Ivermectin as an Adjunct Therapy in Parkinson's Disease: A 2026 Evidence Review

OneDayMD Evidence Review  |  Integrative Neurology  |  Repurposed Drugs

Published: February 2025  |  Last Updated: June 26, 2026  |  Medically Reviewed by the OneDayMD Editorial Team

OneDayMD Editorial Team — Integrative Neurology Series

Dopaminergic neuron degeneration in the substantia nigra is the hallmark of Parkinson's disease. Ivermectin's effects on cholinergic and P2X4 pathways may offer a novel adjunctive approach.

Quick Answer

Ivermectin (IVM), an established antiparasitic drug, is being investigated as an adjunct to levodopa (L-DOPA) in Parkinson's disease. Preclinical studies show IVM increases dopamine release in the dorsal striatum by activating striatal cholinergic interneurons and modulating nicotinic acetylcholine receptors. It also acts as a positive allosteric modulator of P2X4 receptors, which regulate dopaminergic activity. A 2024 peer-reviewed publication (Cell & Bioscience) and a 2025 clinical case series by Dr. William Makis provide accumulating — though still early — evidence. No clinical trials have been completed. Off-label use requires physician supervision.

Table of Contents

1. Abstract
2. Introduction
3. Pathophysiology of Parkinson's Disease
4. Ivermectin's Mechanisms of Neuromodulation
5. Evidence Review: Key Studies
6. Emerging Clinical Case Reports (2025)
7. Evidence-Tier Summary Table
8. Integrative Nutrition for Dopaminergic Health
9. Discussion
10. Limitations & Research Gaps
11. Conclusion
12. Using AI to Personalize This Information
13. FAQ
14. References

⚠️ Medical Disclaimer: This article is for educational and informational purposes only and does not constitute medical advice. Ivermectin is not FDA-approved for Parkinson's disease. Off-label use should only occur under the supervision of a licensed physician with appropriate clinical monitoring. Individual results vary. Always consult your neurologist before modifying your treatment plan.

Abstract

Background:	Parkinson's disease (PD) affects more than 10 million people worldwide and is characterized by progressive dopaminergic neurodegeneration in the substantia nigra pars compacta. Long-term levodopa (L-DOPA) therapy, the current gold standard, is associated with motor fluctuations, dyskinesias, and declining efficacy.
Objective:	To synthesize the available preclinical and emerging clinical evidence on ivermectin's dopaminergic, cholinergic, and neuroprotective mechanisms and evaluate its potential as an adjunct therapy in PD.
Methods:	Narrative review of PubMed-indexed preclinical studies, peer-reviewed publications, doctoral thesis research, and documented clinical case reports from 2016–2026.
Key Findings:	Three preclinical studies (Khoja et al. 2016; Warnecke et al. 2020; Wi 2021) and one peer-reviewed mechanistic publication (Wadsworth et al. Cell & Bioscience 2024) collectively demonstrate that IVM increases dorsal striatum dopamine release primarily through cholinergic interneuron activation and nicotinic acetylcholine receptor modulation. Emerging 2025 clinical case reports suggest meaningful symptom improvement in PD patients using IVM ± fenbendazole.
Conclusion:	Ivermectin represents a biologically plausible, low-cost adjunct candidate in Parkinson's disease. Well-designed human clinical trials are urgently needed to translate preclinical promise into clinical practice.
Keywords:	ivermectin, Parkinson's disease, dopamine, L-DOPA, P2X4, cholinergic interneurons, neuroprotection, repurposed drugs, fenbendazole, neurodegenerative disease

1. Introduction

Parkinson's disease (PD) is the second most common neurodegenerative disorder globally, affecting an estimated 10–12 million individuals and carrying a substantial burden of motor disability, cognitive decline, and reduced quality of life. The cardinal features — resting tremor, bradykinesia, rigidity, and postural instability — arise primarily from the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the consequent depletion of dopamine in the striatum.

Current pharmacotherapy centres on dopamine replacement strategies. Levodopa (L-DOPA), converted to dopamine in the brain, remains the gold standard. However, long-term L-DOPA use is complicated by motor fluctuations, peak-dose dyskinesias, and the wearing-off phenomenon — problems that worsen as the disease advances and dopaminergic terminals are further lost. These limitations drive ongoing investigation into adjunct therapies capable of extending L-DOPA efficacy, reducing required doses, and potentially slowing disease progression.

Drug repurposing — identifying new indications for existing, well-characterized compounds — has emerged as a cost-effective and accelerated strategy in neurodegenerative disease research. Ivermectin (IVM), a macrocyclic lactone antiparasitic with over four decades of clinical use, has attracted increasing scientific interest for its neuromodulatory properties beyond its antiparasitic mechanism. This review synthesizes the emerging evidence base supporting IVM as a candidate adjunct therapy in PD, with emphasis on its dopaminergic and cholinergic mechanisms, safety profile, and the emerging clinical case series from 2025.

2. Pathophysiology of Parkinson's Disease: Targets for Adjunct Intervention

PD pathology is multifactorial. The key pathological processes relevant to ivermectin's potential mechanisms include:

2.1 Dopaminergic Neurodegeneration

The nigrostriatal pathway — projecting from SNpc dopaminergic neurons to the striatum — is the primary site of neurodegeneration in PD. By the time motor symptoms emerge, approximately 60–80% of dopaminergic neurons have already been lost. The resulting striatal dopamine deficit disrupts basal ganglia circuitry, producing the characteristic motor phenotype.

2.2 Alpha-Synuclein Aggregation and Lewy Bodies

Pathological aggregation of alpha-synuclein (α-syn) into intracellular inclusions (Lewy bodies) is the defining histological feature of PD. α-Syn aggregates disrupt synaptic vesicle trafficking, mitochondrial function, the endosomal-lysosomal pathway, and protein degradation systems, ultimately triggering neuronal death. Emerging evidence suggests α-syn can propagate between neurons in a prion-like fashion, driving disease progression. Any intervention capable of reducing neuroinflammation or improving cellular proteostasis could theoretically modulate α-syn burden.

2.3 Neuroinflammation

Microglial activation and elevated pro-inflammatory cytokines are consistently observed in the PD brain. Pathological α-syn activates microglia and drives a chronic neuroinflammatory state that accelerates dopaminergic neuron death. Anti-inflammatory interventions, including those targeting purinergic receptor signalling, represent a rational therapeutic strategy.

2.4 The Cholinergic-Dopaminergic Interface

The dorsal striatum contains a sparse but functionally critical population of cholinergic interneurons (CINs), which account for only 1–3% of striatal neurons yet exert powerful, frequency-dependent modulation of dopamine release via nicotinic acetylcholine receptors (nAChRs) on dopaminergic terminals. CINs can trigger dopamine release independently of dopaminergic cell body firing — a property of significant therapeutic relevance when dopaminergic neurons are depleted. Agents that activate CINs or potentiate their output can, in principle, augment residual dopaminergic function.

3. Ivermectin's Mechanisms of Neuromodulation

IVM's principal antiparasitic mechanism — potentiation of glutamate-gated chloride channels in invertebrates — does not apply to vertebrates, where these channels are absent. Instead, IVM exerts its mammalian neuromodulatory effects through several vertebrate ion channel targets:

① P2X4 Receptor Positive Allosteric Modulation

P2X4 is a purinergic ionotropic receptor that mediates calcium influx and facilitates downstream dopamine secretion. IVM acts as a positive allosteric modulator of P2X4, stabilizing the channel in the open state and preventing its internalization. In pathological states — including PD, ALS, multiple sclerosis, Alzheimer's disease, chronic neuropathic pain, epilepsy, and several neuropsychiatric disorders — P2X4 overexpression or dysregulation has been documented in microglia and neurons, suggesting a shared mechanistic pathway amenable to IVM modulation.

② Nicotinic Acetylcholine Receptor (nAChR) Modulation & Cholinergic Interneuron Activation

Wadsworth et al. (2024) demonstrated that IVM's primary mechanism for increasing striatal dopamine release operates through the cholinergic system. IVM enhanced striatal CIN firing and modulated nAChR activity on dopaminergic terminals. Crucially, antagonizing nicotinic receptors abolished IVM's effects on dopamine release — while P2X4 receptor inactivation did not — establishing nicotinic modulation as the dominant pathway for IVM's dopaminergic augmentation in the striatum.

③ Anti-Neuroinflammatory Properties

Preclinical studies suggest IVM may modulate alpha-synuclein aggregation pathways and reduce microglial neuroinflammation. Its established anti-inflammatory properties in peripheral tissues extend to potential CNS benefits, particularly in states of barrier disruption. If confirmed in PD models, this could address one of the core drivers of progressive neurodegeneration.

④ Mitochondrial Protection

Mitochondrial dysfunction is a well-established contributor to dopaminergic neuron death in PD. IVM has shown mitochondria-protective properties in cellular models, potentially preserving the energy metabolism of vulnerable nigrostriatal neurons. This mechanism is currently under investigation in neurodegenerative disease research.

4. Evidence Review: Key Preclinical and Mechanistic Studies

Study 1 — Preclinical Animal Model

Khoja et al. (2016) — Foundational Evidence of IVM + L-DOPA Synergy

This foundational preclinical study first demonstrated that the combination of ivermectin and L-DOPA produced greater dopamine-mediated motor behavior changes than L-DOPA alone in a rodent model of dopamine depletion. The synergistic motor improvement implicated the purinergic system — specifically P2X4 receptors — as a modifiable target to potentiate conventional PD pharmacotherapy, establishing the scientific rationale for subsequent investigations.

Evidence Tier: Tier 3 — Preclinical (rodent model). Limited direct human applicability.  |  Significance: Hypothesis-generating; founded the IVM-PD research programme.

Study 2 — Preclinical Animal Model

Warnecke et al. (2020) — Sex-Dependent Dopaminergic Effects & Lead Candidate Designation

Using the 6-OHDA mouse model of dopamine depletion — the most widely validated preclinical PD model — Warnecke et al. demonstrated that IVM significantly altered rotational behaviour in both male and female mice, with notable sex-dependent differences in response magnitude. The authors formally proposed IVM as a lead candidate for adjunct use alongside L-DOPA in PD patients, lending institutional credibility to the repurposing hypothesis. Published in Behavioural Brain Research and indexed on PubMed (PMID 32668263).

Evidence Tier: Tier 3 — Preclinical (6-OHDA mouse model). Sex differences noted.  |  PubMed: PMID 32668263

Study 3 — Doctoral Research

Wi (2021) — P2X4 Receptor Modulation in MPTP and 6-OHDA Models

Dongwook Wi's doctoral thesis at USC systematically investigated IVM's interaction with P2X4 receptors in two validated PD models: the 6-OHDA and MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) models. The research confirmed that P2X4 receptor activation by IVM increased intracellular calcium and dopamine secretion, and that IVM-mediated P2X4 modulation altered dopamine-dependent behaviours in a therapeutic direction when combined with L-DOPA. This work delineated the purinergic pathway as a mechanistically coherent target.

Evidence Tier: Tier 3 — Preclinical (dual animal models). Mechanistic depth.  |  ResearchGate

⭐ Study 4 — Peer-Reviewed Mechanistic Publication (KEY STUDY)

Wadsworth et al. (2024) — Ivermectin Increases Striatal Cholinergic Activity to Facilitate Dopamine Terminal Function

Cell & Bioscience (2024) 14:50 | DOI: 10.1186/s13578-024-01228-2 | BYU / University of Southern California | PubMed PMID 38632622

This is the most mechanistically detailed published study to date on IVM's dopaminergic effects. Using ex vivo electrochemical detection (fast-scan cyclic voltammetry) in the dorsal striatum, Wadsworth and colleagues demonstrated that IVM increased single-pulse dopamine release. Key findings included:

• IVM significantly enhanced electrically-evoked dopamine release in the dorsal striatum.
• Inactivation of P2X4 receptors (using 5-BDBD) did NOT abolish IVM's effects on dopamine release — challenging the primacy of the P2X4 hypothesis and identifying nicotinic pathways as dominant.
• IVM attenuated nicotine-induced changes in dopamine release, and pharmacological antagonism of nicotinic acetylcholine receptors completely prevented IVM's dopaminergic effects — establishing nAChR modulation as the primary mechanism.
• IVM enhanced striatal cholinergic interneuron (CIN) firing, elevating dopamine levels through increased terminal excitability rather than changes in vesicular content.
• These findings indicate IVM may benefit individuals with dopaminergic circuit dysfunction — including PD — by leveraging the preserved cholinergic architecture of the striatum.

Evidence Tier: Tier 2b — Peer-reviewed mechanistic study with established ex vivo methodology. Translational gap: human pharmacokinetics and CNS penetration at therapeutic doses require further study.

5. Emerging Clinical Case Reports (2025)

While clinical trials in PD remain absent, a series of documented case reports has emerged from physicians using IVM off-label in 2025. These reports do not constitute clinical evidence of efficacy, but they are hypothesis-generating and inform future trial design.

Important Caveat: The following are uncontrolled observational reports. They are subject to placebo effects, natural disease fluctuation, and reporting bias. They should not be interpreted as proof of efficacy.

Case Report 1 — Nebraska, USA (August 2025)

77-Year-Old Male — 8-Year History of Parkinson's Disease

Shared by Dr. William Makis MD (McGill Medicine) on Substack and X.com in August 2025. The patient had an 8-year history of PD with established motor features including shuffling gait, postural instability, slumping posture, and significant tremor. Treatment was initiated in March 2025 with:

• Ivermectin: 1 mg/kg/day, titrated to 1.5 mg/kg/day
• Fenbendazole: 888 mg/day

After 4 months, the patient's daughter reported to Dr. Makis that the treating neurologist, upon re-evaluation, stated he was questioning whether the patient still had Parkinson's disease and noted the patient looked healthier than he ever had. The patient's shuffling gait, stooped posture had substantially resolved, and tremor was minimal.

Source: Dr. William Makis, X.com @MakisMD | August 2025  |  Evidence Tier: Tier 4 — Uncontrolled case report / testimonial.

Case Report 2 — Post-COVID Parkinsonism

Elderly Female — Post-Vaccination Parkinsonism-Like Syndrome

An X.com case posted in August 2025 by @Eileen_Graf5689 described an elderly woman who developed Parkinson's-like features (pill-rolling tremor, shuffling gait, flat affect, progressive non-verbal state, fatigue, rigidity) following COVID-19 vaccination and subsequent COVID infection. Her daughter, a retired RN, administered ivermectin 15 mg twice daily. The patient reportedly resolved her neurological symptoms within 4 weeks.

Editorial note: This case may represent post-COVID/spike protein-related neurological syndrome rather than classical idiopathic PD, though the clinical overlap is of scientific interest given ivermectin's known anti-spike protein and anti-inflammatory properties.

Evidence Tier: Tier 4 — Uncontrolled case report / social media report.

Broader Clinical Context — Dr. Makis's Neurology Programme (2025)

Dr. Makis has reported treating dozens of neurology patients — including those with Parkinson's disease, Alzheimer's disease, and multiple sclerosis — with high-dose IVM protocols since 2025. A video shared on X.com on October 10, 2025 (accumulating over 320,000 views) described what Makis calls an "accidental discovery" after noting neurological improvement in patients originally treated for other indications. He describes using doses of 60–72 mg per day in PD, with patients previously on maximum standard therapy experiencing dramatic recovery, including return to previously lost activities such as golf. These results await independent verification and formal publication.

6. Evidence-Tier Summary Table

Study / Source	Year	Design	Key Finding	CEBM Tier
Khoja et al.	2016	Preclinical (rodent)	IVM + L-DOPA > L-DOPA alone for motor behavior	Tier 3
Warnecke et al.	2020	Preclinical (6-OHDA mouse)	IVM alters rotational behavior; sex-dependent effects; lead candidate designation	Tier 3
Wi (PhD Thesis)	2021	Preclinical (6-OHDA + MPTP)	P2X4 modulation → ↑ DA secretion; IVM modulates dopamine-mediated behaviors	Tier 3
Wadsworth et al.	2024	Cell & Bioscience (peer-reviewed)	IVM ↑ striatal DA release via CIN activation and nAChR modulation; P2X4 not primary mechanism	Tier 2b
Makis — Case 1 (Nebraska)	2025	Uncontrolled case report	Near-complete PD symptom resolution after 4 months IVM + fenbendazole	Tier 4
Makis — Post-COVID Parkinsonism	2025	Uncontrolled case report	PD-like neurological symptoms resolved in 4 weeks on IVM 15mg BID	Tier 4

CEBM = Centre for Evidence-Based Medicine evidence hierarchy. Tier 1 = systematic review of RCTs; Tier 2 = individual RCT or high-quality observational/mechanistic study; Tier 3 = preclinical/animal data; Tier 4 = case reports/expert opinion.

7. Integrative Nutrition for Dopaminergic Health in Parkinson's Disease

Any discussion of adjunct pharmacotherapy in PD should be situated within a broader integrative framework. The following dietary strategies and supplements carry evidence relevant to dopaminergic and neuroprotective outcomes in PD:

Intervention	Proposed Mechanism in PD	Evidence Quality
Mediterranean Diet	Reduces systemic inflammation; polyphenols protect dopaminergic neurons	Moderate (observational)
Ketogenic Diet	Ketone bodies provide alternative fuel for mitochondrially-challenged neurons; reduces neuroinflammation	Moderate (pilot RCTs)
N-Acetylcysteine (NAC)	Replenishes glutathione; antioxidant protection of dopaminergic neurons; functional connectivity changes documented in PD (PubMed 2026)	Emerging (clinical)
CoQ10 / Ubiquinol	Mitochondrial Complex I support; reduced in PD brains; antioxidant	Moderate (RCTs, dose-dependent)
Magnesium	NMDA receptor antagonism; neuroprotection; cofactor for dopamine synthesis	Observational
Aerobic Exercise	↑ BDNF; promotes dopaminergic neuron survival; improves motor function	Strong (multiple RCTs)
Avoid: Soursop (Annona muricata)	Annonacin content linked to atypical Parkinsonism in a case-control study (PMID 10440304)	Moderate (case-control)
Curcumin	α-Syn disaggregation; anti-neuroinflammatory; crosses BBB at high doses	Preclinical / pilot human

This table is not exhaustive. Always discuss supplements with your neurologist, as some may interact with L-DOPA or other PD medications (e.g., high-protein meals reduce L-DOPA absorption; tyramine-rich foods may interact with MAO-B inhibitors).

8. Discussion

The accumulated preclinical literature and the landmark 2024 Cell & Bioscience publication establish a mechanistically coherent basis for ivermectin's dopaminergic effects. The identification of nicotinic acetylcholine receptor modulation — rather than P2X4 activation alone — as the primary mechanism for IVM-induced striatal dopamine release is a significant refinement. It explains why IVM may preferentially augment dopamine output in conditions where dopaminergic terminals are reduced but the cholinergic interneuron population (which is relatively spared in early-to-mid PD) remains intact.

The potential for IVM to permit lower L-DOPA doses — reducing the cumulative dose exposure that drives dyskinesias — represents a clinically meaningful hypothesis. The dose-limiting complications of chronic L-DOPA therapy remain the single greatest obstacle to long-term PD management; any adjunct capable of extending the therapeutic window of L-DOPA warrants urgent clinical investigation.

The 2025 case series, while anecdotal and methodologically limited, cannot be dismissed entirely. The magnitude of reported improvements — including neurologist re-evaluation questioning the diagnosis — and the relatively rapid time course (4–8 weeks) are noteworthy. Whether these outcomes reflect true disease modification, symptomatic augmentation of dopaminergic signalling, anti-inflammatory effects on co-existing spike protein-related neuroinflammation, or placebo effects remains unresolved.

IVM's excellent established safety profile — including the absence of CNS toxicity documented at doses up to 10 times the standard antiparasitic dose in a 2002 controlled study — and its global availability as a generic drug position it as an attractive candidate for a formally designed phase II clinical trial in PD.

9. Limitations and Research Gaps

The existing evidence base carries significant limitations that must be acknowledged:

• No completed human clinical trials exist for IVM in idiopathic PD. All mechanistic data is from preclinical or ex vivo models.
• Blood-brain barrier penetration at clinical doses remains uncertain. IVM is a P-glycoprotein substrate and is actively effluxed from the CNS; the doses required for therapeutic CNS concentrations in humans have not been established.
• Optimal dosing is unknown. Case reports describe a range from 12–72+ mg/day, far exceeding standard antiparasitic dosing, with no pharmacokinetic data supporting safety at these levels in the PD population.
• Interaction with standard PD medications — including L-DOPA, dopamine agonists, and MAO-B inhibitors — has not been formally assessed.
• Sex differences observed in animal models (Warnecke 2020) may have clinical significance that has not been explored in human populations.
• Case report bias is significant. Published case reports overwhelmingly represent positive outcomes; neutral or negative cases go unreported.
• Diagnosis verification is absent in clinical case reports. Parkinsonism has multiple causes; some reported "PD" cases may represent post-viral, drug-induced, or atypical Parkinsonism — conditions with different prognoses and potential IVM responsiveness.

10. Conclusion

Ivermectin represents a scientifically grounded, biologically plausible candidate adjunct therapy in Parkinson's disease. The convergence of its P2X4 modulatory properties, cholinergic interneuron activation, and nicotinic acetylcholine receptor modulation offers three mechanistically distinct but complementary pathways through which IVM could augment residual dopaminergic function in the PD brain.

The 2024 Cell & Bioscience publication by Wadsworth et al. represents the most rigorous mechanistic evidence to date and provides a strong scientific foundation for clinical translation. The 2025 clinical case reports, while not constituting evidence of efficacy, generate compelling hypotheses and underscore the urgency of formal human trials.

Given IVM's established safety profile, generic availability, global accessibility, and multi-mechanistic neuromodulatory properties, a properly designed, placebo-controlled phase II clinical trial in PD patients is scientifically justified and ethically warranted. OneDayMD will continue to monitor and update this evidence review as new data emerges.

11. Using AI Tools to Personalize This Information

AI assistants can help you understand how the evidence in this article applies to your specific situation, medication regimen, or loved one's diagnosis. Here is how to use each major platform effectively:

AI Tool	Suggested Prompt / Approach
Claude (Anthropic)	"I have PD [describe stage, medications, duration]. Based on the Wadsworth 2024 Cell & Bioscience paper on ivermectin and dopamine, what questions should I ask my neurologist about adjunct options?"
ChatGPT (OpenAI)	Upload this article as a PDF. Ask: "Summarize the mechanism by which ivermectin may enhance dopamine in Parkinson's and what evidence tier each study represents."
Gemini (Google)	"Search for the latest 2025–2026 clinical trials on ivermectin and Parkinson's disease and compare them to the preclinical evidence from Warnecke 2020."
Perplexity AI	"What is the current scientific consensus on ivermectin as an adjunct therapy in Parkinson's disease as of 2026? Include PubMed citations."

12. Frequently Asked Questions

Can ivermectin treat Parkinson's disease?

Current evidence from preclinical studies and early clinical case reports suggests IVM (ivermectin) may enhance dopaminergic signalling and offer neuroprotective effects as an adjunct to standard therapies such as L-DOPA. It is not FDA-approved for PD and should not replace conventional treatment. Rigorous clinical trials are needed to confirm efficacy and establish safe dosing regimens.

How does ivermectin interact with L-DOPA in Parkinson's disease?

IVM appears to increase dopamine release in the dorsal striatum through activation of striatal cholinergic interneurons (CINs) and modulation of nicotinic acetylcholine receptors (nAChRs) on dopaminergic terminals. When co-administered with L-DOPA in animal models, the combination produced greater dopamine release and improved motor behavior than L-DOPA alone — potentially enabling lower L-DOPA doses and reducing dyskinesia risk.

What is the P2X4 receptor and why does it matter in Parkinson's disease?

P2X4 is a purinergic ionotropic receptor that mediates calcium influx and downstream dopamine secretion. Dysregulation of P2X4 has been linked to PD, ALS, multiple sclerosis, Alzheimer's disease, chronic neuropathic pain, epilepsy, and neuropsychiatric disorders. IVM acts as a positive allosteric modulator of P2X4, stabilizing the open state — though the Wadsworth 2024 study suggests the dominant dopaminergic mechanism operates through nicotinic rather than P2X4 pathways specifically in the dorsal striatum.

Does ivermectin cross the blood-brain barrier?

IVM exhibits poor penetration of the blood-brain barrier in mammals under normal conditions, as it is actively effluxed by P-glycoprotein — a property contributing to its excellent safety profile in antiparasitic use (J Drugs Dermatol 2016). However, in the context of neuroinflammation or barrier compromise, limited CNS entry may occur. The doses required to achieve therapeutic CNS concentrations in PD specifically have not been established in human pharmacokinetic studies.

Is ivermectin safe for Parkinson's disease patients?

IVM has an established safety record in its approved antiparasitic indications. A 2002 study documented no CNS toxicity at doses up to 10 times the highest FDA-approved dose (PubMed PMID 12362927). However, the safety profile at the higher doses used in 2025 clinical case reports (1–1.5 mg/kg/day or 60–72 mg/day) specifically in PD patients — who may have altered neurological vulnerability or drug interactions — has not been formally evaluated. Physician supervision is essential.

Does ivermectin cause serious neurological adverse events?

At standard doses, IVM has not been associated with CNS toxicity in humans. A controlled escalating-dose study in healthy adults showed no evidence of CNS adverse effects at up to 10× the standard dose (PubMed 2002). Neurological adverse events (encephalopathy) have been rarely reported in the context of very high doses or in patients with conditions that compromise the blood-brain barrier.

What nutritional factors support dopaminergic health in Parkinson's disease?

Key dietary interventions with PD-relevant evidence include: the Mediterranean diet (anti-inflammatory, neuroprotective polyphenols), ketogenic diet (mitochondrial support), NAC (antioxidant; functional connectivity changes documented in a 2026 PubMed study), CoQ10/ubiquinol (mitochondrial Complex I), magnesium, and regular aerobic exercise (BDNF upregulation). Patients should avoid soursop (Annona muricata), which has been linked to atypical Parkinsonism in a case-control study.

What did the Wadsworth et al. 2024 study find about ivermectin and dopamine?

Wadsworth et al. (Cell & Bioscience 2024) demonstrated using ex vivo electrochemical measurement that IVM significantly increased single-pulse dopamine release in the dorsal striatum. The mechanism was primarily through activation of cholinergic interneurons (CINs) and modulation of nicotinic acetylcholine receptors — not through P2X4 alone. IVM also attenuated nicotine-induced alterations in dopamine release, suggesting complex and nuanced modulation of the cholinergic-dopaminergic interface relevant to Parkinson's disease.

13. References

1. Wadsworth HA, Warnecke AMP, Barlow JC, et al. Ivermectin increases striatal cholinergic activity to facilitate dopamine terminal function. Cell & Bioscience. 2024;14(1):50. doi: 10.1186/s13578-024-01228-2. PubMed PMID 38632622
2. Warnecke AMP, et al. The macrocyclic lactones ivermectin and moxidectin show differential effects on rotational behavior in the 6-hydroxydopamine mouse model of Parkinson's disease. Behavioural Brain Research. 2020. PubMed PMID 32668263
3. Wi D. The Role of Ivermectin on P2X4 Receptors in Regulating Behavior Responses in the Parkinson's Disease Models. PhD Thesis, University of Southern California. 2021. ResearchGate
4. Makis W. IVERMECTIN and FENBENDAZOLE Testimonial — 78 year old Nebraska PARKINSON'S DISEASE patient of 8 years. X.com @MakisMD. August 2025. Source
5. Campbell WC, et al. Safety profile of ivermectin at escalating doses: No CNS toxicity at 10× standard dose. 2002. PubMed PMID 12362927
6. Lyons MF, et al. Over 25 years of clinical experience with ivermectin: an overview of safety for an increasing number of indications. J Drugs Dermatol. 2016. Source
7. NAC is associated with changes in functional connectivity in patients with Parkinson's disease. PubMed. 2026. PubMed PMID 41619526
8. Caparros-Lefebvre D, Elbaz A. Possible relation of atypical parkinsonism in the French West Indies with consumption of tropical plants: a case-control study. Lancet. 1999. PubMed PMID 10440304
9. Zhang B, Sulzer D. Frequency-dependent modulation of dopamine release by nicotine. Nature Neuroscience. 2004.
10. Sulzer D, Cragg SJ, Rice ME. Striatal dopamine neurotransmission: regulation of release and uptake. Basal Ganglia. 2016;6(3):123–148.

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Medically Reviewed by: OneDayMD Editorial Team  |  Last Updated: June 26, 2026

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