Insight
Exploring the entourage effect in psychedelic mushrooms

Published
4 months agoon

As hypothesised with cannabis, could the ‘entourage effect’ play a role in the therapeutic effects of psilocybin mushrooms?
Put forward by Dr Ethan Russo in 2011, the entourage effect is a hypothesis that different compounds in cannabis work synergistically to create a therapeutic effect. This is as opposed to compounds such as THC or CBD working in isolation.
However, the hypothesis has been touched on a handful of times in the scientific literature in relation to psychedelic mushrooms.
One instance is the 1989 paper ‘Biotransformation of tryptamine derivatives in mycelial cultures of Psilocybe’ by Dr Jochen Gartz, who proposed a synergistic relationship between compounds in the mushrooms.
Another example is a 2015 paper ‘Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice’ by Zhuck et al, who observed the effect of psychedelic mushroom extracts on mice was much stronger than pure psilocybin.
Clinical trials
With a sharp increase in clinical trials and research looking at the therapeutic potential of psilocybin for mental health conditions, more research is needed to understand how mushrooms work to have therapeutic effects.
Currently, the majority of clinical trials and research into psilocybin are using isolated psilocybin. However, much like cannabis, psychoactive mushrooms contain many other compounds that could play a role in the reported therapeutic effects.
Additionally fuelling this theory are the many anecdotal reports that suggest different species of psychoactive mushrooms have their own unique effects.
Mycologist Alan Rockefeller specialises in DNA sequencing and fungi photography and has discovered and named the psychoactive mushroom species Psilocybe allenii, along with co-authoring a 2020 publication characterising five psilocybe species.
Speaking to Psychedelic Health, Rockefeller commented: “No one really knows whether the entourage effect occurs with mushrooms.
“It is difficult to study because the same batch of mushrooms will have different effects in different people, and the same person on different days.”
Challenges with multi-compound research
Often, synthetic psilocybin is used in research because running clinical trials and conducting research on organic, multi-compound medicines can pose a number of challenges.
They often contain hundreds of different compounds – for example, cannabis has over 400 known compounds including THC, CBD, CBG and CBN. Some of the different compounds contained in species of psilocybe mushrooms include psilocybin, psilocin, baeocystin and norbaeocystin.
Having a large volume of different compounds can make identifying which ones are active and what their impact is difficult to measure. To add to this, the concentrations of these compounds can vary depending on factors such as growth conditions and processing techniques.
In this context, the standardisation of multi-compound medicines is a huge challenge, as medicine consistency, reproducibility and dosing all become very difficult. However, these are essential factors when it comes to conducting clinical trials and receiving approval for medicines from regulators.
“There are a dozen different tryptamines that can occur in mushrooms, plus a few beta-carbolines and hundreds of other molecules – so there is probably more than just psilocybin having an effect,” said Rockefeller.
“Studying one compound at a time is hard enough, studying mixtures of hundreds of compounds is much more difficult. Without pure compounds, it is difficult to get repeatable results.
“It is possible that the therapeutic potential is different depending on the different compounds in the mushrooms. It’s also possible that psilocybin is the only thing that matters, and the other compounds are mostly inactive.”
Further challenges with researching multi-compound medicine and understanding the entourage effect in psychoactive mushrooms, is understanding the pharmacokinetics – which is absorption, distribution, metabolism and excretion – and pharmacodynamics – effects on the body.
Then, there is then the challenge of understanding the compounds’ interactions with other drugs.
Challenges with regulations
Cannabis has faced many challenges when it comes to its medical use. While the USA has legalised medical cannabis in most states and more countries across Europe and the rest of the world are embracing medical cannabis, only three cannabis-based medicinal products (CBMPs) have been approved for use in the UK, for example.
These contain isolated cannabinoids extracted from the cannabis plant and do not contain a variety of cannabinoids.
To add to these challenges, in many countries, regulators require rigorous efficacy and safety data of medicines before they can be approved, and frameworks for investigating this are designed for single-compound medicines.
Researching psilocybin is already incredibly expensive due to high licensing costs due to it being place placed in Schedule 1 of the UN Convention on Psychotropic Substances 1971, along with drugs such as raw opium.
Investigating the multiple compounds contained within psilocybin species of mushrooms would add to these costs, as research and trials into multi-compound medicines require significant financial support.
Securing such funding can be a major challenge as investors may perceive higher risks associated with this type of research.
“The different active compounds in mushrooms need to be separated or synthesised, and clinical trials need to be done with the various pure compounds and these compounds in various combinations,” Rockefeller concluded.
You may like
Psilocybin analogue shows positive results in Phase 2 depression study
Mychedelica launches to revolutionise psychedelic medicine
Clerkenwell Health calls for volunteers to support groundbreaking psychedelic research
Short Wave Pharma: innovating eating disorder care with psychedelics
Compass Pathways launches Phase 3 psilocybin trial in UK
Canada recommends launch of Veterans psychedelic research programme

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.
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.
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.
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.
Insight
Beyond Psilocybin: the fascinating world of functional mushrooms

Published
3 weeks agoon
10th November 2023
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.
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.

A report has revealed that the consumption of ayahuasca is increasing in several countries.
Published by Carlos Suárez Álvarez and the International Center for Ethnobotanical Education, Research and Service (ICEERS), the report documents ayahuasca use across the Netherlands, Spain, the USA and Colombia.
Ricard Faura, the Bridge Weaver for ICEERS and collaborator on this research, commented: “It is clear that the global landscape of ayahuasca practices is evolving dynamically and steadily and this global expansion presents great challenges.
“It is therefore crucial to have a clear understanding of what is happening. This is why our research sheds light on the details of this expansion in various countries around the world and contributes to formulating a more inclusive and informed future.”
Use across continents
The report reveals that Colombia, which has deep-rooted cultural ties with ayahuasca, has the highest percentage of ayahuasca drinkers among the studied nations.
The prevalence was attributed to the ayahuasca practices within Indigenous communities and the support they have received at the institutional level.
The country with the second highest prevalence of ayahuasca drinkers is Spain, followed by the Netherlands, where, the report highlights, a long-standing ayahuasca community faces tightened regulations on the importation of the medicine, reflecting the delicate balance between traditional practices and legal frameworks.
However, the USA is the country with the highest number of ayahuasca drinkers globally.
Reported deaths
According to the report, there is an estimated four million ayahuasca drinkers worldwide.
Following analysis of deaths reported by the media, the report found 58 documented cases of ayahuasca-related deaths.
ICEERS has stated that so far “no forensic examination has determined that ayahuasca caused these deaths”.
ICEERS stated: “This ICEERS research underscores the importance of accurate reporting, responsible practices, and informed dialogue about ayahuasca.
“The organisation encourages further research and open discussions to support the well-being of individuals seeking the benefits of ayahuasca in a diverse range of cultural and legal contexts.
“This analysis not only broadens the understanding of ayahuasca’s global footprint but also navigates the complex terrains of legal, cultural, and social factors that shape ayahuasca consumption in diverse contexts.
“These findings underscore the need for a well-informed, respectful approach to ayahuasca to support its reverent integration across diverse landscapes.”
The Netherlands, Spain, the USA and Colombia countries have are part of an in-depth research project published by ICEERS earlier this year.
Recent Articles
- Psychedelic therapy programmes launch to address heartbreak, burnout and more
- Psilocybin analogue shows positive results in Phase 2 depression study
- Ketamine: understanding the K-Hole
- Mychedelica launches to revolutionise psychedelic medicine
- Clerkenwell Health calls for volunteers to support groundbreaking psychedelic research
- Short Wave Pharma: innovating eating disorder care with psychedelics
Trending
- Psychedelic therapy programmes launch to address heartbreak, burnout and more
- Psilocybin analogue shows positive results in Phase 2 depression study
- Ketamine: understanding the K-Hole
- Mychedelica launches to revolutionise psychedelic medicine
- Clerkenwell Health calls for volunteers to support groundbreaking psychedelic research
Trending
- Opinion2 years ago
Clerkenwell Health is launching a free UK psychedelic therapist training programme
- Insight2 years ago
Mixing psychedelics with lithium poses significant risk of seizures
- Medicinal2 years ago
MDMA therapy for PTSD granted innovation passport by UK
- Research2 years ago
LSD trial for the treatment of adult ADHD initiated
- Markets & Industry12 months ago
Where can I find training for psychedelic therapy?
- Medicinal2 years ago
MDMA: the love drug?
- News2 years ago
Awakn’s second psychedelic therapy clinic to open in London
- Research2 years ago
London to host Europe’s first commercial psychedelic clinical trial facility