Nov 13, 2026 · @Yoon Hang Kim MD

About Dr. Kim

Yoon Hang Kim MD is board-certified in Preventive Medicine and practices integrative and functional medicine. He is the author of eight books — including Integrative Oncology: Evidence-Based Strategies to Support Cancer Treatment, MCAS: Epidemic in Plain Sight, and two volumes on low-dose naltrexone (LDN Primer and LDN for Clinicians) — and more than 25 peer-reviewed articles. He also founded the LDN Support Group, an online community of roughly 10,000 members. Learn more at yoonhangkim.com.

Abstract

A 2026 PET imaging study from Toronto's Centre for Addiction and Mental Health (CAMH) reported approximately 16–20% reductions in striatal VMAT2 binding — a marker of dopamine-terminal integrity — in adults with long COVID and prominent neuropsychiatric symptoms, with regional reductions correlating with apathy, motor slowing, and memory impairment. These findings provide measurable biological correlates for symptoms too often dismissed as psychological. However, popular coverage describing irreversible "dopamine damage" overstates what the data establish. VMAT2 binding is an indirect presynaptic marker; it cannot distinguish altered dopamine signaling from terminal remodeling or neuronal death, and a 20% reduction in binding is not equivalent to a 20% loss of neurons. The study was cross-sectional and drew on a highly selected population — all participants had apathy and depressive-spectrum symptoms, with no psychiatric control group — which limits generalizability and leaves causation, permanence, and reversibility unresolved. VMAT2 PET remains a research tool, peripheral dopamine testing is not a valid substitute, and dopamine-directed therapies (including a patented rasagiline and dopamine-precursor strategy) are hypotheses for clinical trials rather than validated treatments. The evidence supports dopamine-circuit dysfunction as a plausible, increasingly measurable contributor to a subset of long-COVID symptoms — not a proven permanent lesion, and not Parkinson's disease.

Introduction

If you follow long COVID research, you've probably seen the headlines: "COVID destroys dopamine neurons" or "Long COVID causes Parkinson's-like brain damage." These claims are understandable — they originate from a genuinely important 2026 PET imaging study — but they outrun what the data actually supports. As clinicians, we owe our patients a more careful reading.

The study in question, published in eBioMedicine by researchers at Toronto's Centre for Addiction and Mental Health (CAMH), provides meaningful evidence that dopamine-system dysfunction may contribute to a subset of long-COVID neuropsychiatric symptoms. That is a significant finding. But there is a wide gap between "measurable dopamine-circuit abnormality" and "irreversible brain damage," and that gap has real clinical consequences — for the patients sitting across from us who are frightened, and for the premature treatment decisions those headlines can drive.

This post walks through what the study found, what it did not establish, and what it means for how we think about and manage long-COVID patients with cognitive, motivational, and motor complaints.

The 2026 CAMH PET Study

The researchers studied 24 adults with long COVID and persistent neuropsychiatric symptoms — brain fog, fatigue, apathy, motor slowing — alongside 24 age-matched healthy controls (with an expanded exploratory control group of 43). Using positron emission tomography (PET), they measured VMAT2 (vesicular monoamine transporter 2), a protein that packages monoamine neurotransmitters, including dopamine, into synaptic vesicles. In the striatum, VMAT2 binding serves as a well-established marker of dopamine-terminal integrity — the same marker used in Parkinson's disease research.

The key finding: long-COVID participants showed approximately 16–20% lower VMAT2 binding across three striatal subregions compared to controls.

What makes this more than a blunt "brain fog" observation is the anatomical specificity. The regional reductions tracked with distinct functional impairments:

These region-symptom correlations align with what we know about the functional anatomy of dopaminergic circuits — the ventral striatum drives motivation and reward processing, the putamen supports motor execution, and the caudate participates in cognitive flexibility and memory retrieval. The fact that the imaging abnormalities map onto the circuits that support the impaired functions is what makes this paper worth taking seriously.

That biological coherence should not be mistaken for uniform statistical strength. The apathy and dominant-hand motor correlations were prespecified secondary analyses; the delayed-memory association was exploratory. Given the small sample and multiple statistical comparisons, none of these should be treated as definitively established — the apathy (P = 0.0069) and motor (P = 0.010) correlations did not cross the authors' own suggested exploratory threshold of roughly 0.004, while the memory correlation (P = 0.0029) did, which is not the same as formal significance after multiplicity adjustment. The pattern is real and interesting, but it requires replication.

That said, these remain associations, not proof that dopamine-terminal injury caused the symptoms. Three limitations deserve particular emphasis.

First, this was a cross-sectional study with no longitudinal component. It cannot tell us whether these changes preceded infection, developed after it, or will resolve over time.

Second — and most important for interpreting the paper — the study population was highly selected. Every long-COVID participant had apathy and was required to exhibit at least five neuropsychiatric symptoms consistent with a major depressive episode, and those with preexisting neurological disorders were excluded. This is a distinct neuropsychiatric phenotype, not a representative cross-section of long COVID. There was also no psychiatric disease-control group, which leaves the specificity of the findings uncertain. The results may not generalize to patients whose predominant manifestations are post-exertional malaise, dysautonomia, or other non-neuropsychiatric symptoms.

Third, the sample was small, which compounds the multiple-comparisons concern noted above.

Does Reduced Signal Mean Brain Damage?

This is the question that matters most clinically, and it is the one most frequently answered too quickly in popular coverage. There are three distinct biological possibilities that the PET findings cannot yet distinguish:

1. Altered presynaptic function without structural loss. The dopamine system may be functioning abnormally — reduced vesicular storage capacity or altered VMAT2 transporter expression — while the neurons and their terminals remain anatomically intact. This is the interpretation most directly supported by what the tracer actually measures: VMAT2 is a presynaptic vesicular transporter, not a readout of receptor density or overall dopamine release. Think of it as a software problem, not a hardware one.
2. Injury or remodeling of nerve terminals. The dopamine-releasing axon terminals in the striatum may be impaired, retracted, or reduced in number, while the parent dopaminergic neurons in the substantia nigra and ventral tegmental area remain alive. This is a structural change, but it is not the same as neuronal death — terminals can, under some circumstances, regenerate.
3. Irreversible neuronal loss. The dopamine-producing neurons themselves may have died. This is the Parkinson's disease scenario, and it is the claim that generates the most fear.

The PET findings are consistent with any of these. An accompanying commentary in the same journal specifically cautioned that reduced VMAT2 binding could reflect altered vesicular storage or adaptive presynaptic changes rather than irreversible neuronal loss. A 20% reduction in marker binding does not mean that 20% of dopamine neurons have died. It does not mean that brain dopamine concentrations have fallen by 20%. These are different measurements, and conflating them leads to clinical conclusions the data does not support.

This distinction is not academic hand-waving — it has direct implications for prognosis, patient counseling, and treatment expectations. Functional changes or terminal remodeling could potentially be reversible, whereas neuronal death is not. Crucially, though, there are no longitudinal VMAT2 data from this cohort showing that anything normalizes over time: reversibility remains a possibility, not a finding. What we can say with confidence is that telling patients their dopamine neurons have been destroyed is not supported by the current evidence.

The Inflammation Hypothesis

The biological plausibility of this finding rests heavily on the neuroinflammation story. Earlier PET imaging from the same CAMH research group had already demonstrated increased markers of neuroinflammation — specifically, elevated translocator protein (TSPO) signal — in dopamine-rich brain regions of long-COVID patients. The newer VMAT2 study found reduced dopamine-terminal markers in overlapping regions.

It is worth being precise about what TSPO measures. It is an indirect marker associated with glial activation and related processes, not a specific readout of inflammatory injury to dopamine neurons. Elevated TSPO signal tells us something is happening in those regions; it does not, on its own, establish that inflammation is damaging dopaminergic cells.

That convergence is suggestive. Persistent neuroinflammation damaging vulnerable dopaminergic pathways is a plausible mechanism, and it aligns with what we see in other post-infectious and neuroinflammatory conditions where dopamine circuits are disproportionately affected. The nigrostriatal and mesolimbic dopamine pathways have long been recognized as selectively vulnerable to inflammatory insults — a susceptibility thought to relate to their high metabolic demands, extensive axonal arborization, and relatively limited antioxidant defenses.

Broader mechanistic literature adds additional layers: inflammation-related changes in the expression of tyrosine hydroxylase (the rate-limiting enzyme in dopamine synthesis), altered dopamine transporter function, disrupted vesicular packaging, and downstream effects on basal ganglia circuits involved in effort-based decision-making, reward processing, and arousal regulation.

However, most of this mechanistic evidence comes from experimental animal models or from other inflammatory and infectious conditions — not from direct measurements in long-COVID patients. The CAMH findings are consistent with this framework, but they do not prove the causal chain. Whether neuroinflammation causes the dopamine-terminal changes, results from them, or simply accompanies another upstream process remains an open question.

One additional point worth noting: a biological disturbance of dopaminergic motivation circuitry is not the same thing as unwillingness or lack of effort. If confirmed, this would mean that some long-COVID patients are struggling against a neurochemical headwind when they try to initiate and sustain activity. That reframing has value for both clinicians and patients — but it should not be extended to claim that dopamine dysfunction explains every patient's fatigue or cognitive symptoms. Long COVID remains a heterogeneous condition with likely multiple contributing mechanisms.

Clinical Implications

Diagnostic Testing

VMAT2 PET imaging is a research tool, not a clinical test for long COVID. It is expensive, not widely available, and has not been validated as a diagnostic or prognostic marker in this population. The CAMH study also found that peripheral blood biomarkers did not reliably mirror the central dopamine-system abnormalities seen on PET. In practical terms, this means that ordering a serum dopamine level — something patients may request after reading about this study — will not tell you what is happening in the striatum. Central and peripheral dopamine systems are substantially independent, and a blood draw is not a substitute for neuroimaging.

Treatment

The findings provide a biological rationale for clinical trials of dopamine-supporting therapies. They do not provide evidence that those therapies already work for long COVID. This is an important distinction that gets lost in translation.

The CAMH investigators have proposed studying rasagiline, an MAO-B inhibitor that reduces dopamine breakdown, as a potential intervention. They have also discussed dopamine precursor strategies. The senior investigator explicitly stated that these approaches should not be initiated outside the context of a clinical trial based on this study alone.

Two additional considerations are relevant here. First, the study discloses a pending patent involving rasagiline and a dopamine-precursor strategy for long-COVID treatment. That does not invalidate the imaging findings, but it is appropriate context when evaluating therapeutic claims — and it is the kind of disclosure we would expect patients to want to know about. Second, "off-label dopaminergic therapy" is not a single risk profile; adverse effects differ meaningfully across agents. MAO-B inhibitors like rasagiline carry interaction and, at higher doses, tyramine-related considerations; levodopa and dopamine precursors carry their own concerns, including impulse-control disorders and, with chronic use, dyskinesia. Notably, the proposed precursor strategy involves tyramine, whose interaction with MAO inhibition is a specific and well-recognized safety consideration. None of this argues against future trials — it argues that those trials, and any off-label use, need careful design and monitoring rather than enthusiasm driven by a single imaging study.

The Parkinson's Disease Question

Patients will ask this. Colleagues will ask this. The answer, as of now, is that we do not know.

The VMAT2 marker used in this study is the same class of marker used to assess dopamine-terminal integrity in Parkinson's disease. That is what gives the finding its clinical resonance — and its potential to frighten. But reduced VMAT2 binding in a cross-sectional study of long-COVID patients does not establish that long COVID is early Parkinson's disease, that these patients will develop Parkinson's disease, or that the observed changes represent progressive neurodegeneration.

It is tempting to reassure patients by comparing the magnitude of these VMAT2 reductions to the neuronal loss seen in Parkinson's disease — but that comparison is misleading, because it sets two different measurements side by side: striatal VMAT2 terminal binding in this study versus substantia nigra cell-body loss in Parkinson's. In fact, the investigators noted that some of the regional VMAT2 reductions fell in a range comparable to mild-to-moderate Parkinson's disease or REM sleep behavior disorder.

So the honest reassurance is not that the reductions are "too small to worry about." It is more specific: a cross-sectional imaging abnormality, whatever its magnitude, does not by itself establish a progressive neurodegenerative process. Whether these changes are static, reversible, or progressive is precisely what this study cannot determine — and precisely what longitudinal follow-up will need to answer.

Dopamine, Endorphins, and LDN: A Research Hypothesis

A caveat up front: this section is speculative, and it should be read that way. The CAMH study did not examine low-dose naltrexone (LDN), opioid-receptor activity, or endorphin dynamics. What follows is a hypothesis, not a mechanism. But for those of us who use LDN in long COVID — and who have watched patients tolerate it unpredictably — the dopamine findings raise a question worth putting on the research agenda.

Opioid and dopamine signaling are deeply intertwined within the brain's reward and motivation circuitry. Endogenous opioid tone modulates dopaminergic activity in the ventral striatum — precisely the region where this study found the reductions most strongly linked to apathy. LDN works, in part, by transiently blocking opioid receptors and prompting a compensatory rise in endorphin signaling. It is at least biologically plausible that a reward system already perturbed by long COVID might respond differently — more briskly, or less comfortably — to that kind of modulation.

This is offered strictly as a hypothesis. There are no data showing that long-COVID dopamine changes predict LDN response or intolerance, and it would be a mistake to present one as explaining the other. But it is exactly the kind of mechanistically grounded question that integrative clinicians are positioned to notice and that merits formal study. If altered striatal dopamine signaling does shape how patients respond to LDN, the implications for dosing, titration, and patient selection would be real — and it would be an original contribution to a literature that has so far treated the opioid and dopamine systems largely in isolation.

Conclusion

Dopamine-circuit dysfunction is a plausible, increasingly measurable contributor to a subset of long-COVID cognitive, motivational, and motor symptoms. The 2026 CAMH study advances our understanding meaningfully — it moves the conversation from "something is wrong in the brain" to "here is a specific neurochemical system that appears to be affected, with anatomically coherent symptom correlations."

What it does not do is prove permanent neuronal loss, establish a validated treatment target, or predict who will develop neurodegenerative disease. The clinically defensible position is this: we are getting closer to understanding one of the biological mechanisms behind long-COVID neuropsychiatric symptoms, and that is genuinely encouraging for the development of targeted therapies. But we are not there yet.

For our patients, the most honest and helpful framing avoids implying more individual certainty than a small, group-level study can support: "Researchers have identified changes in dopamine-related brain signaling in a small group of people with long COVID. There is real biology being uncovered here, and it may help explain symptoms like low motivation, slowed thinking, and fatigue. But we can't assume that every patient's symptoms arise from this same mechanism, we don't yet know whether these changes are permanent, and we don't yet have proven treatments that target them. The research is moving in a direction that should give us better answers."

That is not a dramatic headline. But it is what the evidence supports, and it is what our patients deserve to hear.

Sources

• Liu YK, et al. Loss of vesicular monoamine transporter 2 in the striatum of long COVID and its relationship to neuropsychiatric symptoms. eBioMedicine. 2026;130:106339.
• Corrigendum to "Loss of vesicular monoamine transporter 2 in the striatum of long COVID." eBioMedicine. 2026;132:106472 (published September 5, 2026).
• Guedj E, Beckman D. Dopaminergic vulnerability in long COVID: striatal PET imaging at the brain–body interface (accompanying editorial). eBioMedicine. 2026.
• Centre for Addiction and Mental Health (CAMH). Research announcement, July 10, 2026.
• CIDRAP. New study offers clues about long COVID's brain symptoms.
• Pharmacy Times. Brain imaging study links long COVID to dopamine neuron injury, pointing to repurposed treatments.
• Background on neuroinflammation and dopamine signaling: PMC11054322 (2024).