Beyond Psilocybin: These Mushrooms May Offer Brain-Boosting Compounds, Too

While the trippier fungi have stolen the show, several of their relatives are being investigated to treat common mental health conditions and neurodegenerative disorders.

Psilocybin, a psychoactive compound found in some psychedelic species of fungi, has received a flood of attention in recent years for its potential in treating mental health conditions like anxiety, depression and PTSD. But it isn’t just trippy fungi that could deliver major brain benefits:

Scientists are also looking into a host of other species that could help combat conditions affecting the mind, such as neurodegenerative disorders like Alzheimer’s and Parkinson’s disease and common mental illnesses.

Fungi have long attracted scientific inquiry. For starters, they’re known to offer diverse, powerful collections of compounds called secondary metabolites that help them compete in the wild. These compounds have already provided us with a range of life-saving drugs, such as the antibiotic penicillin, the chemotherapy treatment Taxol, and the cholesterol medication Lovastatin.

Many types of fungi are sold in the U.S. as supplements in the form of ground powders. Lab experiments, meanwhile, typically extract biologically-active compounds using ethanol, certain enzymes or other agents that seem to boost their positive effects.

And while recent epidemiological studies have identified a possible link between regularly eating mushrooms and a reduced risk of cognitive decline, researchers hope to incorporate the powerful fungi-derived compounds into more targeted treatments.

Currently, the vast majority of studies have analyzed the effects of fungi extracts and certain isolated compounds on cells and rodents, along with relatively tiny samples of humans, so it’s far too early to make any conclusions.

Still, some results have nevertheless been encouraging. Here are some varieties that are currently being studied for their potential brain benefits:

Shiitake

While it’s one of the most popular edible mushrooms worldwide, you may not know that Lentinula edodes has also received attention in labs for its possible neurological applications. Shiitake are particularly prized for carbohydrates called polysaccharides, specifically beta-glucans, that are also found in the cell walls of various fungi. Beta-glucans offer a variety of possible advantages, including their ability to reduce inflammation, regulate the immune system and combat infections. 

In recent years, scientists have found that beta-glucans can improve gut microbiome diversity in mice. This is a win for the brain, because the two are closely linked via a two-way communication channel called the gut-brain axis. In fact, feeding mice beta-glucans from Shiitake mushrooms helped counteract the cognitive impairments caused by a high-fat diet — which wreaks brain inflammation — a 2021 Journal of Translational Medicine study found.

Lion’s Mane

The hairy-looking Hericium erinaceus, commonly referred to as lion’s mane, is found in Asia, Europe and North America on decaying or dead trees. Research has indicated that it could help treat or prevent a wide range of conditions, including cancer, diabetes and high cholesterol. Among other medicinal mushrooms, this species has received particular attention for its potential neuroprotective properties. These may stem from chemical compounds that can promote cell growth, fight inflammation and regulate reward pathways within the brain. 

Studies in mice and cells have accordingly suggested that lion’s mane may improve mental function in people with Alzheimer’s and help treat epilepsy. Small human trials suggest it could mitigate depression, improve sleep quality and alleviate early-stage cognitive decline, but researchers have called for more rigorous studies in people.

Cordyceps

This parasitic genus of fungus is known to get gruesome. For example, the Ophiocordyceps unilateralis species can infiltrate the bodies of ants via spores and turn them into “zombies” before sprouting out of the insects’ heads. Fittingly, Cordyceps even inspired a zombie-themed horror video game series

Despite their frightening behavior toward insects, humans have long prized these Cheeto-like fungi. Chinese medicine has used the Ophiocordyceps sinensis species to promote lung and kidney health since at least the 18th century. Natural forms of O. sinensis, which grow high in the Tibetan Plateau and Himalayas on ghost moths, can cost up to $63,000 a pound. Research teams therefore commonly study samples of this species that have been cultivated in labs.

In recent years, various varieties of Cordyceps have been studied for their anti-inflammatory, antitumor, immune system-regulating and neuroprotective properties, among others. Their various powers are thought to come from a unique compound called cordycepin, along with polysaccharides and sterols, which are somewhat similar to the cholesterol produced by humans. 

Experiments with animal models have demonstrated that the compounds within Cordyceps could help mitigate learning and memory impairment, symptoms associated with neurological diseases like Alzheimer’s and Parkinson’s disease. This could occur through various mechanisms, including cordycepin’s ability to prevent neuronal cell death.

Chaga

The Inonotus obliquus fungus, commonly called chaga, typically grows as a parasite on birch trees in cold climates. It has long been incorporated in folk medicine in China, Korea, Japan and eastern Europe. And historical sources claim that 12th-century Kiev Prince Vladimir Monomakh used chaga to get rid of a lip tumor.

As with the other fungi on this list, the polysaccharides within I. obliquus may offer a range of helpful properties, including antitumor, anti-fatigue, antioxidant, antiviral and anti-inflammatory effects.

So far, compounds isolated from chaga have been shown to protect against Alzheimer’s and Parkinson’s diseases in cell studies by mitigating oxidative stress, which can cause excess unstable molecules called free radicals to attack brain cells. While some medicinal fungi have received human trials, albeit tiny ones, chaga does not appear to have been tested in humans for any possible neurological benefits. 

Reishi

Known as the “Mushroom of Immortality” in Korea and China, reishi, or Ganoderma lucidum, sprouts up on dying or dead trees, including maple, elm and oak. In Chinese medicine, reishi is used to boost overall health and longevity. Like plenty of other sought-after fungi, reishi may get its magic from substances such as sterols, polysaccharides and peptides.

Reishi offers a laundry list of potential benefits, such as sedative, anti-inflammatory, antiviral, and antitumor effects. Evidence suggests that it could prove a helpful treatment for neurodegenerative conditions. Studies performed on cells and animals have highlighted the possibility that the polysaccharides from Ganoderma lucidum could, for example, slow the progression of Alzheimer’s disease. These substances may encourage neuron growth in the brain and alleviate cognitive decline.

Results in humans, however, haven’t been as promising. A first-of-its-kind experiment in just 42 people with Alzheimer’s disease found that spore powder made from G. lucidum failed to improve symptoms or enhance patients’ quality of life measurements, according to a 2018 Medicine study. But the authors noted that it was a brief treatment period (six weeks) and small sample size.

If future research succeeds (and plenty more is needed), this mushroom could perhaps compete with widely prescribed antidepressants. Reishi extracts seemed to exhibit an effect comparable to that of the SSRI fluoxetine in studies from 2017 and 2021 performed on mice. Its relative Ganoderma applanatum might also help ease depression and anxiety, according to another mouse experiment.

Beyond that, a small study in 64 women with fibromyalgia failed to find statistically significant effects of Ganoderma lucidum supplementation on subjective measures like feelings of happiness, depression and life satisfaction. But researchers did notice a positive trend in these outcomes post-treatment, as reported in the journal Healthcare in 2020. And in a 2011 study assessing reishi’s effect on fatigue in breast cancer patients, subjects reported reduced anxiety and depression.

By Molly Glick

Source: Beyond Psilocybin: These Mushrooms May Offer Brain-Boosting Compounds, Too | Discover Magazine

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Should You Microdose to Treat Depression

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If you asked 100 people about psychedelics, you’d most likely get 100 opinions based on their firsthand experience, strong condemnation or stories from their adventures at Woodstock in the ’60s. No matter what people might know or think they know about psychedelics, the 40-year moratorium that closed down related research in the ’70s is now coming to an end. Psychiatrists are beginning to realize that strategic, supervised use of these psychopharmacological drugs is helping people with mental disorders including obsessive-compulsive disorder, post-traumatic stress disorder, alcoholism, depression and cluster headaches. Still, are there enough scientific studies to warrant the use of these drugs in mainstream society?

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I’ll admit that talk of psychedelic therapy to treat depression makes me nervous. In researching my book, Unstoppable, I looked at other key triggers that can mimic psychological disorders like depression and , such as inflammation, nutritional deficiencies, hormonal changes, side effects from medications, gut imbalances and food sensitivities. The reality is, depression is complex. What works for one may not work for another. Any successful treatment must first identify the root cause of one’s depression successfully, which can be a complex process if not done under the right medical care. A psychedelic treatment isn’t suddenly going to fix a nutritional deficiency, for example, but it may help target other symptoms and behaviors that correspond with depression. This is why it was critical to set my own biases aside and speak to an expert.

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I was fortunate enough to interview Dr. Domenick J. Sportelli, who is board-certified by the American Board of Neurology and for General Psychiatry and fellowship-trained and Board Certified in Child and Adolescent Psychiatry. He also specializes in human behavior and psychopharmacology. I wanted to get the most current information on the use of psychedelics in treatment for depression, anxiety and PTSD, so I first asked him first to clarify what psychedelics were.

“The term ‘psychedelic substance’ refers to an exogenous substance [derived outside the body] that, when taken into the body in various ways, physiologically, neurologically and psychologically manifest an internal personal experience of altered states of consciousness,” he explains. “This includes perceptual distortions, hallucinations, synesthesia [a mixing of the senses], altered sense of time and space, as well as potentially inducing what researchers call a ‘mystical experience’ — a sense of oneness, of noetic experience and an undefinable but profoundly spiritual quality.”

Is there enough evidence to support psychedelic therapy? 

Sportelli wants to make clear that the most researched psychedelics — LSD, psilocybin (mushrooms), peyote, MDMA, DMT and ketamine — have different mechanisms of action and even induce subtle, subjective experiential differences. Although each is grouped under the term “psychedelics,” they are quite disparate.

Dr. Sportelli is cautiously optimistic about the multitudes of large-scale, university-based testing and prior research compiled decades ago, but worries about the abiliity to circumvent bureaucracy and conduct safe, credible and substantial testing today. He does add that recent testing of psilocybin, LSD, ketamine and MDMA in particular has generated cause for optimism, and that they will likely have a place not only in continued, diverse research design and protocol, but eventually in therapeutic use.

What types of depression can psychedelics treat?

If we were to look at the onset of most mental illnesses, the majority start to become evident between the ages of 11 and 24, according to the National Institute of Health. With only 42 percent of people getting treatment, most typically do not seek out assistance until a secondary mental illness occurs several years later.

When asked how broadly psychedelics might be able to help treat people with depression, Sportelli concedes that, “Unfortunately, research hasn’t determined the level of scientific data to specify the type of depression or mood disorder that psychedelic therapy will benefit.” But he does add that research and data are beginning to show statistically significant improvements in mood, reduced anxiety, change in positive personality traits over time, the possibility of reducing addictive behaviors, reduction in suicidal tendencies and increased personal insight.

Do psychedelics treat the symptoms or the cause?

According to Dr. Sportelli, depression stems from a mix of genetic, biological, neurological, psychological and sociological factors. Recent research has demonstrated how the chemical breakdown of psilocybins closely resembles that of serotonin, and indicated the promising interplay of select hormone transmission. Dr. Sportelli stresses the critical role that these drugs might offer in mood disorders is at the forefront of the pharmaceutical quest for treatment.

“We have never seen substances like these that can potentially change the way that we look at our life and change perspective with lasting results,” he says, noting that they might be able to help “supercharge psychotherapy.”

Is this ultimately a recommend treatment, and where does one turn for it?

“At this time, in the U.S., I would only recommend this treatment be a part of, and under the close supervision of, a university-based IRB [Institutional Review Board]-monitored clinical trial,” Sportelli emphasizes. Before any psychiatric treatment, Dr. Sportelli also recommends a full medical and neurological evaluation to rule out any of the multitudes of medical circumstances that can manifest as a primary mood disorder, and reiterates that significant and often profoundly adverse outcomes associated with such powerful, mind-altering chemicals need to be weighed further as well. That’s why, as part of any regulated trial, all the necessary medical workups would be completed before participation.

Is the stigma around psychedelic therapy warranted? 

Sportelli acknowledges that there is a safety concern associated with psychedelics, and does not condone their recreational or illict use. But he does believe that regulated clinical trials, judicious and ethical research methodology and the progression for therapeutic intervention should not be overlook based on previous stigma and possible misclassification.

Related: 50,000 Entrepreneurs Tell Us How to Avoid Stress and Anxiety

I’ve never been one to throw the baby out with the bathwater. After interviewing Dr. Sportelli, I hold hope for the future, but also a concern for those who may seek out this kind of treatment without an accurate medical diagnosis. My number-one hesitation remains — that is we simply do not have the studies to show which types of depression psychedelic therapy successfully treats, which may result in people attempting to use a hammer when in fact they need a nail.

Either way, if you are to venture into this arena, find someone who specializes in it. The risk of going it alone could come at too a high price.

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