immunology part-6: ldn updates and dosing information

Immunology Part-6:

LDN Updates and Dosing

Information

Dr. Paul S. Anderson

1.5 hours Pharmacology CE – April 20, 2021

© PS Anderson and www.ConsultDrA.com 2021

1(c) PS Anderson - www.ConsultDrA.com 2021

http://www.consultdra.com/

Abstract

Since the publication of the data regarding cyclic dosing

from St. George’s University by Liu, et. al in 2016 the

question of continuous dosing of LDN versus cyclic dosing

has been posed.

In this presentation Dr. Anderson will discuss the cell and

tumor biology – pharmacology interface where this idea

comes from and develop the concept using new

immunobiology data around LDN. He will share dose

strategies and clinical applications.

(c) PS Anderson - www.ConsultDrA.com 2021 2

Outline:

I. Introduction

II. What really is “Low Dose” Naltrexone and Why do we use it?

III. MOA: How does it work?

IV. Data Updates – Immunobiology – Condition Data

V. Oncology and Naltrexone

VI. Why is it SO Nonlinear…

VII.Practicalities


QUESTIONS ABOUT -----? Go here:

https://www.consultdranderson.com/contact/



If you are reading the slides and not listening to audio:

• A LOT is not on the slides.

• Many questions I get are answered in the audio portion

• So, it’s fine to skim the slides but please do both the “A”

and the “V” parts

• Thank you!


Note: This is an update:

• Prior LDN webinar is still valid, and I am not repeating

much from that here.

https://www.consultdranderson.com/courses/28-immunology-

part-1-low-dose-naltrexone/

• The point is to update the cell and tumor biology regarding

LDN, new research publications etc. Especially publications

and clinical vignettes of the past three years.


https://www.consultdranderson.com/courses/28-immunology-part-1-low-dose-naltrexone/

Excellent review of what we know and MOA data:


Why an update?

• Confusing dosing strategies

• To cycle or not to cycle?

• Is less better?

• Is more better?

• Or????



Low Dose???

Where did the “magic” 4.5 mg dose come from?

According to the LDN Research Trust:

In the 1980s, Dr. Ian Zagon and Dr. Patricia McLaughlin (at Penn State) began investigating LDN.

Bernard Bihari, MD, (1931-2010) was the discoverer of the clinical effects of low-dose naltrexone (LDN) in humans. In his groundbreaking clinical trial of patients with HIV/AIDS at Downstate Medical Center in 1985-86.


Where did the “magic” 4.5 mg dose come from?

At an LDN Research Trust Conference I spoke with a colleague of Dr.

Bihari, regarding where the idea of “What actually is ‘low dose

naltrexone?’”…

“In an interview Dr. Bihari said ‘we know lower doses

work. We know we see the best clinical results

between 1 and 10 mg daily. So, we set the idea of

“low dose” at 4.5 – 5 mg.’ Yes, that is it.”



We know more about “How it

Works”

Clinician / Patient Experience

LDN Thoughts

• Although rarely an effective mono-therapy:

– I usually see LDN as an excellent adjunct to all the usual

interventions.

– Many people (who do not have initial aggravations – see

below) state that they do not notice a difference BUT

when you withdraw the LDN they do report aggravation

of Sn/Sx


Other Clinicians:

• Over the years I have interacted with a number of clinicians who report clinical benefits in ”cyclic dosing” of LDN in many patients.

• More and more are following those guidelines for cancer patients

• Most non-oncology indications have been in autoimmune patients

• Some have been in chronic pain patients

• Dr. Bihari does not feel that there is a need for any such breaks from the daily use of LDN, whereas, Dr. Lawrence feels that there might be some sort of accommodation that might occur. He advocates taking a break about every 10 days or so I think (not sure about the schedule because I have never taken an intentional break, I have missed a dose once or twice and never noticed a difference on those days when I did).


Dr. MR Lawrence and Cycling in AI:

Dr Lawrence liking cycling dose as he has MS (His notes from another blog) This

temporary increase in symptoms may also perhaps be explained when we consider the

manner in which this drug is expected to work. Initially, MS occurs due to a reduction in

the activity of the controlling influence of the suppressor T-cells within the immune

system. During an acute relapse, the overall number of T-cells is reduced, the normal

balance of helper T-cells and suppressor T-cells is disrupted and the damaging helper

(CD-4) T-cells tend to predominate. This is the situation most pronounced during an

acute relapse but occurs similarly, but to a lesser extent, in chronic progressive MS.

Under the influence of LDN there will be an expected increase in the overall numbers

of T-cells but, because the CD-4, helper T-cells tend to predominate at this time, an

increase in their numbers will expectedly tend to increase MS symptoms. It is only

when the numbers of suppressor T-cells effectively "catch up" that the normal balance

is restored and symptoms once again diminish and improve. Dr. M R Lawrence


The “Norwegian” Alternative Dosing Strategy

patterned after information from Dr. Tom Gilhooly

Norwegian document notes that “a larger dose of LDN possibly can be used to

reduce or avoid aggravation of symptoms that can occur with the traditional

dose strategy for LDN. It also suggests that this strategy is more suitable for

patients who have constant inflammatory conditions in the body (eg.

fibromyalgia, ME, progressive MS, arthritis, etc).”

• Original Norwegian document translated to English by Brian Haviland and

Steinar Hauge for Facebook group “GotEndorphins LDN”

• https://ldnresearchtrust.org/sites/default/files/Dr%20Tom%20Gilhooly%20LD

N%202013%20Conference.pdf


Steinar Hauge of the Norwegian LDN site www.ldn.no

At a low dose (1.5 mg) "stimulation and stabilization" is strong and immune suppression is

hardly present. When immune suppression is weak and the immune system is stimulated,

the autoimmune reactions are enhanced and many are experiencing symptom aggravation

until stabilization occurs.

At 3 to 4.5 mg the "stimulation and stabilization" action is at maximum strength and the

immune suppression is weaker. This explains why starting at a 3 mg dose may give a

tough startup sometimes.

At high doses (6 mg) the immune suppression action is strong and "stimulation and

stabilization" is weaker. Therefore symptom aggravation will likely be less but your immune

system will still be gently stimulated and the stabilization of the immune system will be in

place gradually.


Steinar Hauge of the Norwegian LDN site www.ldn.no

This groups idea comes from the basis that:

“LDN first stimulates and then stabilizes the

immune system as a result of increased endorphin

levels.”

(This idea does match the data I quote below from

McLaughlin 2015).

**NOTE: They do NOT recommend this in cancer.


Dose reduction from 6 mg (2 x 3 mg) LDN:

1. Try 6 mg for a few days but stop if experiencing severe discomfort. It may take a few

days before any effect happens.

2. If one feels worse after directly starting at 6 mg (3 mg BID) LDN or if one feels worse after a

period of 6 mg LDN then the dose is probably too high and should be lowered down to 4.5

mg.

3. If one has dosed at 6 mg (3 mg BID) LDN for 2 to 3 weeks with good effect, try to decrease

to 4.5 mg. If results are not as good at 4.5 mg, then go back to 6 mg and stay at this dose

even longer before again trying to reduce to 4.5 mg. Attempting to move periodically to 4.5

mg may provide better results. N.B. If reduction does not give better results, you can

continue to use 6mg (3mg BID) as standard dose.

4. Whether to take 3 mg, 4.5 mg or 3mg BID as standard dose is individual and will vary from

person to person. If one has reduced the dose to 4.5 mg and has had good effects then

stay at this dose. If the effects are still poor, but better than the 6 mg, one can try to vary

between 3 and 4.5 mg to see what dose works best. When you have found the dose that

seems to work best (eg. 3mg, 4,5mg or 3mg BID), then stay at this dose.


Cort Johnson. Weird Dosing, Backward Protocols and Rejections – in ME/CFS and Fibromyalgia

• “Loading Dose” idea then tapering

• Higher doses of 6 mg QD to BID

• Interesting case descriptions

https://www.healthrising.org/blog/2020/03/02/strangeness-low-dose-naltrexone-

chronic-fatigue-fibromyalgia-dosing/


LDN does appear to have a distribution of effects

through a variety of dose and timing schedules:

• Immune stimulation and balancing / modulation appear to be at doses under

5 mg.

• Doses above 5 – 6 mg (and higher) are more immunosuppressive

• And, just as humans have differing effect from opiate drugs from person to

person, some people may experience these “modulating versus suppressive”

effects at lower doses.

– See also: Toljan K, Vrooman B. Low-Dose Naltrexone (LDN)—Review of

Therapeutic Utilization. Medical Sciences. 2018; 6(4):82.

https://doi.org/10.3390/medsci6040082


LDN: Suppression even at 7 mg

Animal Experimental Models

PA Note: Of note the LDN dose was too high (eq to 7 mg IV in a human) so the larger suppression is likely exaggerated.

“The OGF-OGFr pathway regulates proliferation of peripheral immune cells following stimulation by MOG35–55 antigen. Exogenous OGF or endogenous OGF following LDN treatment inhibited CD4+ and CD8+ T and B cell replication within the spleen and draining inguinal nodes within the first week of immune-related response, and in spinal cord tissue on day 15 following antigen stimulation. These data support that modulation of the OGF-OGFr pathway is an effective therapeutic paradigm for MS.”McLaughlin PJ, McHugh DP, Magister MJ, Zagon IS. Endogenous opioid inhibition of proliferation of T and B cell subpopulations in response to immunization for experimental autoimmune encephalomyelitis. BMC Immunol. 2015;16:24. Published 2015 Apr 24. doi:10.1186/s12865-015-0093-0


Suppressive dose (animal model) at 10 mg/kg:

N. Xu, et al. Naltrexone (NTX) relieves inflammation in the collagen-induced- arthritis CIA) rat models

through regulating TLR4/NFκB signaling pathway. International Immunopharmacology 79 (2020) 106056

NTX could relieve the severity of arthritis in CIA rat models, and10 mg/kg is the optimal

dose. NTX could regulate T lymphocyte subsets: CD4+/CD8+T cells, Th1/Th2 cells and

Th17/Treg cells, decrease the expression of the proinflammatory cytokines TNF-α, IL-

6, IL-12 alpha and IL-17, increase the expression of the anti-inflammatory cytokine IL-

10, and regulate immune responses to reconstruct the immune balance to alleviate

inflammation. NTX could interact with MOR and DOR in the spleen, inhibit the

TLR4/NF-κB signaling pathway and regulate systemic immune responses to alleviate

inflammation. In addition, NTX could interact with KOR and DOR in synovial tissues

inhibiting the TLR4/RANKL/NF-κB pathway to decrease the erosion of articular

cartilage and bone tissue in joints by inhibiting osteoclast differentiation. Therefore,

NTX could provide RA patients with a new alternative therapy, especially for those who

may not have obvious therapeutic effects from traditional control drugs and biological

agents, with broad application prospects and great clinical feasibility.



Immunology

Clin Rheumatol (2014) 33:451–459

Double blind crossover FMS study at 4.5 mg QHS:


Luke Parkitny and Jarred Younger. Reduced Pro-Inflammatory Cytokines after Eight

Weeks of Low-Dose Naltrexone for Fibromyalgia. Biomedicines 2017, 5, 16;

doi:10.3390/biomedicines5020016

10-week, single-blind, crossover investigation of the immune effects of LDN in

women with FM. Each participant first took part in a two-week baseline phase

that was immediately followed by an eight-week LDN administration phase.

While participants were told they could receive the placebo at any time during

the protocol, no placebo capsules were actually administered

Rx: During the medication administration phase, each participant self-

administered LDN at a 4.5 mg oral dose, taken in capsule form, at least one

hour before going to bed at night. A change to a lower dose of 3.0 mg was

made available to the participant if they experienced unpleasant adverse

effects at the standard dose.


Luke Parkitny and Jarred Younger. Reduced Pro-Inflammatory Cytokines after Eight

Weeks of Low-Dose Naltrexone for Fibromyalgia. Biomedicines 2017, 5, 16;

doi:10.3390/biomedicines5020016

Cytokines: In our primary analyses, we found the following inflammatory

plasma markers to be significantly reduced at Drug compared to BL

(baseline): IL-1, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-10, IL12p40, IL-12p70,IL-15, IL-

17A, IL-27, IFN-, TGF-, TGF-, TNF-, and G-CSF

We found that the cytokines most suppressed by LDN are known to

promote nociception, allodynia, and hyperalgesia, including TNF-α, IL-1β,

IL-2, IL-6, IL-15, and IL-17


Bolton MJ, Chapman BP, Van Marwijk H. BMJ Case Rep 2020;13:e232502.

doi:10.1136/bcr-2019-232502

This series of three case reports compiled by people with

long-term ill-health due to chronic fatigue syndrome shows

the range of responses they observed when taking LDN,

from life changing to a reduction in some symptoms only.

Treatment doses ranged from 4 to 12 mg.


Olli Polo, Pia Pesonen & Essi Tuominen (2019) Low-dose naltrexone in the

treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Fatigue: Biomedicine,

Health & Behavior, 7:4, 207-217, DOI: 10.1080/21641846.2019.1692770





A low dose (3.0–4.5 mg/day, low-dose naltrexone, LDN) appears to

have an opposite effect [to high dose naltrexone], enhancing the

endorphin effect [5].

This is thought to have relevance in illnesses such as ME/CFS,

where insufficient secretion of opioid peptides affects immune

response or pain control [6,7], or the release of pro-

inflammatory cytokines [8,9].

Recently, LDN was shown to restore the impaired transient

receptor potential melastatin 3 ion channel function in natural

killer cells of ME/CFS patients [10].


MS

These observations have been optimized to work in favor of therapeutic treatment of MS. Thus, LDN has become a widespread therapeutic used to safely inhibit inflammatory processes by inhibiting proliferation of T-lymphocytes and B-lymphocytes following a peripheral autoimmune trigger, and to inhibit T-cell infiltration into the CNS (17).

From: Multiple Sclerosis: Perspectives in Treatment and Pathogenesis. Ian S. Zagon and Patricia J. McLaughlin (Editors), Codon Publications, Brisbane, Australia. ISBN: 978-0-9944381-3-3; Doi: http://dx.doi.org/10.15586/codon.multiplesclerosis.2017.ch8

Quoting [17]. McLaughlin PJ, Zagon IS. Duration of opioid receptor blockade determines clinical response. Biochem Pharmacol. 2015;97:236–246. http://dx.doi.org/10.1016/j.bcp.2015.06.016



Citation: Cant R, Dalgleish AG and Allen RL (2017) Naltrexone Inhibits IL-6 and TNFαProduction in Human Immune Cell Subsets following Stimulation with Ligands for

Intracellular Toll-Like Receptors. Front. Immunol. 8:809. doi: 10.3389/fimmu.2017.00809

Endometriosis?

O. V. Golianovskyi, et.al. Prospective of low dose

naltrexone use in treatment of autoimmune pathology

and endometriosis. Reproductive Endocrinology No. 55

(2020) / Gynecology 11-2020


I’d download the next paper before the authors are

all killed mysteriously…

Or me…


Choubey - 2020

LDN stimulates the release of b-endorphins by acting on the opioid receptor (Gold et al., 1982; The Uses of Low- Dose Naltrexone in Clinical Practice, 2020). LDN acts as a TLR4 antagonist, in a human pilot study (4.5mg of LDN daily) significantly reduced serum pro-inflammatory cytokines (IL)-1, IL-2, IL-12, IL-18, etc (Parkitny and Younger, 2017). Importantly, low cost, low side effects, no reports of LDN interactions with other medications, and oral availability make LDN as a lucrative option to be used as an immunomodulatory agent and may be considered for use in combination with antiviral drugs or hydroxychloroquine for the treatment of severe or critical cases of COVID-19.

Our data provide a proof-of-concept for the potential feasibility of repurposing of FDA approved non-peptide opioid antagonist; naltrexone as host-targeted broad-spectrum antiviral therapies to combat COVID-19 infections. The next step will be to confirm data in COVID-19 patients. LDN alone or as an adjuvant therapy with hydroxychloroquine or an antiviral agent may give physicians more time to provide supportive treatment for patients with COVID-19.



Oncology

1983 Observations:

Dichotomous biological responses following different dosages of naltrexone and

thus different durations of opioid receptor blockade were first reported in 1983 (18).

Low dosages (0.1 mg/kg) of naltrexone inhibited the growth of the neuroblastoma

tumors, but higher dosages (10 mg/kg) of naltrexone were not more inhibitory and, in

fact, resulted in enhanced tumor growth. This was the first indication that the action

of receptor blockade did not directly correlate with antagonist dosage (18).

*** Note this is 7 mg versus 70 mg Naltrexone***

From: Multiple Sclerosis: Perspectives in Treatment and Pathogenesis. Ian S. Zagon and

Patricia J. McLaughlin (Editors), Codon Publications, Brisbane, Australia. ISBN: 978-0-

9944381-3-3; Doi: http://dx.doi.org/10.15586/codon.multiplesclerosis.2017.ch8

Quoting [18]: 18. Zagon IS, McLaughlin PJ. Naltrexone modulates tumor response in

mice with neuroblastoma. Science 1983;221:671–673.

http://dx.doi.org/10.1126/science.6867737



https://ldnresearchtrust.org/rof-angus-dalgleish-md-role-ldn-

cancer-management-low-dose-naltrexone

LDN 03-11-2020

https://ldnresearchtrust.org/rof-angus-dalgleish-md-role-ldn-cancer-management-low-dose-naltrexone

LDN + Chemosensitization

• All three showed positive cell line sensitization when

dosed on a cyclic basis (next slide):

1. Gemcytabine

2. Oxaliplatin

3. Cyclophosphamide


LDN High versus Low dose:

• The following slide depicts the effect of two variables:

– Low versus High dose of LDN

– Continuous versus punctuated LDN dosing

– Both assessed via cell number and percent viability.

• The dose as well as dosing strategy both affected these

criteria.



LDN HDN LDN HDN

No break - Break - No break - Break No break - Break - No break - Break

https://ldnresearchtrust.org/sites/default/files/202

0-04/Dosing-Info-a4_0.pdf

Protocol guideline from the LDN website for cancer:

1.5mg daily for 7 days increasing by 1.5mg weekly until

on 4.5mg for 7 days. Once stable on dose of 4.5mg for 7

days – start alternating 3 days on 3 days off if indicated.

** Of note, for simplicity and patient compliance I use 4

days on and 3 days off so they are on a weekly cycle.


Oncology Dosing

Starting doses can be anywhere from 0.5 mg to 1.5 mg and is increased up to

4.5 mg; which is the maximum dose for Low Dose Naltrexone. Specifically for

cancer patients, the dose should be a goal daily for at least 7 days before

starting an "on/off cycle"

● An "on/off cycle" consists of 4 days on and 3 days off LDN

● The 3 days off should fall directly before chemotherapy treatment.

Although there are no known contraindications with chemotherapy, it is

recommended to avoid use together until further research is completed

It has been seen in some cancer patients, that taking a CBD product on the 3

days off increases the anti-tumor effect of LDN



Case

Comments – Why?:

• “I find LDN works best when Vitamin D levels are

optimized.”

• “I never start LDN early in an AI case or they flare.”

• “All my LDN patients seem to flare.”

• And so on…


Brief case pair:

• I will verbally describe two autoimmune cases that

had different responses to LDN with a standard 1.5

/ 3.0 / 4.5 dose taper.

• Both had remitting and relapsing MS with

complaints of transient neuropathy, transient

aphasia and fatigue.


Brief case pair:

• Case-1 aggravated with all doses and

required an increase to 3 mg BID for a month

then a reverse taper to 4.5 mg which

ultimately was cycled 4 days on and 3 days

off.


Brief case pair:

• Case-2 had no aggravation and had

symptomatic lessening at the 3-week mark on

her 4.5 mg dose.

• She was stable at 4 weeks and then went to a

4 day on / 3 day off cycle and stayed stable.


The difference?

• The underlying parts of the case and how well they were

being addressed:

– GI function and health

– Environmental toxicity

– Nutrient absorption and sufficiency

– Endocrine balance

– Physical factors (Movement, physical medicine etc.)


Alternative dose forms:

● Sublingual drops

o Drops are placed under the tongue from a dropper bottle

● Creams: 0.5 mg/mL

o Useful for children who you have difficulty administering the other

formulations, or those who are allergic to additives in other formulations of LDN



Practicalities

To dose at night or morning:

• May be better at night

• Likely not a huge issue (especially with sleep disruption

and nightmares)

• Try in the PM first and switch to AM as needed for the

case

• It is better to use it sometime than not…


After a great deal of research and many thousands of

doses in multiple medical indications:

• As with everything in medicine, nobody knows

everything.

• Humans and their immune systems are not all the

same.

• We of course want “one answer / one protocol” to

use – which is not reasonable when interacting with

the human immune system.




• There are known outliers in LDN response, and

sometimes very low or ultra low dose schedules

work when “typical” doses do not.

• Similarly, sometimes higher doses work (especially

in FMS / CFS-ME) when typical doses do not.

• So, this has led me to the following clinical

conclusions:




• In cancer I generally ramp up to 4.5 mg in 1.5 mg

increments for 1-2 weeks then cycle 4.5 mg 4 days

on and 3 days off.

• In very sensitive cancer patients I will ramp the

dose up 0.5 mg at a time (and still cycle the dose 4

days on and 3 off).




• In autoimmunity I either use a 0.5 mg slow taper or a 1.5 mg taper, and then when an effective dose is found (usually between 1.5 and 4.5 mg assessed over 4 weeks on a 7 day a week dose) I then (if tolerated) cycle that 4 days on and 3 off as well. If cycling isn’t tolerated, then do 7 days a week.

• If the patient is sensitive and aggravates (especially in CFS-ME / FMS or uncontrolled autoimmunity) Then the idea of suppressive doses first (such as 3 mg BID for 2-4 weeks; then a ramp down) are worth trying.




• In some patients regardless of the use of more “standard” dosing they will still not be able to tolerate the standard dose ranges.

• These are times where a “Very-low” or “Ultra-low” dose strategy may be required.– Toljan K, Vrooman B. Low-Dose Naltrexone (LDN)—

Review of Therapeutic Utilization. Medical Sciences. 2018; 6(4):82. https://doi.org/10.3390/medsci6040082


VLDN - ULDN

In a dosing range at less than 1 mcg per day, oral naltrexone or intravenous

naloxone potentiate opioid analgesia by acting on filamin A, a scaffolding

protein involved in mu-opioid receptor signaling. This dose is termed ultra low-

dose naltrexone/naloxone (ULDN). It has been of use in postoperative control

of analgesia by reducing the need for the total amount of opioids following

surgery, as well as ameliorating certain side-effects of opioid-related treatment.

A dosing range between 1 mcg and 1 mg comprises very low-dose

naltrexone (VLDN), which has primarily been used as an experimental adjunct

treatment for boosting tolerability of opioid-weaning methadone taper.

Med. Sci. 2018, 6, 82; doi:10.3390/medsci6040082

(*A super bad ass lit review of the relevant data.)


VLDN

To investigate the feasibility of administering antagonists with opiates without

intense withdrawal during detoxification, 5 methadone maintained patients were

evaluated while tapering methadone and receiving at the same time very low

(0.125 mg), then increasing daily doses of naltrexone in the course of a 6-day,

day hospital treatment. Reduced quantities of adjunctive medications were

administered, as compared to the standard protocols, the treatment was

completed without incidents or particular discomfort and all patients were easily

induced to naltrexone maintenance by the day of discharge.

Mannelli P, Gottheil E, Buonanno A, De Risio S. Use of very low-dose

naltrexone during opiate detoxification. J Addict Dis. 2003;22(2):63-70.

doi: 10.1300/J069v22n02_05. PMID: 12703669.


ULDN J Pain and Symptom Management – Vol25 No6, 2003http://rsds.org/wp-content/uploads/2014/12/ultra-low-dose-oral-naltrexone.pdf

• We present a patient with painful diabetic peripheral neuropathy who experienced significant improvement after the addition of an “ultra-low” dose of oral naltrexone (1microgram twice daily) to his opioid regimen. This observation suggests that an “ultra-low” dose of oral naltrexone can be utilized safely and may be another strategy to increase the potency of an opioid agonist.

• “ultra-low” doses, caused prolongation of the action potential duration (APD).6 This excitatory opioid effect was blocked by “ultra low” doses of naltrexone or naloxone.

• A compounding pharmacy prepared a solution of 1 mg of naltrexone (from powder) in 1 liter of sterile water. A total of 100 cc of the solution was stored in a caramel container, delivered to the patient, and kept out of the light in the refrigerator. We instructed the patient to take 1 cc twice daily


Jackson D, Singh S, Zhang-James Y, Faraone S and Johnson B (2021) The Effects

of Low Dose Naltrexone on Opioid Induced Hyperalgesia and Fibromyalgia.

Front. Psychiatry 12:593842. doi: 10.3389/fpsyt.2021.593842



LDN Prescribing

LDN Dosing in Oncology

• DOSING:

– In the oncology setting (and patient not on opiates) I will

ramp the dose faster:

• Often 2.5 then 4.5 mg

• Alternatively (if I feel a slower ramp is needed) 1.5 then 3.0

then 4.5 mg ramped up every 2-4 weeks.

• CYCLE: 4 days “on” and 3 days “off”


LDN and Opiates

• DOSING:

– Offer ULDN FIRST!

– If the patient is on opiates and CONSENTS to a trial of LDN I tend

to go slower:

• 0.5 mg X 2 weeks

• 1 mg X 2 weeks

• 1.5 – 2.5 mg X 1 month

• 3.5 – 4.5 mg terminal dose


LDN and Opiates

• In Opiate using patients there are many factors which can make LDN either not

interfere or cause interference and breakthrough pain.

– If patient is on OPIATES:

• 10-20% will have cross reactivity / Breakthrough pain

– Decrease in opiate effect

– Must disclose this and monitor

• 80-90% will not

• Slower ramping up of dose is needed to assess

• You may find a dose at which there is no opiate inhibition and then one in

which there is as you ramp up. – So STOP at the one with no breakthrough!


LDN Dosing in Autoimmunity / Infections etc.

• DOSING:

– In the auto-inflammatory setting (Patient with more stable case) I

tend to dose:

• 1 mg X 1 month

• 1.5 – 2.5 mg X 1 month

• 3.5 – 4.5 mg terminal dose

• (An alternate strategy is 1.5 mg X 2 weeks, 3 mg X 2 weeks then

4.5 mg)


Always consider the stability of the case:

At a low dose (1.5 mg) "stimulation and stabilization" is strong and immune suppression is

hardly present. When immune suppression is weak and the immune system is stimulated,

the autoimmune reactions are enhanced and many are experiencing symptom aggravation

until stabilization occurs.

At 3 to 4.5 mg the "stimulation and stabilization" action is at maximum strength and the

immune suppression is weaker. This explains why starting at a 3 mg dose may give a

tough startup sometimes.

At high doses (6 mg) the immune suppression action is strong and "stimulation and

stabilization" is weaker. Therefore symptom aggravation will likely be less but your immune

system will still be gently stimulated and the stabilization of the immune system will be in

place gradually.


Higher dose to “calm” then try to taper

1. Try 6 mg for a few days but stop if experiencing severe discomfort. It may

take a few days before any effect happens.

2. If one feels worse after directly starting at 6 mg (3 mg BID) LDN or if one

feels worse after a period of 6 mg LDN then the dose is probably too high and

should be lowered down to 4.5 mg.

3. If one has dosed at 6 mg (3 mg BID) LDN for 2 to 3 weeks with good effect,

try to decrease to 4.5 mg. If results are not as good at 4.5 mg, then go back to 6

mg and stay at this dose even longer before again trying to reduce to 4.5 mg.

Attempting to move periodically to 4.5 mg may provide better results. N.B. If

reduction does not give better results, you can continue to use 6mg (3mg BID)

as standard dose.


Higher dose to “calm” then try to taper

4. Whether to take 3 mg, 4.5 mg or 3mg BID as standard dose is individual and

will vary from person to person. If one has reduced the dose to 4.5 mg and has

had good effects then stay at this dose. If the effects are still poor, but better

than the 6 mg, one can try to vary between 3 and 4.5 mg to see what dose

works best. When you have found the dose that seems to work best (eg. 3mg,

4,5mg or 3mg BID), then stay at this dose.

5. Most of these cases WOULD NOT be amenable to cyclic dosing for a while…


PEDIATRIC DOSE CALCULATIONS

• General Rules:

• It is very important to maintain precision when using these rules to determine the correct dose of medication

for the pediatric patient. Therefore, it is suggested to use the following rounding rules:

• Weight Doses (mg)

• When calculating doses in weights, medications that are less than 1 mg should be rounded two decimal places

(hundredths place).

• Doses that are 1mg - 10 mg should be rounded to one decimal place (tenths place).

• Doses greater than 10 mg should be rounded to the whole number.

• Volume Doses (mL)

• Doses that are less than 1 milliliter should be rounded to two decimal places (hundredths place).

• Doses greater than 1 milliliter should be rounded to one decimal place (tenths place).



* As a general rule in practice over the past decades we

have found that the application of “Clark’s Rule” has yielded

great safety and efficacy in calculating pediatric doses for

both IV and Oral medications. The other methods are listed

for technical accuracy.



1. Clark's Rule is a medical term referring to a procedure used to calculate the amount of medicine to give to a child aged 2-17. The procedure is to take the child's weight in pounds, divide by 150lbs, and multiply the fractional result by the adult dose to find the equivalent child dosage.

• Pediatric dose = [child’s weight (lb) / 150 (lb)] x Adult dose

• For example: If an adult dose of medication calls for 30mg and the child weighs 30lbs. Divide the weight by 150 (30/150) to get 1/5. Multiply 1/5 times 30mg to get 6mg. (Or convert the fraction to a decimal and multiply – 0.20 in this case).

Common IV example:

• Adult goal dose is 100 grams IV Vitamin C

• Child weighs 25 pounds

• [25 lb / 150 lb] x 100 grams

• 1/6 x 100 grams [convert to a decimal]

• 0.167 x 100 grams = 16.7 gram dose max



2. Young’s Rule: utilizes similar concepts as Fried’s Rule except it is based on the child’s age in years. When given

the adult dose of a medication it is possible to use this formula to find the correct pediatric dose.

Pediatric dose = [child's age in years / child's age in years + 12 years] x Adult Dose

3. Fried's Rule is a method used to calculate the correct dose of medication for the pediatric patient when given

only the adult dose. This method should not be considered as accurate as the nomogram method because it is

based on the assumption that the child is of average size and utilizes age rather than weight. It is important to note

that because age does not necessarily indicate the patient's weight, medication adjustments may be necessary once

the patient's response is determined.

• Fried's rule is a method of estimating the dose of medication for a child by dividing the child's age in months by

150 and multiplying the result by the adult dose.

Pediatric dose = child's age in months / 150 x Adult Dose



3. The Nomogram method is utilized to determine the correct pediatric medication dosage based specifically on

the patient's size. The patient's size is identified as body surface area (BSA) in meters squared (M2). The average

adult client (weighing 150 - 154 lbs) will have a BSA of 1.73M2. The nomogram chart can be used to identify the

patient's BSA based on their height and weight (in. and lbs. or cm and kg).

• The surface area is determined where a straight line connecting the patient's height and weight crosses over the

BSA column.

• Once the BSA of the patient is determined the following formula can be used to calculate the correct pediatric

dosage:

Pediatric dose = Child's BSA in M2 / 1.73M2 x Adult Dosage

Some data derived from the pharmacology databank at: http://www.austincc.edu/rxsucces/ped2.html


Select Resources:

• LDN Research Trust: https://ldnresearchtrust.org/

• Pain, Opiates and ULDN https://vimeo.com/358998952

• ULDN-Opioids: https://www.khemcorp.com/ultra-low-dose-

naltrexone-for-lower-opiate-tolerance-research-summary/

• Cancer and LDN https://vimeo.com/168562089 (The one I’m in....)


https://ldnresearchtrust.org/

https://vimeo.com/358998952

https://www.khemcorp.com/ultra-low-dose-naltrexone-for-lower-opiate-tolerance-research-summary/

https://vimeo.com/168562089

QUESTIONS ABOUT (CE Cert, etc.) -----? Go here:




AAMP Conferences – 18 Cat-1 CME

• Spring - May 21, 22 & 23

– CHRONIC INFECTION CASES

– https://aampconferences.com/aamp-spring-conference-2021/

• Fall – September 24, 25 & 26

– ONCOLOGY

– https://aampconferences.com/aamp-fall-conference-2021/


https://aampconferences.com/aamp-spring-conference-2021/

https://aampconferences.com/aamp-fall-conference-2021/

89

Thank You – Questions?

(c) PS Anderson - www.ConsultDrA.com 2021

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