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Re: Parnate: weight gain, & the literature - Adam

Posted by Adam on December 15, 1999, at 11:45:04

In reply to Re: Parnate: weight gain, & the literature - Adam, posted by Zeke on December 15, 1999, at 10:26:36

> I am referring to limited, controlled use of entactogens (eg, MDMA) in psychotherapy, in persons where fear and anxiety are roadblocks to insight and expression.

I understand that. I was acting as one of those minions of Satan you referred to above, mostly. This is, I believe, one of the early clinical uses of MDMA (after it lost favor as an appetite supressant), yes?

I think two factors must be considered:
> 1. A protocol of giving the entactogen and several hours later giving an SSRI (and perhaps deprenyl) would aloow for the beneficial effects but minimize possible neurotoxicity. Use of the levo isomer of MDMA appears safer as it excludes delayed damage -- loss of uptake sites. SSRIs may offer no protection from this toxicity, but again is is stereospicific.
> 2. Lack of effective treatment (often) allows for high levels of glucocorticoids (eg, cortisol) which also have documented neurotoxicity. This toxicity however, has been more clearly linked with behavioral deficits and abnormalities.

There are probably all kinds of potential sources of neurotoxicity associated with use of MDMA, and from what I can see, the subject is still open to debate. That significant neurotoxicity even occurs from recreational use is a point of debate, it appears.

> (And you're taking deprenyl right?!!!)

Yes. Um, I'm not sure what this statement means. Perhaps you are referring to this: taking deprenyl means exposure to l-methamphetamine (some similarities to MDMA) and l-amphetamine. To be honest, I find it rather difficult to understand why people, especially on high oral doses of selegiline, don't have more problems than they do. Serotonin syndrome and spontaneous hypertension seem like obvious potential problems, and yet nobody gets these things with high-dose selegiline monotherapy. I read about selegiline, and it seems like the magic molecule. It protects against oxidative stress by upregulating expression of things like superoxide dismutase. It has antipressor properties that not only protect against its own sympathomimetic metabolites, but even other pressor stimuli like tyramine (IF you take it in small doses). People say it enhances memory and sex drive. What doesn't deprenyl do?

> Yet I think you'd agree that the significant toxicity is to 5HT processes, and this seems to occur when MDMA is carried inside the neuron, and thus the protective effect of an SSRI. I susbect that MDMA competes with 5HT for entry so initially there is very little MDMA uptake and damage.
> As for free radical damage, there are MAOis but also other central antioxidants.
I am frankly a bit confused by the things I read about MDMA and how it causes neuron damage. Excitotoxicity? Oxidative stress? Neither, both, other things?

I've seen references to use of deprenyl and SSRIs in protecting against MDMA-induced neurotoxicity. In the clinical setting, use of deprenyl at any dose within the time frame needed to give this supposed protective effect would be a tough sell indeed. Not to say you're wrong. I honestly don't know.

> I think selective MAO inhibitors will be their resurrection. Side effects and interactions are few(er) and rare, and efficacy in depression is being demonstrated. What do you think?

I'm sure they are efficacious. I don't think they will replace the old, non-selective MAOIs, though. The doctors I am working with right now seem rather unimpressed with the RIMAs, and that appears to be the consensus, in this country at least. What excites me is the transdermal delivery system. It gives the benefits of an MAOI with fewer side effects and no dietary restrictions. I'm not certain why this approach isn't being explored with other MAOIs besides selegiline. I think the head of the study I am participating in mentioned something about Parnate, at least, being a little "too toxic" for this, but I'm not sure what that means (skin irritation?) Maybe its just money, since the patents ran out on the big three a long time ago. But other MAOIs could conceivably be developed, maybe some that are more tolerable in general than the older ones, for transdermal delivery too. This is way, way cool if you ask me.




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