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MDPV as SSRI augmentation?

R

rnd.id.

Bluelighter
Joined
Jan 1, 2006
Messages
179
Hello!

The background of this silly idea: Sertraline has been effective for my depression in some regards, but I'm still experiencing strong fatigue and lack of initiative. A DRI could conceivably be effective against this 8)

So, I've been thinking about adding low, daily doses of MDPV (which I've never tried, but assuming it is similar enough to other stims). I seem to remember from the other threads that MDPV's half-life is suitable for this.

Thoughts about tolerance development at low doses? Any other ideas or warnings? Thanks :)

rnd.id.
 
MDPV is completely untested as a long-term theraputic in humans, so the idea of taking it chronically sounds a tad sketchy. It seems that methylenedioxy-substituted compounds will always be more toxic than their naked amphetamine homologues, due to dopamine-like oxidation after the methylene spacer is cleaved. Also (at least in my opinion, others will likely vary), MDPV is a horrible "feeling" drug, with loads of peripheral stimulation, headaches and nausea. In terms of psychostimulant effects, I found it to be dirtier than methylphenidate and less effective for ADHD. If you want a little dopaminergic action without the "nastiness" of MDPV, I would try modafinil, methylphenidate or bupropion first. If you are experiencing a lot of fatigue and drowsiness, modafinil (like 200-300mg qAM) might be the winner, due to its long half-life.
 
Thanks, some good points. Are there any studies on the possible MDMA-like neurotoxicity? (not that I don't think your cleavage theory is reasonable.)

I thought bupropion had among the worst peripheral per central stimulation ratios, but I'm not sure why I think that, might be totally wrong :) About the MPh, ADHD prescriptions for adults are not very common here, as far as I'm aware :(
 
rnd.id. said:
I thought bupropion had among the worst peripheral per central stimulation ratios, but I'm not sure why I think that, might be totally wrong :)
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Not when taking it as prescribed. Of course I think you do have to overdose it for it to act anything like a stimulant, in which case nasty side effects are a skipped heartbeat and a misfired synapse away.

Doctors actually prescribe bupropion in tandem with selective serotonin reuptake inhibitors at therapeutic dosage not infrequently.

Sorry this doesn't address your question exactly- just didn't want anyone thinking that taking 150mg of bupropion is more dangerous than doing crystal meth or whatever.
 
rnd.id. said:
Hello!

The background of this silly idea: Sertraline has been effective for my depression in some regards, but I'm still experiencing strong fatigue and lack of initiative. A DRI could conceivably be effective against this 8)

So, I've been thinking about adding low, daily doses of MDPV (which I've never tried, but assuming it is similar enough to other stims). I seem to remember from the other threads that MDPV's half-life is suitable for this.

Thoughts about tolerance development at low doses? Any other ideas or warnings? Thanks :)

rnd.id.
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Not a good idea. You will end up abusing MDPV, no matter how much you think you wont


Doctors actually prescribe bupropion in tandem with selective serotonin reuptake inhibitors at therapeutic dosage not infrequently.
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Quite a bit to reverse the 'chemical castration' that SSRI's can produce. Now if you're wanting a dopaminergic for sex, then MDPV might just be the thing you're after =D
 
IMO the somewhat short MDPV duration is problematic, honestly. It could work OK if you don't get a lot of peripheral effects from it -- personal reactions seem to vary quite a bit on this note.

If you would still like to add a dopaminergic to the SSRI, it may be more useful to get the transdermal methylphenidate thingy, which offers a degree of control.

Your difficulties with volition and drive (and emotion I imagine) not being helped (or being worsened) by the SSRI are not unusual at all.
 
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toe: Hmm, I see. Maybe I'll try the bupropion some time.

fastandbulbous said:
Not a good idea. You will end up abusing MDPV, no matter how much you think you wont
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Yeah, that's a likely outcome... as I said, it's just a silly idea :) But I really was thinking about how to decrease fatigue, not how to get high (which is so futile with stims).

grue: hmm, I wouldn't say the sertraline has actually decreased volition, though it's hard to compare directly to the baseline state. The occasional euphoria upon dose increases was probably rather helpful.

About the duration: I vaguely remember something like "6-8 hours", which would seem to be just right for wake->on/sleep->off.

hugo24: As f'n'b already replied, that one apparently isn't so suitable if the ordered life that is being planned includes some sort of regular sleep ;)

melange: Barely... tried modafinil two times or so. Nothing unambiguously above placebo. Also tried adrafinil (supposedly metabolized to modafinil), which also didn't clearly exceed placebo at regular doses, but for some reason kept me up for a day when I ate a lot of them...
 
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low doses of MDPV....ROTFLMAO.

and what F&B said in first post. modra/adra inmnsho being adrenergics sans DA effects are dirtier and, um, useless.

desoxy is like having a Tazzie Tiger as opposed to a poodle as a pet or an ICBM vs pellet gun. not for kids. or those who know time.
 
nanobrain: To my knowledge the real mechanism of action of adra/moda is poorly understood yet.

*threadjacks his own thread* - but since it was mentioned here:

I've been on adrafinil for a few days, 900-1200mg/day. I noticed an increased inclination towards debating stuff and some fancy language use (of course it didn't actually increase my abilities, I just feel a bit more in the mood to use them). This could be placebo or coincidence, of course.

Attention is also altered; I'm not yet sure whether positively or negatively.

Oh, and some increase in heart rate I think; thought these substances were not supposed to do that?
 
Responsibility and garbled yet precise impersonation of homeopathic treatment? O and dont forget extra help ;)
 
nanobrain said:
low doses of MDPV....ROTFLMAO.

and what F&B said in first post. modra/adra inmnsho being adrenergics sans DA effects are dirtier and, um, useless.
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Modafinil and friends aren't really adrenergic in the sense most people think, AFAIK. They don't produce a lot of peripheral stimulation or HR/BP problems, I don't think.

Their activity is very complex. DA is obviously involved.

Dopaminergic-adrenergic interactions in
the wake promoting mechanism of modafinil
by
Wisor JP, Eriksson KS.
Molecular Neurobiology Laboratory,
SRI International, 333 Ravenswood Avenue,
Menlo Park, CA 94025, USA.
Neuroscience. 2005;132(4):1027-34

ABSTRACT

Adrenergic signaling regulates the timing of sleep states and sleep state-dependent changes in muscle tone. Recent studies indicate a possible role for noradrenergic transmission in the wake-promoting action of modafinil, a widely used agent for the treatment of excessive sleepiness. We now report that noradrenergic projections from the locus coeruleus to the forebrain are not necessary for the wake-promoting action of modafinil. The efficacy of modafinil was maintained after treatment of C57BL/6 mice with N-(2-chloroethyl)-N-ethyl 2-bromobenzylamine (DSP-4), which eliminates all noradrenaline transporter-bearing forebrain noradrenergic projections. However, the necessity for adrenergic receptors in the wake-promoting action of modafinil was demonstrated by the observation that the adrenergic antagonist terazosin suppressed the response to modafinil in DSP-4 treated mice. The wake-promoting efficacy of modafinil was also blunted by the dopamine autoreceptor agonist quinpirole. These findings implicate non-noradrenergic, dopamine-dependent adrenergic signaling in the wake-promoting mechanism of modafinil. The anatomical specificity of these dopaminergic-adrenergic interactions, which are present in forebrain areas that regulate sleep timing but not in brain stem areas that regulate sleep state-dependent changes in muscle tone, may explain why modafinil effectively treats excessive daytime sleepiness in narcolepsy but fails to prevent the loss of muscle tone that occurs in narcoleptic patients during cataplexy.
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Also rather interesting, somewhat unrelated though:

Modafinil exerts a dose-dependent antiepileptic effect mediated by adrenergic α1 and histaminergic H1 receptors in mice

C.R. Chena, W.M. Quc, M.H. Qiub, X.H. Xua, c, M.H. Yaoa, Y. Uradec and Z.L. Huangb, c, Corresponding Author Contact Information, E-mail The Corresponding Author
aDepartment of Pharmacology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China
bState Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China
cDepartment of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan
Received 5 April 2007; revised 18 June 2007; accepted 19 June 2007. Available online 30 June 2007.

Abstract

Epilepsy is characterized by neuronal hyperexcitability and hypersynchronization. Disruption of electroencephalographically (EEG) synchronized epileptiform discharges may be a possible therapy for epilepsy. In the present study, to clarify the role of EEG desynchronization on epilepsy, we investigated the effect of modafinil, a potent wake-promoting substance with EEG desynchronization activity, on epilepsy in mice and clarified the receptors involved in the suppression of seizure caused by maximal electroshock (MES) and pentylenetetrazol (PTZ) kindling models. Modafinil given at 22.5, 45, and 90 mg/kg, i.p. significantly decreased the incidence of tonic hindleg extension in MES seizure models, and protected against PTZ-induced convulsive behaviors in a dose-dependent manner. In addition, modafinil at 180 mg/kg exerted an antiepileptic effect in the MES model; however, at the same dosage it increased the seizure stage in the PTZ-kindling model. The antiepileptic effect in both MES and PTZ models was antagonized by the adrenergic α1 receptor antagonist terazosin, but not by the adrenergic α2 receptor antagonist yohimbine or by dopaminergic receptor antagonists, SCH-23390 (for D1 receptors) and haloperidol (for D2 ones). Pyrilamine, a histaminergic H1 receptor antagonist, counteracted the antiepileptic action of modafinil in the PTZ induced-kindling model, but not in the MES seizure model. Taken together, the present findings indicate that modafinil exerted its antiepileptic effect via adrenergic α1 and histaminergic H1 receptors, and might be of potential use in the treatment of epilepsy.

Keywords: Maximal electroshock; Pentylenetetrazol; Pyrilamine; Seizure; Terazosin


Corresponding Author Contact InformationCorresponding author at: State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China. Tel.: +86 21 5423 7479.
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