A Study on Naltrexone

Subjects and methods: 86 patients received the drug treatment, while 30 patients received no treatment. Results: Overall tinnitus distress was significantly reduced for the drug treatment group, while for the waiting control group this was not the case. No significant effect could be obtained for tinnitus intensity. A closer look at the data indicates that this effect is mainly generated due to a significant difference in the 50 mg drug treatment group for tinnitus distress. Conclusion: our results indicate that naltrexone might have an effect on tinnitus distress

http://www.ncbi.nlm.nih.gov/pubmed/23110786

 

A friend got complete remission from taking Naltrexone although not having very serious tinnitus.

http://www.google.com/patents/WO2011145062A1?cl=en

 

Hmm interesting; study results look not too bad..

 

The tinnitus duration in those patients in which tinnitus remitted completely ranged between 3 months and 9 years.
​

Interesting, i guess this may be easier to get than Retigabine

 

Mmmmmmm... Naltrexone is supposedly an opioid antagonist, yet Tramadol (another pain med - which I tried for mood enhancement, not really tinnitus) is a mild opioid agonist! How they hell that works is beyond me. Both opioid related pain killers but inverse action... or something???

Anyway, if anyone has experience with Naltrexone please share. Not much came up on a Tinnitus Talk search, yet I think I have heard it mentioned before, somewhere.

Best, Zimichael

 

@Zimichael I think it was mentioned in a paper I read about possible off-label prescriptions for tinnitus. Maybe you read the same one.

 

The drug is used to treat addiction, especially to alcohol, like Acamprosate. (The latter was also tested on tinnitus.) Naltrexone helps with addiction by affecting dopamine. And dopamine pathways are implicated in tinnitus. But note Naltrexone helps with tinnitus distress, not volume. However, it is possible that by favorably affecting mood, you will be able to habituate. Some people do habituate to loud tinnitus, though most people--myself included--believe this must be very difficult.

Med Hypotheses. 2005;65(2):349-52.
Tinnitus dopaminergic pathway. Ear noises treatment by dopamine modulation.
Lopez-Gonzalez MA1, Esteban-Ortega F.

Abstract
To date, the neurophysiological model has been used to explain the complexity of tinnitus. However from now on, the tinnitus dopaminergic pathway opens new horizons for ear noises management. Tinnitus perception takes place in prefrontal, primary temporal and temporo-parietal associative areas, as well as the limbic system. Dopaminergic neurotransmitters go through prefrontal, primary temporal, temporo-parietal associative areas and the limbic system. Tinnitus perception and dopaminergic pathway share the same cerebral structures, which control attention, stress, emotions, learning, memory and motivated behavior. Distress of tinnitus emanates from these same cerebral functions. The dopaminergic pathway can be modulated by agonists and antagonists of their receptors and can reduce the perception of tinnitus, such as sulpiride, amisulpride, olanzapine, quetiapine, ziprasidone, zuclopenthixole and aripiprazole, still under investigation, that together with sound treatment as the Sequential Sound Therapy, and a personal contact with the patient, constitute a tinnitus integral treatment.​

Sulpiride also affects dopamine and, taken with melatonin, has been studied as favorably reducing tinnitus perception:

J Otolaryngol. 2007 Aug;36(4):213-9.
Sulpiride and melatonin decrease tinnitus perception modulating the auditolimbic dopaminergic pathway.
Lopez-Gonzalez MA1, Santiago AM, Esteban-Ortega F.

OBJECTIVES:
Sulpiride and melatonin decrease dopamine activity. Sulpiride, a D2 antagonist of dopamine receptors, and melatonin, a pineal substance with antidopaminergic action, are administered to tinnitus patients to decrease tinnitus perception.

DESIGN:
A prospective, randomized, double-blinded, placebo-controlled study was done.

SETTING:
General otorhinolaryngologic consultation for 2002-2004 in Seville, Spain.

METHODS:
One hundred twenty patients consulted for subjective tinnitus. They were included randomly in four groups of 30. One group took sulpiride (50 mg/8 h) alone, the second group took melatonin (3 mg/24 h), the third group took the same doses of sulpiride (50 mg/8 h) plus melatonin (3 mg/24 h), and the fourth group took placebo (lactose 50 mg/8 h), all for 1 month. Ninety-nine patients completed the study.

MAIN OUTCOME MEASURES:
Clinical history, tonal audiometry, tympanometry, and tinnitometry were done at the beginning and end of the study. Subjective grading of tinnitus perception and a visual analogue scale (0-10) were done for evaluation of results.

RESULTS:
Based on the subjective grading, tinnitus perception diminished by 56% in patients treated with sulpiride, by 40% in patients treated with melatonin, by 81% in patients treated with sulpiride plus melatonin, and by 22% in patients treated with placebo. Based on the visual analogue scale, tinnitus perception diminished from 7.7 to 6.3 in patients treated with sulpiride, to 6.5 in those treated with melatonin, to 4.8 in patients treated with sulpiride plus melatonin, and to 7.0 in those treated with placebo.

CONCLUSIONS:
Sulpiride and melatonin reduce tinnitus perception, decreasing dopamine activity. The tinnitus auditolimbic dopaminergic pathway has broad therapeutic implications. [emphasis added]
​

Some people my also find this article interesting, but it does not refer to tinnitus. However, the article does refer to chronic pain:

Pleasure in the brain is primarily mediated through the neurotransmitter dopamine. Neurons in the ventral tegmental area (the starting post for those dopamine tracts I talked about a few days ago) respond to sex, drugs, rock n' roll, food, and communicate with some other neurons in the nucleus accumbens, and a third neural network in the amygdala and the ventromedial prefrontal cortex. These are all segments of the "medial dopamine tracts" I reviewed at some length a few days ago. It may be of interest that those of you who derive pleasure from other people's pain (schadenfreude) experience your mischievous pleasure here as well.

Pain is experienced in the aptly named "cortical pain network," which are regions of the brain a little separated from the pleasure centers. The different areas of the pain network collect sensory pain (such as a splinter in one's finger) and emotional pain. Typically, experiments used to isolate pain circuitry in the brain involve "aversive stimuli" such as electric shock.

So it turns out that social pleasure and pain have hijacked these evolutionary circuits of pleasure and pain, so that if you score a date with that hot chick and share a high five with your frat brothers, or you get arrested for that meth lab you are running in the basement of the chemistry building at school, you will experience the pleasure and pain in the same areas of the brain that you experience sex and electric shock. It hurts to be human, sometimes. If you feel that you are fairly treated and are feeling cooperative, your pleasure centers are stimulated. If you grieve the loss of a loved one, your cortical pain network lights up.

And what about opiates or wheat exorphins or binge eating? Turns out those activities stimulate the dopamine reward centers of the nucleus accumbens. That new weight loss drug is a combination of two older drugs, naltrexone and buproprion (wellbutrin). Naltrexone is a straight-up opiate blocker. It is FDA-approved to reduce cravings for alcohol, but to be honest I use it more often for people trying to kick an oxycodone or heroin habit. You have to be off opiates for a couple weeks or risk an exceedingly uncomfortable precipitated withdrawal, and once you are on naltrexone, your opiate tolerance will drop like a rock, so if you go back to using like you used to, you could easily overdose. But naltrexone isn't a controlled substance, and if you take your medicine as prescribed and try to use opiate drugs on top of it, those drugs won't work. There's nothing like a pharmacologic lock on the opiate system to help out an opiate addict. Naltrexone has been studied in binge eating and in gambling, and for some people, it seems to help. I've used it on a couple of occasions for sleep eating with extreme carb (grain) cravings with some success, also in patients with celiac who can't seem to kick the wheat habit. Naltrexone use requires monitoring of the liver, and typical side effects include upset stomach. But both of those are less noxious than a heroin habit in my opinion, but every case is different and risks and benefits must be discussed for each situation. [emphases added]​

For further reading on naltrexone and dopamine--specifically as applied to alcoholism--please see this article:

http://www.post-gazette.com/news/he...ed-effects-in-alcoholics/stories/201006300241

​

References:

http://www.ncbi.nlm.nih.gov/pubmed/15922111

http://www.ncbi.nlm.nih.gov/pubmed/17942035​

http://evolutionarypsychiatry.blogspot.com/2010/12/pleasure-pain-wheat-and-psychopharm.html​

 

So if I take 3mg melatonin daily I might see some decrease in t perception? This might make sense as I was taking melatonin nightly and stopped last week and since then have felt my t to be more noticeable and more instances of fleeting t. I'm going to go back on it and see what happens.

 

Geez @jazz you sure do come up with "definitive" research in stunning fashion. Great stuff above, cutting to the chase of once again, how complex and involved tinnitus is. Changing my 'perception' of T is not that much of a warm and fuzzy as finding something that would 'stop it'. Not sure my perception could change much more at current volume and reactivity, except if totally out of it c/o 3 or 4 glasses of wine, etc. No prescription needed.

Oh well...Back to the drawing board. Zimichael

 

@Rube Yes, I think it helps. NAC helps too. I'm not sure how long you've had tinnitus. These supplements might be most effective early on. That said, I've taken melatonin nightly and it does help me sleep, and, I believe, helps with my tinnitus the next day. I've found both supplements (melatonin and NAC) useful. Neither has eliminated my tinnitus, but both have helped turned down the volume. (I just wish they were a cure!)

@Zimichael Actually, alcohol either attenuates or exacerbates tinnitus. Unfortunately, I'm the latter. Wine and beer generally make me loud.

 

FWIW I've been taking LDN on and off for a couple months. It does... something. Tends to spike me, actually, but then if I back off it for a couple days it will be quieter than usual? So, basically like taking morphine in reverse, which isn't surprising given the chemistry.

I don't have much more conclusive than that to say. But it is interesting.

 

What was your dosage?

 

@linearb, I presume you're not taking LDN anymore? Would LDN be a good thing for someone without an autoimmune disorder?

 

@DebInAustralia, I'm also considering to take Naltrexone, especially since Prof. Dirk De Ridder prescribes it to so many. Not sure about the dosage though.

 

How exactly does Naltrexone work for tinnitus?

 

The study implies that it more so affects the emotional response to tinnitus rather than its actual perception. Higher doses show better results. Unfortunately the full text is hidden behind a paywall. So other than what is available on the .gov site the information will cost $42.00.

 

LDN can drive down TNF-alpha = neuroinflammation.

 

0.5 - 4.5mg. Start low.

 

Does Dr. De Ridder still give this drug to tinnitus patients?

 

Yes he still recommends it.

I'm still not in a fabulous place with my tinnitus.

Still considering LDN or Naltrexone.

Conundrum since I've read conflicting reports on it helping vs. spiking tinnitus on low and high doses.

A doctor has suggested that taking LDN might actually activate NMDA receptors, which might explain why some people report their tinnitus spikes on it.

I only know of 3 people (there are probably others) who have improved on LDN/ Naltrexone.

Any others tried it?

 

Do you recall your doses?

Did you ever try Naltrexone at higher doses?

 

Hi @DebInAustralia -- So sorry to hear how things continue to be difficult for you. I just ran across an article on Glycine last night. It mentions NMDA receptors, and it appears to me it has the potential to help some people's tinnitus. I'm going to order some today.

L-GLYCINE: THE BRAIN, THE GUT, THE TISSUES

In the Brain & Nervous System

In the brain and nervous system, L-glycine acts as an inhibitory neurotransmitter. Glycine tends to induce a sedative or inhibitory effect, while also being capable of improving mood and cognition. It may be effective for convulsions and seizures (1), as well as to promote relief from pain, insomnia and headaches.

High dose glycine have been shown to control OCD symptoms (2). In a double blind, placebo-controlled trial, high doses of L-Glycine demonstrated an ability to improve symptoms of schizophrenia (5). Glycine has been shown to improve sleep quality (3), as well as significantly improve symptoms that are caused by sleep deprivation (4).

Glycine receptors are found in the hippocampus, along side GABA and glutamate receptors. The hippocampus, part of the limbic system is a central means to processing memory, emotion, and may even be a regulator of the autonomic nervous system. Glycine is a co-agonist of NMDA glutamate receptors, and may possibly compete with glutamate at the receptors.​

EDIT:

I forgot that I ordered Glycine in the past in the form of TMG, which is supposed to be better than simple Glycine. Just did a reorder on Amazon and am looking forward to putting it in my morning tea. Here's an old bookmark I discovered when looking into this again.

TRIMETHYLGLYCINE OR TMG

by Dr. Lawrence Wilson

Research update 11/11/15: I suggest that women only should reduce the dosage of TMG to 1000 mg daily. The research is that we found that some women’s bodies were becoming a little yin on the 3000 mg dosage, even though the product is excellent in its other effects.

Trimethylglycine or TMG is a recent and amazing addition to all nutritional balancing supplement programs. I have recommended it since January 2013. TMG is a vitamin-like substance. It functions as an anti-oxidant, anti-inflammatory, energy booster, methyl donor, and more.

TMG is also called betaine because it was first isolated from sugar beets. It is not the same as betaine hydrochloride, however. I now add it to all nutritional balancing programs. The dosage is up to 1000 mg daily for women and up to 3000 mg daily for men. Children need less, depending on their size...

TMG has an overall parasympathetic effect. TMG seems to help restore balance to the autonomic nervous system, especially in those who are following a complete nutritional balancing program. This may be one of its most important benefits.

Hair mineral analyses reveal that about half the population has an autonomic nervous system imbalance that I call sympathetic dominance. It means their sympathetic or fight-or-flight nervous system is “on” too much of the time. This is very damaging for anyone’s health. A supplement of TMG can help reverse this imbalance, and thus contribute greatly to healing. For more on this important topic, read Sympathetic Dominance on this website.
​

 

I have tried Glycine. Never helped me.

I'd be concerned about trying it again given its ability to open the NMDA ion channels.

 

No, and definitely not.