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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 anesthetic 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. (You can read about the recreational or dark side of ketamine in Guy’s essay, at the end of this article. With over 20 years of street experience, I advise that you read what he has to say before going out and buying or trying street ketamine.)

2020 saw ketamine hit the headlines again as a successful treatment within clinics for patients suffering from treatment resistant depression.

Is ketamine really a psychedelic? Coined by Humphry Osmond (a British psychiatrist who gave Aldous Huxley his first dose of mescaline in LA in 1953, inspiring him to pen The Doors of Perception) the word psychedelic means “soul-revealing”, or “mind-manifesting” in Greek. Those words could certainly be used to describe Huxley’s essay. Many ketamine users would say “soul-revealing” is also descriptive of their experiences.

Ketamine is also a horse tranquilizer. It’s sometimes called a “dissociative” psychedelic hinting at a sense of disconnection, often from others, their environs, or users’ own bodies—but who knows? Perhaps they’re connected to something else. So the trip is quite different from something like mescaline or LSD, yet as with classic psychedelics like LSD, psilocybin, or ayahuasca,ketamine infusion therapy has shown promise as a treatment for depression, PTSD, OCD, anxiety, and even addiction.

Unfortunately ketamine is a lot more dangerous, and not nearly as effective as our beloved tryptamines (LSD, psilocybin, & DMT – including its derivatives & analogs & of course ayahuasca, the magical Amazonian brew). While ketamine may almost instantly resolve treatment-resistant depression, and even suicidality – which is undeniably a good thing – the relief may only last a week.

Ketamine treatment usually involves multiple infusions, and are often combined with psychotherapy. Ketamine infusion therapy that includes psychotherapy tends to be more successful. Still, in some cases a patient may need to get weekly or monthly infusions for years. So, while ketamine is a very effective short-term depression treatment, it’s not exactly a cure. As with other psychedelics, the trick might be to change your depressive habits – including your habits of thought – in the immediate aftermath, while your brain is still maleable from the experience.

It’s worth noting that a few magic mushroom and ayahuasca trips will trigger longer-term neuroplastic changes, accompanied by deep insights and lifestyle changes that can dispell depression for years.

(Clearly, we’re advocating that you give tryptamines a try before you get yourself in a k-hole. However if you still want to know more about ketamine – how it works and about its potential to treat depression, anxiety, addiction, & OCD, read on.)

 

Ketamine poison or remedyMoonlight Circus by BisBiswas

 

The ketamine market

 

Despite its risk of abuse, because of its anesthetic 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 means doctors can use it off label.

So ketamine clinics have been proliferating across the US (and now also the UK) and news of it as a panacea is still lighting up the marquees. Of course it will cost you a pretty penny. Since the treatment is experimental and not approved by the FDA, it’s not covered by insurance.

But the ketamine itself is cheap for the clinics. At just 0.1 – .5mg/kg per infusion, generic, medical grade ketamine costs doctors less than a dollar per patient, but of course, they charge you around $400 for the visit. Don’t worry, you can get a discount by buying a package (get eight shots in two months for the low price of $3,000!).

 

“As if the medical industry needed a boon,” I mumble through my depressed fog as I walk across town to the clinic to start a new round of ketamine infusions for $400/pop. My brain lost its plasticity, became rigid again this month after learning that my mother is facing bankruptcy as a result of medical debt. The house will be foreclosed on, and my thoughts are darkened with the certainty that I will never have my own home, and will be forever a victim of the rental market, paying my own and my mother’s rent to BlackRock til the day we die. I better work harder so I don’t lose my job, I think. After the ketamine shot, everything will be okay. For a week or so.

 

Most clinics offer ketamine in conjunction with therapy, but of course that’s extra. Many also offer ketamine infusions as a standalone treatment. The company MindBloom has quickly become a chain, and claims to be making ketamine infusion therapy as affordable as a visit to the psychiatrist.

MindBloom began offering ketamine treatment as telemedicine during the pandemic – sending packages of ketamine through the mail. I suppose the patients insufflated their powdery parcel as they connected with a nurse over Zoom. What could go wrong?

The startup was recently accused of negligence. Apparently it paid for its “low prices” by cutting and underpaying staff, and didn’t have enough trained therapists to ensure positive outcomes, among other oversights.

Still, if you’re going to use ketamine, any clinic should be safer than street ketamine, because the risk of addiction if you’re using it regularly on your own is high.

 

What is ketamine like?

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 spacey and empty, leaving you feeling a bit down.

 

Ketamine therapy for depression

 

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

Ketamine is also promising for those at risk of suicide; it has been found to significantly lower suicide ideation.

Ketamine is also fast-acting – most patients experience near total relief of depressive symptoms within one to 24 hours of treatment. On the down side, the antidepressant effects of ketamine typically wear off within one week to 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 brain-derived neurotrophic factor (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 characteristic of 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 is itself addictive, so it seems an unlikely candidate to treat addiction. However a study from 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 received only the therapy (the control group) continued using.

 

Ketamine 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.

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: relax. Let the experience wash over you.

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 , and a recent study found that supplementation with magnesium enhances ketamine’s antidepressant effects.

 

How does ketamine work?

 

As the main excitatory neurotransmitter in the brain, glutamate binds primarily to NMDA receptors. We need glutamate and NMDA receptors, because they are the main pathway for all learning and memory – but if your memories and learned habits are negative or unhealthy, your existing pathways, or thoughts, may need to be temporarily forgotten, those neural circuits weakened or broken.

Moreover, overactivation or “excitability” of NMDA receptors is implicated in chronic stress and anxiety, and can weaken neurons and cause cell death. The result is neural atrophy, a loss of neuroplasticity, and depression.

As an NMDA antagonist, ketamine temporarily blocks glutamate from binding with NMDA receptors, preventing activation of downstream neurons – interrupting, and causing us to temporarily forget those depressive thoughts.

Is having a break from all that we know what allows our brain to reconfigure itself after a ketamine experience? Momentarily forgetting the bad, are we then able to make new connections and create space for more positive thoughts?

Or is it that ketamine enhances neuroplasticity?

Or could it be both?

Neuroplasticity – something lacking in depressed subjects – is the prevailing theory. The blockage of NMDA receptors sets off a series of chemical processes that increase levels BDNF in the brain, a key protein for the growth of new neurons. BDNF levels are stunted in depressed subjects. People with depression also have more glutamate in the brain than healthy subjects, and their NMDA receptors are overactivated.

A healthy brain is plastic. That is to say, its dendrites are strong, with plenty of dendritic spines. Its synapses are dense, making it easier for neurons to connect. BDNF also supports the growth of new neurons.

By increasing BDNF levels, ketamine stimulates deteriorated parts of the brain to grow. The resulting neuroplasticity helps us to learn and form new thoughts.

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 both 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 discovered 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.

 

 

 

Magic mushrooms are healthy

 

The benefits of magic mushrooms: the research on psilocybin & mental health

 

By Katalina Lourdes

 

While sitting in the stairwell of my friend’s basement, I watched a photon come alive in a beam of light. When I closed my eyes, I saw God in the form of a pulsating star. This was my first experience on magic mushrooms.

As a teenager I refused to take my antidepressants on principle. I believed that my depression was trying to tell me something. I think this is often the case, that it signals a problem in your environment. Though resisting treatment risks prolonging depression – which is also bad for your health -there are alternatives to pills. In retrospect, I believe my experiences with magic mushrooms resolved my depression.

A recent study compared the efficacy of psilocybin (the active ingredient in magic mushrooms) against Lexapro, a typical SSRI, in treating depression. After six weeks of treatment, 57% of the patients who had taken psilocybin no longer met the criteria for depression, versus just 28% for the Lexapro group – suggesting that magic mushrooms may be twice as effective as traditional anti-depressants.

My teenage brain was onto something. Back then, getting your hands on mushrooms was a pretty underground thing. Fast-forward 20 years and psychedelics are a hot new trend, winning attention from the mainstream as a “miracle cure” for the our mental health epidoemic.

 

Research on the benefits of magic mushrooms

 

The first study to establish the value of magic mushrooms after limited research was reauthorized by the FDA in 1992 was carried out by Dr. Roland Griffiths at Johns Hopkins University in 2000. The results, published in 2006, paved the way for further psychedelic research.

The experiment was meant to assess the ability of psilocybin to induce mystical experiences. A high dose was administered to a small sample of healthy adults who regularly engaged in religious or spiritual practices, and two-thirds of the participants rated the experience among the five most meaningful experiences of their lives. 

These findings were replicated in a 2011 follow up study, in which participants showed improved attitudes, mood, and social relationships after taking four doses of psilocybin in a supported environment. The benefits of magic mushrooms persisted in follow ups both two and 14 months later. 78% of participants said the psilocybin sessions were among the five most meaningful experiences of their lives, and 94% said the same in a follow up 14 months later. None of the volunteers reported negative consequences resulting from the experiences.

In this study, each participant received eight hours of preparation, and had four sessions with four different dosages of psilocybin. Researchers found that the most effective distribution of the doses was from lowest to highest dose (5, 10, 20, & 30mg/kg). 

At the 14 month follow up, participants were asked to describe how the psilocybin experiences had impacted their lives. Here are some of their responses:

 

“I have a stronger desire for devotion, have increased yoga practice and prayer. I have better interaction with close friends and family and with acquaintances and strangers… I feel more certain of my career as an author. I need less food to make me full. My alcohol use has diminished dramatically… I consider myself to be better [at self-care] now than before the study…”

“I feel that I relate better in my marriage. There is more empathy – a greater understanding of people and understanding their difficulties and less judgment. Less judging of myself too.”

“I am more aware and accepting [of everyone]. I have a thousand ideas to write about and am making time and space in my life to accommodate them.”

 

Magic mushrooms, depression, and anxiety

 

Scientists (and more importantly, their funders) aren’t that interested in mystical experiences or benefits like creativity. Instead they’ve been in a dash to discover – and prove to regulators – the benefits of magic mushrooms in treating psychological disorders.

In a study of cancer patients published in 2016, those who took a high dose of psilocybin reported increased well-being and optimism, a higher quality of life, and lower depression and anxiety scores. Over 80% of patients continued to experience positive life changes at a six month follow up. Though in this study the patients didn’t receive therapy as a part of the experiment, they did talk about their lives beforehand and debrief their experiences afterwards with monitors. These findings have been replicated in other studies.

In a 2020study, 24 non-cancer patients with major depression received psychotherapy and two sessions of psilocybin. Four weeks later, 71% had a 50% or more reduction in their depression scores, and over half of participants were in complete remission.

In another study looking at the effects of psychedelics in non-clinical contexts, users reported being less depressed or suicidal after their trips.

An examination of existing data from a national survey also found that lifetime psychedelic use is negatively correlated with psychological distress and suicidal tendencies (though there was a positive correlation for other types of drug use).

 

Magic mushrooms and OCD

 

Mushrooms may also be useful in alleviating OCD. In a small study, OCD symptoms were reduced by at least 25% in 90% of participants (and by more than 50% in 67% of participants). The study was limited as it only measured symptoms up to 24 hours after ingestion.

However in one case study, a man found his OCD symptoms were greatly alleviated for about three weeks after consuming two grams (a moderate dose) of mushrooms.

Scientists have tested this theory in mice, finding that psilocybin reduces compulsive behavior.

 

Magic mushrooms and PTSD

 

There’s little research so far on psilocybin and PTSD, but what we do know suggests that magic mushrooms could help people who have been traumatized to heal.

Preclinical studies on mice are one source of data. One study found that mice unlearn fear responses faster when given low doses of psilocybin, suggesting that they’re less triggered by negative memories.

A separate study looked at the impact of psilocybin on the connection between the amygdala (the area of the brain that processes fear), the visual cortex (which perceives threats in the environment), and the prefrontal cortex. Hyperconnectivity between the amygdala and visual cortex has been linked to an increase in perceived threats and anxiety, characteristic of people with PTSD.

The authors explain:

 

“the amygdala may actually determine the affective meaning of visual percepts by its effects on sensory pathways — an effect which mainly occurs subconsciously and which may be greatly amplified in psychopathological conditions, such as anxiety disorders or depression. In this context, increased [amygdala] reactivity may lead to an increased attentional focus on negatively valenced environmental or social stimuli and thus effectively blocks out the processing of positive information.”

 

The researchers found that psilocybin reduces the amygdala’s connectivity with the visual cortex in response to threat-related stimuli. This means that after taking psilocybin, we may perceive our environments as less threatening, which could be an important mechanism for resolving PTSD.

Back from mice to men.

The Canadian Center for Mental Health Disparities has been doing important work researching the potential of psychedelics to heal racial trauma.

We commonly think about PTSD in terms of extreme, violent experiences like sexual assault or physical abuse. However Black, Indigenous and People of Colour (BIPOC) experience racism throughout their lives in overt or subtle forms. Everything from systemic discrimination to microaggressions and hate crimes, negative experiences based on racism have long-term impacts that may result in PTSD.

The study surveyed BIPOC in the US and Canada who had experienced racial trauma and recently taken psychedelics in non-clinical environments. The study concluded:

 

“Our lab has found that a single positive experience with a psychedelic drug can help reduce stress, depression, and anxiety symptoms in Black, Indigenous and People of Colour (BIPOC) whose encounters with racism have had lasting harm.”

 

This is one of the CMHD’s first studies on the subject, however it has many more in the pipeline, so if you’re interested in psychedelics and PTSD, and especially its intersections with racial trauma, watch their page.

Psilocybin also favors positive emotional processing, and this, coupled with its tendency to promote introspection and increase neural plasticity, could help patients form new understandings of traumatic experiences. New insights, emotional breakthroughs, and perceiving the world as less threatening all make psilocybin a likely candidate for the treatment of PTSD.

Anecdotal data support these theories, such as veterans taking matters into their own hands and reporting dramatic improvements in PTSD symptoms after taking magic mushrooms.

 

Magic mushrooms and addiction

 

Psilocybin may be able to reduce dependency on drugs and alcohol. Studies from the 1950s on the subject are typically discarded by modern science since they don’t employ current methodologies, and limited research has been carried out in the past decade, but it’s promising.

One study of 10 alcohol dependent people showed that they reduced their consumption following four weeks of psychosocial therapy and two psilocybin trips. Number of drinking days fell by 27%, and heavy drinking days fell by 26%.

An experiment with smokers was more promising. Participants took part in a 15 week course on quitting tobacco and received four weeks of cognitive behavioral therapy. Starting at week five, they had three separate psilocybin trips. Six months later, 80% of the subjects were completely abstinent from smoking.

These were pilot studies, so it’s possible further research will discover ways to improve their efficacy as a treatment here.

 

Qualitative research and personal accounts

While the explosion in research is quite recent, the quantitative research produced just in the past few years into the uses of psilocybin is daunting. So it was refreshing to see that a group of researchers had taken a qualitative approach to what is ultimately a very subjective experience, using an interpretive phenomenological analysis. Meaning, they focused on how volunteers made sense of their own experiences. Thefindings may offer more insight into what it’s like to trip on psilocybin – as well as why it’s effective in relieving anxiety, depression, and PTSD and addiction – than neurobiological explanations. Here are some excerpts from the study:

 

“General themes found in all or nearly all transcripts included relational embeddedness, emotional range, the role of music as conveyor of experience, meaningful visual phenomena, wisdom lessons, revised life priorities, and a desire to repeat the psilocybin experience. 

“Typical themes found in the majority of transcripts included the following: exalted feelings of joy, bliss, and love; embodiment; ineffability; alterations to identity; a movement from feelings of separateness to interconnectedness… 

“Variant themes found in a minority of participant transcripts include lasting changes to sense of identity, synesthesia experiences, catharsis of powerful emotion, improved relationships after treatment, surrender or “letting go,” forgiveness, and a continued struggle to integrate experience.”

 

Researchers and other officials recommend taking psilocybin under professional supervision and in conjunction with therapy, though the benefits of magic mushrooms are often pronounced in its absence.

Other sources of direct experience can be found in Erowid vaults, going back to the early days of the internet. A recent account describing a four gram trip reads:

 

“I was seeing very interesting visuals on the walls and when I closed my eyes. My thought processes were becoming absolutely ridiculous and indescribable. I couldn’t help but find meaning in absolutely everything, as if my life were some divine narrative…

“I felt myself fading away. Everything sounded as if I was very far away. I was having a hard time understanding anyone because I could not hear them very well. As I began to drift away, I was expanding. I was feeling the ground underneath me, the car, the trees and the mountains in the distance. I had the strangest feeling like my head was blooming or exploding in directions I cannot communicate.

“But one of the most interesting sensations was of being in my friends minds. Not that I could read their thoughts or anything, but I felt as I was swimming around in their heads. It was very peaceful. I felt in communion.”