Experience with LDN? low dose naltrexone

If you have tried LDN, what did you experience?

  • Useful improvement

    Votes: 17 38.6%

  • No change

    Votes: 19 43.2%

  • Worsening of ME

    Votes: 3 6.8%

  • Other adverse event

    Votes: 5 11.4%
  • Total voters
    44
Hutan said:
If given the choice of a trial of only LDN or Abilify, I think I'd vote for Abilify, because I think the potential side effects from Abilify are worse, and so it is more important to know if there is really an off-setting benefit.
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As someone who knows nothing about drug trials ... would it be feasible to save research money by running two concurrent trials, e.g. LDN and low-dose Abilify? Of course there would be additional costs to design two protocols and recruit two sets of cohorts, but you wouldn't think the cost of setting up a centre and assembling a team to run one trial would necessarily double if you ran two.
 
Hutan said:
How does the person know that the improvement isn't a fluctuation in illness caused by something else?

I got as far as buying some naltrexone with the intention of making up some solutions, but by the time I had read around the evidence, I lost interest. I haven't seen anything sufficiently convincing. The balance of anecdotal reports seemed to be very much on the negative/no effect side. I do think that good trials would be useful as it is so widely promoted, including by doctors who specialise in treating ME.

Perhaps the suggested 'no one size fits all' dosage problem could be largely overcome by having a baseline assessment for a month (e.g. including actimetry and daily pain scores), then a 3 month period when the dosage is adjusted to get to what the person thinks is the best dose in that time, and then three months at the 'individual best dose' with a treatment assessment in the last month. I'm not sure that the side effects are so predictable that they would break the blinding.

Do people who have tried LDN think that a trial like that would work? Obviously longer baseline, titration and stable dose treatment periods would be better if possible.

If given the choice of a trial of only LDN or Abilify, I think I'd vote for Abilify, because I think the potential side effects from Abilify are worse, and so it is more important to know if there is really an off-setting benefit.


At the risk of going off-topic, my PEM and that of many others here involves pain. I describe my pain when in PEM as like being crushed. It might be like the 'bone-crushing pain' that you get when you have the flu. ME/CFS is more than just fatigue. Mister Person, you might like to check out some of the discussion threads on PEM and other symptoms in https://www.s4me.info/forums/symptoms-and-signs-discussions.197/ - you could ask your questions there.
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That's the nub isn't it?

Fluctuation had only been in the downward spiral and LDN coincided with plateau and improvement and was the sole change . Difficult for someone to not attribute it if you are hoping for an effect - the catch .

The option would be to titrate off - if you have improvement would you risk losing that ?

Both these improvements were in severely affected ( and female) - I would be particularly keen to see a mixed sex trial done with this group - perhaps they offer the potential for particular insights . The catch 22 is facilitating this .

We are only begining to unravel differences in illness presentation and mechanism between gender.
If hormones are part of this ( and I believe they are) then this becomes more important.
 
Maybe a crossover trial with all participants doing 6 months each on low dose abilify, LDN and placebo, and double blinded as to which they are on. I guess you would need a couple of weeks washout period between each, and a couple of months at the start testing baselines and symptom variability for each patient.
6 months on each drug should give time to do a gradual dose increase.

Measures could be a combination of constantly worn wearable that record steps, HR, HRV, time upright and sleep. And daily quick record on an app of pain, overall symptom level and cognitive capacity / activity and side effects/new or worsening symptoms, perhaps with a weekly cognitive test supplied on the app.
 
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Trish said:
Maybe a crossover trial with all participants doing 6 months each on low dose abilify, LDN and placebo, and double blinded as to which they are on. I guess you would need a couple of weeks washout period between each
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There might have to be a significantly longer period between the treatments, as I see it's recommended that Abilify isn't stopped suddenly. The titration down might take 'weeks or months', to avoid tardive psychosis.
 
I don't know whether that applies to the low dose versions of the drugs, but yes, if necessary a longer decreasing and washout period.
It would mean patients commiting to about 2 years on the trial including preliminary and washout times, which is a lot to ask, but worth it if sufficient participants can be found. The alternative would be 3 groups each only doing one of the drugs or placebo, which would be quicker but you'd need more people.
 
Jonathan Edwards said:
Any particular reason to think that?
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See comment above from @Helene Abilify at or below 2 mg/day seems to result in a dramatic improvement for many patients, with several returning to work and others becoming un-bed-bound. A few have also tried rexulti/vraylar and have reported that they also work. I don't know of anyone who has trialed piribedil, but it is a partial dopamine agonist and also doesn't have an affinity for serotonin receptors, so it may be a cleaner drug. Problem with these drugs is that many patients experience tolerance/tachyphylaxis/poop-out after several months, present company included. But others have reported no tolerance/poop-out and continued response even after 4 years or so. Ron Davis estimated that a robust trial for Abilify in MECFS would cost around USD $10 million. Also mentioned above is that Jared Younger recently received funding to do an LDN trial for LC.
 
Trish said:
Maybe a crossover trial with all participants doing 6 months each on low dose abilify, LDN and placebo, and double blinded as to which they are on. I guess you would need a couple of weeks washout period between each, and a couple of months at the start testing baselines and symptom variability for each patient.
6 months on each drug should give time to do a gradual dose increase.

Measures could be a combination of constantly worn wearable that record steps, HR, HRV, time upright and sleep. And daily quick record on an app of pain, overall symptom level and cognitive capacity activity and side effects/new or worsening symptoms, perhaps with a weekly cognitive test supplied on the app.
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Trish said:
I don't know whether that applies to the low dose versions of the drugs, but yes, if necessary a longer decreasing and washout period.
It would mean patients commiting to about 2 years on the trial including preliminary and washout times, which is a lot to ask, but worth it if sufficient participants can be found. The alternative would be 3 groups each only doing one of the drugs or placebo, which would be quicker but you'd need more people.
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I'd be willing to participate in a trial like that. I'd even be willing to invest in a smartphone for it (lol i dont have one at the moment & have resisted getting one as i find texting soooo difficult on the touch screens)

The challenge with including a cognitive test on the app is that my ability to think straight & perform cognitive related tasks fluctuates wildly, from fully functional to cant remember whats just been done, recall more than 1 number in sequence, work the remote control, type any word correctly spelt, or understand whats being said to me unless its in sentences of 2-4 words. So taking the test would give a misleading result.

As has been said the trouble is with all these people saying they get better/have improvement there is no way to know if its down to the drug, placebo or natural illness fluctuation/something else. So istm a trial is the only way forward if we really want to know.
 
Hutan said:
How does the person know that the improvement isn't a fluctuation in illness caused by something else?
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I think this is a real problem with a lot of reports of benefits of trying different drugs. I also feel there could be a natural bias to reporting positive effects in that to get a drug to try I assume someone has to go to the doctor and feel well enough to do that and for many with ME I wonder if dealing with doctors (and asking to try new things) is something that only happens on a upward fluctuation.
 
Adrian said:
I think this is a real problem with a lot of reports of benefits of trying different drugs. I also feel there could be a natural bias to reporting positive effects in that to get a drug to try I assume someone has to go to the doctor and feel well enough to do that and for many with ME I wonder if dealing with doctors (and asking to try new things) is something that only happens on a upward fluctuation.
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Yep. I've found the majority of patients underestimate the effect that natural fluctuations have, and sometimes they don't consider it at all. I think a patient is more likely to want to try a new intervention when they are in a crash — feeling desperate etc. Coming out of a crash would likely coincide with sourcing a medication, or whatever the intervention is, so starting a medication may be associated with an upswing in health.
 
Hutan said:
I got as far as buying some naltrexone with the intention of making up some solutions, but by the time I had read around the evidence, I lost interest. I haven't seen anything sufficiently convincing. The balance of anecdotal reports seemed to be very much on the negative/no effect side. I do think that good trials would be useful as it is so widely promoted, including by doctors who specialise in treating ME.
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Is it an over the counter drug? I had assumed it would need to be perscribed by a doctor.
 
Adrian said:
Is it an over the counter drug? I had assumed it would need to be perscribed by a doctor.
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In the uk it needs to be prescribed and then you have to buy it privately but it works out at less than £30 a month. Or you can get pills online from a pharmacy abroad but I think you still need a consultation with one of their drs. If you get pills then you have to make it into a solution yourself and take small amounts of that.
In the uk if your nhs dr won’t prescribe then the pharmacy in Scotland that provides the medication will let you have a phone consultation with their dr at a reasonable price (£50 I think)
 

I just wanted to post this re safety and side effects -

Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization
Karlo Toljan1,* and Bruce Vrooman2,3
2018 Dec;
6. SAFETY AND SIDE EFFECTS
Available pharmacological information describing the safety profile of naltrexone [9] reveal that except for precipitating withdrawal in opioid abuse the only major concern was hepatocellular injury ensuing from 300 mg daily administered dose. The usual daily 50–100 mg naltrexone therapy is considered fully safe for humans with minor behavioral side effects not entirely caused by the therapy itself, but rather due to the patient population having an underlying pathophysiological background of alcohol or opioid abuse. Due to naloxone having poor oral bioavailability, systemic adverse effects following this route of administration are minimal. Improper parenteral administration could potentially lead to side effects [10], but in a real-case scenario the drug is usually administered under professional medical care. In regard to LDN, data on actual side-effects linked to the drug is still scarce. Conducted clinical trials indicate that vivid dreaming and insomnia might occur following treatment initiation, but that this might be addressed by changing the drug taking timing from usual bedtime to morning hours or these sleep disturbances resolve on their own with ongoing therapy [14,44]. Any side-effects making the therapy intolerable might happen on individual basis, for example, a case of immune-related thrombocytopenia possibly related to LDN therapy as an idiosyncratic reaction in a patient affected by MS [95]. Low-dose naltrexone, VLDN, and ULDN are all tolerable according to present studies in humans, even with concurrent opioid therapy. In the latter case, a precipitated opioid withdrawal could be managed by lowering the dose, as experience with VLDN demonstrates. In case of immunosuppression, for example, recipients of donor organs, it remains to be investigated if LDN-related immune modulation might cause adverse effects.

7. CONCLUSIONS AND FUTURE DIRECTIONS
Proper clinical trials are needed in order to establish evidence that could lead to correct indications, mode of administration, and other aspects necessary for effective clinical pharmacology of LDN, VLDN, and ULDN. Since these modalities possess a limited commercial attractiveness for industry, executing strongly designed studies is an arduous process. Cancer research based on sound preclinical evidence regarding roles of LDN in opioid growth factor signaling might possibly be of specific public health interest. Moreover, developing LDN, VLDN, or ULDN as parts of multimodal treatment combinations might also entice researchers and developers to bring these respective drug properties to a clinical setting. Based on current reports of numerous benefits and an excellent safety profile, clinical use of LDN may be seen as a reasonable option in patients with fibromyalgia or IBD. In a hospital setting, ULDN could be investigated further as an additional option to increase postoperative analgesia or to reduce opioid-related side effects. New clinical applications are possible, given that LDN may be considered for sublingual, cream, or spray forms. Smart-drug design is also an option, for example, the case of PTI-609. A recent review evaluating LDN in pain-related syndromes concluded that even though a potential exists, current evidence is limited [96]. The enormous number of patients taking it as an alternative treatment prompts the biomedical community to engage and investigate these modalities in order to scrutinize ‘the potential’ and actually determine whether or not any clinically valid tools actually exist.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313374/
 
Roseway Labs is another option for the LDN in the UK and they also offer an alternative filler of rice flour if using capsules. They also offer olive oil as an alternative to the excipients used by Dicksons for liquid LDN. I can’t comment as I haven’t used this, but I am not sure how well these mix. I would be inclined to make my own using distilled water at home and capsules filtering out microcrystalline, which is how many Private Doctors are suggesting we get around the problem of excipients and titration by prescribing 50mg tablets.

Roseway offer a consultation (same as Dicksons) and then write you a script. Highly recommended.

Another option is Courier Pharmacy. They don’t offer an option without excipients, just liquid LDN (this is the cause of side effects for many of is) but they *could be persuaded if enough of us were to use them I think - https://www.courierpharmacy.co.uk/Autoimmune-Conditions-239-treatment
 
Mister Person said:
I don't have ME. I have chronic widespread pain, but I have PEM(that's why I'm here lol) , that is the progressive worsening of my pain with minimal effort among other symptoms. Another Wierd thing about me is my pain is mainly non gi abdominal pain, and while I do get fatigue it comes and goes. LDN worked for me! It did what it was supposed to do, but it didn't change my life because it didn't stop me from PEM and it made managing PEM harder because my PEM is ever ongoing, there is no such thing as being stable for me. I was in a rush to find out if it would work for me, so I took 2x0.5,2x1.0, and then at 1.5 I could pretty much feel it coursing through me you could say. PEJE(Professor Emiritus Jonathan Edwards), I'm wondering, do you think fibromyalgia patients who experience pem might be related to me in anyway? Are there any conditions out there that can cause exertion problems in the same way as ME?

I believe there must be some link between my PEM and ME PEM, but I can't say for sure that it's the same. Bc pain is pain... And fatigue is fatigue...

There are some odd clues about me. Does anybody else have a large short spike in symptoms when they land from jumping? Or when they get a fright/surprise?
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This makes me think of MCAS. Mast cell activation after my own experience. Sorry I know you didn’t ask me but I had such a hell of a time with it I am keen to spread the message! Payback for the smallest of actions once I had that was awful. Pain was also very different. It is often misdiagnosed as fibromyalgia. LDN works for MCAS.
 
Arisoned said:
This makes me think of MCAS. Mast cell activation after my own experience. Sorry I know you didn’t ask me but I had such a hell of a time with it I am keen to spread the message! Payback for the smallest of actions once I had that was awful. Pain was also very different. It is often misdiagnosed as fibromyalgia. LDN works for MCAS.
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Hmmm. My abdominal pain is non GI though. Interesting note though.
 
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