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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 5 of 5. This is the beginning of the thread.
Posted by Larry Hoover on January 6, 2003, at 9:45:56
There is an entirely novel regulatory pathway under study, based on research into the effects of cannabis on mood. The natural brain chemical which binds to the "cannabinoid receptor", known as anandamide, can be potentiated by blocking the enzyme responsible for its degradation, something like blocking the enzyme monoamine oxidase. Blocking this anandamide-degrading enzyme has similar effects to benzodiazepines in rodents.
Modulation of anxiety through blockade of anandamide hydrolysisSatish Kathuria1, Silvana Gaetani1, Darren Fegley1, Fernando Valiño1, Andrea Duranti2, Andrea Tontini2, Marco Mor3, Giorgio Tarzia2, Giovanna La Rana4, Antonio Calignano4, Arcangela Giustino5, Maria Tattoli5, Maura Palmery6, Vincenzo Cuomo6 & Daniele Piomelli1
The psychoactive constituent of cannabis, 9-tetrahydrocannabinol, produces in humans subjective responses mediated by CB1 cannabinoid receptors, indicating that endogenous cannabinoids may contribute to the control of emotion. But the variable effects of 9-tetrahydrocannabinol obscure the interpretation of these results and limit the therapeutic potential of direct cannabinoid agonists. An alternative approach may be to develop drugs that amplify the effects of endogenous cannabinoids by preventing their inactivation. Here we describe a class of potent, selective and systemically active inhibitors of fatty acid amide hydrolase, the enzyme responsible for the degradation of the endogenous cannabinoid anandamide. Like clinically used anti-anxiety drugs, in rats the inhibitors exhibit benzodiazepine-like properties in the elevated zero-maze test and suppress isolation-induced vocalizations. These effects are accompanied by augmented brain levels of anandamide and are prevented by CB1 receptor blockade. Our results indicate that anandamide participates in the modulation of emotional states and point to fatty acid amide hydrolase inhibition as an innovative approach to anti-anxiety therapy.
Posted by jonh kimble on January 6, 2003, at 17:19:56
In reply to Novel treatment for anxiety: just published, posted by Larry Hoover on January 6, 2003, at 9:45:56
Wow. This is very interesting. Any potential meds available for human use on the horizon? Also, I read somewhere that the chemical amantadine(?) works closely with dopamine. Any thoughts?
Posted by utopizen on January 6, 2003, at 19:49:27
In reply to Re: Novel treatment for anxiety: just published, posted by jonh kimble on January 6, 2003, at 17:19:56
> Wow. This is very interesting. Any potential meds available for human use on the horizon? Also, I read somewhere that the chemical amantadine(?) works closely with dopamine. Any thoughts?
>20 years, like everything else. Which means I'll be 40. Fat and 40. My life will be over by then anyhow. Thanks, pharmaceutical companies. Thanks!
Posted by Larry Hoover on January 7, 2003, at 9:17:27
In reply to Re: Novel treatment for anxiety: just published, posted by jonh kimble on January 6, 2003, at 17:19:56
> Wow. This is very interesting. Any potential meds available for human use on the horizon?
As Utopizen said, that would be many years off. However, if you get into a clinical trial (also years off), you could "test the waters" sooner than anyone else.
>Also, I read somewhere that the chemical amantadine(?) works closely with dopamine. Any thoughts?
Amantadine is an interesting substance. It's one of the few drugs which acts as a potent antiviral agent, and is particularly effective against a class of viruses that includes the Borna virus. About a decade ago, psychiatric disorders were thought to be linked to infection by this virus, and amantadine showed some remarkable results in *some* patients with treatment-resistant depression. Amantadine is also a dopamine agonist, which is to say, it activates some dopamine receptors as if dopamine was present, when it is not present.
Research into Borna infection and mood disorders didn't really give any concrete results, but people are still looking at amantadine treatment.
Bipolar Disord 2000 Mar;2(1):65-70
Amantadine in depressive patients with Borna disease virus (BDV) infection: an open trial.Dietrich DE, Bode L, Spannhuth CW, Lau T, Huber TJ, Brodhun B, Ludwig H, Emrich HM.
Department of Clinical Psychiatry and Psychotherapy, Medical School Hannover, Germany. dietrich.detlef@mh-hannover.de
OBJECTIVE: Originally introduced into pharmacotherapy as an antiviral compound, amantadine was shown to also have multiple pharmacological eftfects on the central nervous system. In addition. only a few studies reported on certain antidepressive properties of amantadine. This effect was highlighted by the discovery of its antiviral effect on Borna disease virus (BDV), which is hypothesized to be an etiopathogenetic factor to subtypes of affective disorders. Therefore, the therapeutical use of amantadine in BDV-infected depressive patients was investigated. METHODS: In this open trial, amantadine was added to antidepressive and or mood-stabilizing compounds treating BDV-infected depressed patients (n = 25) with bipolar or major depressive disorders. Amantadine was given twice a day (100-300 mg/day) for a mean of 11 weeks. Antidepressive treatment response was measured on the Hamilton rating scale for depression (HAM-D) and/or with an operationalized diagnostic criteria system (OPCRIT: version 3.31). Virological response was measured by expression of BDV infection parameters in blood samples. RESULTS: The overall response rate of the amantadine augmentation in the BDV-infected patients with regard to depressive symptoms was 68% after a mean of 2.9 weeks of treatment. Bipolar I patients improved faster and did not show any following hypomania. In addition, the decrease of depression tended to correspond with the decrease in viral activity. CONCLUSION: Amantadine appears to show a remarkable antidepressive efficacy in BDV-infected depressive patients. The antidepressive effect in this open trial appeared to be comparable to standard antidepressives, possibly being a result of its antiviral effect against BDV as a potentially relevant etiopathogenetic factor in these disorders.
Posted by jonh kimble on January 8, 2003, at 22:04:29
In reply to Re: amantadine » jonh kimble, posted by Larry Hoover on January 7, 2003, at 9:17:27
Ya I meant anandamide, but strangely enough, what I said made pretty good sense. I was just reading up on amantadine, and perhaps this was a freudian slip... or for those that are realistic, an occasional mistake that made sense.
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