denBefore 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

2020 saw ketamine hit the headlines 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’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. We’ll get to the recreational, or dark side, of ketamine later.

 

 

Ketamine poison or remedyMoonlight Circus by BisBiswas

 

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 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 less effective – or at least, its effects are shorter lived.

Ketamine clinics, like the company MindBloom, offer ketamine injections 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.

MindBloom, however, has recently been accused of negligence, as it pursues profit at the expense of having enough trained therapists and ensuring positive outcomes.

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 just too high.

 

What is ketamine like?

The ketamine high isn’t 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.

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 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 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.

 

 

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 while 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, while 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 while 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.

 

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, there are alternatives to medication. 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. 20 years later, psychedelics are a hot new trend, winning attention from the mainstream as a “miracle cure” for the US’ mental health pandemic.

 

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 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 who took four doses of psilocybin in a supported environment showed improved attitudes, mood, and social relationships in follow ups both two and 14 months later, demonstrating the long-term benefits of magic mushrooms. 78% 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.

The improved results in this second study likely had to do with repeated trips. Each participant had four sessions with four different doses, randomized. Researchers found that the most effective distribution of the doses was from lowest to highest dose. They also further optimized set and setting,; each participant received eight hours of preparation.

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. That’s where the money is.

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, 27 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 more easily able to let go of negative memories, or at least stop being triggered by reminders of them.

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.”

 

So, the researchers found that psilocybin reduces the amygdala’s connectivity with the visual cortex in response to threat-related stimuli. Which means that after taking psilocybin, we perceive our environments as less threatening. This 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 their trauma 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, with more veterans taking matters into their own hands, and reporting dramatic improvements in PTSD symptoms after taking magic mushrooms.

 

Magic mushrooms and addiction

 

Psilocybin has been found 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 even 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.”

 

How do magic mushrooms work?

 

Psilocybin acts like serotonin, activating its receptors, specifically binding to 5-HT2A and 5-H2C receptors. However it doesn’t follow the usual serotonergic pathways of our brains. Instead, normal pathways are disrupted, and the psilocybin activates new 5-HT2A/C receptors, forging new pathways, new connections, strengthening synapses, and creating new thoughts. When the psilocybin finally leaves us, our brain remembers some of those new thoughts, which we may experience as profound or life-changing insights.

Psilocybin’s serotonergic stimulation is also supposed to reducethe connectivity of the default mode network (DMN). The DMN is the part of our brain involved in self-referential thought, reflection but also rumination. It’s where we go when we’re thinking about ourselves, and deactivating these pathways when we’re depressed may be a key mechanism for psilocybin’s therapeutic effect.

Finally, when we’re under a lot of stress, depressed, or have PTSD, that stress response over time suppresses, atrophies, or even kills off a lot of our neurons.  Regions of our brain may even be seen to shrink as a result, especially the prefrontal cortex and hippocampus.

Serotonergic psychedelics such as psilocybin, LSD, and DMT have been found to directly reverse some of that atrophy by increasing the number of dendritic spines on neurons, and strengthening and creating new synapses. Psychedelics may or may not stimulate the creation of new neurons, but they at least help them grow, and these extra dendritic spines and synapses create more opportunities for diverse thoughts and new connections to be formed. This neural flourishing lasts well beyond the trip, which bodes well for future resilience, learning, decision-making, empathy, and creativity.

Scientists call the increased ability to form new connections “neuroplasticity”, and credit these structural brain changes with the revelations as well as long-lasting benefits that can come from psychedelic therapy. However our subjective, metaphysical experiences feel more than biological; there must be an element of magic.

 

 

 


“Our normal word-conditioned consciousness creates a universe of sharp distinctions, black and white, this and that, me and you and it. In the mystical consciousness of being at one with infinite Oneness, there is a reconciliation of opposites… there is an immediate experience of our solidarity with all being and a kind of organic conviction that in spite of the inscrutabilities of fate, in spite of our own dark stupidities and deliberate malevolence, yes, in spite of all that is so manifestly wrong with the world, it is yet, in some profound, paradoxical and entirely inexpressible way. All Right. For normal waking consciousness, the phrase, ‘God is Love,’ is no more than a piece of wishful positive thinking. For the mystical consciousness, it is a self-evident truth.”

– Aldous Huxley

 

 

 

 

 

 

 

“The artist’s task is to save the soul of mankind; and anything less is a dithering while Rome burns. Because of the artists, who are self-selected, for being able to journey into the Other, if the artists cannot find the way, then the way cannot be found.”

― Terence McKenna

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Our culture, self-toxified by the poisonous by-products of technology and egocentric ideology, is the unhappy inheritor of the dominator attitude that alteration of consciousness by the use of plants or substances is somehow wrong, onanistic, and perversely antisocial. I will argue that suppression of shamanic gnosis, with its reliance and insistence on ecstatic dissolution of the ego, has robbed us of life’s meaning and made us enemies of the planet, of ourselves, and our grandchildren. We are killing the planet in order to keep intact the wrongheaded assumptions of the ego-dominator cultural style.”

― Terence McKenna