GABA-mediated Inhibition Might Be Effective Treatments for Tinnitus, says Dr. Tzounopoulus

Toward a Cure for Tinnitus

Toward a Cure for Tinnitus

Thanos Tzounopoulos, Ph.D., assistant professor of otolaryngology and neurobiology at the University of Pittsburgh School of Medicine, discusses the findings of a Pitt-led tinnitus study. The study, published in Proceedings of the National Academy of Sciences (April/May 2011), found that tinnitus is the result of under-inhibition of key neural pathways in the brain's auditory center.

More to follow.....

 

Tinnitus Caused by Too Little Inhibition of Brain Auditory Circuits, Study Finds
ScienceDaily (Apr. 18, 2011) — Tinnitus, a relentless and often life-changing ringing in the ears known to disable soldiers exposed to blasts, unwary listeners of too-loud music and millions of others, is the result of under-inhibition of key neural pathways in the brain's auditory center, according to scientists at the University of Pittsburgh School of Medicine in the Proceedings of the National Academy of Sciences. The discovery, which used a new technique to image auditory circuits using slices of brain tissue in the lab, points the way to drug development and effective treatment for a condition that currently has no cure.

Prior research has shown that auditory circuits in the brain are more excitable in tinnitus sufferers, but until now it has not been clear whether that is due to hyperactivity of excitatory neural pathways, reduced activity of inhibitory ones, or a bit of both, explained senior investigator Thanos Tzounopoulos, Ph.D., assistant professor of otolaryngology and neurobiology, Pitt School of Medicine.

"This auditory imbalance leaves the patient hearing a constant ringing, buzzing or other irritating noise even when there is no actual sound," he said. "Tinnitus drowns out music, television, co-workers, friends and family, and it profoundly changes how the patient perceives and interacts with the world."

According to the American Tinnitus Association, tinnitus is the most common service-connected disability among veterans of the Iraq and Afghanistan conflicts. Of the 50 million who have experienced it, 16 million have symptoms severe enough to seek medical attention and 2 million tinnitus sufferers are unable to carry out day-to-day activities.
To identify what goes wrong in the brain's auditory circuits, Dr. Tzounopoulos' team created tinnitus in a mouse model. While the rodent was sedated, one ear was exposed to 45 minutes of 116 decibel (dB)-sound, equivalent to an ambulance siren. Intense noise exposure is thought to lead to damage in the cochlea, an inner ear structure critical to the neural transmission of sound waves, and clinically undetectable hearing loss.

Several weeks later, the scientists confirmed the exposed mice had tinnitus by conducting startle experiments in which a continuous, 70dB tone was played for a period, then stopped briefly and then resumed before being interrupted with a much louder pulse.
Mice with normal hearing could perceive the gap and, because they were aware something had changed, were less startled than mice with tinnitus, whose ear ringing masked the moment of silence in between the background tones.

The scientists then sought to determine what had gone wrong in the balance of excitation and inhibition of the auditory circuits in the affected mice. They established that an imaging technique called flavoprotein autofluorescence (FA) could be used to reveal tinnitus-related hyperactivity in slices of the brain. Experiments were performed in the dorsal cochlear nucleus (DCN), a specialized auditory brain center that is crucial in the triggering of tinnitus. FA imaging showed that the tinnitus group had, as expected, a greater response than the control group to electrical stimulation. Most importantly, despite local stimulation, DCN responses spread farther in the affected mice.

Dr. Tzounopoulos' new experimental approach has resolved why tinnitus-affected auditory centers show increased responsiveness. After administering a variety of agents that block specific excitatory and inhibitory receptors and seeing how the brain center responded, his team determined that blocking an inhibitory pathway that produces GABA, an inhibitory neurotransmitter, enhanced the response in the region surrounding the DCN in the control brain slices more so than it did in the tinnitus slices.

"That means the DCN circuits are already 'disinhibited,' or blocked, in tinnitus," Dr. Tzounopoulos explained. "We couldn't block inhibition anymore to elevate the evoked response, like we could in the normal brain. And, when we blocked another inhibitory circuit mediated by the neurotransmitter glycine, or when we blocked excitatory pathways, there was no difference in the responses between the groups."

This means that agents that increase GABA-mediated inhibition might be effective treatments for tinnitus, he added. Dr. Tzounopoulos' team is now trying to identify such drugs.

Co-authors of the paper include Jason W. Middleton, Ph.D., and Courtney Pedersen, of the University of Pittsburgh; Taro Kiritani and Gordon M.G. Shepherd, M.D., Ph.D., of Northwestern University; and Jeremy Turner, Ph.D., of Southern Illinois University.
The research was funded by the National Institutes of Health, the U.S. Department of Defense, the American Tinnitus Association, and the Albert and Ellen Grass Faculty Award.

 

THEN AS I WAS RESEARCHING THE GOOD DR. AND HIS FINDINGS, I CAME ACROSS THIS:


Medical Marijuana and Tinnitus

What Is Tinnitus?
Tinnitus is simply described as ringing in the ears. However, tinnitus has multiple levels of severity and can cause other complications. Furthermore, there are several causes of tinnitus. The symptoms of tinnitus include ringing, whooshing, roaring, hissing, chirping, buzzing or roaring in the ears. This can occur with a sensation of other sounds being cancelled out. The sounds are not actually occurring outside of the body but are still perceived by the sufferer of tinnitus.
Tinnitus can be chronic or it can occur only a few times over a lifetime. It can also happen in one ear or in both ears. In some cases, it is a slight sound, causing little discomfort. In other cases, it feels very loud and interferes with normal hearing. Many people experience tinnitus over the course of their lifetimes with no debilitating or long-term complications. Others are disabled by it. Ludwig van Beethoven is a prime example of a person with debilitating tinnitus. Tinnitus can be a symptom of something minor or it can be a symptom of a severe condition such as hearing loss, thyroid conditions, brain tumors and heart disease.
Given the various conditions that can cause tinnitus, there are numerous ways that medical marijuana can help. It can aid in chemotherapy in individuals who have brain tumors causing tinnitus and medical marijuana can help treat thyroid conditions. These are just a few examples of how medical marijuana can get to the root cause of tinnitus. It also appears to treat the symptom itself in some patients. Of course, it will often depend on the cause and potential for other treatment. In some cases, medical instruments like hearing aids and noise generators are the preferred treatment.

Medical Marijuana and Tinnitus

Tinnitus and Medical Marijuana Research
Tinnitus research has conclusively shown that it is a brain problem. Of course, it can stem from problems in the ear. However, it is occurring in the brain. This was proven when people with complete hearing loss, including cutting of the auditory nerve, presented with tinnitus. Therefore, any treatment for tinnitus that does not involve treating complications, underlying conditions and producing sound in the ear must affect the body on a neurological level.
Dr. Thanos Tzounopoulos is a leading researcher in tinnitus. He discovered the plasticity of the auditory brain stem. Put simply, the auditory messages in the brain can "learn" to be more sensitive to certain stimuli. He published his research in 2009. In 2011, he published further research that showed exaggerated activity in the brains of mice with tinnitus. Tzounopoulos has also made breakthroughs in the understanding of the endocannabinoid system, which he finds controls plasticity in the brain. It is also what reacts to medical marijuana. He compares tinnitus to chronic pain and addiction, which also involve plasticity in the brain and are also treated with medical marijuana. While this does not shed light on the precise mechanism by which medical marijuana provides relief for tinnitus, it does show the components of the mechanism.
Thanos Tzounopoulos, Ph.D. is currently on the cutting edge of research in this area. His findings are still relatively new and he is still working on this research, so there may be more information forthcoming about the endocannabinoid system and tinnitus soon. He is currently working as an assistant professor at the University of Pittsburgh and is part of their auditory research group.

Tinnitus Complications and Medical Marijuana Research
As mentioned above, some of the conditions that cause tinnitus can be treated with medical marijuana. Additionally, some of the complications of tinnitus can also be treated with medical marijuana. These complications include anxiety, insomnia, depression, irritability and difficulty concentrating. Doctors may prescribe medical marijuana to treat these complications, particularly insomnia, anxiety and depression. Medical marijuana may also be used to treat conditions that can co-occur with tinnitus, resulting in relief from both tinnitus and the other conditions. One example of such a condition is PTSD. Soldiers often experience tinnitus and hearing loss resulting from explosions. They are also among the most common PTSD patients. There is research supporting the use of medical marijuana for all of the abovementioned symptoms and conditions. Therefore, it has potential as a multipurpose drug.

 

HIS WORK IS DEMONSTRATED IN THIS COLORFUL PDF DOC:

http://pittmed.health.pitt.edu/Winter_2011/static.pdf

 

Calin -
A few months ago, I was listening to National Public Radio. They were interviewing a musician who had severe tinnitus. It almost sounded like medicinal marijuana has cured his "T". The interview was a bit confusing.

On the otherhand, I've read the marijuana can increase "T". Haven't tried the stuff since college myself.

 

I remember back in the day smoking and then falling asleep. I gave it try recently in the hopes maybe it would help the T and possibly that it would at least help me sleep if nothing else. The first time I smoked way too much. This is not your dad's weed. I tried it again, smoking just a tiny amount. For me it had no effect on the T. And actually prevented me from sleeping. Made me kinda paranoid too. I really wanted to like it but alas, it's not for me. Another disappointment. I have friends who use it for sleep with great results.

 

Hi Karl,

I am fairly new to T at still just under a month. I used to smoke pot back in highschool but my wife enjoys her weed from time to time. I decided to give it a shot the last few days to see how it was. For me this stuff is a miracle so far. I couldn't say the ringing goes away but I am able to separate the sound and ignore it almost (Hard to explain).. It also allowed me to sleep fine the last 3 days.

Although I am hoping I don't have to smoke weed every day to go to sleep it has helped this last couple of days and I am sure I will be doing it from time to time until hopefully I am cured. Still optomistic about that...

 

We did some work on this a month or so ago, here's the thread, my brain still aches as I looked up every possible edible component to increase GABA, Picamilion works for Markku, however were all different!!!

Mock Turtle if your reading this Did Picamilion work for you???

I have had a busy Promotion at work here in UK, then another one overseas in May so have not had chance to try it

Nootropics can enhance Gaba, we all respond different to these.

https://www.tinnitustalk.com/thread...s-tinnitus-perception-in-an-animal-model.271/

 

Hi Joe, I have been on Picamillion (2x150) a day for the last 7 days and haven't noticed any improvements. I will keep going for a month or so to see if I notice anything.

 

Jim -

Yep: Paranoia. That's how I remember the experience.

Back in the 1970's, I do remember getting the munchies and going to a local subshop, called "Avogadro's Number". This was way before Subway Sandwich shops. Avogadro's had mattresses laying all over the floors. (Think of the cleanliness. Yuck!) Everyone was stoned, eating their sandwiches, stretched out on these mattresses. Perhaps a few of them even had "T".

Interesting posts about this subject. My wife was going to kill me if I started smoking weed.