LDN and Opioids

There are four situations involved. Please read carefully and then let's see if there are still questions.

Situation1: A regular LDN user has breakthrough pain.

Situation2: A regular LDN user is going in for surgery and will need opioids.

Situation 3: Opioids in an emergency situation.

Situation 4: Someone who has been on regular opioid dosing and wants to start LDN

Situation 1:

 A regular LDN user has breakthrough pain. Some users clear LDN quickly enough that an opioid will have effects even 4 hours after their LDN dose. More typically people will need a 12 hour gap. Risk/downside if 12hr is not enough time -- most likely the opioid will not give the expected pain relief. More info:

Regarding opiate meds the general policy is to avoid them with LDN. If an opiate dose is taken too soon after LDN it may not be effective. If LDN is taken too soon after an opiate dose the person may have withdrawal symptoms.

It is possible for *some* that a 12 hour gap will be enough to take one medication after

the other. However these things are so individual and it’s possible for someone to have

a strong reaction as per an LDN user-

“I took an opioid after being off of LDN for 54 hours. I was so sick. The stomach

cramping and massive vomiting that occurred made me wish for death. I literally laid

on the bathroom floor for an hour because I could not take a deep enough breath to

call for help. I barely could move. I had taken this meditation before so I know I wasn't

having a bad reaction to it. I’ve never experienced anything like this”

Tramadol is OK for many. It is a synthetic opioid and an SNRI.  It may be enough taken with a gap from your LDN dose. If that is not enough and you get to the point you need to use stronger opioids, it seems to be doable occasionally for some (not necessarily all!) LDN users in the

following way:

Quoting Jayne Crocker from LDNNow, "Dr Turel talks about using pain meds/opiates with LDN in this interview and recommends you space them 12 hours apart (around the 7 min mark in the video).

Anyone who has been taking LDN for any disease (not just cancer) and finds they need

to take pain meds for breakthrough pain can do so providing they allow sufficient time

for the LDN to clear the receptors. Dr Turel, neurologist uses this approach for his MS

patients. I have done this and my partner still does on occasion for his MS with

success. None of us want to take opiates but sometimes in times of need.”

https://www.youtube.com/watch?v=f2iSWKypWks "

Additional comments from a well known LDN doctor. Please note my comment to her in the comments section.
Low-Dose Naltrexone (LDN) CAN be taken with opioids (but only sometimes)!...

https://www.youtube.com/watch?v=rK8rz19ySP0 

Situation 2:

 A regular LDN user is going in for surgery and will need opioids. It is not possible to say for sure how much LDN clearing time is needed for the opioids to be effective. The risk of them not working in a "daily home pain" situation is orders of magnitude different from if they don't work for someone on the operating table or following surgery. Therefore we feel that the downside of missing a few days of LDN healing is less risky and we advise a 3 to 7 day gap before surgery. Some need more time than others. Some need to go off LDN for the minimal time to avoid the return of symptoms. LDN can typically be restarted at the same dose 48hr after the last opioid dose. If it has been more than a month since LDN was stopped it may be best to titrate up. It may be OK to go up faster than usual. Regardless it will be good to let your anesthesiologist know your situation.

Additional comments from an LDN pharmacist:

Should You Take Low Dose Naltrexone (LDN) Before Surgery?...

https://ldnresearchtrust.org/should-you-take-low-dose-naltrexone-ldn-surgery%C2%A0 


Situation 3:

 Opioids in an emergency situation. Try non-opioid pain relief first. Otherwise it's *possible* that higher opioid doses may be effective. Linda Elsegood of LDN Research Trust was kind enough to exchange emails with me regarding this issue. She says,

"In ER they use high doses of opiates you don’t need extra high being on LDN. The

standard dose they use is enough. Over the last 11 plus years since I founded the LDN

Research Trust, I have learnt from many doctors what we don’t need to carry warning

cards in case of Emergency. If the worst happens we will be alright with the same

treatment as those not taking LDN."

In a previous email she told me that pain specialist Dr. Pradeep Chopra had informed

her that high enough doses of opioids will work in spite of the LDN. I suppose the dose

used in a hospital emergency situation is typically going to be larger than a home

dose. Nausea is sometimes an issue with opioids regardless of whether LDN is in the

picture or not.

So bottom line is we may not need to worry about being on LDN in an emergency

situation. If we have advance notice of an upcoming situation like surgery I think we

should still stop LDN dosing 3 to 7 days ahead of time. However I thought I should add

these "contrary opinion" comments to the thread and the document:

LDN pharmacist Skip Lenz posted: “I am involved, as an expert witness, on a case involving a patient

on naltrexone going into an ER and basically being overdosed with an opiate. No pain

relief at all. So with all due respect maybe I can give their names [Linda and Dr.

Chopra] to the defense and we can duke it out in court. We always ask if you are on an

opiate and if so you do not get LDN from us.! end of story......

Tell the ER crew that you are on naltrexone and cannot take an opiate. There is a

myriad of other drugs that can be taking in its stead....such as Ultram [Tramadol] or

Ultracet [Tramadol plus Tylenol] either oral or IV.”

An additional comment about "clearing time" from Skip Lenz:

"According to Gold Standard, a peer reviewed pharmacology data base, the half life is

between 4-6 hours. What this means is that you will have half of the naltrexone that

you absorbed in your system 4-6 hours after you have taken the drug. According to

Pharmacotherapy by Dipiro, a standard in pharmacy education, it takes 5 times half life

to have 99.997% of the drug out of you body. As we get older we all experience

achlorhydia, a decrease in stomach acid, which will effect those folks taking ldn

compounded with a calcium filler. I am involved, as an expert witness, in two cases

involving a physician who told his patients that it was ok to use ldn and opiates, "just

separate them by 4 hours". Unfortunately due to HPPA rules I can't give you all the

info, but suffice to say that the two patients had problems that required

hospitalization."

An example of a patient that had pain relief issues:
https://www.ldnscience.org/research/no-antagonists-for-an-antagonist-one-pitfall-of-chronic-oral-low-dose-naltrexone-no-antagonists-for-an-antagonist 

I think we sometimes assume that we need opiates to get "real" relief. Seems like we

should ask for non-opiate relief if possible--

On a bracelet etc I would put "Try non-opiate pain relievers first" -- I think that will work

better than saying something about LDN which many won't understand or something

like "No opiates!" because if the non-opiates don't work you will want them to have the

option of trying the opiates. Depending on how fast your system clears LDN the

opiates may work for you or may work at a higher dose


Alternatives for pain relief when opioids are not effective....
https://app.screencast.com/fciy0XHgx6bpv 

In the above two situations -- regarding how to resume LDN afterwards. These things vary with the individual but if the opioid use has not been that long then typically 48 hr from the last opioid dose will be enough time to restart LDN and generally one can start at the same dose they stopped a
t unless they have stopped LDN for more than a month in which case it may be better to titrate. May be able to go faster than usual.

Situation 4:

 Regarding the two week gap before starting LDN after regular opioid dosing. It's a different situation when someone who has been on regular opioid dosing wants to start LDN vs. an LDN user who needs occasional help with breakthrough pain.

The first person has likely damaged their internal opioid system. This makes it more likely that they will have withdrawal problems if they take LDN without the longer gap. See the info below.

The quote below is from the Naltrexone package insert. *Some* people may not need as much time, but unfortunately this can't be predicted. Because the effects of precipitated withdrawal can be quite severe we choose to err on the side of caution and suggest a two week gap. Precipitated withdrawal from taking naltrexone may develop within minutes. It can to last up to 48 hours.

"To prevent occurrence of precipitated withdrawal in patients dependent on opioids, or exacerbation of a pre-existing subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting REVIA treatment. An opioid-free interval of a minimum of 7 to 10 days is recommended for patients previously dependent on shortacting opioids. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as two weeks."

https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/018932s017lbl.pdf

Post about someone’s experience with not having adequate clearing time before starting LDN:

 I ran across this comment from someone that I thought was worth passing on as we continue to see reports of patients on opiates being told by their doctors or pharmacists that an LDN dose is "too low to be a problem."

"Just don't let your dr tell you it won’t put you into detox if you are taking opiods. I was on Vicodin for pain, at the time my dr put me on ldn. I specifically asked him, won't that throw me into withdrawals? He said "No, no, it's a super low dose, and it won't affect the pain med's effectiveness". Against my better judgment, after reading about this new (to me) drug, I took it. That was the scariest night of my life. I had these horrible, uncontrollable muscle contractions in legs neck arms... but it wasn't like muscle cramps; I just couldn't quit, like, stretching (that was the really bad, scary part) also, cold sweats, stomach cramps, couldn't sleep, and this horrible, like depressed anxious feeling all night long and into the next day. I just wanted to jump out of skin. I assume this was opiate withdrawal. My pain meds did not work for a week after that, even though I kept taking them. Naltrexone is VERY strong stuff. I believe he rx'd 2 mg. I took one capsule. It was horrendous. Very scary. Needless to say, I quit taking it. It took me a week to get back to normal. If I am ever able to get off pain meds I might try it, but DON’T TAKE ANY AMOUNT OF THIS IF YOU WERE ON OPIOIDS UNLESS YOUR INTENTION IS TO STOP USING OPIOID PAIN MEDS. I WAS REALLY pissed at my dumbass dr. (was actually a Physicians Asst.) He thought it was funny when I told him a month later what happened. He chuckled, and said, "Well, every one is different. Now we know.") "

Some patients are in too much pain to stop opioids for two weeks before starting LDN. These folks may want to learn about ULDN (UltraLDN a very low dose typically starting at 0.001mg) which can be taken with the opioid dose, makes it more effective and assists with tapering. More info:

If you have been on regular opiate doses (including Tramadol) you cannot add LDN to your routine without risk of precipitated and potentially dangerous withdrawal as well as increased pain. Precipitated withdrawal from taking naltrexone may develop within minutes. It can to last up to 48 hours.

The options are:

1) Stop all opiates for two weeks after following an established tapering schedule and then start LDN dosing. Probably good to start at 0.5mg and build. IMO avoid Avicel (cellulose) filler.

OR

2) Add ULDN doses to your current opiate doses and work towards tapering the opiates and building towards a LDN dose. Usual starting ULDN dose is 0.001mg. It is taken with the opiate and makes it more effective rather than blocking it. This reduces tolerance and helps with tapering. More details on this route follow.

I should say that *some* people will be able to start LDN level doses faster than others, however there is no way to predict who these people are. I'm posting a few links for those that might think "I'll just give it a shot" -- our experience is it's better to err on the conservative side.

It's unfortunate that many pharmacists and doctors don't understand what they may be letting their patients in for when starting LDN after regular opiate dosing. In the Facebook group we had an unfortunate situation where a member refused to take our advice and insisted that her doctor was an expert. She ended up in the ER with seizures:

Has anyone started taking this and had a really bad reaction? I've been in the hospital Saturday morning. I went in for back to back seizures two hours after taking my first dose 1ml of naltrexone I was seizing 2-5 times an hour for two days. I'm now in neuro step down from ICU unit. Yesterday they wanted to try to repeat the issue to see if it was ldn or not and the nurse gave me 3mls after I argued with her because she tried to give me 50 MLS smh anyhow this time the seizures started back up, I began flushing, deep nerve pain along with surface skin nerve pain that made my skin feel like it's on fire, I steerer tripping out really bad with the room spinning more then any narcotic my pan specialist has ever tried. Soon after muscle spasms started in my abdomen that were so violent that it was forcing air out of my lungs my O2 started plummeting and tmi it caused liquid diarrhea and total bowel incontinence because the spasms in my abdomen were so harsh. I've had five colonoscopies before and they had noting on this. It's coming out if my system now and I'm doing a little better but I'm still here now while my diaphragm heals, I can go back to eating and drinking on my own and be re-hydrated. I knew I wasn't going to die because I knew the meds would be put if my system eventually but I've never felt so much like I'm dying in my life.”


Two more drastic examples:

Naltrexone and Opiates. Effect of inappropriate naltrexone use in a heroin misuser..... http://emj.bmj.com/content/20/4/381.full

PRECIPITATED WITHDRAWAL REACTION TO OPIATES IN CASES OF IMPROPER USE OF NALTREXONE….

https://www.journal-imab-bg.org/stat.../vol07_1_75-77str.pdf

 You can learn more about using ULDN as a way to transition off opiates and onto regular LDN at this group:

NOPE Non-Opiate Pain-relief Experiences. ULDN / Naltrexone & other options.....................https://www.facebook.com/groups/1593950197487522/

This doctor has spoken at LDN conferences. This is some good info but IMO her 0.35mg dose is just a low LDN dose or VLDN. ULDN dosing should start at 0.001mg and higher doses may cause precipitated withdrawal:

Low-Dose Naltrexone (LDN) CAN be taken with opioids (but only sometimes)!...

https://www.youtube.com/watch?v=rK8rz19ySP0 

Ultra Low Dose Naltrexone – For Lower Opiate Tolerance – Research Summary…..

http://accurateclinic.com/wp-content/uploads/2018/08/Ultra-Low-Dose-Naltrexone-For-Lower-Opiate-Tolerance-Research-Summary.pdf

Opioid Antagonists in Pain Management….

https://www.practicalpainmanagement.com/.../opioid...

A Fresh Look at Opioid Antagonists in Chronic Pain Management….

https://www.practicalpainmanagement.com/treatments/pharmacological/fresh-look-opioid-antagonists-chronic-pain-management

Ultra-low-dose opioid antagonists enhance opioid analgesia while reducing tolerance, dependence and addictive properties .........https://accurateclinic.com/wp-content/uploads/2018/08/Ultra-low-dose-opioid-antagonists-enhance-opioid-analgesia-while-reducing-tolerance-dependence-and-addictive-properties-1.pdf 

Ultra-Low Dose Oral Naltrexone Decreases Side Effects and Potentiates the Effect of Methadone…

https://www.jpsmjournal.com/article/S0885-3924(03)00139-8/fulltext

Antagonists of excitatory opioid receptor functions enhance morphine's analgesic potency and attenuate opioid tolerance/dependence liability…. https://www.ncbi.nlm.nih.gov/pubmed/10666516 

Paradoxical effects of the opioid antagonist naltrexone on morphine analgesia, tolerance, and reward in rats…. https://www.ncbi.nlm.nih.gov/pubmed/11805221 

Treating chronic pain with low dose naltrexone and ultralow dose naltrexone:

a review paper… https://ldnresearchtrust.org/sites/default/files/treating-chronic-pain-with-low-dose-naltrexone-and-ultralow-dose-naltrexonea-review-paper.pdf

Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial….

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2657183/

Adding ultralow-dose naltrexone to oxycodone enhances and prolongs analgesia: a randomized, controlled trial of Oxytrex….. https://www.sciencedirect.com/science/article/pii/S1526590006007875

Oxycodone plus ultra-low-dose naltrexone attenuates neuropathic pain and associated mu-opioid receptor-Gs coupling….. https://www.ncbi.nlm.nih.gov/pubmed/18468954

Lessons Learned on Combining Opioids and LDN for Fibromyalgia... [Note: in our opinions her ULDN doses are too high -- more in LDN territory]……..

https://www.drginevra.com/post/lessons-learned-on-opioids-and-ldn-for-fibromyalgia

POTENTIATION OF BUPRENORPHINE ANTINOCICEPTION WITH ULTRA-LOW DOSE NALTREXONE IN HEALTHY SUBJECTS….

https://www.ncbi.nlm.nih.gov/pubmed/20728384

“Ultra-Low Doses of Naltrexone Enhance the Antiallodynic Effect of Pregabalin or Gabapentin in Neuropathic Rats”…. https://www.facebook.com/notes/ldnnow/uldn-and-neuropathy-tactile-allodynia/10155071463888391/

ULDN not mentioned but some interesting topics – addiction vs. dependence, suboxone, detox, withdrawal etc 2 links---

Suboxone Debate: What Is the Big Problem with Buprenorphine?... https://drugabuse.com/blog/suboxone-debate-dont-rehabs-use-buprenorphine/ 

Detoxing from Suboxone – Fear is Caused by a Lack of Knowledge….
 http://www.pbod.org/detoxing-suboxone-fear-caused-lack-knowledge/

Opiate Withdrawal Remedies: Be Prepared, Get Comfy, Get Support…
 https://workithealth.com/blog/opiate-withdrawal-remedies

ULDN/LDN not mentioned but a useful article…
How To Taper Off Opiates Without Withdrawal – The “Art of Tapering”….

https://opiateaddictionsupport.com/how-to-taper-off-opiates-without-withdrawal/

THIS LINK IS REGARDING FULL STRENGTH NALTREXONE (EG: 50MG DOSE) HOWEVER THE SAME CAUTIONS APPLY TO LDN WHICH IS WHY WE SUGGEST ULDN LEVEL DOSING OR A TWO WEEK GAP FROM THE LAST OPIATE DOSE BEFORE STARTING LDN
JUMP TO THE SECTION HEADED “PRECIPITATED OPIOID WITHDRAWAL” HTTPS://WWW.DRUGS.COM/PRO/NALTREXONE.HTML#S-34089-3
AND FROM THE “INFORMATION FOR PATIENTS” SECTION:
“PATIENTS SHOULD BE OFF ALL OPIOIDS, INCLUDING OPIOID-CONTAINING MEDICINES, FOR A MINIMUM OR 7 TO 10 DAYS BEFORE STARTING NALTREXONE HYDROCHLORIDE IN ORDER TO AVOID PRECIPITATION OF OPIOID WITHDRAWAL. PATIENTS TRANSITIONING FROM BUPRENORPHINE OR METHADONE MAY BE VULNERABLE TO PRECIPITATION OF WITHDRAWAL SYMPTOMS FOR AS LONG AS TWO WEEKS. ENSURE THAT PATIENTS UNDERSTAND THAT WITHDRAWAL PRECIPITATED BY ADMINISTRATION OF AN OPIOID ANTAGONIST MAY BE SEVERE ENOUGH TO REQUIRE HOSPITALIZATION IF THEY HAVE NOT BEEN OPIOID-FREE FOR AN ADEQUATE PERIOD OF TIME, AND IS DIFFERENT FROM THE EXPERIENCE OF SPONTANEOUS WITHDRAWAL THAT OCCURS WITH DISCONTINUATION OF OPIOID IN A DEPENDENT INDIVIDUAL. ADVISE PATIENTS THAT THEY SHOULD NOT TAKE NALTREXONE HYDROCHLORIDE IF THEY HAVE SYMPTOMS OF OPIOID WITHDRAWAL. ADVISE ALL PATIENTS, INCLUDING THOSE WITH ALCOHOL DEPENDENCE, THAT IT IS IMPERATIVE TO NOTIFY HEALTHCARE PROVIDERS OF ANY RECENT USE OF OPIOIDS OR ANY HISTORY OF OPIOID DEPENDENCE BEFORE STARTING NALTREXONE HYDROCHLORIDE TO AVOID PRECIPITATION OF OPIOID WITHDRAWAL.” NOTE THAT THIS WARNING IS NOT ABOUT ULDN.

Related: Low-Dose Naltrexone to Prevent Intolerable Morphine Adverse Events: A Forgotten Remedy for a Neglected, Global Clinical Need....

https://academic.oup.com/painmedicine/article/16/6/1239/2460766

A possibly useful add-on: Acetyl-L-carnitine in the management of pain during methadone withdrawal syndrome… https://www.ncbi.nlm.nih.gov/pubmed/18978503

Interesting study that uses 0.1mg doses of LDN …

Outpatient Detoxification Completion and One-Month Outcomes for

Opioid Dependence: A Preliminary Study of a Neuropsychoanalytic

Treatment in Pain Patients and Addicted Patients....

http://bit.ly/2UpcgeD

BE SURE TO ALSO REVIEW THE FILES IN THE NOPE GROUP ESPECIALLY THE ONE MICHAEL WROTE.

Related -
We periodically hear reports of doctors saying Naltrexone is an opioid. Evaluating what the doctor said would require knowing what they meant. Many doctors and ER staff are confused thinking that Naltrexone is an opioid like oxycodone etc. This is not correct as oxy is an opioid agonist whereas Naltrexone is an antagonist meaning it blocks the opioid receptors.
However it is not strictly incorrect to say that Naltrexone is an opioid in the chemical sense:
"Naltrexone is a semi-synthetic opioid with competitive antagonist activity at mu opioid receptors."
https://pubmed.ncbi.nlm.nih.gov/26546222/ 
"Naltrexone, also known as N-cyclopropylmethylnoroxymorphone, is a derivative of oxymorphone (14-hydroxydihydromorphinone). It is specifically the derivative of oxymorphone in which the tertiary amine methyl substituent is replaced with methylcyclopropane."
https://en.wikipedia.org/wiki/Naltrexone#:~:text=naltrexone%20being%20effective.-,Chemistry,substituent%20is%20replaced%20with%20methylcyclopropane.
When someone say "opioid" we think of opioid agonists, but it seems that (perhaps unfortunately) the term may apply to antagonists as well. Good for us to be aware of this in terms of not being overeager to take the doctor to task without further clarification.
Related: In case your doctor is confused thinking LDN/Naltrexone is an opioid agonist:
https://ldnresearchtrust.org/what-is-low-dose-naltrexone-ldn 

This document compiled by Brian Haviland  - LDN International

On Reddit:

https://www.reddit.com/r/LowDoseNaltrexone/ 

On MeWe:

https://mewe.com/group/68184bdfb6f32649cc96d0f6