in the past, or things that may go wrong in the future.

How the ego can cause harm:

Your ego takes you away from the present moment. Imagine living your whole life thinking about the past and the future, and then realizing at the end that all you ever had was the present moment – but you were too stuck in your head to fully engage your senses and enjoy the world around you. You can read more about the ego here: (https://www.ihasco.co.uk/blog/entry/2206/get-to-know-your-ego)

Psychedelics and the Default Mode Network:

Psychedelics reliably induce an altered state of consciousness known as ‘ego dissolution’. The term was invented, well before the tools of contemporary neuroscience became available, to describe sensations of self-transcendence: a feeling in which the mind is put in touch more directly and intensely with the world, producing a profound sense of connection and boundlessness.

Here’s where psychedelics come in. These drugs alter maladaptive self-models, because they affect the neural mechanisms that self-awareness springs from. At the point of ego dissolution, two things seem to happen. One, the integrity of the self-model degrades. And two, we no longer take it for granted that our experience must be interpreted by that model.

When the self falls apart and is subsequently rebuilt, the role of the self-model seems to become visible to its possessor. Yes, this offers a psychological reprieve – but more importantly, it draws attention to the difference between a world seen with and without the self. For an anxious or depressed person, psychedelics make it possible to appreciate the intermediate, representational role of the self-model. Ego dissolution offers vivid experiential proof, not only that things can be different, but that the self that conditions experience is just a heuristic, not an unchangeable, persisting thing. Read more on this fascinating concept here: (https://aeon.co/essays/psychedelics-work-by-violating-our-models-of-self-and-the-world).

A research article published in August 2019 titled Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects showed that the ego-dissolution can be achieved with psilocybin and meditation.

The extent of ego dissolution and brain connectivity predicted positive changes in psycho-social functioning of participants 4 months later. Psilocybin, combined with meditation, facilitated neurodynamic modulations in self-referential networks, subserving the process of meditation by acting along the anterior–posterior DMN connection. The study highlights the link between altered self-experience and subsequent behavioral changes.

Unfortunately, the entire article is not available to view without purchase, but the abstract can be viewed here: https://doi.org/10.1016/j.neuroimage.2019.04.009

Our opinion at Alkamystik Journeys:

Psilocybin assisted therapy that takes into consideration the mind-set and setting can achieve conscious mind expansion, allowing the ego to get the hell out of the way. To use Huxley’s phrase, the doors of perception can be opened and we can free our minds from old thoughts that hold us back, no longer serve us and block us from reaching our full potentials as humans. This ego dissolution and integration with the universe has the potential to expand one’s connectedness, creativity and overall well-being.

Ketamine is an option that is currently legal and readily available for use. We emphasis the importance of the ‘mind-set’ or intention, which directly challenges the DMN.

Even if one is not considering psychedelic assisted treatments, being aware of this concept of the DMN and the ego, can be beneficial for changing one’s mind-set. Be curious about your actions, your strong emotions and where they are felt in your body. Be aware of your mind “time-traveling”. Be more cognizant of being present in the here and now. Look around and bring your mind back to the present. Notice 5 things your eyes are seeing. Next, notice 4 things your ears are hearing. Then notice 3 things your body is sensing (the tightness of your shoes, your watch, your hat, etc.). Now notice 2 smells. And last, what taste can you identify in your mouth. If none, pop a mint, or piece of candy, chocolate, take a drink, savor that moment. This present moment… and make it last.

Your Mind-Set refers to the preparation and expectations of both the voyager and the guide.

Per James Fadiman’s book The Psychedelic Explorer’s Guide: It is invaluable to write out beforehand what you hope to learn, experience, understand, or resolve. One can use this opportunity for a focused inquiry into very specific psychological, spiritual or social concerns. But it is also important to remain open to engaging in whatever arises from the psychedelic encounter.

At Alkamystik Journeys, we emphasize the importance of developing a mind-set or intention many days before you even undergo a journey. We will work with you to develop a very succinct and positive intention that you will focus on as you begin your experience. It is very important to realize that every journey will be different and it is very important to remain open to the experience. The concept of “flow” will enable you to lessen your expectations and develop a deeper trust for your own healing process.

Ketamine is the ONLY legal psychedelic medication currently (excluding cannabis).

Ketamine is classified as an Analgesic and Anesthetic.

Ketamine at lower doses to treat psychiatric conditions such as depression, suicidality and anxiety is considered an off-label use.

Ketamine can be administered via IV, IM, rectal, intranasal, oral and sublingual routes.

Clinical studies have generally detected no long-term impairment of behavior or personality functioning as a result of repeated ketamine use. Ketamine has been shown to be useful as a neuroprotective agent to prevent brain damage from head trauma, strokes, heart attacks, epileptic seizures, low oxygen levels and low blood sugar levels. There has been recent concern about toxicity to the urinary system. Ketamine was approved in 1970 (anesthesia) for children, adults and elderly. Ketamine is included in the World Health Organization model list of essential medications. (The Ketamine Papers, 2016).

About 20 years ago, researchers discovered that a low dose of ketamine (about one-tenth the amount used for anesthesia) worked as a fast-acting antidepressant.

Ketamine works on glutamate, the most common chemical messenger that regulates much of the nervous system and also plays an important role in the brain’s response to experiences. Neuroimaging studies have shown that ketamine increases glutamate release in the prefrontal cortex, a surge that is likely associated with its rapid antidepressant effects as well as its dissociative side effects. 

But scientists still don’t know exactly what initiates the glutamate release, or whether it’s even the main driver behind the relief of depression and anxiety.

“We believe that this rapid burst of glutamate activates downstream receptors, which can trigger new synapses to grow,” says Lace M. Riggs, a neuroscience Ph.D. candidate at the University of Maryland School of Medicine who co-authored a recent review of ketamine’s use as an antidepressant. “While we’ve made a lot of progress to understand this process, it probably only scratches the surface of ketamine’s full mechanism of action as an antidepressant.”

https://www.discovermagazine.com/mind/how-ketamine-helps-alleviate-depression

Brain Derived Neurotrophic Factor (BDNF) and Increased Neuroplasticity

Ketamine and three types of commonly prescribed oral antidepressants bind directly to a receptor for the brain derived neurotrophic factor (BDNF), a protein that encourages growth and differentiation of new nerve cells. Ketamine, however, binds to the BDNF receptors within minutes instead of days, which may be why patients experience relief immediately.

As for increasing the brain’s plasticity, this is not in and of itself a good thing, but rather a neutral process. If someone experiences stressful situations during a period of increased neuroplasticity, it could translate into negative emotions.

The first 72 hours post treatment are crucial for successful integration.

https://www.discovermagazine.com/mind/how-ketamine-helps-alleviate-depression

The KAP model includes calming practices for patients during treatment, like wearing an eye mask, focusing on breathing and listening to specific music.

Since ketamine increases neuroplasticity and can temporarily induce an altered state of consciousness, some practitioners believe that it’s critical to administer the medicine in a safe, supportive setting. Research is validating that breakthroughs come more quickly when ketamine is paired with therapy.

“It helps to have a therapist process the experience with you and integrate any insights from ketamine treatment into your daily life, that’s how people can make lasting changes in how they react to depression triggers in the future.”

https://www.discovermagazine.com/mind/how-ketamine-helps-alleviate-depression–

Even though ketamine has been around for 50 years, we don’t know that repeat dosing is safe. One reason the FDA hasn’t approved off-label ketamine as a treatment for depression is because of a lack of long-term, formal data that proves it’s safe. But since ketamine is already widely available, there’s less incentive for pharmaceutical companies to fund testing that provides that data.

Contraindications for Oral Ketamine Treatment administered in the home setting:

•History of ketamine abuse or dependence

•Active psychosis or mania

•Diagnosis of Schizophrenia or Schizoaffective disorder

•Active suicidal ideations or suicide attempt in past year

•Glaucoma

•Increased intracranial pressure

•Pregnant/Nursing

•Medical clearance required for:

•Uncontrolled hypertension

•Congestive Heart Failure

•COPD

•Hyperthyroidism