The Effectiveness of Microdosed Psilocybin in the Treatment of Neuropsychiatric Lyme Disease: A Case Study

Lyme borreliosis, caused by Borrelia burgdorferi sensu lato and transmitted by Ixodes ticks, can produce persistent, multisystem illness in which neuropsychiatric complaints such as anxiety and depression may predominate. Co-infections transmitted by the same ticks — notably Bartonella spp., Babesia and Mycoplasma spp. — often complicate the clinical picture and may contribute to psychiatric manifestations. The pathophysiology described in the paper emphasises neuroinflammation and microbe-triggered autoimmunity, including the production of anti-neuronal antibodies and proinflammatory cytokines; this model has parallels with syndromes such as PANS and motivates a multimodal treatment approach combining antimicrobials, psychotropic agents and anti-inflammatory interventions. Kinderlehrer frames the present report around an apparent treatment gap: some patients with neuropsychiatric Lyme disease are intolerant of, or resistant to, standard antimicrobial and psychopharmacologic therapies, and options that modulate autoimmune neuroinflammation without broad immune suppression are limited. The study describes a single immunocompetent patient whose chronic, treatment-refractory neuropsychiatric symptoms remitted after he began microdosed psilocybin, and it situates this case against emerging literature that highlights both serotonergic and anti-inflammatory properties of psilocybin. The paper's stated aim is to document this clinical observation and to argue for further research on microdosed psilocybin in neuropsychiatric Lyme disease and related autoimmune encephalopathies.

This paper is an individual case report. The subject was an immunocompetent 70-year-old male with documented polymicrobial tick-borne infection including neuroborreliosis, babesiosis (PCR positive), and evidence suggestive of bartonellosis. The extracted text does not present a formal case series or systematic data collection; rather, it provides a clinical history, diagnostic findings, treatment attempts, and the observed response to self-initiated microdosing. Intervention details reported: the patient began oral microdosing of desiccated whole psilocybin-containing mushrooms at 100 mg three times per week, with the dose increased to 125 mg after two weeks. Informed consent to publish the history was obtained from the patient; no institutional review was required according to the author. There was no formal comparator or control, and no pre-specified outcome measures beyond clinical symptom change as reported in the patient's history and follow-up. Follow-up described in the text extends to at least two years after starting microdosing, during which remission of depression and anxiety was maintained.

The case history traces symptom onset at age 46 with acute fever, rigors, myalgias, drenching sweats and splenomegaly; laboratory testing at that time was positive for acute Lyme disease. Initial treatment with oral doxycycline resolved the febrile episodes but the patient developed severe insomnia and anxiety that persisted despite multiple rounds of antibiotics (doxycycline, clarithromycin, cefuroxime) over ten months. Five years after onset, babesiosis was diagnosed by PCR; a three-week course of azithromycin plus atovaquone produced a Herxheimer reaction (a transient worsening of symptoms) with panic attacks but then symptom reduction. Over the subsequent two decades the patient experienced recurrent relapses characterised by anxiety, panic attacks, depression, cognitive dysfunction, insomnia and somatic symptoms (fatigue, neck pain, myalgias, night sweats), each relapse typically lasting about two years. Trials of antidepressants such as sertraline and mirtazapine were initially somewhat helpful but later not tolerated. At age 70 a relapse followed a change in antimicrobial regimen; he became unable to tolerate antimicrobials without clinical worsening, benzodiazepines increased depressive symptoms, and sertraline provided no benefit. The patient began microdosing psilocybin (100 mg orally three times weekly, increased to 125 mg after two weeks). Within two days there was a noticeable improvement in mood and by two weeks he was consistently well; the author reports sustained remission of depression and anxiety for at least two years while continuing the regimen. The patient had expected a possible benefit only after two weeks and estimated his chance of improvement at 50%, and therefore reported surprise at the rapid onset of benefit. The report also notes that the diagnosis of bartonellosis was supported by later response to SMZ-TMP and serologic testing, and throughout the history co-infections are presented as likely contributors to the persistent neuropsychiatric illness.

Kinderlehrer interprets the clinical course as most consistent with neuropsychiatric symptoms driven by tick-borne infections and associated autoimmune neuroinflammation. The discussion emphasises that co-infections are common in persistent Lyme disease and that symptom timing, lack of prior psychiatric history, clustering of physical and psychiatric relapses, and Herxheimer reactions all support an infective and immune-mediated aetiology rather than a primary idiopathic psychiatric disorder. Given that some patients with neuropsychiatric Lyme disease are intolerant of psychotropic agents and antimicrobials, the author argues for exploration of therapies that modulate inflammation without broad immunosuppression. Psilocybin is discussed in two mechanistic lights: as a serotonergic agonist (notably at 5-HT2A and other serotonin receptors) and as an agent with putative anti-inflammatory and immunomodulatory actions. The rapid clinical response in this case is presented as compatible with an anti-inflammatory mechanism, and the paper cites in vitro and review evidence that psilocybin-containing extracts can reduce proinflammatory mediators (for example TNF-α, IL-1β and IL-6) in immune cells. The author reviews the limited and methodologically heterogeneous literature on microdosing, noting that most reports are anecdotal or open-label and subject to expectancy and placebo effects; controlled trials such as Cavanna et al have methodological limitations (small sample, short duration, dose choice and exclusion of people with anxiety or depression) that limit conclusions. Safety observations are summarised from prior macrodose studies — where short-term dysphoria or anxiety were the main adverse reactions and no long-term effects were reported over 8–16 months — and from microdosing reports that list short-term physical discomfort, impaired cognition and anxiety as the main harms. Overall, the paper acknowledges the anecdotal nature of the present observation and calls for prospective, double-blind, placebo-controlled studies that separately evaluate psilocybin and LSD, include subjects with anxiety and depression, and are adequately matched and of sufficient duration to assess both benefit and safety in populations with neuropsychiatric Lyme disease and autoimmune encephalopathies.

The author concludes that agents capable of modulating autoimmune neuroinflammation without suppressing immunity may have therapeutic value in neuropsychiatric Lyme disease. In this single case, an immunocompetent male with documented neuropsychiatric Lyme and co-infections experienced marked and sustained improvement in depression and anxiety after initiating microdosed psilocybin three times weekly. While evidence for macrodosed psilocybin in some psychiatric disorders is growing, evidence for microdosing remains limited and largely anecdotal; nevertheless, the anti-inflammatory properties of psilocybin may make it a candidate for further study in microbe-induced autoimmune neuropsychiatric syndromes. The paper closes by calling for rigorous double-blind, placebo-controlled trials in matched clinical populations to evaluate efficacy and safety in this difficult-to-treat group.