Before Dawn by Bisbiswas

 

The ketamine craze: Ketamine infusion therapy for depression & PTSD

Ketamine clinics for depression and PTSD are popping up like wildflowers, but is it a poison or a cure?

 

ketamine for depression, PTSD, anxiety

By Katalina Lourdes & Guy

 

Ketamine’s first recorded synthesis was back in 1956. It was approved for use in the US on humans and animals in 1970, and it became the most commonly administered battlefield anaesthetic during the Vietnam War. However during the 1980s it emerged on the street and became popular within the rave party and gay scene as a drug to get high on.

Though not widely used recreationally in the US, over the past decade ketamine has become UK teenagers’ “drug of choice”. Maybe they’re self-medicating… but the consequences of ketamine addiction can be serious. We’ll get to the recreational, or dark side, of ketamine later.

2020 saw ketamine hit the headlines once more as a successful treatment within clinics for patients suffering from treatment resistant depression. As with classic psychedelics like psilocybin, ketamine infusion therapy has shown promise as a treatment for depression, PTSD, OCD, anxiety, and even addiction.

 

Ketamine poison or remedyMoonlight Circus by BisBiswas

 

Despite its risk of abuse, because of its anaesthetic and pain-relieving applications, ketamine is a Schedule 3 substance in the US, as opposed to Schedule 1 like magic mushrooms, LSD, or MDMA. That makes it a lot easier to conduct research on ketamine and use it in clinical trials, and means that doctors can use it off label.

It’s because ketamine has approved medical applications that ketamine clinics are now able to proliferate across the US (and now also the UK), and news of it as a panacea is lighting up the marquees. The irony, of course, is that ketamine is much more dangerous than psilocybin, and probably less effective – or at least, its effects are shorter lived.

Ketamine clinics, like the company MindBloom, offer ketamine injections or infusion therapy, sometimes in conjunction with psychotherapy, Since the treatment is experimental and not approved by the FDA, it’s not covered by insurance – though some clinics are making ketamine infusion therapy as affordable as a visit to the psychiatrist.

 

How does ketamine work?

Ketamine is an NMDA receptor antagonist. NMDA receptors are activated by glutamate, the main excitatory neurotransmitter in the brain.

Overactivation or “excitability” of NMDA receptors is implicated in chronic stress and anxiety, and eventually leads to neural atrophy, a loss of neural plasticity, and depression.

As an NMDA antagonist, ketamine temporarily blocks glutamate from binding with NMDA receptors, preventing activation of downstream neurons (which we might experience as negative thoughts if we’re depressed). Glutamate is the most abundant neurotransmitter in the brain, and it’s especially involved in learning and memory and the formation of long-term neural pathways (known as long-term potentiation, or LTP).

The prevailing theory is that a series of chemical processes are then set off that increase levels of brain-derived neurotrophic factor (BDNF), a key protein for the growth of neurons, which is stunted when NMDA receptors are overactivated.

Blocking NMDA receptors also causes glutamate to activate more AMPA receptors, the other main glutamatergic receptor. In situations of chronic stress, AMPA receptors are underactive and there are fewer of them at synapses. However AMPA receptors are key to synaptic plasticity; they stimulate short-term and long-term potentiation, or the creation of new neural pathways.

ketamine and depression
A healthy synapse versus one under chronic stress, as in when NMDA receptors are overactivated

Neuroscientists believe ketamine’s antidepressant effect to be achieved by increasing the number of AMPA receptors and by stimulating BDNF in the brain, fostering the growth of new neurons and dendrites, and strengthening synapses. All of this increases neuroplasticity, or how healthy and flexible our brains are, which is thought to play a key role in the antidepressant effects of all psychedelics. 

This is a general overview; the exact mechanism by which ketamine relieves depression is still being investigated.

A recent study found that the antidepressant effects of ketamine may be through one of its metabolites, hydroxynorketamine.

Serotonin may also play a role. A 2020 study found that ketamine treatment increased binding with serotonin 1B receptors in the hippocampus of depressed patients.

 

What is ketamine like?

The ketamine high isn’t exactly like that of classic psychedelics such as LSD or psilocybin. It’s dissociative, so it can make you feel disconnected from your body as well as your regular thoughts and emotions. Users report feeling like they’re floating, with changes in perception and dreamlike states.

Mentally it’s not for the faint hearted; it’s a powerful tranquilizer and the trip is intense, introspective and psychedelic. As a street drug, ketamine can be quite moreish on a low dose so it’s very easy to go over on the second line… and then you may end up in a “K-hole”, coming around a few hours later with no memory of what happened.

The comedown is spacy and empty, leaving you feeling a bit down.

 

Ketamine infusion therapy for depression

We’ve known for at least 20 years that ketamine relieves depression. Since then, several studies have found ketamine infusion therapy to reduce depressive symptoms in patients with treatment resistant depression, meaning, those who have failed to respond to traditional antidepressants. 

Ketamine is fast acting, known to relieve depression almost instantaneously. It’s also promising for those at risk of suicide; ketamine has been found to significantly lower suicide ideation.

Most patients experience near total relief of their depressive symptoms within one to 24 hours of their treatment. On the down side, the antidepressant effects of ketamine typically wear off within one month, so it’s not a cure.

It seems that as a long-term treatment, patients need to receive injections weekly or monthly, though by combining ketamine infusions with psychotherapy their effects may last longer.

 

Ketamine infusion therapy for PTSD

People who have been through a traumatic event, or repeated or chronic events, can develop PTSD or chronic C-PTSD. Common symptoms include depression, flashbacks, anxiety or panic, and nightmares. However PTSD can also manifest in difficulty concentrating, cognitive impairments, loss of interest and detachment, emotional dysregulation, and reckless behavior. 

Since these symptoms are also common in those suffering from neural lesions or traumatic brain injury, a group of researchers theorized that PTSD may also be caused by a lack of synaptic connectivity.

They write:

“It is well established that chronic stress causes neural atrophy and decreases the number of synapses within cortical and limbic circuits implicated in the regulation of mood, cognition, and behavior. Glutamate synapses are the dominant form of synaptic connectivity in these circuits.”

So they hypothesized that ketamine could treat PTSD based on how it is thought to treat depression – building the strength of synapses by increasing BDNF, the number of AMPA receptors, and the number and strength of dendrites, the branches at the receiving ends of neurons.

Now that theory is being tested. A study just published in the American Journal of Psychiatry found that a two-week course of six ketamine infusions significantly improved symptoms of PTSD, and the effects lasted for nearly a month. Research on humans is still limited, but at least one other study has found similar results. More research has been done on rats, suggesting that ketamine can help us forget bad memories.

 

Ketamine and OCD

Since glutamate is thought to play a central role in the obsessive thought patterns which plague OCD, ketamine has been investigated as a possible treatment. A 2013 study found that treatment with ketamine had rapid and stable results, reducing symptoms of OCD in half of participants for at least one week.

 

Ketamine and addiction

Ketamine can itself be addictive, so it seems an unlikely candidate to cure addiction. However one study in 2019 found that one ketamine treatment plus five weeks of mindfulness-based therapy resolved cocaine addiction in 44% of participants for at least six months, while all of those who only received the therapy (the control group) continued using.

 

Ketamine & esketamine for anxiety

Though the effects aren’t as pronounced as they are for depression, a few studies have also found ketamine to be somewhat effective in treating anxiety. In one study, ketamine was found to reduce social anxiety but not generalized anxiety compared to placebo.

A couple of studies found that esketamine significantly reduces both depression and anxiety in chronically ill patients.

Generally ketamine is a sedative, however another study found that experiencing anxiety during ketamine infusions for depression was associated with poor outcomes. So the first word of advice to those seeking ketamine treatment for depression might be: just relax.

A second word of advice? If you’re having ketamine treatment, take magnesium supplements along with it. Ketamine and magnesium are thought to work in similar ways to treat depression, and a recent study found that supplementation with magnesium enhances ketamine’s antidepressant effects.

 

A look at recreational ketamine use across the pond

 

ketamine craze: cure or poison?

 

In England, where ketamine is widely used as a party drug, people are seeing the dark side of ketamine, as young men in their 20s are starting to have bladder problems. This is because ketamine breaks down the wall of your bladder over time.

Here’s Guy’s take, or

The case against caning K

If you develop a habit and regularly take a lot of street ketamine, you will fairly soon start running into some serious problems, as tolerance grows rapidly. In the beginning it’s fairly cheap, selling at around 20 pound a gram in the UK — that’s enough to get you well and truly munted for up to five hours. And if you start using at the levels given to sedate animals like elephants and horses, your problems will deepen as your usage goes up and tolerance builds.

The obvious drawbacks are the onset of adverse physical effects after heavy or long-term use of ketamine. These are worse than most other street drugs; primarily the rapid destruction of your bladder and urinary function. It’s sad to see teenagers that have been caning k for a few years simply pissing their pants and having seriously painful stomach cramps.

People’s experiences are individual and specific, so whilst Jill who had a little dabble here and there for a few years managed to walk away unscathed and actually benefited from her experiences, Jack spent way too much money and is having a tough time trying to stay off it whilst suffering psychosis, kidney, and bladder problems. You can never know another person’s capacity to say no or have an understanding of how other drugs, medications, and personal traumas are affecting another person’s ability to make positive decisions.

Other associated problems may include scenarios such as where a person on ketamine walks into a busy road oblivious to their surroundings. Unfortunately it is also used by rapists, gay and heterosexual. Finally, it is illegal in most jurisdictions, so you could do hard time if caught dealing or importing–situations many addicts fall into whatever drug they are on to either fund usage or settle mounting drug debts.

An alcoholic who drinks hard liquor morning noon and night could develop cirrhosis of the liver, slurred speech, and a switchy personality, and whilst some may quietly destroy themselves others may be easily manipulated into violence and vicious cycles of low self-esteem, prison, and toxic relationships.

The recent studies have found that ketamine infusion therapy can immediately alleviate a person’s suffering who is suicidal, however the studies also show that after a period of two weeks the person is likely to be back in the same state of depression, so there is no long term gain.

Popular street drugs are popular because they give you a rush or cause an intoxicating effect, and a good experience will give you confidence to try it again. I suppose what I’m hinting at is that making a career out of ketamine will end up doing you serious harm physically and emotionally. While a short course may have benefits, it comes with no recommendations from my end.

 

how to talk to a depressed or suicidal friend

 

How to talk to a depressed (or even suicidal) friend

(Note: this article won’t prepare you to be a trained crisis counselor, so keep crisis hotline numbers, which are listed at the end of this article, handy. however, if a friend comes to you for help, one of the best things you can do is listen. below a crisis counselor tells us how.)

 

Suicide isn’t something most of us want to think about, let alone talk about. However we have to be real: the suicide rate has risen by 33% over the past 20 years, and it’s the 10th leading cause of death in the US. Before the pandemic, depression affected over 20% of the population.

The Covid crisis has made things worse for most people. A year later, the CDC now estimates that 40% of the population is struggling with anxiety or depression. Young people are being hit hardest, with a staggering 55-60% of people aged 18-29 experiencing symptoms. There’s been a corresponding rise in suicide attempts by children and teenagers.

These are conversations we may need to have at some point with friends and loved ones, uncomfortable as they may be.

So I asked my friend Sam how we should talk to friends that are depressed, or may even be suicidal. Sam’s been working at a suicide hotline for the last five years.

 

Why do people do it?

The first thing I ask Sam is, why do people do it? I try to get him to open up as to some of the common reasons that people make that decision, or make the call to the suicide hotline. After thousands of conversations with suicidal people, he must have some insight.

“Everything you can think of and then some,” is his response. He can’t comment on any leading causes, nor can he give me any stories. I figure tight-lipped is a trait you’d want in a suicide counselor.

What he can say is, “It’s never just one thing, it’s always a whole bunch of things.”

“It’s like a full grocery bag that you just keep piling stuff in, and eventually it breaks. It wasn’t that last thing that broke it, it was all of those things.” 

So there’s sometimes a straw that breaks the camel’s back, but it’s never just that. 

And of course, it’s subjective.

“People don’t kill themselves because of facts,” he says, “they kill themselves because of their thoughts and feelings.”

I pry a little further, curious if there’s a class dynamic, or if he’s noticed poverty as a factor.

“There’s an incredible diversity of people with access to a telephone,” he says. He resassures me that plenty of calls come from people from higher socioeconomic backgrounds. “Mental illness knows no class distinction,” he says

It would make sense that the most disadvantaged would have the least access to resources, like a therapist, or even a crisis hotline number, which likely skews his sample.

Anyways, Sam never claimed to be an expert in mental health statistics. So I did a little more research and found that, as usual, things are worse for the poor. Before Covid, both poverty and substance use disorders were found to be positive predictors of first-time suicide ideation. And poverty puts children and teenagers at greater risk of suicide.

So we may after all have to look out for the least among us, in wealth and stature. It also means that younger people may be having to look out an awful lot for each other.

Though according to Sam, many rich people are desperately unhappy, too. Which leaves me wondering, “Who does this world even work for?”

However this also means no one is immune, and depression and suicide can affect anyone’s family or social network. And we can all learn something about how to be there for others from crisis hotline workers.

 

So how should we talk to a depressed friend?

“Listen,” Sam says again and again.

“You’re not going to solve their problem,” he says. “What you can do is help them get through a moment.”

Our help shouldn’t be their be-all-end-all support system, and nor should we expect ourselves to single-handedly pull them out of their rut. However if we’re put in this delicate position, one of the best ways to help is by listening.

Unfortunately we get in our own way a lot. Sam says it’s normal for us – even those of us who think of ourselves as good communicators – to want to direct the conversation.

Since we naturally want a positive outcome, it’s easy to get distracted by that. However Sam emphasizes the need to keep the focus on the person. We might think that our advice can solve the other person’s problems, but it can’t, he says.

Put yourself in their shoes. More than anything, that person often needs someone to listen, to feel heard and understood.

Only ask open ended questions. A question that can be answered with a yes or no doesn’t encourage people to open up – and it means you’re directing the conversation (without even realizing it).

Here are some examples (but you can come up with your own list):

  • How have you been doing lately?
  • Why do you think you’ve been feeling that way?
  • What happened that makes you think that?
  • What do you think might help you?
  • How can I support you?
  • What do you want to do?

Above all, shut up and listen. We should, “Be cognizant of our own needs becoming impediments, and focus on creating a safe space for people to vent.”

 

What not to do

“Whether or not we have a good intention doesn’t matter in how effective we are at communicating,” Sam tells me.

If someone tells you they’re having suicidal thoughts, try not to freak out on them. This can make things worse. By staying calm, you make it safe for them to open up to you. But even then, we all struggle to communicate and listen.

“A person is not a problem to be solved,” Sam says. “It’s a process, it’s not about solving things.”

“We’re all bad communicators,” he says, “and we all have the same problems when it comes to communication.”

Careful! Even when we think we’re helping, we unconsciously find ways to try to control the conversation, whether because we feel uncomfortable and we’re nervous, because we think we know better, maybe we’re too eager to help, or even just eager to get out of the conversation.

“Have great respect for that which you do not know,” he says. “Just because you don’t understand someone, it doesn’t make them confused.”

Here are a few communication traps to avoid:

  • Patronizing, or treating the person as if they’re a sociological category. 
  • Trapping. Or asking leading questions like, “Have you tried… therapy?” “Have you tried… exercise?”
  • Minimizing the persons concerns. We might think it would help to reframe what seems like a difficult problem as “not that bad” or that it “could be worse”, but this can also make a person feel dismissed and unheard.
  • Anticipating – or finishing another’s sentences or thoughts for them.
  • And there’s scoreboarding, which is focusing on making your points instead of listening out of some need to be right.

 

How do you know if someone is depressed or suicidal?

“It’s often intuitive,” he says. “Look for clues, like has their behavior changed, are they taking care of themselves?”

Because so many people are isolated these days, it can be difficult to know who’s in trouble. It’s good to check in with friends you think might be vulnerable or having a hard time. And if you think someone you know is seriously depressed and might harm themselves, don’t ignore it. 

Don’t avoid the person, or act like everything is okay. “Depressed people are very observant,” Sam says, and they’ll usually notice if people are acting differently around them. So if it’s the elephant in the room, don’t be afraid to say that you notice it.

“They know it makes people uncomfortable, because it forces them to consider something that most people would prefer not to think about,” he says. So a lot of people who are suffering with suicidal thoughts may not bring them up because they think it will make people uneasy.

On the other hand, there’s a certain finesse involved. If your friend is depressed and you want to create a safe space where they can open up to you, maybe don’t just come out and say, “Hey buddy you seem really depressed lately wanna talk about it?”

Try to avoid judgmental language. Obviously if they’re hinting at it, or otherwise confided in you, they’ve opened up a door that makes it easier to communicate with them about serious issues.

If they’re more secretive, or not a close friend, you’ll have to use your best judgment to determine if and how to bring these issues up with them.

Sam suggests “tip-toeing your way into the conversation,” as you would into a pool, for instance by bringing up changes in their behavior.

For example, you might “tip-toe” your way in by asking something like, “I noticed you haven’t been leaving your room much, is everything okay?” or “You’ve been quiet lately, is something on your mind?”

Even if they say they’re okay, if they’re clearly not, you can leave your proverbial door open for them to chat with you. Make sure they know that they can text or call you if they need anything or just want to talk. Or invite them out for a coffee just to talk about life.

On the other hand, if someone is practically begging for help, pay attention.

“Take people seriously if they express or hint that they’d like to kill themselves,” Sam says. “Whether or not you think they’ll go through with it, it’s a call for help and a sign of something being seriously wrong.”

However, before diving (or tip-toeing) into a conversation, first ask yourself “Do I really want to get into this?” Because if you’re not willing to sit down and really listen, maybe you shouldn’t be the one having that conversation. If not, hotline numbers are below.

Remember, the golden rule: listen.  And empathy helps. That whole “do unto others” bit.

However if it becomes too much for you, or you don’t feel like you’re helping, get them to talk to a mental health worker or crisis counselor. Even calling a suicide hotline with them might help them overcome anxiety about making a call that could be the first step in getting help.

 

Just being there

There are other ways of supporting your depressed friends. Remember, they’re likely feeling alone, so just spending time with them or watching a movie (or chatting with them online or on Zoom) can make a big difference.

“Just being there has value,” says Sam. “We’re social creatures.”

listening to your friends

 

Sam adds that it may be tempting to want to hear a “thank you” at the end of the conversation. But people in distress are often so preoccupied by their problems they can’t think beyond them. 

“So sometimes you won’t get a thank you and that’s fine. Just being there listening – especially if they feel like they were heard,” can save someone else’s life, or at least get them through a moment.

 

If you or someone you know may be considering suicide, contact the National Suicide Prevention Lifeline at 1-800-273-8255 (en español: 1-888-628-9454; deaf and hard of hearing: dial 711, then 1-800-273-8255) or the Crisis Text Line by texting HOME to 741741. You can also find resources at the Samaritans website.