Research

BACKGROUND: Up to 37.7% of patients experience symptoms beyond 12 weeks after infection with SARS-CoV-2. To date care for people with long covid has centred around multidisciplinary rehabilitation, self care and self pacing. No pharmacotherapy has been shown to be beneficial.

METHODS: In this single centre interventional pre post study, the safety of Low Dose Naltrexone (LDN) was explored in patients with Post COVID-19 Syndrome (PCS), defined by NICE as patients with ongoing symptoms 12 or more weeks after initial infections with SARS-CoV-2 where alternative explanation for symptoms cannot be found. Patients were recruited through a Post COVID clinic, had a baseline quality of life questionnaire in symmetrical Likert format, were prescribed 2 months (1 mg month one, 2 mg month two) of LDN and repeated the same questionnaire at the end of the second month. Patients were monitored to adverse events.

FINDINGS: In total 52 patients participated of whom 40(76.9%) were female. The median age was 43.5 years(IQR 33.2–49). Healthcare workers represented the largest occupational cohort n = 16(34.8%). The median time from diagnosis of COVID-19 until enrolment was 333 days (IQR 171–396.5). Thirty-eight participants (73.1%) were known to commence LDN, two of whom (5.3%) stopped taking LDN post commencement due to new onset diarrhoea and also described fatigue. In total 36(69.2%) participants completed the questionnaire at the end of the two-month period. Improvement was seen in 6 of 7 parameters measured; recovery from COVID-19, limitation in activities of daily living, energy levels, pain levels, levels of concentration and sleep disturbance (p ≤ 0.001), improvement in mood approached but was not significant (p = 0.054).

CONCLUSIONS: LDN is safe in patients with PCS and may improve well-being and reduce symptomatology in this cohort. Randomised control trials are needed to further explore this.

Recalcitrant cases of Hailey-Hailey disease successfully managed with low-dose naltrexone

Cancer is associated with chronic inflammation and disruption to normal immune function. As such, the ability to thrive in a chronically inflamed microenvironment is regarded as a hallmark of cancer. Therefore, targeting inflammation and/or correction of aberrant immunity has been a therapeutic aim. The aim of the present study was to describe the use of a novel immunotherapy, called IMM-101, which is a naturally occurring, heat-killed whole cell mycobacterium, used in combination with conventional treatments in patients with prostate cancer. The present study analysed and presented data from six patients diagnosed with prostate cancer, some of whom have metastatic disease. Treatment regimens included the use of IMM-101, the correction of vitamin D3 levels, and combination with other agents that have anti-inflammatory and immune-modulatory abilities, such as bromelain and low-dose naltrexone (LDN). Clinical responses were detected in the patients when IMM-101 was commenced and further improvements were seen when an anti-inflammatory agent was used in unison. Combination therapy quickly led to a reduction in prostate-specific antigen levels, and stabilisation of disease was often achieved as indicated by repeat MRI and PET scans. Few side effects of any kind were observed when using these combination treatments. In conclusion, IMM-101 treatment alongside an anti-inflammatory agent, such as bromelain and/or LDN, may be considered an active and safe drug combination, and is a regimen that should be considered for treating patients with prostate cancer.

Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on antagonists of mu-opioid receptor effect on tumor progression and prognosis in different types of cancers and an evaluation of the available findings on their mechanism of action. We have found studies related to methylnaltrexone (MNTX) and naltrexone (NTX) usage in cancer outcomes-related setting. We found consistent preclinical evidence of a potential action of MNTX and NTX on cancer growth and spread mediated mainly by effect on the opioid growth factor receptor (OGFr) axis, which results in depressed cell replication. However, clinical results are scarce and limited to poor-quality evidence. Further high-quality studies are warranted to study antagonists of mu-opioid receptor role as a therapeutic option in different types of cancer, especially in patients where the classical treatment causes unacceptable side effects.

Lichen planopilaris (LPP) is a cicatricial alopecia that presents with patchy or diffuse hair loss at the vertex or parietal scalp. The literature has limited evidence on treatments for this challenging disease, with most reports involving small groups of patients with varied or suboptimal clinical responses. Amongst individuals who do respond to therapy and eventually achieve disease remission, hair regrowth within scarred alopecic patches is rare.1 Herein, we report a patient with biopsy confirmed LPP who demonstrated remarkable hair regrowth at a previously scarred alopecic patch after initiating low-dose naltrexone (LDN) and platelet-rich plasma (PRP), despite minimal response to 4 months of prior therapy with intralesional corticosteroids, topical clobetasol, topical minoxidil, finasteride, doxycycline, and ketoconazole shampoo. This case highlights the importance of remaining flexible and diligent in therapeutic approaches to LPP and the need for more robust literature on prognosis and treatment options for LPP patients.

OBJECTIVE: The International Classification of Disease defines burning mouth syndrome (BMS) as a chronic intraoral burning sensation, with no identifiable local or systemic cause. Since current management is often unsatisfactory, the aim of this report is to describe a new treatment modality (i.e., low-dose naltrexone [LDN]).

STUDY DESIGN: A 62-year-old woman presented with the complaint of burning on the tongue of 3 years' duration. Existing comorbidities were fibromyalgia, irritable bowel syndrome, headache, and interstitial cystitis. Her reported pain intensity ranged from 2/10 (morning) to 8/10 (evening) on a numeric rating scale. With the diagnosis of BMS and hyposalivation, and in light of her current clonazepam use and fibromyalgia, a dry mouth protocol and LDN (3 mg) were prescribed.

RESULTS: After 1 month, her pain intensity decreased by 50%, with no pain upon awakening. After 2 months, the widespread pain associated with her chronic morbidities also reduced by 50%, and her headache disappeared. After adjusting LDN dose to 4.5 mg, the patient was stable at 6 months, with 50% reduction of widespread pain and 2/10 BMS pain, and no reported side effects.

CONCLUSIONS: These preliminary results suggest that LDN may be a feasible and effective treatment for BMS, especially in patients' refractory to traditional treatment.

A cross-sectional questionnaire study was performed, where 41 ALS patients reported their use of off-label treatments, as well as self-perceived HRQOL using the RAND-12 questionnaire. A majority of respondents used riluzole. Of the 41 respondents, 18 (43.9%) reported use of off-label medications and 18 (43.9%) used nutritional supplements. Low-dose naltrexone was the most commonly used off-label medication, whereas vitamins accounted for most of the nutritional supplements. The respondents' RAND-12 component scores were significantly lower than those of the general population. Low-dose naltrexone and vitamin B were associated with a better physical component score. Most of the respondents in our study adhere to the recommended treatment protocols, as less than half of them reported using off-label medications or nutritional supplements against ALS. Positive correlations between physical HRQOL and use of low-dose naltrexone or vitamin B were demonstrated. These results warrant further investigations.

Pharmacotherapeutic options continue to expand for the treatment of chronic non-cancer pain. There has been an increasing emphasis on multimodal analgesia. This strategy employs use of multiple analgesic medications each with a distinct mechanism of action, which when administered concomitantly may provide profound analgesia. The authors describe evidence from randomized controlled trials and systematic reviews on a variety of established medications including anti-inflammatory agents, opioids, anti-convulsants, anti-depressants, N-methyl-D-aspartate receptor antagonists, sodium channel blockers, cannabinoids, and alpha-2-receptor blockers. Furthermore, they provide developing evidence on more novel pharmacotherapeutics including alpha lipoic acid, acetyl-L-carnitine, low dose naltrexone, calcitonin gene-related peptide antagonists, targeted toxin therapy, Nav1.7 inhibitors, neurotensin agonists, purinoceptor antagonists, and sigma-1 receptor antagonists. Furthermore, the authors review the safety and adverse effect profile for these agents. In this era of the opioid epidemic, clinicians should first offer non-opioid analgesics and employ a multimodal analgesic strategy. Current guidelines recommend a personalized approach to the chronic pain treatment, in each case accounting for type, location, severity, and chronicity of pain. Clinicians should also carefully consider the risk-to-benefit ratio to the patient based on the drug side effect profile, patient age, and comorbidities. In accordance with the stepwise approach outlined by the World Health Organization (WHO) analgesic ladder, clinicians should administer non-opioid analgesics plus adjuvant analgesics initially for mild pain, followed by adding weak opioid agonists for moderate pain, and strong opioid agonists and minimally invasive interventions for severe pain.

Naltrexone has historically been used to treat various substance use disorders, but recent discoveries have sparked interest in using low-dose naltrexone (LDN) to manage chronic pain. This study compared pain levels reported by patients before and after at least 2 months of LDN treatment to those reported by patients with the same painful diseases, who did not take LDN. Overall, patients who took LDN reported significantly more pain relief than patients who did not take LDN. How LDN alleviates pain seems complex, but apparently involves an anti-inflammatory effect on cells in the brain and spinal cord. LDN is extraordinarily safe, with no known risks (unlike most standard pain medications), and should be studied more in the treatment of chronic pain.

AIM: To evaluate the use of low-dose naltrexone (LDN) as a broad-spectrum analgesic.

METHODS: Retrospective cohort study from a single pain management practice using data from 2014 to 2020. Thirty-six patients using LDN for ≥2 months were matched to 42 controls. Pain scores were assessed at initial visit and at most recent/final documented visit using a 10-point scale.

RESULTS: Cases reported significantly greater pain reduction (-37.8%) than controls (-4.3%; p < 0.001). Whole sample multivariate modeling predicts 33% pain reduction with LDN, with number needed to treat (for 50% pain reduction) of 3.2. Patients with neuropathic pain appeared to benefit even more than those with ‘nociceptive’/inflammatory pain.

CONCLUSION: LDN is effective in a variety of chronic pain states, likely mediated by TLR-4 antagonism.

Fibromyalgia and depression are frequently comorbid. We propose a hormonal system model in understanding the underlying endogenous opioid system dysregulation in fibromyalgia with the utilization of the cold pressor test (CPT) in clinical practice to monitor treatment response to low-dose naltrexone (LDN) and the subsequent remission of major depressive disorder by restoring opioid tone. A 60-year-old professional on permanent disability presented with refractory depression and chronic widespread pain after years of multiple failed medication trials. Rating scales confirmed severe depression, Hamilton Rating Scale for Depression (HAM-D) of 20, a short cold pressor test (CPT) time of 21 seconds, and a face pain scale (FPS) of 8/10. Physical examination assessing for fibromyalgia was diagnostic, with 18/18 positive tender points.

LDN, a minor increase in trazodone, and transference-focused psychotherapy were employed. The patient’s CPT time increased modestly. The patient achieved remission of both conditions in 10 weeks when both disorders were treated at once (FPS and HAM-D of zero), restoring the quality of life, relatedness, and motivation. Some fibromyalgia patients may achieve remission of comorbid depression with concomitant low-dose naltrexone (LDN) treatment that is widely used “off label” to treat pain. LDN is a promising alternative for the treatment of chronic pain in fibromyalgia with its safety profile, high tolerability, and absence of abuse potential. Our unique finding is that without successful LDN treatment of fibromyalgia, remission of depression may be unlikely.