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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by anita on September 18, 2000, at 8:54:43
Hi fellow amateur psychopharms,
I am confused about the connection between glutamate and dopamine as it pertains to depression. I have read in past posts that, simplistically, decreasing glutamate decreases dopamine, and increasing glutamate increases dopamine. However, I've also read that decreasing glutamate transmission increases dopamine release in a part of the brain I can't remember but I think is part of the so-called limbic system. And that glutamate agonists are potential meds for schizophrenia.
I am curious from a practical standpoint, as Lamictal, which supposedly decreases glutamate, has improved my mood swings and severe depressive episodes, yet dopamine enhancers improve my depression dramatically, albeit only for a time.
Any info that can shed light on this issue would be great, highly technical stuff included.
Thanks,
anita
Posted by AndrewB on September 23, 2000, at 13:28:17
In reply to Glutamate and dopamine confusion!, posted by anita on September 18, 2000, at 8:54:43
Anita,
Reading this post, your post to Scott and your other past posts- I can only shake my head. Something causes the dopaminergic action of meds to poop out on you and cause a rebound effect after awhile.
You ask about glutamte and dopamine. This brings up an interesting point and also points to a med that you may want to look into.
Ketamine is an NMDA antagonist. The NMDA is one of two receptors for glutamate.
Ketamine has been shown to have an antidepressant effect (Antidepressant effects of ketamine in depressed patients, Berman, Biol Psychiatry 2000, Feb 15).
Furthermore, and possibly related to this, ketamine directly inhibits reuptake of dopamine and enhances the spontaneous release of dopamine. Ketamine also has an indirect dopaminergic effect due to the prevention of hippocampal inhibitory effect on the nigrostriatal dopaminergic system by the blockade of NMDA receptors and L-glutamate transmission.
Note that ketamine is a scheduled drug and is abused in higher doses. It also has the legitimate use for anesthesia. But in much smaller doses it can be effective as an arousal agent and mood enhancer. Dr. Goldstein frequently uses ketamine with good results in the form of nasal spray for his CFIDS patients.
One person who uses ketamine in this form describes it as a mild stimulant, antidepressant, analgesic and cognition enhancer.
I would like to try ketamine nasal spray. I have to get my hands on some of it first though.
AndrewB
Posted by anita on September 23, 2000, at 20:18:29
In reply to Re: Glutamate and dopamine confusion!, posted by AndrewB on September 23, 2000, at 13:28:17
Andrew,
Yes, I shake my head too! Ketamine sounds interesting -- if you find out a way to get it, please let me know. I do already take Lamictal, a glutamate antagonist, which I feel has helped my mood swings tremendously. I am about to try amantadine, but I do not have high hopes for it.
I'm still a little confused about glutamate, tho -- if it is an inhibitory neurotransmitter, wouldn't it decrease dopamine, and even more by increasing GABA? Would that negate the NMDA-related increase?
anita
> Anita,
>
> Reading this post, your post to Scott and your other past posts- I can only shake my head. Something causes the dopaminergic action of meds to poop out on you and cause a rebound effect after awhile.
>
> You ask about glutamte and dopamine. This brings up an interesting point and also points to a med that you may want to look into.
>
> Ketamine is an NMDA antagonist. The NMDA is one of two receptors for glutamate.
>
> Ketamine has been shown to have an antidepressant effect (Antidepressant effects of ketamine in depressed patients, Berman, Biol Psychiatry 2000, Feb 15).
>
> Furthermore, and possibly related to this, ketamine directly inhibits reuptake of dopamine and enhances the spontaneous release of dopamine. Ketamine also has an indirect dopaminergic effect due to the prevention of hippocampal inhibitory effect on the nigrostriatal dopaminergic system by the blockade of NMDA receptors and L-glutamate transmission.
>
> Note that ketamine is a scheduled drug and is abused in higher doses. It also has the legitimate use for anesthesia. But in much smaller doses it can be effective as an arousal agent and mood enhancer. Dr. Goldstein frequently uses ketamine with good results in the form of nasal spray for his CFIDS patients.
>
> One person who uses ketamine in this form describes it as a mild stimulant, antidepressant, analgesic and cognition enhancer.
>
> I would like to try ketamine nasal spray. I have to get my hands on some of it first though.
>
> AndrewB
Posted by SLS on September 23, 2000, at 20:43:34
In reply to Re: Glutamate and dopamine confusion! » AndrewB, posted by anita on September 23, 2000, at 20:18:29
Personally, I feel that Lamictal possesses pro-dopaminergic properties that are different than, and in addition to its purported ability to reduce extracellular glutamate levels. Its mood-stabilizing properties and its antidepressant properties may not be related, although perhaps synergistic for some.
Anita, that you feel better with Lamictal does not surprise me given your responses to dopaminergic agents. I wish I had this all figured out to be able to help you. I am curious if you have ever combined Effexor with Wellbutrin or tried an MAOI.
You'll find something. Just keep snooping. You're on the right track.
- Scott
Posted by AndrewB on September 24, 2000, at 9:33:35
In reply to Re: Glutamate and dopamine confusion! » AndrewB, posted by anita on September 23, 2000, at 20:18:29
Anita,
I do not have a clear understanding of these things. But a few comments. Glutamate is considered excitatory and counters GABA. Also, lamotrigine, when combined with ketamine, increases the mood elevating effect of ketamine (Attenuation of the neuropsychiatric effects of ketamine with lamotrigine; Arch Gen Psychiatry 2000 Mar; 57(3)). BTW, I think I have found a source for Ketamine. I will try to remember to let you know if I receive it.
Best wishes,
AndrewB
Posted by Cam W. on September 24, 2000, at 10:47:45
In reply to Re: Glutamate and dopamine confusion!, posted by AndrewB on September 24, 2000, at 9:33:35
Andrew - Ketamine can be not fun. Known as "Special K" at raves it can cause hallucinations, as well as a sense of wellbeing. Also the anterograde amnesia can be embarrassing or even harmful. It is also used in animal and human models to 'induce' psychosis (they don't let researchers use PCP on humans anymore). Ketamine binds to the PCP site on the NMDA receptor, blocking the calcium flow (I believe, but am not sure) or, in other words, disinhibiting dopamine transmission.
I was reading a textbook on hallucinations and there was an incidence of ketamine being used in a string of sexual assaults. Seems these guys were pretending ketamine to be cocaine and getting women blitzed and then taking them "home". The women realize what is happening at the time, but have no memory afterward. Also, enough ketmine causes catatonia, so these women couldn't move while they were assaulted. The way that the sickos were caught is that one woman who was assaulted was drinking a lot of cranberry juice (the real, bitter stuff, not the cocktail kind) and this probably increased the excretion of the ketamine (probably due to acidification of the urine). She was able to identify her attackers, where the other women had no memory of the attacks (other than the obvious assault to their bodies).
If you use ketamine, be careful (IMHO) - Cam
Posted by AndrewB on September 25, 2000, at 1:26:31
In reply to Re: Glutamate and dopamine confusion! » AndrewB, posted by Cam W. on September 24, 2000, at 10:47:45
Thanks for the warning Cam. I've read about some of the scary side effects- psychosis, amnesia, disassociation.....
I'm interested in ketamine in a form highly diluted with saline solution used in a nasal spray. I'm of the idea that ketamine, like amisulpride, has two faces; very different effects at low and high doses.
I don't want to get high. I don't smoke, drink or take recreational drugs. I consider my mind too fragile to be taking such joy rides.
AndrewB
This is the end of the thread.
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