Mushrooms and OCD: Potential Brain Pathway Insights

Some compounds found in mushrooms have drawn scientific interest for their potential effects on brain function, particularly in relation to obsessive-compulsive disorder (OCD). While much of the focus has been on hallucinogenic species, non-psychedelic varieties may also influence brain activity.

Biological Compounds in Select Mushroom Varieties

Mushrooms contain bioactive compounds that may affect neurological function. Among them, tryptamines, beta-glucans, and secondary metabolites have been studied for their interactions with neurotransmitter systems and cellular signaling pathways relevant to OCD.

Tryptamines

Tryptamines are structurally related to serotonin, a neurotransmitter involved in mood regulation and compulsive behaviors. Psilocybin, found in Psilocybe species, converts into psilocin, which activates serotonin 5-HT2A receptors. A JAMA Psychiatry (2020) study found psilocybin significantly reduced OCD symptoms in a small clinical trial. Other tryptamines, such as norbaeocystin and aeruginascin, are less understood. While research primarily focuses on hallucinogenic species, non-psychedelic mushrooms like Pleurotus and Agaricus contain trace tryptamine derivatives that may subtly affect serotonin signaling. Further study is needed to determine their role in OCD-related neural circuits.

Beta-Glucans

Beta-glucans, polysaccharides in fungi like Hericium erinaceus (lion’s mane) and Ganoderma lucidum (reishi), are known for immunomodulatory effects but also influence neuroplasticity. A study in International Journal of Molecular Sciences (2021) found Hericium erinaceus beta-glucans promoted nerve growth factor (NGF) expression in the hippocampus, a region linked to compulsive behaviors. Animal studies suggest beta-glucans improve cognitive function and reduce anxiety-like behaviors, though human research remains limited. Given OCD’s association with impaired neuroplasticity, beta-glucans’ ability to enhance neuronal growth warrants further exploration.

Secondary Metabolites

Mushrooms also produce secondary metabolites like erinacines, ganoderic acids, and sterols, which may have neuroactive properties. Erinacines, found in Hericium erinaceus, promote NGF synthesis, supporting neural regeneration. A Behavioural Neurology (2022) study reported that erinacine-enriched extracts reduced compulsive behaviors in rodents. Ganoderic acids from Ganoderma lucidum have neuroprotective effects, modulating oxidative stress and inflammation. Sterols such as ergosterol, a precursor to vitamin D2, have been investigated for their influence on neuronal excitability and serotonin receptors. While their impact on OCD remains speculative, their role in neurochemical balance merits further study.

Interactions With Brain Signaling Pathways

Mushroom-derived compounds interact with neurotransmitter systems, particularly serotonin, glutamate, and dopamine, which regulate compulsive behaviors and cognitive flexibility.

Psilocybin and psilocin primarily act on serotonin 5-HT2A receptors, altering cognitive processing and reducing repetitive thoughts. A NeuroImage (2020) study found psilocybin modulated connectivity between the default mode network (DMN) and the cortico-striatal-thalamo-cortical (CSTC) circuit, a neural loop linked to OCD. This suggests serotonergic modulation may alleviate compulsive behaviors. Other tryptamine derivatives in mushrooms could influence serotonin receptors in subtler ways.

Glutamate, the brain’s primary excitatory neurotransmitter, is implicated in OCD due to CSTC circuit hyperactivity. Erinacines from Hericium erinaceus enhance synaptic plasticity by modulating NMDA receptor activity and promoting NGF expression. A Frontiers in Cellular Neuroscience (2021) study found erinacine-enriched extracts facilitated long-term potentiation in hippocampal neurons, crucial for adaptive learning and behavioral flexibility. This suggests mushroom-derived molecules may help normalize glutamatergic signaling.

Dopaminergic pathways, involved in reward processing and habit formation, also play a role in OCD. Overactive striatal dopamine signaling is linked to compulsivity. Ergosterol, a precursor to vitamin D2 found in mushrooms, has been studied for its effects on dopamine receptors. A Neuropharmacology (2022) study indicated dietary sterols influenced dopamine transporter expression in the striatum, suggesting potential implications for compulsivity.

Observations in OCD-Related Research

Studies exploring fungal compounds and OCD have provided intriguing insights. Clinical and preclinical research suggests these compounds may influence compulsive behaviors through various neurological mechanisms.

Human trials on psilocybin’s effects on OCD have shown promising results. A Journal of Psychopharmacology (2009) study reported significant reductions in obsessive thoughts and compulsions following psilocybin administration, with effects lasting beyond the psychedelic experience. Participants described a loosening of rigid thought patterns, correlating with changes in functional connectivity in compulsivity-related brain regions. These findings align with neuroimaging studies showing psilocybin disrupts hyperconnectivity in the CSTC circuit. Larger controlled trials are needed to assess long-term efficacy and safety.

Animal models using marble-burying and nestlet-shredding assays—common tests for compulsivity—have shown psilocybin reduces repetitive behaviors, likely through serotonin 5-HT2A receptor activation. Research on non-hallucinogenic mushroom extracts suggests certain fungal metabolites may have anxiolytic and cognitive-enhancing effects, offering alternative intervention possibilities.

Possible Roles of Non-Hallucinogenic Species

Non-psychedelic mushrooms may also have neurological effects relevant to OCD. Edible and medicinal species contain bioactive compounds that influence neurotransmitter systems and synaptic plasticity without inducing altered states of consciousness, making them potential candidates for long-term use.

Hericium erinaceus (lion’s mane) has been studied for its ability to promote NGF synthesis, which supports neuronal survival and connectivity. A Phytotherapy Research (2019) randomized controlled trial found Hericium erinaceus supplementation improved cognitive function and reduced anxiety-like symptoms over 12 weeks. While direct OCD studies are lacking, these cognitive and mood benefits suggest a potential mechanism for symptom modulation.

Some fungal metabolites also influence neurotransmitter balance. Triterpenoids from Ganoderma lucidum (reishi) interact with GABAergic and serotonergic pathways, both implicated in OCD. Preclinical research suggests reishi extracts may reduce excessive neuronal excitability, a factor in compulsive urges. Ergothioneine, an antioxidant in Pleurotus ostreatus (oyster mushrooms), has been linked to cognitive resilience and stress adaptability. Given oxidative stress’s potential role in OCD, ergothioneine’s neuroprotective effects may indirectly support symptom management.