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‘The potential of psychedelics is immense and will only continue to grow’

Young bioscientist Freya Masters tells us why this is an exciting time to be involved in the field.



Freya Masters is a recent graduate from the University of St Andrews where she studied biochemistry. She tell us why we’re in the middle of a very exciting period for psychedelics research.

‘Think of the brain as a hill covered in snow, and thoughts as sleds gliding down that hill…think of psychedelics as temporarily flattening the snow…suddenly the sled can go in other directions, exploring new landscapes and, literally, creating new pathways’

This snow metaphor, devised by Mendel Kaelen, a postdoc at Imperial College London, describes the experience of a trip using psychedelics.

The word psychedelic derives from Ancient Greek words which translate to ‘mind-manifesting’.

It is thought that the experience of a trip is due to a powerful increase in brain ‘plasticity’, a biological process which causes alterations in neural circuitry, thus ensuring corrections in the brain’s structure and function.

Whilst the first lab-based experiment with the famous hallucinogenic lysergic acid diethylamide (LSD) was conducted in 1943 by Dr Albert Kurland, psychedelic substances have been used for thousands of years in culture.

Such substances are derived from mushrooms, tropical plants or cacti. Indeed, shamans dwelling in forests used N,N-Dimethyltryptamine (DMT) to access the spirit world and little mushrooms doused in honey were eaten by the Aztecs, who called the mushrooms teonanacatl (‘flesh of the gods’).

The ‘classic’ psychedelics, such as LSD or DMT, act as agonists at the 5-HT2A receptor, in doing so functioning to stimulate specific physiological responses, such as typical hallucinogenic effects.

The 5-HT2A receptor binds serotonin (or 5-hydroxytryptamine), the crucial hormone responsible for feelings of well-being and aiding bodily processes such as sleeping or digestion.

5-HT2A receptors are located in a brain region called the ‘default mode network’, which is active when we recall memories or daydream.

Therefore, this region is also most affected by psychedelics as they bind to and activate its 5-HT2A receptors.

The effects of classic psychedelics set in within 20-90 minutes of administration – for example, an increased heart rate or a distorted sense of time.

Second class psychedelics or ‘entactogens’, such as 3,4-Methyl​enedioxy​methamphetamine (a bit of a mouthful so we’ll call it the more commonly known MDMA) act as serotonin-releasing agents, resulting in feelings of empathy and wellness during a ‘trip’.

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One classic psychedelic is psilocybin, the psychoactive compound found in ‘magic’ mushrooms which was extracted in its pure form from the mushroom Psilocybe Mexicana by the swiss chemist Dr Albert Hofmann in 1959.

The use of entheogenic (a psychoactive substance for spiritual development) mushrooms by westerners was encouraged in the early sixties by the Mazatec curandera (‘medicine woman’) María Sabina, who used them when practicing veladas, sacred ceremonies.

Psilocybin is produced by over 200 species of fungi (or mushrooms) belonging to the genus Psilocybe, which are found in both tropical and subtropical regions of Mexico, South America and the United States.

Once in the body, psilocybin is converted to psilocin, by the removal of a phosphate group.

Psilocin is structurally similar to serotonin and is a modulator of serotonin receptors, conferring typical mind-altering effects of euphoria, a distorted sense of time or altered perception typically for two to six hours.

As the sixties progressed, taking psychedelics such as psilocybin for ‘trips’ was considered as illicit, with warnings of usage risks including birth defects and damage to chromosomes.

However, in more recent times, the field of psychedelic-assisted psychotherapy has exploded, with the past ten years seeing an exponential increase in research into the application of psychedelic substances for the treatment of depression, anorexia and Post-Traumatic Stress Disorder (PTSD) to name only a few conditions, or for the cessation of alcoholism and smoking.

Also in the past decade, the UK has seen the demand for antidepressants more than double.

During lockdown, a 20% increase in the number of antidepressant/anxiety prescriptions was observed in the US.

In that sense, the coronavirus pandemic can also be viewed as a global mental health crisis.

A new breakthrough in mental healthcare is required.

Psychedelic therapy could be this much-needed, fresh line of treatment over the more conventional drug therapies.

Indeed, in 2019, the Food and Drug Administration (FDA) stated that psilocybin-assisted therapy is a ‘breakthrough therapy’.

With the opening of centres for studying the therapeutic potential of psychedelics, such as the University of California (Berkeley) and John Hopkins university in Baltimore, major shifts have occurred in the field.

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Here in the UK, Imperial College London opened the world’s first centre committed to researching the clinical potential of psychedelic compounds: The Centre for Psychedelic Research (founded in April 2019). Several ‘landmark’ studies have been conducted into the exciting therapeutic possibilities of psilocybin at Imperial.

One such study, which focused on twenty patients with the treatment-resistant form of depression, elucidated that psilocybin may play a role in resetting the neural circuitry involved in depression.

Whilst the sample size was small, the benefits of psilocybin were perceived to last up to five weeks after treatment, with one such benefit to be an observed reduction in blood flow to the amygdala.

This is the region of the brain involved in processing emotions including fear or stress.

Additionally, the selective serotonin reuptake inhibitor (SSRI) escitalopram was tested against psilocybin; this study is among the most thorough conducted for a psychedelic medicine. 

SSRIs, which normally function to create novel connections in the brain, increase neuroplasticity to moderate the stress response, however their mode of action is not curative.

Whilst the results of the study indicated that psilocybin achieved a reduction in depression to the same extent as escitalopram, with strong suggestions that psilocybin even surpassed the SSRI in terms of performance, conclusions were ambiguous, with larger-scale trails for longer periods of time required.

This was due to the study’s focus on the depression metric to assess outcomes, a measure recognised by the FDA. Essentially, different measurements of well-being may have conferred other results.

Another exciting study by Imperial has involved patients who have suffered from anorexia nervosa for over three years.

It is thought that psilocybin may function at a pharmacological level in targeting the imbalance of serotonin in the brain characteristic of anorexia nervosa and by prompting developmental changes, for example in encouraging feelings of self-worth.

Through eight study visits, variable psilocybin doses were administered, and progress checked through a combination of psychological measurements, magnetic resonance imaging (MRIs) and electroencephalogram (EEG) recordings.

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The follow-up period of the study is currently ongoing.

Imperial have also been the first to elucidate the effects of LSD, one of the most potent classical psychedelics and a highly controversial drug in society, in the brain through modern brain imaging.

LSD was initially synthesised from lysergic acid (derived from the fungus Claviceps purpurea among other species) by Albert Hofmann in 1938.

It is known that LSD shares common chemical structures with psilocybin and DMT and is thought to bind to serotonin and dopamine receptors such as 5-HT2C and 5-HT1A.

Initial studies for the therapeutic application of LSD were conducted in the 1950s.

However, after the criminalisation of LSD in the USA in 1996, the therapeutic potential of this psychedelic remained unknown.

More recently, the most promising therapeutic application of LSD has been for the treatment of alcoholism as well as for reducing anxiety in those patients who are living with a life-threatening disease.

It is important to note that the studies outlined in this article took place under conditions which were highly controlled, with drug therapy administered in combination with crucial psychotherapy support in regulated environments.

The placebo effect (in which a patient believes in the fake drug’s – the placebo’s – treatment benefits and starts to feel better) also presents a challenge to the interpretation of results.

Additionally, experimentations with powerful psychedelics such as MDMA (an amphetamine derivative), present a risk of an enduring psychotic reaction or substance abuse.

Despite these limitations, the potential of psychedelics for the treatment of conditions such as PTSD or depression is immense and will only continue to grow, as research in this exciting field develops.

The general hope is that, within the next few years, psilocybin therapy in particular will be licensed and marketed in North America and Europe.

One day, through extensive scientific research, psychedelic-therapy may be used in place of normal drug therapies, to enable thoughts, like sleds, to explore afresh and forge novel, healing connections in the minds of those who need it most.

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Psilocybin therapy for end-of-life care supported by 79% of Canadians



The Entourage Effect in Mushrooms: Natural psilocybin may outperform synthetic

A new survey has revealed that over 79% of Canadians support psychedelic-assisted therapy for existential distress at the end of life.

People facing a terminal diagnosis often experience significant distress. Depression, anxiety, existential distress and loss of meaning or purpose can make this type of diagnosis difficult to deal with.

Current treatments consist of counselling of cognitive behaviour therapy (CBT), but these are not always effective for everyone, creating a need for innovative new approaches to end-of-life care.

Increasing research is now showing that psychedelic therapy may be beneficial for treating existential distress in patients diagnosed with incurable diseases.

For example, a review published in 2018 in Neuropsychopharmacol Biol Psychiatry found that patients with life-threatening diseases associated with symptoms of depression and anxiety benefitted from the anti-anxiety and anti-depressant properties of psychedelics.

The studies reviewed anecdotally reported that patients experienced quality of life improvements along with a reduced fear of death.

A randomized double-blind trial carried out by John Hopkins University also revealed that high-dose psilocybin produced significant decreases in depression, anxiety and death anxiety, and improvements in quality of life, life meaning, and optimism.

A further clinical trial from New York University found that 60% to 80% of participants experienced anti-anxiety and anti-depressive effects from the treatment, along with benefits for existential distress, quality of life, and attitudes towards death, noting that “the psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression.”

Supporting psychedelics for end-of-life care

In light of psychedelic therapy’s inclusion in Canada’s Special Access Programme in 2022, which enables authorised patients to receive access to these therapies if other treatments have been unsuccessful, a team of researchers set out to understand the public’s opinion on the potential easing of rules surrounding the medical use of psilocybin.

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The survey, published in Palliative Medicine and carried out by Michel Dorval and Louis Plourde at Université Laval’s Faculty of Pharmacy and researchers from McGill University, Université de Montréal and UQAR, revealed that nearly four out of five Canadians support the use of psilocybin as a treatment for end of life existential distress.

In a statement, Dorval commented: “Studies have already shown that psilocybin, combined with psychotherapy, produces rapid, robust and lasting anxiolytic and antidepressant effects in patients suffering from advanced cancer.

“This substance can bring about a profound awareness that leads the patient to view existence from a different perspective. Treatment with psilocybin, combined with psychotherapy, can produce relief for up to six months.

“Our results seem to indicate that the social acceptability of this intervention is high in the Canadian population. If we consider only Québec respondents, the acceptability rate is similar to the national average.”

The findings also revealed that public support for psilocybin is higher among respondents who have already been exposed to palliative care, as well as higher in respondents who have already used psilocybin.

“Having been close to loved ones at the end of life, or having witnessed their distress, could explain this openness to new approaches designed to help people at this stage of their life,” added Dorval.

“There are still many prejudices against psychedelic substances. Familiarity with these substances probably helps to better understand their true effects as well as their therapeutic potential.”

The authors write: “The social acceptability of psilocybin-assisted therapy for existential distress at the end of life is rather high in Canada. These findings may contribute to efforts to mobilise resources and improve access to this emerging therapy in palliative and end-of-life care settings.”

See also  Psilocybin therapy for end-of-life care supported by 79% of Canadians

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Ketamine: understanding the K-Hole



Ketamine: understanding the K-Hole
Photo by Gary Meulemans on Unsplash

Ketamine is an FDA-approved medical anesthetic and recently a prescription nasal spray version of ketamine called esketamine (Spravato) was approved for treatment-resistant depression.

Ketamine is an interesting drug because it can exist in three different forms, R-ketamine (the aesthetic version), S-ketamine (the psychedelic version), and a mixture of the two (racemic ketamine).

Ketamine is typically used to put you under before surgery, however, lighter doses that don’t put you to sleep are being used to treat depression, pain, and other mental health and substance use disorders.

These “off-label” uses have led to the popularization of the therapeutic use of ketamine. This has given rise to ketamine clinics where one can pay out-of-pocket for a dose administered by a doctor in a luxuriously curated “set-and-setting” (more on ketamine therapy in Nina’s Notes #18).

The patented, FDA-approved formulation of S-ketamine, Spravato, is estimated to generate $1 billion in revenue in 2023.

In addition to the rise in ketamine use for mental health, and despite its legality, the recreational use of ketamine is rising in popularity and has quite a history of illegal recreational use.

A term frequently used with the recreational use of ketamine is “k-hole”. People use it by saying things like, they are “stuck in a k-hole” or they could have “fallen into a k-hole.”

What is a k-hole?

A k-hole is the term referring to the dissociated, trance-like state that sometimes follows acute, excessive use of ketamine.

K-holes most often occur in recreational settings, like a nightclub or house party.

The dissociative effects of ketamine are dose-dependent, meaning the more you administer the greater the felt effects.

Receiving a ketamine treatment at a ketamine clinic will likely not result in a k-hole. The dose for the therapeutic experience is finely measured for the client, is administered in a safe clinical setting, and a physician can closely monitor the medicine’s effect.

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When in a k-hole, one may be unable to interact with surroundings, control motor functions or maintain awareness of their external reality. An individual may temporarily be unable to speak, walk properly or maintain their balance. They may even find themselves feeling temporarily “paralyzed” or physically inhibited.

These motor-control symptoms are often paired with a strong internal experience, visions or visuals and an altered state of consciousness.

Experientially, it can feel like “falling into a hole” which is where the term k-hole comes from. K-holes can last as long as 5 minutes or up to roughly 30 minutes.

For some, experiencing a k-hole can be highly transformative and powerful, for others it may be a frightening experience.

Why does it happen?

Ketamine is a dose-dependent drug, the larger the dose, the bigger the effects.

While entering a k-hole is rarely the aim of a ketamine user, it can easily happen in a party setting where people may be taking multiple doses within a short period of time.

Ketamine is a white powder, similar to cocaine, which many users ingest through snorting. If a ketamine user has a history of cocaine use, they may use the drug at the same frequency due to previous habits, which can sometimes lead to k-holing.

Why is that? It’s because the half-lives of cocaine and ketamine are both short, but very different.

The half-life of ketamine

Half-life is the time it takes for the total amount of a drug in the body to be reduced by 50%. The half-life of ketamine is about 2.5 hours.

This means that it takes 150 minutes for a dose of ketamine to become a half dose in your body. Meanwhile, the ketamine high lasts about 30-45 minutes. In comparison, the half-life of cocaine is 40-90 minutes, and the high is about 15-25 minutes. Cocaine is metabolized very quickly and the high lasts about a third of the half-life of the drug.

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So half of the drug is cleared from the body at close to the same rate as the user feels the effects. Drug gone = effects end.

Because the half-life of Ketamine is about 150 minutes and the high is about 1/5th of that, a user could be going for a second, third or even fourth dose before half of the first dose is metabolized by the body.

So, with repeating doses, the total amount of ketamine in your body builds over time. A user may not feel the strong effects of ketamine anymore, but they still have more than half of a dose still in their body. When they take another dose, they risk falling into a k-hole.

What happens in a k-hole?

A k-hole can lead to intense feelings of dissociation causing feelings of being disconnected from or unable to control one’s own body.

It may also affect the ability to speak and move easily. One way to think about a k-hole is a state between intoxication and a coma. Some refer to a k-hole as an out-of-body or near-death experience. A k-hole can be frightening and induce strong feelings of powerlessness. This can be especially intense if the ability to speak is affected.

Others might not notice someone in a k-hole. They might just look immobile and intoxicated, but their mind is far from quiet. They may be experiencing vivid, dream-like hallucinations and distortions of time and space. Other k-hole symptoms include confusion, unexplainable experiences and floating sensations.

While some people find the psychedelic experience enjoyable, others find it terrifying. Some describe falling into a k-hole like a bad LSD trip. Keep in mind the whole experience may last from 10 minutes to an hour.

See also  Psilocybin therapy for end-of-life care supported by 79% of Canadians

Signs of a ketamine overdose

Know the signs of a ketamine overdose so that if someone at a party is exhibiting symptoms, you can get them immediate medical attention.

Although the risk of an overdose from ketamine is low, it can increase outside of a clinical setting. The overdose risks are higher when ketamine is mixed with other substances such as alcohol, opioids or other recreational drugs.

Overdose symptoms can include anxiety, chest pain, elevated blood pressure, hallucinations, loss of consciousness, nausea or vomiting, rapid or irregular heart rate, and seizures.

A k-hole, however, is a common experience due to excessive use of ketamine over a short period of time. It is not a ketamine overdose.

Though a k-hole is a temporary experience, there are several long-term side effects with extended recreational ketamine use, such as bladder problems, cognitive effects, heart problems, and seizures.

While there is no way to guarantee a perfectly safe experience with ketamine, using it outside of doctor supervision, its effects can be extremely unpredictable compared to other drugs.

With the rising popularity of ketamine in both medical and recreational spheres, this calls for a balanced perspective, appreciating the therapeutic potential of ketamine while being acutely aware of its potent effects and the dangers of excessive use.

This article was first published on Nina’s Notes and is republished on Psychedelic Health with permission.

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Beyond Psilocybin: the fascinating world of functional mushrooms



Beyond Psilocybin: the fascinating world of functional mushrooms

I typically write about psilocybin, the hallucinogenic compound in mushrooms. But mushrooms have many more interesting properties than just psilocybin.

There are well over 14,000 species of mushroom-producing fungi that have been identified so far. It is believed that many more exist and have yet to be discovered. In 2017, an article in Microbiology Spectrum estimates that there are between 2.2 and 3.8 million different species of fungi.

Functional mushrooms are a category of mushrooms that have been traditionally used for their health benefits.

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They have been incorporated into Eastern medicine for thousands of years, especially in Asian cultures. These mushrooms are not your typical culinary mushrooms. They are often found in supplements, teas or other preparations to be used for health-enhancing benefits.

Popular Functional Mushrooms

Reishi (Ganoderma lucidum)

Known as the “mushroom of immortality,” reishi mushrooms are often used for immune support and to promote relaxation.

Reishi mushrooms may positively affect white blood cells, a critical part of your immune system. A 2006 study found that ingesting reishi could increase the number of white blood cells in those with colorectal cancer.

They were also shown to improve the function of lymphocytes in athletes when they are exposed to stressful conditions.

Reishi mushrooms may also reduce fatigue and depression.

Lion’s Mane (Hericium erinaceus)

This pom-pom shaped mushroom is native to North America, Asia and Europe.

It is recognized for its potential neuroprotective effects, protecting nerves from disease or decline.

Lion’s mane has also been studied for its effect on neurons, and has gained the title “the smart mushroom” due to its potential to boost cognitive function and minimize brain fog.

It may also have potential benefits in addressing the cognitive decline associated with conditions like Alzheimer’s and Parkinson’s diseases. The bioactive compounds in Lion’s mane, hericenones and erinacines, may promote the production of growth factors and protect against brain damage.

Chaga (Inonotus obliquus)

Chaga is a black, parasitic mushroom, which looks like a lump of burnt coal.

It’s high in fiber, low in calories, but rich in minerals and vitamins.

Chaga has been used to treat diabetes, parasites, tuberculosis, and inflammation.

The oldest reference to the use of chaga mushrooms as a medicine comes from Hippocrates in his Corpus Hippocraticum, in which chaga is used to wash wounds.

For medical treatment, chaga is usually ground to a fine powder and made into a tea for its antioxidant properties and immune support.

Cordyceps (Cordyceps sinensis)

Fortunately, not the Cordyceps that infect the brains of mankind in the popular The Last of Us series.

Though creepy to look at, Cordyceps is a fungus that lives on certain caterpillars in the high mountain regions of China.

It is traditionally used to boost energy and improve athletic performance.

Cordyceps is believed to increase the flow of oxygenated blood throughout the body, boost metabolic rates, increase stamina and help muscle recovery.

Turkey Tail (Trametes versicolor)

Turkey tail is valued for its immune-boosting properties, specifically its medicinal properties as an antitumor, antimicrobial, immunostimulant and antioxidant.

It is also believed to improve bone strength and regulate blood glucose.

And some report that turkey tail can prevent urinary tract infections (UTIs) and protect against age-related cognitive decline.

Shiitake (Lentinula edodes)

Apart from being a popular culinary mushroom, shiitake is also known for its immune-modulating effects.

Traditional Chinese medicine considered shiitake a food that enhances vital energy. It is a great source of nutrients, high in protein, low in fat, and contains iron, calcium, zinc, along with vitamins B, E and D.

Easily accessible at any grocery store or market, shiitake mushrooms can be prepared to eat, or taken as a supplement for its functional properties.

What are some popular functional mushroom products?

You may have seen Ultimate Shrooms in your local health store. It’s a product that contains Cordyceps, Reishi, Chaga, Lion’s mane, Turkey Tail, Maitake, Shiitake and Oyster mushrooms.

Live Ultimate, the brand behind Ultimate Schrooms recommend adding two tablespoons with a full glass of water, juice or smoothie in the morning on an empty stomach.

Mushroom Coffee is also gaining popularity, like the product Four Sigmatic which contains Chaga and Lion’s Mane.

Some functional mushrooms, like Reishi, are less appetizing when eaten in their natural form. Thus people have begun consuming them in a power form, adding them to smoothies, teas and coffee, to improve the taste.

Functional mushrooms can offer a wide range of health benefits, though it’s essential to purchase mushrooms from a reputable source, and understand their proper preparation. Not all claims for health benefits have been substantiated by clinical trials.

It is also important to consult a healthcare professional before incorporating functional mushrooms into your diet and routine, especially for those with pre-existing medical conditions.

This article was first published on Nina’s Notes and is republished on Psychedelic Health with permission.

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Psychedelic Health is a journalist-led news site. Any views expressed by interviewees or commentators do not reflect our own. We do not provide medical advice or promote the personal use of psychedelic compounds. Please seek professional medical advice if you are concerned about any of the issues raised.

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