For millennia, fungi have occupied a paradoxical position in human culture, simultaneously revered for their nutritional, therapeutic and mystical properties while also being feared for their toxicity. Yet in the past several decades, we have seen a resurgence of interest in mushrooms, both for their physical/immune/antioxidant/and metabolic effects, as well as their potential benefits in mental health disorders.

The Spiritual/Mental Health Connection

The use of “magic mushrooms” i.e., psilocybin treatment for major depression, anxiety and PTSD, has been studied at the John’s Hopkins Center for Psychedelic and Consciousness Research over the past several years. There are now multiple scientific publications exploring the use of psilocybin for mental health. Some of these publications have demonstrated, in double-blind, randomized controlled trials, that psilocybin treatment (PT) can help with major depressive disorder (MDD), compared to standard serotonin reuptake inhibitors:

The results of this trial published in the prestigious journal the Lancet, showed: “Six-week intensive treatments with either psilocybin or escitalopram (with psychological support) for Major Depressive Disorder (MDD) were associated with long-term improvements in depressive symptom severity. The greater degree of improvement in the Psilocybin Treatment (PT) arm at follow-up on psychosocial functioning, meaning in life, and psychological connectedness suggests (it) warrants future research.”

Apart from beneficial effects in PTSD and MDD, research has also shown improvements in getting people to quit smoking, help with alcohol and substance abuse, and easing existential anxiety in people with terminal cancer. In follow-up studies evaluating the effect of PT on major depression researchers at Johns Hopkins University have shown that the substantial antidepressant effect of psilocybin-assisted therapy, given with supportive psychotherapy, may last for at least one year in a select group of patients. The list of growing scientific publications highlighting the potential mental health benefits of this class of mushrooms is impressive. This is only a small fraction of the scientific papers on the subject:

Academic Publications

Carrithers, B. M., Roberts, D. E., Weiss, B. M., King, J. D., Carhart-Harris, R. L., Gordon, A. R., Pagni, B. A., Moreau, M., Ross, S., Zeifman, R. J. (2025). Exploring serotonergic psychedelics as a treatment for personality disorders. Neuropharmacology, 272, 110413.

Richard, J., Scott, J., Nayak, S.M., Sepeda, S., Lowe, M. X., Jackson, H., Garcia-Romeu, A. (2025). Patterns of Internalizing Problems, Substance Use and Cognitive Flexibility Before and After Naturalistic Psilocybin Use: A Repeated Measures Latent Profile Analysis. Int J Ment Health Addiction.

Mathai, D. S., Roberts, D. E., Nayak, S. M., Sepeda, N. D., Lehrner, A., Johnson, M. W., Lowe, M. X., Jackson, H., & Garcia-Romeu, A. (2025). Shame, Guilt and Psychedelic Experience: Results from a Prospective, Longitudinal Survey of Real-World Psilocybin Use. Journal of Psychoactive Drugs, 1–12.

Richard, J. & Garcia-Romeu, A. (2025). Psychedelics in the Treatment of Substance Use Disorders and Addictive Behaviors: A Scoping Review. In: Potenza (Ed.). Current Addiction Reports.

Zombie Fungus/Cordyceps

My prior Medical Detective Substack on the benefits of mushrooms and eating Zombie fungus was an introduction into this fascinating world of fungi. In that Substack, I discussed the health benefits of Cordyceps, where it has been shown to help with athletic performance, glucose tolerance, promoting longevity with neuroprotective properties, while potentially supporting the microbiome, memory/concentration and mood.

I had mentioned in that Substack that in my cli-fi novel, Starseed R/evolution, I had a tongue-in-cheek depiction of zombies, mixed with people dressed like zombies, listening to the rock group the Zombies. What I neglected to mention is that the people attending this Woodstock festival had all been given a packet of magic mushrooms before entering, as they all suffered from major depression in part from climate destruction… I had even mentioned in Starseed one of the researchers listed above, Robin Carhart-Harris, who was doing research on the topic years ago.

Mushrooms for Enlightenment?

Spiritual seekers across the globe have accessed psilocybin as a way of accessing expanded states of consciousness for millennia, although none of my spiritual teachers have ever endorsed it for that purpose. In fact, they have encouraged the slow, steady approach of recognizing the nature of mind through progressive stages of meditation and accumulation of merit as a way of stabilizing and deepening the understanding of our human/spiritual connection while reaching our full potential. Please see my 5 part series on meditation to learn more about the enlightenment teachings I received from my Karma Kagyu Tibetan teachers. These instructions are from orally transmitted teachings which I received over several decades:

I can verify the power of these teachings after being around these enlightened masters for long periods of time. Although I myself have no experience and have been diligent in practicing certain tantric practices for decades, part of my plan going forward is to dedicate more time specifically towards Mahamudra meditation as I get older. Why? With my prior spiritual lineage, I may have accumulated a few habits worth getting rid of.

Zen Judaism

The quotes below are from the book, Zen Judaism, from David M Bader, who clearly understands a few things about meditation and the way my mind works:

“Zen is not easy. It takes effort to attain nothingness. And then what do you have? Bupkis.”

“Be aware of your body. Be aware of your perceptions. Keep in mind that not every physical sensation is a symptom of a terminal illness.”

“Breathe in. Breathe out. Breathe in. Breathe out. Forget this and attaining Enlightenment will be the least of your problems.”

“The Tao does not speak. The Tao does not blame. The Tao does not take sides. The Tao has no expectations. The Tao demands nothing of others. The Tao is not Jewish.”

“Drink tea and nourish life; with the first sip, joy; with the second sip, satisfaction; with the third sip, peace; with the fourth, a Danish.”

“Wherever you go, there you are. Your luggage is another story.”

“Accept misfortune as a blessing. Do not wish for perfect health, or a life without problems. What would you talk about?”

“The journey of a thousand miles begins with a single Oy.”

“If there is no self, whose arthritis is this?”

One Tibetan teacher of mine, the Very Venerable Thrangu Rinpoche, also clearly encouraged humor for mental health purposes. However, when meditation, medication, and humor is not enough….

Medical Use of Psylocibin in Treatment-Resistant Mental Health

Notwithstanding, there is a role for psilocybin and science is starting to explore its potential. I have had severely depressed patients resistant to standard therapies whom I have referred to the Johns Hopkin’s program. In an evaluation of the safety and abuse research Johns Hopkins researchers suggest that “if it clears phase III clinical trials, psilocybin should be re-categorized from a schedule I drug—one with no known medical potential—to a schedule IV drug such as prescription sleep aids, but with tighter control.” For more information see: https://www.hopkinsmedicine.org/psychiatry/research/psychedelics-research

In a world where so many of our military veterans suffer with severe PTSD, not to mention those who have lost families during the Covid pandemic, and/or suffer from substance abuse as well as resistant depression and anxiety, this mushroom derivative has clear scientific potential to improve suffering when used in the right medically-controlled setting. Research is ongoing.

Medicinal Mushrooms

Among the vast kingdom of fungi, apart from those listed above, a select group known as ‘medicinal mushrooms’ has transcended their culinary use, forming the backbone of traditional Chinese medicine (TCM) and other ancient healing systems. The species, including Cordyceps sinensis (Cordyceps, the ‘caterpillar mushroom), Inonotus obluquus (Chaga), Hericium erinaceus (Lions Mane), Ganoderma lucidum (Reishi), Trametes versicolor (Turkey Tail), Lentinula edodes (Shiitake) and Grifola frondosa (Maitake) are now the subject of rigorous modern scientific inquiry.

The Bioactive Basis: Polysaccharides, Triterpenes, and Mechanisms of Action

The primary therapeutic efficacy of medicinal mushrooms is largely attributed to 2 classes of compounds: polysaccharides, particularly beta 1, 3/1, 6-D- glucans, and triterpenes. These compounds act as biological response modifiers (BRM’s) that help to regulate and restore homeostatic balance.

We discussed beta glucans in our last SUBSTACK. These macromolecules are recognized as “non-self” danger signals by pattern recognition receptors (PRRs) on immune cells, most notably the Dectin-1 receptor found on macrophages, dendritic cells, and natural killer (NK) cells. This recognition initiates a cascade of immune signaling that significantly enhances both innate and adaptive immunity.

Use in Cancer

This immune activation leads to increased phagocytosis, elevated production of critical cytokines (e.g., interleukins and interferons), and the proliferation to differentiate of T lymphocytes and NK cells. In Oncology, beta glucan from mushrooms are believed to work synergistically with conventional treatments by augmenting the host antitumor response rather than by directly killing cancer cells, positioning them as valuable complementary agent. Most of the mushrooms we are discussing, including shiitake, maitake, and reishi share similar beta glucan structures. See Table 1 from the article quoted above.

Triterpenes: the 2^nd Major Class of Compounds

Terpenoids are the other major class of compounds that are responsible for the anti-inflammatory, hepatoprotective (liver protective) and adaptogenic qualities of the mushrooms. In species like Reishi, these bitter tasting molecules, such as the ganoderic acids, exhibit structural similarities to steroid hormones. Triterpenes function by inhibiting key enzymes involved in inflammatory pathways, such as the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, and by supporting the adrenal glands response to chronic stress thereby assisting the body in maintaining equilibrium under duress. The combined action of immunomodulatory polysaccharides and adaptogenic triterpenes provides a holistic foundation for the vast array of health benefits reported across the various medicinal mushrooms species.

Chaga: Inonotus obliquus: The Antioxidant Powerhouse

Chaga, a parasitic fungus that primarily grows on birch trees in cold climates, is visually distinct, forming a charcoal like sclerotium. Historically used in Russian and Siberian folk medicine, Chaga’s therapeutic reputation is overwhelmingly centered on its exceptional antioxidant properties. It’s black exterior is rich in melanin, a compound that provides one of the highest measured ORAC (Oxygen Radical Absorbance Capacity) values found in nature.

The key bioactive components in Chaga includes a high concentration of polyphenols, triterpenoids, and complex melanin’s. The combined action of these molecules provides a powerful defense against oxidative stress, implicated in the pathogenesis of chronic diseases. Therapeutic properties of I. obliquus extracts include anti-inflammatory, anticancer, anti-diabetic, anti-obesity, hepatoprotective, reno (kidney) protective, anti-fatigue, antibacterial, and antiviral activities.

Chaga extracts have also shown promise in managing metabolic health by potentially improving insulin sensitivity and reducing low density lipoprotein (LDL) cholesterol, suggesting a role in mitigating risk factors for cardiovascular disease and type II diabetes. Considering that some of our patients reactivate viral infections interfering with their long-term health, whether post Covid or not, the antiviral/immune supporting properties of mushrooms makes them an attractive addition to a holistic health program.

Lions mane, Hericium erinaceus: The Nootropic Fungi

Lions mane, recognizable by its cascading, shaggy appearance resembling a Lions mane, stands out among medicinal fungi for its remarkable affinity for the nervous system. It has earned the title of a “smart mushroom” or nootropic due to its unique capacities to support neurological and cognitive health.

The Neuroprotective and cognitive enhancing effects of Lions mane are tied to two specific families of compounds: hericenones, found predominantly in the fruiting body, and erinacines, isolated mainly from the mycelium. The chemical structures of main constituents of H. erinaceus, including hericenones, erinacines, and other relevant molecules, are shown in detail in the article below:

There are multiple bioactive components in Lions mane. These molecules are unique among fungal compounds because they can cross the blood brain barrier and induce the synthesis of Nerve Growth Factor (NGF). NGF is a neurotrophin-a protein essential for the survival, maintenance and regeneration of sensory and sympathetic neurons. By promoting NGF production, Lions mane facilitates neurogenesis in the repair of myelin sheaths, which are crucial for rapid and effective neural signaling. A trial of Lions mane is clearly indicated in demyelinating diseases like chronic Lyme disease, chronic Bartonella, Multiple sclerosis (MS) and Chronic Demyelinating Inflammatory Polyneuropathy (CIDP).

Clinical studies of Lions mane

Clinical studies have provided compelling human evidence for its cognitive benefits. A landmark double-blind, placebo-controlled trial involving older Japanese adults with mild cognitive impairment showed that consumption of Lions mane led to significantly improved cognition function scores compared to the placebo group. Notably, the effect diminished after cessation of supplementation, suggesting a sustained intake is necessary to maintain benefits.

Beyond cognitive performance, research suggests that Lions mane may hold therapeutic potential for mood disorders. It’s anti-inflammatory effects and ability to influence neurotransmitter systems are being investigated for their role in reducing symptoms of anxiety and depression. It’s rich fiber content and anti-inflammatory properties have also been shown to support gut health, which is increasingly recognized as being interconnected with brain health via the gut brain axis. The bioactive compounds in Lion’s mane are involved in blocking common inflammatory pathways like NF-kB and COX-2 and ongoing studies are being conducted examining its effects in neurodegenerative diseases, including Alzheimer’s and Parkinsons to support overall brain health.

Scientific research suggests mushrooms can function as a key health support in the broad-range of chronic illnesses discussed above and can easily be integrated into mainstream approaches to help improve outcomes. Next week, in Part three we will discuss Reishi, the mushroom of immortality, as well as Maitake, Shiitake and Turkey Tail. Stay tuned.