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Microdosing: separating fact from fiction

Experts discussed microdosing at the Microdose Wonderland conference in Miami. 



US collective to push for regulated access psychedelic microdoses

A group of experts gathered to discuss microdosing, and separate the fact from the fiction on the safety and efficacy of the practice. 

The last few years have seen a rapid emergence of people self-medicating with low doses of psychedelic substances such as psilocybin or LSD – known as microdosing. Reports of increased productivity, and reduced anxiety and depression have been grabbing headlines, but does the evidence support this?

Discussing the benefits and the “shadow side” of microdosing at the Microdose Wonderland event, conference panel members explored the paradoxes of the practice.

The experience of microdosing

Panel host, Paul Austin, founder and CEO of Third Wave highlighted that Albert Hoffman first talked about microdosing in a High Times article in the mid-70s, noting how 25 microgrammes of LSD would be useful as an antidepressant.

Austin described the practice as “something that has been a bridge between our normal waking state of consciousness and the chaos that comes from high doses of psychedelics.”

“For me, microdosing sheds a lot of anxiety, lets me be really present in conversations,” said Steven Holdt founder and CEO of Tune In Psychedelics. “So, instead of my brain running through a million things in my mind, I can actually be open and listen to people and connect with people better.”

Countering this experience, Dr Erica Zelfand, physician at Simba Health, noted: “Microdosing has helped me feel like everyone is mad at me, and like I am really nervous and want to go home and hide. So, I don’t microdose. I have experimented with it a little bit, that’s the psilocybin and then if I microdose LSD, I turned into a cyborg and get a lot of work done, and I don’t want to talk to you. 

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“That being said, I know that we are all wired a little differently and I do help my patients with microdosing, and that does different things for different people. So, I have seen the benefits that way.”

Natasha de Jong, co-founder and CEO of Earth Resonance, added: “What we have noticed is that the microdose is going help with breaking unhealthy habits – it is not from a force of willpower. I would describe it as being more from an “inner being”, a source that is giving you insights into why you are actually showing the behaviour and giving you the answers to that. 

“It gives you the insight to actually make a change and choose differently, and you can do it now. Not tomorrow, not yesterday – you live here in the now. Tthat is where microdosing helps you – to live in the present moment and to not worry about what’s tomorrow or fears for the future or worries.  I think it is also such a beautiful tool for PTSD through really integrating that.”

Limited research

Current clinical research is limited: the University of Chicago carried out a study on micorodsing LSD, and the Beckley Foundation looked at microdosing for brain-derived neurotrophic factor (BDNF), along with an experimental citizen science research study exploring the placebo effect of microdosing, and a further study has suggested psilocin (psilocybin is converted to psilocin in the gut upon ingestion) could cause cardiotoxic effects, to name a few. 

Panel member, Judy Blumstock, founder and CEO of Diamond Therapeutics, which is carrying out research on microdosing and published a paper earlier this year , said: “I think that 2021, when we look back at it, is going to be a watershed year – not just our study – but a couple of other studies.

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“They will be showing these very low dose effects in animals that I think are a watershed for us this year.”

Gregory Ferenstein, CEO at Frederick Research, added: “I think what the [placebo] study showed was that if you do psychedelics without any help, without any professional oversight or mindfulness practice, you are not going to get much out of it. And I don’t think that’s controversial.”

Calibrating dosing 

Austin highlighted the importance of calibrating microdoses due to individual differences, noting “what might work for someone is going to be totally different for another individual”. 

Dr Zelfand said: “So far as I know, there is no substance that I have found – a medicine, herbal, natural or synthetic – that works well for everybody. 

“What I have found is that the people who tend to do well with microdosing are the folks who are willing to take a more active role in their healing and who aren’t expecting the microdose to just solve all the problems for them so they can take a backseat and get better. 

“These are the folks that are wanting to maybe meditate more regularly or put their phones down at 8 pm and have less screen time and make other healthy changes in their lives. The microdosing is like a four-wheel drive for them to do that.”

The shadow side of microdosing

Although anecdotal evidence is pointing to a number of benefits from the practice, some people with certain medical conditions or psychological dispositions should not microdose, highlights Dr Zelfand.

“If we are talking about microdosing being like a kind of amplifier, we need to consider what it is that we’re amplifying. And I have seen microdosing push patients into manic states. And I’m not talking about flow states. I’m talking about true mania, and even psychosis.

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“There is still a lot that we don’t know about psychedelics. We’re learning a lot – from a research perspective is has been a bit like drinking out of a fire hydrant. We have all this information coming at us, and with microdosing, we don’t have as much data yet. So, it’s a little trickier to do studies in human subjects because these are controlled substances, and to do a microdosing study you have to send a person home with the substance, so then you’re trusting them not to divert it.”

Zenfeld notes that although for some the practice can arouse insight and creativity, in some people it can irritate the nervous system.

“In terms of folks who tend not to do well with microdosing, based on the limited literature that we have – individuals who have red green colour blindness, not always, but sometimes, they are at risk of getting “tracers”, which is when objects move, it looks like they have a trail of light after them. 

“Microdosing can also irritate people who have generalised anxiety disorder. So, not social anxiety, or situational, but low-grade anxiety – sometimes it really irritates them. As well, individuals on the autism spectrum tend to need much higher doses than what a microdose is going to give them. And then, individuals with a strong family history or personal history of mania or psychosis.”

The panel concluded by emphasising the importance of mindfulness practice when undertaking a microdosing protocol.

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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.”

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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.

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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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