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RELEASED: Initial Results of COMT-inhibition Study conducted by Dr. Abraham


David S. Kozin

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Dear Community,

The initial results are public.

Dr. Abraham presented the report at the Annual Meeting of the Biological Psychiatry Society earlier this year. I have included a copy of the Abstract in this post and providing a link to Dr. Abraham's additional discussion and graphs at the bottom. My emphasis added, but to restate Dr. Abraham's website: "This study is NOT the gold standard of proof that this approach works. . .These medications are not approved for use in HPPD. Any interest in them should be discussed with your physician."

I know we have discussed COMT, genetic variations and watched the board's discussion move from the serotonin system to the dopaminergic system having originally focused on the GABAergic system. These are not systems locked in single compartments, single receptors and single cell types, but have complex interactions and as you are aware we are just touching the surface of Neural Science and Behavior/Perception. However, the basic discussion was on target: Dr. Abraham hypothesized that inhibition of COMT would reduce symptoms in HPPD. Consequently, COMT inhibitors were tolcapone and Sinemet

Again, these are not approved for HPPD and should only be tried with a clinician. Here is the abstract from the conference:

Catechol-O-Methyl Tranferase Inhibition Reduces Symptoms of Hallucinogen Persisting Perception Disorder

Henry D. Abraham, Psychiatry, Tufts University, Boston, MA

Background: Hallucinogen persisting perception disorder (HPPD) is a poorly understood disorder arising from the use of hallucinogens. It is characterized by continuous visual disturbances which can be lifelong. There is no known treatment. Studies of HPPD patients with qEEG mapping show that the disorder is represented by disinhibition in the cerebral cortex. Inhibition of catechol-O-methyl transferase (COMT) increases inhibition of sensory input in humans carrying the G/G polymorphism. Accordingly, I hypothesized that inhibition of COMT would reduce symptoms in HPPD.

Methods: A single-dose, open label trial of a tolcapone, carbidopa, and L-dopa was conducted in 17 consecutive HPPD subjects. Visual symptoms in each subject were coded on a 0 to 7 Likert scale before, and two hours after, drug administration. A paired Student t-test was used to determine statistical significance.

Results: The mean pre-drug visual symptom score for the entire sample was 4.7 +/- 2.6, compared to the post-drug score of 3.7 +/- 2.8 (P= .001). A post hoc median split of the percent response of each subject was 51% symptom reduction in the upper half of responders compared to 1% in the lower half, suggesting a bimodal sample.

Conclusions: Inhibition of COMT is a novel approach in the treatment of HPPD. The bimodal treatment response is consistent with the action of a functional polymorphism in the COMT gene. Future directions include a double blind, placebo controlled trial of this treatment and a determination of COMT polymorphism in responders and non-responders. Keyword(s): HPPD, COMT, tolcapone, carbidopa, DOPA

(Retrieved from Convention eBook downloaded from: http://www.sobp.org/...?pageid=345267; Kindle Locations 21096-21098. SOBP. Kindle Edition.)

LINK TO Dr. Abraham's Web Page regarding this study: http://amrglobal.pow...atment-for-hppd

Best wishes,

- David Kozin

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Yes, thanks for the report and update. I've tried the Sinemet approach and didn't get any benefit from it. I'm curious about tolcapone though and am wondering if I need both of those medicines for either of them to work.

I see that if Sinemet is to have it's full on desired effect that some peole need the strong COMT inhibitor Tolcapone in order for the Dopamine to be synthesized and reach the brain.

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Yes, thanks for the report and update. I've tried the Sinemet approach and didn't get any benefit from it. I'm curious about tolcapone though and am wondering if I need both of those medicines for either of them to work.

I see that if Sinemet is to have it's full on desired effect that some peole need the strong COMT inhibitor Tolcapone in order for the Dopamine to be synthesized and reach the brain.

Have you tried Tolcapone?

There have been some studies about COMT polymorphisms and actual Parkinson's disease. The conclutions seem to be there is no relationship - two different areas of brain. COMT is the primary 'cleanup' method in the executive center, whereas DAT is the major method in the motor area of the brain (PD). At any rate, HPPD problems are in the cortex (COMT area), not the basal ganglia (PD area).

Wonder if Tolcapone alone would be affective for some? We'll just have to see what kind of trials go on next...

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Have you tried Tolcapone?

There have been some studies about COMT polymorphisms and actual Parkinson's disease. The conclutions seem to be there is no relationship - two different areas of brain. COMT is the primary 'cleanup' method in the executive center, whereas DAT is the major method in the motor area of the brain (PD). At any rate, HPPD problems are in the cortex (COMT area), not the basal ganglia (PD area).

Wonder if Tolcapone alone would be affective for some? We'll just have to see what kind of trials go on next...

I have a sympathetic doctor who I think would prescribe Tolcapone if we start out slow with it. I might try to get it and let you guys know how it goes.

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What's better Entacapone, Stalevo, or Tolcapone? .......anybody know?

Tolcapone is the strongest

I have a sympathetic doctor who I think would prescribe Tolcapone if we start out slow with it. I might try to get it and let you guys know how it goes.

That is the key. Liver enzymes raise in proportion to dose. Watch both and see how it goes.

Perhaps ask your doc if you can get a COMT Polymorphism test.

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COMT Yeah, COMT is an entity (enzyme) hanging around post-synaptically and if you take an inhibitor of COMT it prevents (partially) the metabolism of neurotransmitters in the L-dopa/Dopamine/Norepinephrine chain of in vivo biosynthesis.

In other words COMT inhibitors targets upping concentrations of these neurotransmitters by preventing metabolism of

L-Dopa and monoamines (particularly catecholamines).

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So where do we go from here?

Well, when someone feels like doing a formal study, gets some funding, gets some people to do it, then they will collect more formal results. Then if these formal results look interesting, then debates, and more studies will follow. If these look good, then some practices will introduce the treatment. And it may spread from there.

Give it at least 20 years ... perhaps less if there is money to be made. There are a lot of if..then..if..then..if... before "approved for use in HPPD" Welcome to the world of medical progress. Amazing when you realize this is one of the biggest breakthroughs since use of Klonopin.

The most significant thing at the moment is your doctor may help consider helping you now. Note Dr A's statement "Any interest in them should be discussed with your physician." -- the opening has now been made.

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The research is there ........but is not directly connected to HPPD.

The some total research is Dr A tried these 2 meds on 20 people with HPPD and 1/3 got help with there symptoms. The logic behind the trial was that with people that have COMT gene polymorphisms, increasing dopamine in the cerebral cortex via dampening the breakdown of dopamine inhibits sensory input.

Beyond this, what research is there?

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All the research points to the same thing: COMT inhibition = less dopamine-trail metabolism.

But what i am saying is that HPPD is such an esoteric disorder that you would benefit from looking at other studies (perhaps of other disorders), of which there are many.

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I've put in 15 years already.

I can't do another 15 let alone 20.

This isn't a jail sentence as much as it is a death sentence. Not happening. The trial worked on me tremendously but sinemet alone was useless.

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Welcome to the club Hope---i've had the visual stuff for 15 years and other stuff (dp, anxiety, hard hallucination, depression and/or quasi-mental illness) probably 50-100% of the time.

I've had people drug me a least 2 times (probably more). I've had to drop out of 2 schools. I am surrounded by, in a small town, a tight community of somewhat sociopathic medical peoples (evil, somewhat incompetent, egotistical, god-playing). [doctors, doctors assistants, nurses, psychopharms, psychologists, therapists, pharmacists, powerful community members, rouges, scalliwags, ne'er-do-wells, etc] I have spent 6 out the last 8 months on a constant trip equal in power to 1 tab of "shitty" acid [more likely like 2cB or DOB]. .....So suck it up.

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sociopathic medical peoples

This one makes the blood boil. Perhaps because of insurance and legal crap, over the last 2 decades doctors have shifted from being helpful to being lab robots. The days of clinical diagnosis are about gone. Soon a vending machine will replace doctors ... and of course have even less empathy in helping people. If the computer program does have a standard protocol - too bad for you ... perhaps your not ill even. If there is no treatment protocol for HPPD then apparently HPPD doesn't exist.

To illustrate: Lymes disease. It has become common in the Northeast. Yet the only blood tests for it have high rates of false negative. Some doctors have treated a patient anyway with good results - then they get sued by the insurance company for false claims and treatments.

Another actual example: A couple both have signs of infection. The guy goes in, they run some labs and yup, its a common VD. Doc gives med to the guy. But he won't give meds to the partner unless they come in (and pay), have labs (and pay), and test positive. If they get a false negative, then they cycle goes on and on and on...

This blatant stupidity is now consuming the medical system, at least in U.S.A. What a depressing situation ... just in time for Universal [Non-]Health Care to begin here. A good idea to fill a need but the solution is becoming empty. Talk about polishing the brass on the Titanic.

More madness: A couple years back, 2 issues of the same magazine reported this about pharmacists. First issues: They are going to be replaced by vending machines. Later issue: There is a shortage of pharmacists so this is a great profession to send your kids to college for.

This is one reason why we need to try to solve our own problem with HPPD. And to seek out the very few docs who at least try.

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  • 2 months later...

Well I can attest for at least a two hour period I came to be 99.9999% normal all thanks to this board and dr. Abraham. I spent most of that time crying tears of joy.

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