Does Science Support the Use of Microdosing Stacks

Microdosing different substances such as psilocybin-containing mushrooms or LSD has become more popular in recent years, with the conversation not only focusing on the therapeutic benefits for managing things like depression or anxiety, but also on the perceived integrative benefits these substances might have in areas of our lives away from just the mental health side of things.

The internet is awash with stories of individuals utilising psychedelics to help them cope better in social situations and allow us to develop positive relationships with both ourselves and others, and this is of course a positive thing – but what if there was a way to use certain psychedelics in a way which allows us to ‘optimise’ their benefits in combination with other plants or fungi to support our daily routine? Microdosing stacks may provide a new avenue for those looking to support their mental health with fungi, but are these potential claims even rooted in science?

My experience as a consultant in the fungi industry has allowed me to keep up to date with the latest research surrounding non-psychoactive ‘functional’ mushrooms, such as lion’s mane, reishi, cordyceps, chaga, and turkey tail, as well as experience the benefits first-hand. These fungi have a wide range of benefits and noticeable effects, and we’ll be exploring these mechanisms of action and popular protocols, as well as looking at whether or not the science supports these synergistic combinations.

The concept of using different types of fungi for their combined effect has grown in popularity over the years. One common technique is known as ‘stacking’ – where individuals may use a combination of psilocybin-containing fungi, lion’s mane, and niacin (vitamin B3). This particular combination has been popularised by Paul Stamets, with the belief that this can provide neuroregenerative benefits in a synergistic way, allowing for the development of new neural pathways. This may aid with repairing neurological damage as well as providing benefits on a mental and emotional level. 

Stamets is so convinced that this combination works so well for cognition and neuroregeneration that he has even taken out a patent for it. With the benefits of psychedelic fungi being spoken about largely within the context of depression, there has been a lot of focus on the rewiring of neural pathways, which can facilitate the creation of new possibilities and allow us to potentially step out of the story of our depression, for example. This way of interpreting the benefits from a neurological perspective has made room for a targeted approach to our mental health, particularly when combining psilocybin mushrooms with lion’s mane, which is being closely studied for its brain-boosting benefits. 

The popularity of Paul Stamets in the psychedelic space has led to much focus on his specific stack, and this has made it difficult to find more research to support the use of combinations which involve other psychedelics such as LSD. Even the research to support the Stamets stack is rather lacking, and it seems to mostly come from Stamets himself, as well as the growing anecdotal evidence to support the claims about synergistic effects. 

Some comments on a Reddit post from almost a decade ago have discussed how the introduction of the supplement l-theanine (an amino acid and NMDA receptor agonist, found primarily in green and black tea and some mushrooms) into the LSD experience might potentially take the edge off, with user u/cosmicrush responding: 

I don't know. But it won't just lower or increase. It will modulate. NMDA agonists release gaba too. Theanine would maybe create a more calm and cleaner visual experience I think. Maybe less panicky

The potential to take the edge off a psychedelic experience is an interesting concept when it comes to microdosing, especially when some stacks are intended to enhance, rather than dampen, the experience. Are we possibly losing the potential to go deeper within if we’re taking the edge off the experience, or are we creating a calmer environment where we’re able to explore more safely without the distraction of potential anxiety?

I’m certainly an advocate for people engaging with these substances as they see fit, as long as they’re being taken in a responsible way where people aren’t causing harm to themselves or others, then I don’t think there’s a “one size fits all” when it comes to microdosing. There might be different combinations that work better for some than others, and we’ll explore the science behind the benefits of these added supplements in more detail to see where they can really provide support for microdosing protocols, as some might be wondering whether or not this is just more hype for a wellness trend. 

While some have argued that the microdosing experience is largely down to the placebo effect, there has been some interesting research over the past few years on the effects of consuming low doses of LSD (in the region of 5-20 mcg, for example) and psilocybin mushrooms. Studies have shown positive changes in mood, neurological connectivity, cognition, spiritual and emotional insights, and physiological health (such as pain tolerance). 

The research surrounding microdosing is still in its early stages, but the findings are certainly promising when looking at how these low doses have benefited individuals managing conditions such as depression or anxiety, especially within the context of increasing anecdotal reports of the benefits people are finding from microdosing alone. Individuals may follow certain protocols, such as the one developed by James Fadiman, who advocates for a three-day cycle, where on the first day the microdose is taken, with the second day to allow for reflection and integration, and the third day to allow the body to return to baseline.

The limitations on the research, such as a lack of funding or any standardisation of dosing protocols, have made exploring the benefits of microdosing somewhat challenging, and we’re still in the early stages of understanding how microdosing in combination with other botanicals or supplements might benefit us. There isn’t really much in the way of research when it comes to these combinations, but as we explore the science behind popular additions such as functional mushrooms, we can begin to understand how something like a ‘Stamets stack’ can provide extra support for our experiences, depending on what we need at that time. Although this stack incorporates lion’s mane, there may be other combinations that utilise the benefits of other mushrooms, such as reishi or cordyceps, which can be quite wide-reaching, given the nature of their bioactive compounds, as we’ll see later on. 

Before we dive into the benefits of different types of mushrooms, it’s important to explore how psilocybin mushrooms affect our brain. This helps us understand how to support our experiences with other types of fungi in the best way possible.

It seems that psilocybin mushrooms create a kind of ‘desynchronising effect’, where we experience disruption in areas of the brain responsible for our sense of self, as well as space and time. This disruption in brain connectivity and reduction in our sense of self may be responsible for some of the more psychedelic or spiritual aspects of this experience, where we are able to connect to something greater than ourselves, but also it seems this plays a role in the increase in neuroplasticity (the ability of the nervous system to change its activity in response to intrinsic or extrinsic stimuli by reorganising its structure, functions, or connections). This aspect may provide a natural route for combining psilocybin mushrooms with something such as lion’s mane, where there seems to be good evidence to suggest the active compounds contained within this mushroom also have a role to play in increasing neuroplasticity.

Traditionally used by Buddhist monks in Japan to aid with meditation, this popular fungus is being researched for its ability to potentially improve cognition. Beneficial compounds known as hericenones and erinacines have been shown to increase nerve growth factor (NGF), which is primarily involved in the regulation of the growth, maintenance, proliferation, and survival of certain target neurons. Lion’s mane’s popularity in the supplement market is largely due to the benefits it may have for memory and learning, and research has also shown that it can help to reduce oxidative stress and inflammation, which are linked to ageing and brain diseases. 

Some studies suggest it could protect against conditions like Alzheimer’s and Parkinson’s disease. NGF is involved in the creation of brain-derived neurotrophic factors, which are essential to memory and learning, and its role is primarily to help with the growth, maintenance, proliferation, and survival of nerve cells. 

One small, double-blind, placebo-controlled clinical trial was conducted in Japan by a company that sells mushrooms with 29 adults aged 50-80 who had been diagnosed with mild cognitive impairment. The results over a 16-week period showed that the group that consumed 3 grams of lion’s mane extract in pill form each day performed significantly better on the HDS-R cognitive test (a comprehensive assessment of cognitive abilities for people with dementia) than the placebo group. Despite a positive trend, this effect was blunted by 4 weeks after discontinuing the supplement, which suggests that sustained use of lion’s mane is required to obtain the benefits.

Lion’s mane, or an extracted molecule (Erinacine A), has also been reported to increase NGF expression and secretion, as well as protect against oxidative stress, which can aid with healthy brain ageing. In mice, lion’s mane improved memory, particularly in object recognition tasks, as well as long-term memory. There have been limited human trials, but as the functional mushroom market continues to boom, we’re seeing more people reporting the benefits of lion’s mane to aid with focus, cognition, and even conditions such as anxiety and depression. 

This cognitive benefit is generally what lion’s mane is marketed for, and it makes sense that people would be combining it with psilocybin mushrooms to maximise the synergistic potential of both of these fungi to improve our neurophysiology. While lion’s mane seems to be the most popular functional mushroom supplement, some people can be slightly sensitive to the active compounds and might feel too wired, especially if they’ve consumed this stack later on in the day. The Stamets stack has certainly become popular among those looking to utilise the power of nootropics supplements to improve their cognitive abilities and focus, but there might be other fungi that can provide different benefits, and allow us to take a more personalised or targeted approach to microdose stacking.

It seems that the inclusion of niacin (vitamin B3) is included in the Stamets stack to theoretically ‘flush’ the system, and increase the bioavailability of both the lion’s mane and psilocybin mushrooms, which could lead to some improvement in neurological function in individuals aged 55+. However, the research to support the inclusion of B3 is still in its early stages, and while this is ongoing, we can look to other botanicals and fungi that might also provide some extra support as part of a microdosing stack.

Known as the ‘mushroom of immortality’ in Traditional Chinese Medicine (TCM) and historically recommended for calming the spirit, this mushroom contains beneficial compounds known as triterpenoids, which have been shown to aid with sleep, relaxation, and inflammation. Triterpenoids such as Ganoderic acid A have also been shown to interact with the Gamma-Aminobutyric acid (GABA) pathway. Known as “the brakes of the brain”, GABA is an inhibitory neurotransmitter that lowers neural activity and so helps promote sleep.

Studies have found that the impact Reishi has on the GABA pathway is another reason why it can help us to fall asleep faster and stay asleep for longer. Reishi has also been linked to reducing neuroinflammation, helping with anxiety and depression, decreasing plaque formation, reducing oxidative stress, improving cognition, protecting neurons from damage, and supporting new neural growth. 

This may be a useful mushroom to combine with a microdose of psilocybin for those who might be feeling anxious before their experience. In general, the amount people are taking for a microdose shouldn’t really create a difficult experience, but some individuals might encounter some trepidation as to what to expect, or they might be going through an anxious state in their life and require some extra support. When taken in the evening, especially, reishi can provide a safe and comforting foundation for your microdosing experience, allowing you to calmly integrate the experience and fall asleep more easily. 

The potential to induce a calming and relaxing experience is probably quite appealing for most people, but depending on the situation, there might be those who require support for a more energising or motivating experience. 

This is possibly my favourite mushroom of all, given the huge variety of benefits it offers for both the mental and physical side of things! 

There has been a rich history of traditional use of cordyceps for at least 300 years in TCM and Tibetan folk medicine, with some estimates suggesting it’s been used for over 1,000 years. There are over 350 different species of cordyceps currently known about, only one species – Cordyceps sinensis – has been officially recorded in the Chinese pharmacopoeia since the 1960s, and it is harvested in the wild due to the fungus being a parasite that grows out of a host insect. 

In TCM, it was historically reserved for emperors and warriors, and has been recommended as a tonic to increase vital essence (known as Jing), stamina, and recovery, as well as restoring Yin-Yang balance and qi. It is often prescribed to anyone experiencing asthma, wheezing, allergies, and prone to catching colds, and as well as being traditionally recommended to manage lung issues, there has been some good evidence to suggest that cordyceps can help us utilise oxygen more efficiently.

The main beneficial compound, cordycepin, has been shown to stimulate the body’s cells to produce more of the molecule adenosine triphosphate (ATP) – this is essential for delivering energy to the muscles and improving your body’s use of oxygen during exercise. The cultivated species Cordyceps militaris has been shown to contain higher levels of cordycepin compared to wild varieties, and possibly allow people to consume smaller doses compared to the wild variety, which might allow for a more efficient microdosing protocol when combined with psilocybin mushrooms. 

While the bioactive compounds in these different fungi represent an intriguing opportunity to create a personalised stack to suit your needs, we should note that the bioactive compounds have plausible theoretical mechanisms that might support the benefits of psilocybin mushrooms, although the science behind microdosing stacks is still under-researched. We can certainly draw conclusions from what we understand about different types of fungi and other supplements to see where there might be some complementary benefit, as well as continue to explore the anecdotal reports, but it does seem like the science is generally lacking. 

I appreciate the impact that someone like Paul Stamets has had on engaging people more in the world of mushrooms and popularising the idea of microdosing, particularly when combined with other fungi – but it feels disappointing to not only see a patent on this protocol, but also a lack of scientific rigour to support the idea of stacking. Are people simply expecting the stacks to work and experiencing a placebo effect? This might be the case, and arguably it’s not a bad thing for people to be obtaining some benefit via the power of their own bodies, but when there are companies selling stacks of the back of the Stamets protocol, it might be useful to have some more scientific rigour behind the supposedly ‘groundbreaking’ combination. 

There might even be some potential side effects when it comes to microdosing, such as increased blood pressure or anxiety, and it’s not clear if the long-term use of microdosing stacks is necessarily safe. However, my exploration into the traditional interpretations of functional mushrooms seems to suggest a relatively high safety profile if used in a reasonable way, so as the research into these combinations hopefully increases, we might have more insight into how we can use microdosing stacks efficiently and safely. 

Different ingredients show promise individually, and there seems to be increasing popularity in the interest surrounding microdosing stacks, so the more we can push forward with scientific investigation into the synergistic effects of different combinations, the better we can understand what we can build into a protocol that suits our individual needs. There might be different times of the day to utilise certain botanicals for their desired effects, and this can help support us as we reflect and integrate our experiences.

If we can remain curious as well as being critically minded, we can continue to explore these exciting avenues to optimise the therapeutic potential of fungi and other substances as we shift towards new ways of engaging with our healing.

Oli is one of our community bloggers here at Chemical Collective. If you’re interested in joining our blogging team and getting paid to write about subjects you’re passionate about, please reach out to Sam via email at [email protected]