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We have had a really wonderful stay at Anantmaya, Manali. Beautiful property with not just a view but with some great views. It has that personal touch service that can not be beaten. Food – Superb. Comfort – It has lots of that. Highly recommended. Thanks so much for a very enjoyable holiday!

Anil Advani

It is an awesome place to stay, very good location away from the crowds. Great views, newly constructed resort. Staff is really very helpful and prompt. Food is one of the best I ever had. Give it a try, you will not regret it

Navdeep Singh

One of the best places we have stayed at so far. Amazing resort, amazing hospitality and amazing location

Devika Chatterjee Ahluwalia

One of the best stays in Manali….Was there for 4 nights

Nagra Honey

Awesome resort & Services. one of my best stays

Suman Malik

The Use of Low Dose Naltrexone in the Management of Chronic Pain

Chronic pain is a serious medical condition affecting 1 in 5 people worldwide and up to 40% of the US population. 1,2 Currently available medical therapies for treatment of chronic pain may be unsatisfactory, risky, and expensive to employ. 3,4 Until very recently, physicians utilized opioid therapy widely in the management of chronic non-cancer pain. Because of their highly addictive qualities and side effects such as sedation, dizziness, nausea, etc, opioids have become stigmatized. 5

Low dose naltrexone (LDN) is a novel pain therapy which may fulfill the “4 L’s” that many patients and clinicians look for: low risk, low side effect profile, low dose, and low cost. (Image: iStock)

The opioid crisis has caused and is still causing serious public health issues in our country; in 2017, 29% of people were abusing opioids, 47,000 people died from opioid overdose, and nearly 2 million people were diagnosed with a substance abuse disorder. 6 Many of the over-the-counter (OTC) and non-opioid prescription medications are unsuitable alternatives for treatment of chronic pain as they have many unwanted side effects including GI bleeding, kidney and liver damage, dizziness, and nausea. 3,7 Additionally, both OTC medications/supplements and “alternative” treatments such as cannabidiol (CBD) can be costly to patients, resulting in thousands of dollars a year in out of pocket expenses. 4,8 This financial burden can result in patients receiving little and sometimes no care at all for their chronic pain issues.

There is an emerging interest on the part of patients to seek out nontraditional treatment options for managing their chronic pain. Low dose naltrexone (LDN) is a novel therapy which may fulfill the “4 L’s” that many patients look for when using nontraditional therapies: low risk, low side effect profile, low dose, and low cost . Naltrexone is a mu receptor antagonist medication originally designed and approved for the treatment of opioid addiction at a dose of 50 mg to 100 mg per day. More recently it has been suggested that low dose naltrexone may be utilized for the treatment of chronic pain, in an off-label fashion at a much lower dose: 0.5 mg to 4.5 mg/day. 9 Although the exact mechanism is unknown, it is believed that in this lower dose, naltrexone acts as a glial/immune cell modulator, which decreases pain by helping reduce inflammation. 9,10

In this retrospective case, the authors discuss the outcomes of patients taking once-daily LDN for the treatment of chronic pain.

Case Presentation

Real-world evidence is presented from 16 patients who took prescribed LDN for 1 to 6 months and who were considered LDN-responders (LDN-R) or LDN-partial responders (LDN-PR) (see Table I). Ten patients were female (ages 28 to 83); 6 were male (ages 51 to 89) and, excluding two younger outliers of 28 and 34 years, the average age was about 70 years.

Most patients reported constant pain that was negatively impacting activities of daily living (ADLs) and quality of life, including inability to pursue activities such as house chores, walking, or sitting for an extended period of time. Pain intensity was reported to increase throughout the day.

All the patients’ chief complaints were reported as affecting the cervical and/or lumbar spine, hip and/or sacroiliac regions, or a combination of these locations. Radiation of pain to the arms/shoulders/jaw was common for patients reporting cervical spine pain, and pain radiating into the legs or diffusely into the lower back area was common for hip, lumbar spine, and SI patients. Specific ICD-10 codes for patients in this study included those coding for scoliosis, radiculopathy, intervertebral disc degeneration, myalgia, spondylolysis, cervicalgia, stenosis, neuropathy, arthritis, spinal enthesopathy, multiple sclerosis, and osteoarthritis. Past medical and family histories were otherwise not found to be pertinent to the study results.

Since patients in this study were receiving care at an interventional pain management practice, many had previously undergone interventional pain procedures including steroid injections, trigger point injections, and platelet-rich plasma (PRP) injections, as well as nerve blocks and radiofrequency ablation in the affected area(s).

During the observation period, many patients were taking and/or continued to take various other pain medications such as gabapentin, cyclobenzaprine, naproxen, tramadol, ibuprofen, Tylenol, etc., which were either providing insufficient relief or causing undesirable side effects. As a result of these relative treatment failures, patients were offered treatment with LDN.

Management and Outcome

During the six-month observation period a total of 35 patients received prescriptions for low dose naltrexone. Of the 35 patients receiving LDN prescriptions, 16 continued to use LDN because of improvements in pain and/or function. Patients receiving 50% or better relief in their chronic pain were considered LDN responders (LDN-R). Patients who did not meet 50% pain relief, but who chose to continue LDN because of perceived improvement in quality of life as a result of taking LDN, were considered partial responders (LDN-PR).

Out of 35 patients who received LDN prescriptions, 10 were considered LDN-R, while 6 were considered LDN-PR. The responder rate (total number of LDN prescriptions ÷ number of LDN responders + partial responders) was 46%. Nineteen of the 35 patients discontinued the use of LDN and were determined to be non-responders (LDN-NR) either due to receiving no improvement or experiencing undesirable side effects such as jitteriness or insomnia. Figure 1 shows the distribution of patients in each category.

All patients in the observation period were provided with a printed information and instruction form regarding the use of LDN in the treatment of chronic pain. In addition to written instructions, patients were counseled to only use LDN if it was causing “zero to minimal” side effects, and to discontinue the medication if any unpleasant side effects occurred. A “low and slow” approach to titration of LDN dose was used, and patients were verbally counseled that, vis-à-vis LDN therapy, “more is not necessarily better.” Initial prescriptions were sent electronically to a compounding pharmacy of the patient’s choice. Naltrexone is not a scheduled substance and a medical provider does not require a DEA number to prescribe it.

Patients were provided with an initial quantity of 90 to 120 tablets of naltrexone 1.5 mg. Patients who were finding no relief with low dose opioids (MME <20 mg per day) were advised to discontinue opioids for at least 1 to 2 weeks prior to initiating LDN. Patients who were taking minimal dose tramadol (<100 mg/day) were advised that they did not need to discontinue tramadol prior to institution of LDN therapy, because of tramadol’s low affinity (6,000 times less than morphine) for the mu receptor, and only partial inhibition by naloxone. 11 All patients, including patients taking tramadol, were advised that a withdrawal syndrome could develop if LDN and opioids were taken simultaneously, due to naltrexone’s mechanism of action. 9,12

Some patients who were noting initial improvements in pain at the 0.75 mg to 1.5 mg starting dose asked to accelerate the titration schedule. The clinician on a case-by-case basis approved this, however, patients were reminded that lower doses of LDN could be just as effective as or more effective than higher doses. No patient in the observation period was taking more than 4.5 mg/day.

Follow-up data was collected either during routine follow up or via telephone. Patients deemed to be LDN-NR were not involved in further questioning. Of the LDN-R and LDN-PR, 25% began taking 0.75 mg of LDN once daily on day one, 69% took 1.5 mg on day one, and 6% took 4.5 mg on day one. Eighty-eight percent of these patients increased their dose over a period between 1 week and 1 month to arrive at a stable dose of 4.5 mg daily, and 13% settled on a dose of 3 mg daily. All dosing was once daily. Side effects noted by these patients during the observation period included insomnia (6%), tiredness (6%), hot flashes (6%), and possible increase in migraine headache (6%), however, 75% of patients reported no side effects whatsoever. As a result of patient self-reports of side effects, we now recommend that patients dose LDN once-daily in the morning.

Patients were asked during routine follow-up visit to rate their perceived degree of pain relief from LDN using a modified PGIC questionnaire. 13 Figure 2 shows a summary of patients’ responses to the question, “Compared to before you started LDN, how much better do you feel after taking LDN?” This question was asked by a medical assistant at follow-up visit, or by the research assistant via telephone if patient was not scheduled for a follow-up visit during the observation period. Figure 3 shows perceived improvement over baseline.

A patient was categorized as an LDN responder (LDN–R) if they reported 50% relief or better. Patients in the LDN–R group reported average pain relief of approximately 77%. Figure 3 summarizes the degree of pain relief in LDN–R patients. In some cases, patients who fell into the LDN–PR category still felt very strongly and positively about the impact of LDN on their quality of life, and opted to continue taking LDN.

As an example, one LDN-PR patient reported only 20% relief in pain relief but went on to state that the amount of relief being provided by LDN was helping her in terms of everyday functioning to a significant enough degree that she chose to continue therapy with LDN. Other examples of functional improvements noted by LDN–R and LDN–PR patients are noted in Table II.


There is little clinical reporting available on the safety, efficacy, and “how-to-use” of many currently available alternative therapies. This results in many patients resorting to the use of OTC, “herbal,” and “natural” supplements without professional medical guidance, and oftentimes without any clinical benefit whatsoever. While physical harm may not occur frequently as a result of this practice, subtle financial harm may occur, since many “alternative” therapies are expensive; often costing patients hundreds of dollars per month.

There is a general lack of knowledge regarding the use of low dose naltrexone in the management of chronic pain.

Two significant factors contributing to the utility and efficacy of both prescription generic medications and OTC medications are out-of-pocket costs and potency. Although prescriptions for LDN are not typically covered by commercial and federal drug plans, the average monthly cost of $16 to $20 was found to be affordable (see Figure 4) by most of the patients in the presented study, as well as previously published studies. 14 Currently, LDN therapy requires formulation by a compounding pharmacist, who is subject to federal and state regulations and is able to perform intermittent potency and sterility studies on the medications being prepared for patients.

The potential mechanism of action of LDN has been discussed in the literature (see also, “Naltrexone as an Alternative Treatment for Chronic Fatigue Syndrome,” next page); an in-depth review of the MOA of LDN is beyond the scope of this case series presentation. 9,10 One theory is that LDN acts as a “glial/immune cell modulator,” and in this regard may explain why the medication seemed to have particular benefit for patients suffering with a more “neuropathic” component to their pain. Additionally, it was interesting to note that some patients who were receiving less than 50% relief chose to remain on LDN as it was improving activity tolerance and generalized “energy levels.” The perception of benefit in the patients receiving less than 50% overall relief is consistent with postsurgical pain models, where improvements of 33% are generally considered clinically significant. Our impression is that patients expect far less than 100% relief in order to consider treatment with LDN “successful.” 15,16 When counseling patients we felt it important to set realistic expectations at the outset of therapy; specifically stating that LDN is not a panacea, and that it fails in more instances than it works. In this cohort, however, we found that for LDN–R patients the degree of relief was very high.


This was a non-randomized, retrospective, non-blinded case series in a limited cohort of patients suffering with a variety of pain conditions. The generalized nature of our study can be viewed as a both a “pro” and a “con.” If future research aims to “demystify LDN,” then the applicability of LDN in multiple medical conditions may be suggested by the heterogeneity of the cohort in the presented study. The limited duration of the observation period may be considered a negative. Not all LDN–R patients had been taking LDN for 6 months. Therefore, some of these patients may have experienced a placebo effect. If the observation period was longer, then the placebo effect would likely be less of a factor.

Additionally, the types of pathology/pain treated with LDN in this study was quite varied. However, the liberal application of LDN prescriptions across many different pathological pain states was intentional and should not necessarily be viewed as a negative. In other words, there are very few contraindications to trying LDN in patients suffering from almost any kind of pain, as long as the patient is not taking any form of opioid, and does not have any other known contraindication for the use of LDN (allergy, pneumonia, liver failure, or moderate to severe kidney failure) prior to institution of LDN. A larger sample size and more specific ICD-10 selection criteria would help to clarify indications for and efficacy of this form of therapy.

To better study how LDN works, and for which specific conditions it is best-suited, the cohort needs to be more precise, and larger prospective, double-blind, placebo-controlled studies should be performed. Since LDN is being prescribed off-label and is generic, sponsorship for a large, randomized, double-blind, placebo-controlled study is unlikely. Therefore, further knowledge regarding LDN MOA, dosing, and efficacy may need to come from additional clinical reports documenting “real world evidence” as opposed to a definitive clinical trial.


LDN is a low risk, low cost, and simple to use medication that may be a viable non-opioid treatment option for the management of chronic pain. Despite these positive clinical attributes, professional and public awareness regarding the use of LDN is lacking, and widespread adoption of LDN for the treatment of chronic pain has not occurred. Especially in the setting of a healthcare system where increasingly the financial burden for care is being placed on the shoulders of patients, safe and low-cost alternatives for treatment of pain are needed. Additionally, in the setting of recent documentaries highlighting the lack of consistency in foreign-made generic medication preparations, sources for reliable and consistent prescription medications are needed. Compounding pharmacies that are able to accurately manufacture compounded prescription drugs with consistent potencies will be an ally for both patients and clinicians. Finally, despite the fact that LDN does not provide clinically meaningful reduction in pain for a large percentage of patients who try it, we found that patients in the LDN–R category tended to report a high degree of pain relief, spontaneously described by some patients as being “miraculous.” •