Lichen planopilaris (LPP) is a progressive scarring hair loss condition that can permanently damage hair follicles, often leaving patients with few reliable treatment options. Unlike temporary shedding, LPP appears to involve an autoimmune attack on the hair follicle, with inflammation disrupting the follicle’s normal protective “immune privilege”. This can lead to ongoing scalp symptoms, follicle destruction, and irreversible scarring hair loss. Current treatments, including intralesional corticosteroids, topical therapies, and systemic immunosuppressants, can help some patients, but results are often inconsistent and relapses are common. So, can low-dose naltrexone help?
Low-dose naltrexone (LDN) has emerged as an interesting potential option because of its immunomodulatory and anti-inflammatory effects. At low doses, naltrexone appears to briefly block opioid receptors, which may encourage the body to increase its own endorphin production, including beta-endorphins. These natural signalling molecules may help calm the inflammatory immune responses involved in LPP. While the evidence is still limited, early reports, including a notable case of hair regrowth in previously scarred tissue, suggest LDN may deserve further study as part of a broader treatment strategy for this difficult condition.
Table of contents
- Introduction
- Five Key Takeaways
- 1. Introduction and clinical significance of Lichen Planopilaris
- 2. Pathophysiology of Lichen Planopilaris and immune privilege collapse
- 3. Low-Dose Naltrexone: Pharmacology and mechanisms of action
- 4. Immunomodulatory effects of endogenous opioids and beta-endorphins
- 5. Clinical evidence for LDN in Lichen Planopilaris and related conditions
- 6. Proposed Mechanisms of LDN Efficacy in Lichen Planopilaris
- 7. Safety Profile and Tolerability of LDN
- 8. Future Directions and Emerging Therapeutic Strategies
- Summary
- References:
Introduction
Lichen planopilaris (LPP) is a progressive scarring hair loss condition that destroys hair follicles permanently, leaving patients with limited treatment options and frequent treatment failures. Unlike temporary hair loss, LPP involves an autoimmune attack on hair follicles—a collapse of the protective “immune privilege” that normally shields them from immune attack. This leads to inflammation, follicle destruction, and permanent scarring.
Current treatments—intralesional corticosteroids, topical agents, and systemic immunosuppressants—work inconsistently and often fail. Patients frequently experience relapses and minimal improvement, leaving them searching for alternatives.
Low-dose naltrexone (LDN) represents a novel immunomodulatory approach that’s generating real clinical interest. Originally developed for addiction treatment, LDN at doses of 1–5 mg daily triggers a paradoxical effect: it temporarily blocks opioid receptors, prompting your body to produce more endogenous opioids (particularly beta-endorphins). These natural opioids then suppress the inflammatory immune responses driving follicle destruction in LPP.
The evidence is still emerging, but a remarkable case report documented hair regrowth in previously scarred tissue—an outcome rarely seen in cicatricial alopecia. Combined with a favourable safety profile, low cost, and minimal monitoring requirements, LDN deserves serious investigation as part of a multi-pathway treatment strategy for this challenging disease.
Five Key Takeaways
1. LPP is an autoimmune attack on hair follicles caused by immune privilege collapse
Hair follicles normally exist in a protected state called “immune privilege,” shielded from immune attack by special molecules that suppress inflammation. In LPP, this protection breaks down. CD8 T cells and macrophages infiltrate the follicle, triggering interferon-gamma signalling and follicle stem cell destruction. Once this happens, scarring follows—and hair loss becomes permanent. Understanding this mechanism is crucial because it explains why conventional anti-inflammatory treatments often fail: they don’t specifically restore immune privilege.
2. LDN works through a paradoxical mechanism: blocking opioid receptors triggers endogenous opioid production
At high doses, naltrexone blocks opioid receptors (its original use in addiction treatment). But at low doses (1–5 mg daily), something unexpected happens. The transient blockade triggers compensatory upregulation of your body’s own opioids—especially beta-endorphins. These endogenous opioids then activate opioid receptors on immune cells, suppressing pro-inflammatory T cells and promoting anti-inflammatory macrophages. This is the opposite of what you’d expect from an opioid antagonist, which is why it’s called “paradoxical.”
3. Beta-endorphins suppress the exact immune cells driving LPP: Th1 T cells and pro-inflammatory macrophages
LDN-enhanced beta-endorphins don’t just reduce inflammation generally—they specifically target the pathogenic immune responses in LPP. They suppress interferon-gamma production from Th1 T cells, promote regulatory T cells (which calm inflammation), and shift macrophages toward an anti-inflammatory M2 phenotype. They also reduce oxidative stress and prevent epithelial-mesenchymal transition (EMT) in follicle stem cells. This multi-pathway targeting is why LDN is mechanistically plausible for LPP, even though clinical evidence is still limited.
4. Clinical evidence is emerging but limited: one remarkable case report showed hair regrowth in scarred tissue
The most compelling evidence comes from a 2022 case report by Klein and colleagues documenting a patient with biopsy-confirmed LPP who achieved hair regrowth in previously scarred alopecic patches after starting LDN plus platelet-rich plasma (PRP). This patient had failed 4 months of conventional treatment (intralesional steroids, topical clobetasol, minoxidil, finasteride, doxycycline, and ketoconazole shampoo). Hair regrowth in scarring alopecia is rare, making this case exceptional. However, this is a single case report, not a controlled trial—so larger studies are urgently needed.
5. LDN has a favourable safety profile, low cost, and minimal monitoring—making it an attractive adjunctive option
Unlike conventional immunosuppressants (methotrexate, azathioprine, JAK inhibitors), LDN is well-tolerated with minimal serious adverse effects. The most common side effects are mild and transient: initial sleep disturbances, vivid dreams, and gastrointestinal symptoms that usually resolve within weeks. There’s no increased infection risk, malignancy risk, or organ toxicity. LDN is also inexpensive and requires minimal monitoring. This safety profile makes it an ideal candidate for long-term management of chronic conditions like LPP, and supports its use as an adjunctive therapy alongside other treatments (JAK inhibitors, hydroxychloroquine, PRP, or topical agents).
1. Introduction and clinical significance of Lichen Planopilaris
Lichen planopilaris (LPP) is a primary cicatricial (scarring) alopecia characterised by patchy or diffuse hair loss, particularly affecting the vertex and parietal scalp regions [1]. As one of the most common lymphocytic forms of primary cicatricial alopecia (PCA), LPP represents a significant clinical challenge due to its progressive nature and limited treatment options [2]. The disease predominantly affects women more frequently than men and is characterised by inflammation around hair follicles, leading to destruction of follicular stem cells and permanent hair loss [3].
The aetiology of LPP remains incompletely understood, though substantial evidence indicates an autoimmune pathogenesis involving T-cell-mediated destruction of hair follicles [4]. Clinically, patients often present with pruritus, scalp discomfort (trichodynia), erythema, and scarring alopecia that can progress to extensive hair loss if left untreated [1]. Current therapeutic options, including intralesional corticosteroids, topical agents, and systemic immunosuppressants, demonstrate variable efficacy with frequent treatment failures and relapses [5]. This unmet clinical need has prompted investigation of novel immunomodulatory approaches, including low-dose naltrexone (LDN).
2. Pathophysiology of Lichen Planopilaris and immune privilege collapse
2.1 Hair follicle immune privilege and its disruption
Hair follicles normally maintain a state of immune privilege, a specialised immunological condition that protects the follicle from unwanted immune responses [6]. This immune privilege is mediated through several mechanisms, including downregulation of major histocompatibility complex (MHC) class I and II molecules, secretion of immunosuppressive cytokines such as transforming growth factor-beta (TGF-beta) and alpha-melanocyte-stimulating hormone (alpha-MSH), and recruitment of regulatory immune cells [6]. However, in LPP, collapse of hair follicle immune privilege (HFIP) initiates an aberrant autoimmune response [7].
Recent single-cell RNA sequencing studies have elucidated the follicle-targeted inflammation patterns in LPP, revealing that CD8 effector memory T cells (Tem) and macrophages infiltrate hair follicles, disrupting immune privilege and promoting scarring [8]. The heightened interferon-gamma (IFN-gamma) signalling and STAT1 activation in these Tem cells causes epithelial-mesenchymal transition (EMT) in hair follicle stem cells (HFSCs) [8]. Additionally, macrophage-secreted oncostatin M (OSM) impairs HFSC integrity, contributing to follicular destruction [8].
2.2 Cytokine signalling and T-Cell recruitment
Interferon-gamma plays a central pathogenic role in LPP and related cicatricial alopecias [9]. Cutaneous lichen planus is dominated by IFN-gamma and IL-21A, providing a basis for therapeutic JAK1 inhibition [9]. This Th1-mediated response involves upregulation of MHC class I and II molecules along the follicular epithelium, enhanced expression of stress-induced ligands such as MICA, and recruitment of NKG2D+ T cells [10].
The collapse of immune privilege in LPP is also characterised by significantly decreased expression of TGF-beta, which normally suppresses inflammatory responses and maintains HFSC quiescence [11]. Furthermore, mast cells infiltrating hair follicles in LPP express IL-17A and IL-23 receptors, suggesting they play a role in the pathogenesis of LPP via the IL-23/IL-17 axis [12]. This multifaceted immune dysregulation creates a hostile microenvironment for hair growth and promotes fibrosis and scarring.
3. Low-Dose Naltrexone: Pharmacology and mechanisms of action
3.1 Opioid Receptor Antagonism and the Paradoxical Effect
Naltrexone is a competitive antagonist of mu, delta, and kappa opioid receptors, originally developed for the treatment of alcoholism and opioid addiction [13]. However, when administered at low doses (1-5 mg daily), naltrexone exhibits a paradoxical immunomodulatory effect that differs substantially from its high-dose antagonistic actions [13]. The most prominent mechanism underlying LDN’s anti-inflammatory effects is a transient blockade of opioid receptors that triggers a compensatory upregulation of endogenous opioid production, particularly beta-endorphins [14].
This dose-dependent pharmacological profile is critical to understanding LDN’s therapeutic potential. At ultra-low doses (less than 1 microgram per day), LDN may work through different mechanisms, while very-low-dose naltrexone (VLDN, 50-100 microgramg/kg body weight) primarily inhibits TLR4 and modulates redox homeostasis [15]. In contrast, the conventional LDN dosing range (1-5 mg daily) appears to be optimal for glial cell modulation and systemic immunomodulation [14].
3.2 Endogenous opioid upregulation
The paradoxical increase in endogenous opioids following low-dose naltrexone administration is the cornerstone of its anti-inflammatory mechanism [13]. Beta-endorphin, the primary endogenous opioid enhanced by LDN, is a potent peptide with broad immunomodulatory functions [16]. Beta-endorphin production is regulated through the JAK-STAT1/3 pathway, particularly in lymphocytes activated by interleukin-4 (IL-4), and transfer of IL-4-pretreated cells leads to significantly improved endogenous opioid-mediated pain relief [17].
Multiple studies demonstrate that beta-endorphin-deficient mice possess an enhanced immune response, with increased splenocyte proliferation, elevated IL-2 mRNA levels, and increased splenic macrophage inflammatory cytokines (IL-6 and TNF-alpha) [18]. Conversely, administration of exogenous beta-endorphin significantly reduces inflammatory infiltration, reactive oxygen species, myeloperoxidase, and pro-inflammatory cytokines (IFN-gamma, TNF-alpha), while increasing antioxidant enzyme activity [16]. These findings underscore the critical anti-inflammatory role of beta-endorphin in suppressing pathogenic immune responses.
3.3 Toll-Like Receptor 4 modulation
Naltrexone’s interaction with toll-like receptor 4 (TLR4) represents another crucial mechanism for its anti-inflammatory effects [13]. The blockade of TLR4 signalling reduces NF-kB activation, leading to decreased production of pro-inflammatory cytokines, including TNF-alpha, IL-1b, and IL-6 [19]. Specifically, naltrexone inhibits IL-6 and TNF-alpha production by monocytes and plasmacytoid dendritic cells following stimulation with ligands for intracellular TLR7, TLR8, and TLR9 [19].
The therapeutic potential of TLR4 blockade has been demonstrated in multiple inflammatory contexts. In a murine model of asthma, blocking mu-opioid receptors (which is distinct from LDN’s mechanism) exacerbated airway inflammation, while very-low-dose naltrexone significantly reduced ROS, NO, and inflammatory mediators through TLR4 inhibition and MAPK pathway suppression [15]. In the context of morphine tolerance, TLR4 antagonism using propentofylline or astrocyte inhibitors attenuated tolerance development [20], suggesting TLR4 modulation may be critical for immune privilege restoration.
3.4 Glial cell modulation and neuroimmune interactions
Beyond peripheral immune modulation, LDN exerts significant anti-inflammatory effects through modulation of glial cells in the central nervous system [21]. The evidence that LDN operates as a novel anti-inflammatory agent via action on microglial cells is particularly significant, as these effects appear entirely independent from naltrexone’s better-known activity on opioid receptors [21]. Microglial activation, characterised by morphological changes and increased production of pro-inflammatory cytokines, is a hallmark of neuroinflammatory conditions.
Notably, opioid growth factor (OGF) and low-dose naltrexone impair central nervous system infiltration by CD4+ T lymphocytes in experimental autoimmune encephalomyelitis, a model of multiple sclerosis [22]. This suggests that LDN may reduce T-cell recruitment into inflamed tissue compartments through glial modulation and opioid growth factor receptor (OGFr) activation, mechanisms that could potentially extend to cutaneous immune privilege restoration in LPP.
4. Immunomodulatory effects of endogenous opioids and beta-endorphins
4.1 Opioid receptor expression on immune cells
Immune cells express all major opioid receptor subtypes—mu (MOP), delta (DOP), kappa (KOP), and nociceptin/orphanin FQ (NOP) receptors—at mRNA and protein levels [23]. These opioid receptors are expressed by lymphocytes, granulocytes, monocytes, and macrophages [23]. The distribution of opioid receptors on immune cell populations enables direct cellular communication between the nervous system and immune system through opioid peptides.
Beta-endorphin is produced by various immune cell populations, particularly CD4+ T lymphocytes and macrophages, and its production is upregulated in response to inflammatory signals [24]. Following antigen presentation and T-cell activation, endogenous opioid-producing cells migrate to inflamed tissue, where they release beta-endorphin to activate peripheral opioid receptors on nerve terminals and other immune cells [24]. This localised production of endogenous opioids in inflammatory tissue provides a self-limiting mechanism to suppress excessive inflammation.
4.2 Anti-inflammatory cytokine production and Th1/Th17 suppression
The anti-inflammatory effects of beta-endorphin are mediated through multiple mechanisms affecting T-cell differentiation and cytokine production [17]. IL-4 stimulation of lymphocytes amplifies endogenous opioid peptide expression through JAK-STAT1/3 activation, and these opioid peptide-producing cells exert strong anti-inflammatory effects on innate immunity [17]. When transferred to inflamed tissue, these cells significantly reduce nociception through activation of peripheral opioid receptors.
Beta-endorphin suppresses Th1 and Th17 cell differentiation while promoting regulatory T cell (Treg) development [18]. This is particularly relevant to LPP pathogenesis, where Th1-mediated IFN-? production and potentially Th17 responses drive follicular destruction [9]. Furthermore, endogenous opioid -enkephalin (the major T-cell-derived opioid in mice) completely abolishes the analgesic and anti-inflammatory opioid-mediated activity of CD4+ T lymphocytes when deficient [25], demonstrating the essential role of endogenous opioid peptides in controlling inflammation.
4.3 Macrophage polarisation and M2 phenotype promotion
Macrophage polarisation toward the anti-inflammatory M2 phenotype is significantly enhanced by endogenous opioid peptides [26]. M2 macrophages contain and release higher amounts of opioid peptides, including Met-enkephalin, dynorphin A, and ?-endorphin, compared to M0 and M1 macrophages [26]. Adoptive transfer of M2 macrophages reduces neuropathic pain through opioid peptide production in a naloxone-reversible manner [26], suggesting that LDN-induced opioid upregulation may promote M2 macrophage differentiation and reduce pro-inflammatory macrophage activity.
In the context of LPP, where macrophages infiltrate hair follicles and produce OSM [8], promotion of M2 macrophage differentiation through LDN-enhanced opioid signalling could theoretically reduce follicular destruction and promote anti-inflammatory microenvironment restoration.
5. Clinical evidence for LDN in Lichen Planopilaris and related conditions
5.1 Case Reports and Clinical Experience in LPP
The most compelling evidence for LDN efficacy in LPP comes from a case report by Klein and colleagues (2022), documenting reversible hair loss in a patient with biopsy-confirmed LPP who demonstrated remarkable regrowth of previously scarred alopecic patches after initiating low-dose naltrexone and platelet-rich plasma (PRP) [1]. This case is particularly significant because the patient had minimal response to 4 months of prior treatment with intralesional corticosteroids, topical clobetasol, minoxidil, finasteride, doxycycline, and ketoconazole shampoo [1]. The achievement of hair regrowth in a scarring alopecia, where this outcome is rare, highlights the potential value of LDN as part of a combination therapeutic approach.
A comprehensive review by Duarte Tortelly and colleagues (2019) specifically addressed the use of LDN as an adjuvant therapeutic option in symptomatic alopecias presenting with trichodynia [27]. The authors noted that trichodynia (scalp discomfort presenting as pain, pruritus, or burning) is a common and distressing symptom of hair loss that frequently does not respond to conventional therapies [27]. They proposed LDN as an alternative to be added to the therapeutic arsenal owing to its anti-inflammatory properties, analgesic potential, low cost, and minimal adverse effects [27].
5.2 LDN in Other Inflammatory Skin Conditions
While direct evidence in LPP is limited, LDN has demonstrated efficacy in other T-cell-mediated inflammatory conditions that share pathogenic features with LPP. In Crohn’s disease, another T-cell-mediated inflammatory condition, patients with active disease showed significantly reduced endo-opioid concentrations (especially beta-endorphin and proenkephalin A) compared to healthy controls and patients in remission [28]. This suggests that modulation of the endogenous opioid system through LDN may restore depleted opioid peptide levels in chronic inflammatory conditions.
LDN has also been investigated in multiple sclerosis (MS), another autoimmune condition characterised by T-cell-mediated pathology [22]. The opioid growth factor (OGF) and low-dose naltrexone impair CD4+ T lymphocyte infiltration into the central nervous system in experimental autoimmune encephalomyelitis models [22], suggesting that similar T-cell trafficking restriction could occur in skin disorders like LPP.
5.3 Comparative Analysis with Current Treatment Standards
Current evidence-based treatments for LPP and related cicatricial alopecias demonstrate limited effectiveness [29]. For frontal fibrosing alopecia (FFA), a related primary cicatricial alopecia variant of LPP, 5-alpha-reductase inhibitors, intralesional steroids, and hydroxychloroquine have the highest level of evidence, yet many patients remain treatment-refractory [5]. Hydroxychloroquine shows variable efficacy in LPP, with some patients achieving halted disease progression or modest improvement, but consistent responder patterns have not been identified [30].
JAK inhibitors represent a newer therapeutic approach showing promise in autoimmune conditions. JAK1 upregulation has been identified in cutaneous lichen planus lesions, while JAK3 is the predominant JAK in lichen planus compared to other JAK family members [31]. The effectiveness of JAK inhibition in alopecia areata, with FDA approval for baricitinib and ritlecitinib, suggests that similar JAK-STAT pathway targeting through endogenous opioid mechanisms (as proposed for LDN) may have therapeutic potential in LPP.
PPAR-gamma agonists have also been investigated in primary cicatricial alopecia, including LPP, as PPAR-gamma disruption is implicated in PCA pathogenesis [2]. These approaches, however, are not standardised and require further validation.
6. Proposed Mechanisms of LDN Efficacy in Lichen Planopilaris
6.1 Restoration of Hair Follicle Immune Privilege
The fundamental therapeutic target for LDN in LPP is restoration of hair follicle immune privilege. The collapse of immune privilege is characterised by upregulation of MHC class I and II molecules, downregulation of immunosuppressive cytokines (TGF-?, ?-MSH), and infiltration of pro-inflammatory immune cells [7]. LDN-induced upregulation of endogenous beta-endorphins could theoretically:
(1) Enhance TGF-beta production through regulatory T cell expansion and macrophage polarisation toward M2 phenotype
(2) Reduce MHC class I/II expression through suppression of IFN-?-producing T cells
(3) Reduce MICA and other stress-induced ligands through decreased oxidative stress
(4) Promote IL-10 and other anti-inflammatory cytokine production
6.2 Suppression of Pathogenic CD8+ T Cell and Macrophage Responses
The CD8 effector memory T cells (Tem) and macrophages that infiltrate follicles in LPP are the primary drivers of follicular destruction [8]. Beta-endorphin acts as an immunomodulator that:
(1) Shifts macrophage differentiation toward anti-inflammatory M2 phenotype, reducing OSM production
(2) Suppresses CD8+ T cell IFN-gamma production through mu-opioid receptor signalling
(3) Promotes regulatory T cell differentiation and function
(4) Reduces both lymphocyte and macrophage infiltration into follicles through TLR4 pathway modulation
6.3 Reduction of Oxidative Stress and EMT Prevention
Heightened reactive oxygen species (ROS) generation has been implicated in alopecia areata pathogenesis and is likely also relevant to LPP [32]. Beta-endorphin exhibits potent antioxidant effects through Keap1-independent NRF2 pathway activation [16]. This antioxidant activity could potentially:
(1) Reduce MICA induction on follicular keratinocytes
(2) Prevent EMT in hair follicle stem cells
(3) Restore mitochondrial function in follicular cells
(4) Reduce neutrophil elastase and other inflammatory mediator production
7. Safety Profile and Tolerability of LDN
Low-dose naltrexone is generally well-tolerated with minimal adverse effects compared to conventional immunosuppressive agents [14]. In clinical trials and case reports, the most commonly reported side effects are mild and transient, including initial sleep disturbances, vivid dreams, and gastrointestinal symptoms that typically resolve within the first few weeks of therapy [14]. Serious adverse effects are rare, and LDN has not been associated with the infection risk, malignancy risk, or organ toxicity seen with conventional immunosuppressive medications [14].
The safety profile of LDN is particularly advantageous when considering treatment of chronic conditions like LPP that require long-term management. The low cost and minimal monitoring requirements (unlike methotrexate, azathioprine, or JAK inhibitors) further enhance its utility as an adjunctive or alternative therapeutic option.
8. Future Directions and Emerging Therapeutic Strategies
8.1 Combination Therapies
The case report demonstrating LPP response to LDN plus platelet-rich plasma (PRP) suggests that combination approaches may optimise therapeutic outcomes [1]. PRP contains growth factors and immunomodulatory factors that could synergise with LDN’s opioid-mediated immune modulation. Similarly, combining LDN with:
(1) Topical or intralesional JAK inhibitors (which target parallel STAT pathways to those modulated by beta-endorphin)
(2) PPAR-gamma agonists (which address pilosebaceous lipogenic dysfunction)
(3) Hydroxychloroquine (which provides complementary anti-inflammatory effects)
(4) Low-dose IL-2 (which specifically promotes regulatory T cell expansion)
These combinations could potentially provide superior efficacy through multi-pathway targeting while reducing individual medication toxicity.
8.2 Biomarker-Driven Patient Selection
Future development of LDN therapy in LPP should incorporate biomarker-driven patient stratification approaches [10]. Specific immune signatures, including:
(1) Peripheral blood and lesional IFN-? levels
(2) Th1 vs. Th2 CD4+ T cell proportions
(3) Circulating endogenous opioid peptide concentrations
(4) TLR4 expression and signalling pathway activation
(5) Macrophage infiltration patterns and M1/M2 phenotype ratios
These biomarkers could identify patients most likely to respond to LDN and allow personalised dosing or combination therapy selection.
8.3 Addressing Unanswered Questions
Several critical questions remain regarding LDN use in LPP and require further investigation:
Optimal Dosing and Duration:
While standard LDN dosing is 1-5 mg daily, the optimal dose for cutaneous immune modulation in LPP has not been established. The duration of therapy sufficient to achieve and maintain hair regrowth is also undefined.
Mechanism of Hair Regrowth:
In the Klein case report, hair regrowth occurred in previously scarred tissue, which is exceptional. Understanding whether regrowth represents true restoration of immune privilege or partial recovery of follicular function requires histopathological investigation and cellular mechanistic studies.
Integration with Modern Therapies:
How LDN should be sequenced or combined with JAK inhibitors or other modern immunotherapies in LPP management requires systematic evaluation.
Predictors of Response:
Identification of baseline clinical, histopathological, or immunological features that predict LDN responsiveness would enable rational patient selection.
![]()
Summary
Low-dose naltrexone represents a promising novel immunomodulatory approach for lichen planopilaris with a mechanistic rationale grounded in recent advances in understanding opioid receptor signalling in immune cells. Through transient opioid receptor blockade leading to compensatory upregulation of endogenous beta-endorphins, LDN activates peripheral opioid receptors on immune cells to suppress pro-inflammatory T-cell and macrophage responses, promote regulatory T cell function, modulate toll-like receptor 4 signalling, and reduce oxidative stress. These mechanisms directly target the pathogenic immune privilege collapse that characterises LPP.
While clinical evidence is currently limited to case reports and review-level discussions, the available data suggest LDN merits systematic investigation in controlled trials. The combination of mechanistic plausibility, a favourable safety profile, low cost, and the exceptional case of hair regrowth in scarred tissue justifies prioritising LDN research in primary cicatricial alopecia. Future studies should establish optimal dosing, identify biomarker-based patient selection criteria, elucidate cellular mechanisms of action in follicular tissue, and evaluate LDN in combination regimens with contemporary immunotherapies. Such investigations could establish LDN as an important addition to the limited therapeutic armamentarium for this challenging disease.
Disclaimer: This article is for informational purposes only and does not replace professional medical advice.
References:
[1] [1] E. G. Klein, M. Karim, R. H. Kim, K. L. Sicco, and J. Shapiro, “Reversible Hair Loss in Lichen Planopilaris: Regrowth With Low-Dose Naltrexone and Platelet-Rich Plasma,” SanovaWorks, May 202.https://jddonline.com/articles/reversible-hair-loss-in-lichen-planopilaris-regrowth-with-low-dose-naltrexone-and-platelet-rich-plasma-S1545961622P0671X/
[2] S. Harnchoowong and P. Suchonwanit, “PPAR- Agonists and Their Role in Primary Cicatricial Alopecia,” Hindawi Publishing Corporation, Jan. 2017, doi: https://onlinelibrary.wiley.com/doi/10.1155/2017/2501248
[3] J. S. Lehman, M. M. Tollefson, and L. E. Gibson, “Lichen planus,” Wiley, Jun. 2009, https://onlinelibrary.wiley.com/doi/10.1111/j.1365-4632.2009.04062.x
[4] E. Errichetti, M. Figini, M. Croatto, and G. Stinco, “Therapeutic management of classic lichen planopilaris: a systematic review,” Dove Medical Press, Feb. 2018, doi: https://www.dovepress.com/therapeutic-management-of-classic-lichen-planopilaris-a-systematic-rev-peer-reviewed-fulltext-article-CCID
[5] A. C. Gamret, V. Potluri, K. Krishnamurthy, and R. M. Fertig, “<p>Frontal fibrosing alopecia: efficacy of treatment modalities</p>,” Dove Medical Press, Apr. 2019, https://www.dovepress.com/frontal-fibrosing-alopecia-efficacy-of-treatment-modalities-peer-reviewed-fulltext-article-IJWH#CIT0033
[10] H.-J. Lai, Z.-M. Ye, S. Chen, K. McElwee, and H. Guo, “Immune therapies for alopecia areata: evidence and new perspectives,” Expert Review of Clinical Immunology, Oct. 2025
[13] Ahsan, S. (2026) The evolution of Low-Dose Naltrexone: A comprehensive timeline from opioid antagonist to potential game-changer in chronic autoimmune conditions. Courier Pharmacy. Available at: https://courierpharmacy.co.uk/the-evolution-of-low-dose-naltrexone/ (Accessed: 2 March 2026).
