Medicinal mushrooms as an adjunctive treatment for depression

Undoubtedly, dietary and supplemental interventions in treating major depressive disorder (MDD) are a part of integrative psychiatry, and I would add holistically shaped psychiatric practices. You probably changed many antidepressants from different groups without any subjective or clinical improvement, even though you tried some alternative methods such as repetitive transcranial magnetic stimulation, ketamine infusions, and others. Still, you are stuck in MDD, and you are tired of depression and feeling hopeless. However, there is hope, and worth trying some alternative and holistic treatments. One of them is edible, medicinal mushrooms.

Generally, dietary interventions and changes for people suffering from the major depressive disorder are an ongoing field of research

Edible medicinal mushrooms contain 5-hydroxy-L-tryptophan (5-HTP), a direct precursor of serotonin, one of the neurotransmitters targeted in the pharmacotherapy of MDD (Agata Fijałkowska et al., 2022). Agata Fijałkowska and colleagues exhibited the results of studies on dietary supplementation with three species; Lion’s mane (Hericium erinaceus), Caterpillar mushroom (Cordyceps militaris), and Lingzhi/Reishi (Ganoderma lucidum) (Agata Fijałkowska et al., 2022). Their review article is impressive, with 121 peer-reviewed articles in reference.

Serotonin does not cross the blood-brain barrier; however, L-tryptophan is an exogenous amino acid that acts as a precursor for serotonin synthesis in a metabolic pathway involving tryptophan hydroxylase (TPH) as well as aromatic amino acid decarboxylase (DDC). 5-Hydroxy-l-tryptophan (5-HTP), a product of TPH and an immediate precursor of serotonin, is processed by DDC. Indeed, the total pool of serotonin in the brain is determined by the amount of substrates and the activity of TPH, which is the rate-limiting step for serotonin synthesis. The primary source of serotonin in the brain is the neurons of nine raphe nuclei located in the medial brainstem. The axons of these neurons project to most of the brain, with rostral raphe nuclei mainly sending their serotonergic projections to the forebrain and caudal group to the lower brainstem and spinal cord (Agata Fijałkowska et al., 2022).

Several edible mushroom species have been identified with a relatively high content of 5-HTP. The highest content was detected in all species of Pleurotus (oyster mushrooms), which is popular in vegetarian cuisine (Agata Fijałkowska et al., 2022).

Using Lion’s mane mushrooms (Hericium erinaceus) to treat depression

Chong and colleagues 2019 published an article about using Lion’s mane mushrooms (Hericium erinaceus) to treat depression. Bioactive compounds extracted from the mycelia and fruiting bodies of H. erinaceus have been found to promote the expression of neurotrophic factors that are associated with cell proliferation, such as nerve growth factors. Although the antidepressant effects of H. erinaceus have not been validated and compared to the conventional antidepressants, based on the neurotrophic and neurogenic pathophysiology of depression, H. erinaceus may be a potential alternative medicine for the treatment of depression (Pit Shan Chong et al., 2021).

Griflola frondosa (Fr) S.F. Gray (GF) (Meripilaceae) is a medical fungus commonly known as Maitake or Hui-shu-hua. The α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA receptor) signaling regulated by GF might be essential for its robust antidepressant effects (Hongkun Bao et al., 2017).

Medicinal mushrooms, their bioactive compounds, their use, and completed clinical trials

Giuseppe Venturella and colleagues published a review article in 2021 about medicinal mushrooms, their bioactive compounds, their use, and completed clinical trials. The article is abundant with information and data from over 100 references related to medicinal mushrooms. The authors stated that medicinal mushrooms had been used to promote and maintain good health and treat diseases since ancient times in Asian regions. At the same time, in the West, this approach is considerably more recent. Medicinal mushrooms are reported to have numerous pharmacological actions such as antimicrobial, anti-inflammatory, immunomodulatory, antidiabetic, cytotoxic, antioxidant, hepatoprotective, anticancer, antioxidant, antiallergic, antihyperlipidemic, and prebiotic properties, among others. These activities are attributable to many bioactive metabolites in the mycelium but, above all, in the fruiting body, whose biological effect varies according to the chemical nature and distribution varies according to the fungal species. A lot of research has been done. It is increasingly being undertaken to identify and characterize mycochemicals and define their actions and mechanisms due to the growing interest in using natural products, including as adjuvants in traditional therapies (Giuseppe Venturella et al., 2021).

Regarding bioactive compounds, the most important are polysaccharides, structural components of the fungal cell wall. The polysaccharides have a solid ability to carry biological information. They have antitumor, immunomodulatory, antioxidant, anti-inflammatory, antimicrobial, and antidiabetic activity. In reality, the type and modulation of these biological activities are influenced by the specific structural features of the molecule, such as the weighted degree of branching, backbone linkage, side-chain units, and the type of constituent monosaccharides. The best-known and most abundant are α- and β-glucans. Heteroglycans, peptidoglycans, and polysaccharide-protein complexes also contribute to biological activity. They are primarily responsible for immunomodulatory effects because they bind to specific cell membrane receptors and stimulate particular immune responses. Medicinal mushrooms are usually used in cancer treatments as biological response modifiers (BRMs), helpful in treating cancer, reducing the side effects of therapies, and improving the quality of the patient’s life (Giuseppe Venturella et al., 2021).

Another class of compounds that are very important for their bioactivity are the terpenes, characterized by units of five-carbon isoprene atoms and whose addition of functional groups produces the terpenoids. They modulate the immune system by stimulating the expression of genes coding for proteins involved in the immune response. They also have anti-inflammatory, antioxidant, and antitumor properties. High terpenoid contents are found in mushrooms belonging to the genus Ganoderma P. Karst. Mushrooms are rich in proteins, which have cytotoxic and anticancer properties. In addition, some of them are known for their characteristics and marked immunomodulatory effects. These proteins are indicated as fungal immunomodulatory proteins (FIPs), whose mechanisms of action can be diverse. Proteins also include lectins, which bind reversibly to mono- and oligosaccharides with high specificity, recognizing and interacting with various carbohydrates and proteoglycans on the cell surface. They are involved in many biological activities, such as innate immunity and cell-to-cell interaction, and their immunomodulatory mechanism varies depending on the origin of the compound. They also have immunomodulatory, antitumor, and antiproliferative properties (Giuseppe Venturella et al., 2021).

Other fungal metabolites with bioactivity are phenolic compounds, antioxidants with different mechanisms of action (oxygen scavenging, metal inactivation, free radical inhibition, peroxidase decomposition), laccases (copper-containing oxidases), and fatty acids (Giuseppe Venturella et al., 2021).

Medicinal mushrooms (MM) science made great progress in the last 30 years

Professor Solomon P. Wasser published an excellent review article in 2014, Biomedical Journal; Medicinal Mushroom Science: Current Perspectives, Advances, Evidences, and Challenges. Professor Wasser stated: “Medicinal mushrooms (MM) science made great progress in the last 30 years. A really successful new branch of science (Medicinal Mushroom Science) has been recognized.” (Solomon P. Wasser, 2014). “New classes of MM drugs and different types of MM products have been developed. A unique journal in the field, the International Journal of Medicinal Mushrooms (Begell House, USA), was organized. Approximately 400 clinical trial studies using MMs have been published on different illnesses. More than 50,000 scientific papers have been published, and approximately 15,000 patents dedicated to studying different aspects of MMs have been received.” (Solomon P. Wasser, 2014). However, professor Wasser also stated: “On the other hand, there are many unsolved, serious problems in the future of MM development, which in turn can also affect the continuation of MM science in the 21st century.”

How to approach medicinal mushrooms to make it a successful journey of healing?

Start with your integrative psychiatrist with a friendly and constructive discussion regarding using them. Next, you and your integrative psychiatrist are confident that you are a good candidate; it is absolutely “a must.” Finally, go over your prescriptions and supplements that you regularly use with your pharmacist and integrative psychiatrist. Drug-supplement interactions are possible; however not always predictable in high percentages. Perhaps you are wondering why integrative/holistic psychiatrist? Integrative healthcare brings conventional and alternative approaches to a much broader spectrum; it emphasizes a holistic, patient-centered, and individualized/personalized approach to healthcare and wellness.

This approach is different. It not only treats your acute or chronic disease but also brings balance and healing to your body, mind, and soul. It includes a broad spectrum to treat the whole person and not only focus on one organ or organ system or simply your diagnosis. It is not just to treat your symptoms. This approach can be very demanding because it involves mental health, emotional, spiritual, social, and community aspects. It is complex and requires a well-coordinated team of conventional and alternative healing providers. Nevertheless, these approaches to the treatment brought good results in treatments of many conditions and diseases, such as depression, major depressive disorder, treatment-resistant depression, and other mental health disorders.

Finding a good provider for medicinal mushrooms will take time. It considers the panel of products and services, customer service, and real testimonials. So take your time and fill out the survey (if it is available) truthfully and with as many details as possible. It will help your vendor determine what would benefit you as an initial treatment.

Undoubtedly, healing has to start with you; a good plan, treatment, and following protocol promptly will lead to healing.

“What mental health needs are more sunlight, more candor, and more unashamed conversation.” – Glenn Close

Respectfully,

Holistic Healthful

References:

Agata Fijałkowska, Karol Jędrejko, Katarzyna Sułkowska-Ziaja, Marek Ziaja, Katarzyna Kała, Bożena Muszyńska. Edible Mushrooms as a Potential Component of Dietary Interventions for Major Depressive Disorder. Foods. 2022 May 20;11(10):1489.

Pit Shan Chong, Man-Lung Fung, Kah Hui Wong, Lee Wei Lim. Therapeutic Potential of Hericium erinaceus for Depressive Disorder. Int J Mol Sci. 2019 Dec 25;21(1):163.

Hongkun Bao, Pengzhan Ran, Lijuan Sun, Weihong Hu, Hongliang Li, Chunjie Xiao, Keming Zhu, and Jing Dua. Griflola frondosa (GF) produces significant antidepressant effects involving AMPA receptor activation in mice. Pharm Biol. 2017; 55(1): 299–305.

Giuseppe Venturella, Valeria Ferraro, Fortunato Cirlincione, Maria Letizia Gargano. Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials. Int J Mol Sci. 2021 Jan 10;22(2):634.

Solomon P. Wasser. Medicinal Mushroom Science: Current Perspectives, Advances, Evidences, and Challenges. Biomed J 2014;37:345 356.