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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by Michael Bell on May 10, 2004, at 23:37:54
I just have a few questions about benzo + stim combos:
1) What type and doses of benzo and stim are you using?
2) Does time of day for dosing affect efficacy?
3) Is there any herb, amino acid or med that you've tried which helps prevent tolerance to the stims?
4) Does addition of an SSRI potentiate prosocial effects?
5) If drug holidays are the only way to prevent tolerance to stims, what do you suggest I take in the meantime to lessen the comedown effect?
Thanks.
Posted by Ame Sans Vie on May 11, 2004, at 6:28:37
In reply to For AME and all benzo+stim users!, posted by Michael Bell on May 10, 2004, at 23:37:54
Hiya Michael! LTNS! :-)
> I just have a few questions about benzo + stim combos:
>
> 1) What type and doses of benzo and stim are you using?Klonopin (Roche brand only) 8mg/day -- 2mg 6AM, 2mg noon, 2mg 6PM & 2mg HS.
Adderall (immediate-release) 60-90mg/day -- 30mg 6AM, 30mg noon & 30mg PM (if needed).
> 2) Does time of day for dosing affect efficacy?
Not so much with the Klonopin, and here I stress again, this is assuming *Roche-brand* Klonopin (with the perforated "K"). The 3mg-2mg-3mg dosing schedule I used with Teva clonazepam was a bit uneven, and didn't address my issue of nighttime restless legs and bruxism or morning stiffness. Being able to divide the dose of Klonopin into four equal, evenly spaced doses (including the one before bed) has worked just great.
> 3) Is there any herb, amino acid or med that you've tried which helps prevent tolerance to the stims?
I've been using Delsym (dextromethorphan polistirex, a sustained-release preparation of DXM) to prevent amphetamine-tolerance as long as I've been taking them. So that would be about 8-9 months of use without breaks, and the proof is in the pudding. :-)
I haven't developed any tolerance whatsoever to any of the drug's effects. The dose started at 30mg/day (of the XR formulation), but an extra 30mg capsule later in the day was added onto that after a few weeks because they seemed to wear off too quickly for me. I stayed on that until a couple months ago when I switched to the immediate-release formulation, which I find lasts about eight hours per dose (quite surprisingly!), with a come-up beginning at approximately T+0:15 hours post-dose, a pronounced effect at T+1:00 pursuant, the peak at T+2:00 through T+7:00, followed by a gentle comedown which ends about T+9:00. The only difference I find between the IR and XR formulations of the drug is actually that the IR form lacks the mid-dose sluggishness and consequent "second-wind". So one dose at 6AM *really* kicks in at 8AM, beginning to wear off at 1PM; taking the second dose at noon times everything just perfectly. If I'm planning on making rounds of the bars with friends at night or practicing/playing a gig with my band, I just pop an extra 30mg in the early evening as needed.
But back to the Delsym -- I used to take a full teaspoon of the 12-hour suspension twice daily (that's equivalent to 15mg Robitussin Maximum Strength Cough every six hours). This dose completely prevented any development of tolerance and *may* have even allayed some of the nastier stim side effects by antagonizing some excitatory neurotransmission via glutamate et al. For six weeks now though I've been taking Prozac at 40mg daily, which (along with its ultra-long-half-life metabolite, norfluoxetine) is among the most potent inhibitors of cytochrome P450 IID6 (aka debrisoquine 4-hydroxylase), along with quinidine and paroxetine. CYPIID6 is responsible for the metabolism via O-demethylation (removal of the methyl group at the sixth position in the structure) of dextromethorphan, which primarily acts upon PCP2 and sigma receptors, to the potent NMDA antagonist dextrorphan (DXO; the dextroratory form of the opioid levorphan, which is about equipotent to morphine). Thus I now take twice as much Delsym to ensure a more normal ratio of DXM to DXO in the blood. My doctor and all reseach I've done has assured me that this is perfectly safe (i.e. not nearly a dose sufficient to cause Olney's lesions, etc.). I would use another NMDA antagonist like Emenda (memantine HCl) if it were available to me, even if simply to avoid the simple carbohydrates in the syrup, but Medicaid will only cover three prescriptions monthly now that I've turned 21. I may, on the other hand, finally put my lab scale to good use and order pure dextrorphan tartrate from Sigma-Aldrich (0.5 grams = $63.30) so as to avoid the unnecessary PCP2/sigma activation associated with DXM. Another chemical I'm interested in is Merck, Sharpe and Dome Inc.'s (+)-MK-801 hydrogen maleate (dizocilpine hydrogen maleate), for which the Sigma-Aldrich "Cell Signalling and Neuroscience" catalog provides the following synopsis: "Highly potent and selective non-competitive NMDA receptor antagonist that acts at the NMDA receptor-operated ion channel as an open channel blocker. Inhibits behavioral sensitization to psychostimulants and ethanol." The cost is prohibitive, though -- $43.10/5mg. A more plausible idea may be any one of the following:
Ifenprodil tartrate salt (alpha-(4-Hydroxyphenyl)beta-methyl-4-benzyl-1-piperidineethanol tartrate salt) -- "NMDA antagonist acting at the polyamine site; neuroprotective agent; alpha-adrenergic central and peripheral vasodilator; alpha-2-adrenergic receptor ligand."
Arcaine sulfate salt (1,4-Diguanidinobutane sulfate salt) -- "Potent antagonist at the polyamine site of the NMDA receptor."
7-Chlorokynurenic acid (7-Chloro-4-hydroxyquinoline-2-carboxylic acid; 7-Cl-KYNA) -- "Potent NMDA receptor antagonist; antagonizes the strychnine-insensitive glycine site of the NMDA receptor; prevents neurodegeneration produced by quinolinic acid."
5,7-Dichlorokynurenic acid (5,7-Dichloro-4-hydroxyquinoline-2-carboxylic acid) -- "Potent excitatory amino acid receptor antagonist; active at the strychnine-insensitive glycine binding site of the NMDA receptor."
d-3-Methoxy-N-methylmorphinanhydrobromide -- "Allosteric antagonist at NMDA-controlled ion channels; antagonist at voltage-dependent channels."
Pentamidine isethionate salt (1,5-Bis(p-amidinophenoxy)pentane bis(2-hydroxyethanesulfonate salt)) -- "Neuroprotective; inhibits constitutive nitric acid synthase in the brain; NMDA glutamate receptor antagonist. Antimicrobial against 'Pneumocystis carinii'."
Also important, I feel, is protection from neurotoxic levels of homocysteine -- I take quite a few vitamin/mineral/amino acid/herbal supplements (and here's a link to a post of mine on PB-Alt with a detailed account -- http://www.dr-bob.org/babble/alter/20040418/msgs/341617.html; my Rx dosings have changed a bit, but the rest is the same), but B-12 and its cofactors are undoubtedly most important for this (not to mention avoidance of neurotoxic excitatory substances such as monosodium glutamate and aspartame).
> 4) Does addition of an SSRI potentiate prosocial effects?
I'd have to say that Prozac certainly does, but I hesitate to lump it in with the SSRIs due to its added noradrenergic/dopaminergic effects (and the fact that it's the *only* SSRI that hasn't caused a single side effect for me).
> 5) If drug holidays are the only way to prevent tolerance to stims, what do you suggest I take in the meantime to lessen the comedown effect?
My pdoc has had success in all of his amphetamine-treated patients by supplementing with DXM ever since I brought it to his attention, and also in a couple chronic pain patients -- one taking high-dose Avinza with Roxicodone for breakthrough pain, and one on the 100µg/hr Duragesic patch with Dilaudid for breakthrough pain. This doesn't surprise me at all, considering there are several products down the pipeline that combine opioids with DXM, one being Morphidex.
His patients receiving methylphenidate have not, for the most part, responded as well to DXM augmentation though. He tells me that he's currently toying around with ideas in these particular patients. The most promising, he says, is Wellbutrin XL taken consistently at the max dose tolerated along with a low dose of Strattera during the week, and a higher Strattera dose on the weekends for stim holidays.
Sorry this was so long -- just wanted to cover all my bases!
~Michael
Posted by Michael Bell on May 12, 2004, at 19:23:13
In reply to Re: For AME and all benzo+stim users!, posted by Ame Sans Vie on May 11, 2004, at 6:28:37
Thanks for all the great info, Ame. I'll see if I can put it to use.
Posted by Cressida on May 13, 2004, at 0:52:53
In reply to Re: For AME and all benzo+stim users! » Ame Sans Vie, posted by Michael Bell on May 12, 2004, at 19:23:13
My lord that is a lot of information - someone has done his homework. I take methylphenidate 10mg three times a day. I was taking 60mg of Strattera once a day, but because it is so costly @ almost $200 per bottle of sixty that I chose to go back to using classic Ritalin. I never really noticed much of an affect from Strattera, but I wonder if it would help smooth or lessen the irritating ups and downs that's associated w/ Ritalin? Or perhaps the combination is more effective than either taken alone? The doctor prescribing the Ritalin isn't a psychiatrist but an endocrinologist who is primarily treating my essential hypertenstion. I haven't seen a psychiatrist in a year. Since I'm using methylphenidate again and experience depressive and anxiety symptoms in addition, I scheduled an appointment with a pdoc for later this month. I think I'll discuss the option of polypharmacy with the doctor. I would like to take something to treat both the side effects of Ritalin and my dysphoric depressive-anxious state. Hopefully there is a solution or partial fix.
Posted by Cressida on May 13, 2004, at 1:14:20
In reply to Re: For AME and all benzo+stim users!, posted by Cressida on May 13, 2004, at 0:52:53
As an aside, I've suffered depressive moods and anxiety since before the addition of Ritalin, which was made 5/7/04 - this past Friday. *R* actually lifts the depression, which is a bonus. Unfortunately but not surprisingly it causes nervousness. Furthermore, it brings on a *dull* or *flat* affect, but at the same time somewhat mood-elevating, that's hard to believe; I mean, it is a stimulant.
Posted by chemist on May 13, 2004, at 23:50:09
In reply to Re: For AME and all benzo+stim users!, posted by Ame Sans Vie on May 11, 2004, at 6:28:37
i am impressed....what is your background...a caveat, though, about dilaudid: do you really think this is a drug that needs mentioning on this board? if you are as in the know as you appear to be, i would think this is off the radar....but kudos nonetheless for securing a Sigma-Aldrich catalog.........all the best, chemist
Posted by Viridis on May 14, 2004, at 1:36:49
In reply to Re: For AME and all benzo+stim users! » Ame Sans Vie, posted by chemist on May 13, 2004, at 23:50:09
What's the significance of the Sigma catalog? They'll send them to anyone (I have stacks of them and receive 2-3 a year). You can't order any controlled substance from them without extensive documentation. Sigma is extremely strict about this (believe me, I know!). They sell LSD, MDMA, PCP, cocaine, etc., but only to researchers with tons of goverment paperwork who keep meticulous records of every milligram used and are subject to regular inspections. This isn't a negative post, just a statement that reputable chemical companies are extremely careful about what they sell and to whom.
Posted by Ame Sans Vie on May 14, 2004, at 7:15:47
In reply to Re: For AME and all benzo+stim users! » Ame Sans Vie, posted by chemist on May 13, 2004, at 23:50:09
> i am impressed....what is your background...
Thank you -- my background is simply that of a 21 year-old former agoraphobe. I never stepped out my front door for two years straight, which obviously left me with a lot of time on my hands to research my conditions a little more in-depth than many people have the time to.
> a caveat, though, about dilaudid: do you really think this is a drug that needs mentioning on this board? if you are as in the know as you appear to be, i would think this is off the radar....but kudos nonetheless for securing a Sigma-Aldrich catalog.........all the best, chemist
I don't see anything wrong with mentioning hydromorphone here, especially as I utilized it merely as supporting evidence that DXM and other NMDA antagonists really *do* work to prevent tolerance from developing. Many people are still skeptical, for good reason seeing as there isn't much information available to the layperson concerning these phenomena without having at least an elementary grasp of the intricacies of human neurobiology/neurochemistry. The references to the chronic pain patients were simply to help validate what I was saying.
On a side note, I'd like to say that while I've been busy for a week or two and haven't posted as often as I usually have been for the past two years, I have taken notice of your expansive knowledge of relevant topics here and would like to extend a belated "welcome!" and let you know that you've quickly become a valuable asset to this board.
Take care,
~Michael
Posted by chemist on May 14, 2004, at 7:22:40
In reply to Re: For AME and all benzo+stim users! » chemist, posted by Ame Sans Vie on May 14, 2004, at 7:15:47
...well, it's not all that expansive, believe me.....thanks for the welcome, and all the best, chemist
Posted by Ame Sans Vie on May 14, 2004, at 7:47:16
In reply to Re: For AME and all benzo+stim users!, posted by Cressida on May 13, 2004, at 0:52:53
> My lord that is a lot of information - someone has done his homework.
Oh, it ain't work -- I find the entire subject simply fascinating. I study this crap for fun, lol. Oh, and to learn as well, I suppose. ;-)
> I take methylphenidate 10mg three times a day. I was taking 60mg of Strattera once a day, but because it is so costly @ almost $200 per bottle of sixty that I chose to go back to using classic Ritalin.
Wow, I haven't tried Strattera myself (one of maybe a half-dozen psych meds about which I can say that) so had no idea how expensive it is. No matter how many times I hear about these ridiculous costs, it's always a new experience of enragement that envelops me when I learn how much some people are having to pay for trial after trial after trial of drugs that don't work. <sigh> I'm 21... is my disillusionment/quarter-life crisis showing? lol
> I never really noticed much of an affect from Strattera, but I wonder if it would help smooth or lessen the irritating ups and downs that's associated w/ Ritalin? Or perhaps the combination is more effective than either taken alone?
It's certainly possible (probable, even?) that there would exist some synergism between methylphenidate and atomoxetine. However, as methylphenidate is primarily an inhibitor of dopamine reuptake and atomoxetine inhibits primarily reuptake of norepinephrine, I don't personally see it as being a great choice for augmentation of Ritalin's effects (if it is truly those effects you are after). It seems to me that something dopaminergic would be more effective. Perhaps amantadine (which I coincidentally am going to start taking today for smoking cessation) would be a good choice, as it promotes release of dopamine and, according to some texts, is a dopamine reuptake inhibitor in its own right. A small dose of a dopamine agonist may be helpful, but these are probably out of the question considering the cost associated (worst case scenario being one of the newer, better DA-agonists, Requip -- can cost up to $1,000 monthly). Amantadine, OTOH, is dirt-cheap. I personally found a small rural pharmacy here that quoted my $3 for 30 x 100mg of amantadine and $5.75 for 30 x 350mg carisoprodol; Walgreens and Eckerd both wanted something in the $40 range altogether.
> The doctor prescribing the Ritalin isn't a psychiatrist but an endocrinologist who is primarily treating my essential hypertenstion. I haven't seen a psychiatrist in a year. Since I'm using methylphenidate again and experience depressive and anxiety symptoms in addition, I scheduled an appointment with a pdoc for later this month. I think I'll discuss the option of polypharmacy with the doctor. I would like to take something to treat both the side effects of Ritalin and my dysphoric depressive-anxious state. Hopefully there is a solution or partial fix.
Seeking out a good pdoc is a major, major step in the right direction -- the answers are out there if you look hard enough, and I'm confident you'll find something that ameliorates your current dilemma(e).
> As an aside, I've suffered depressive moods and anxiety since before the addition of Ritalin, which was made 5/7/04 - this past Friday. *R* actually lifts the depression, which is a bonus. Unfortunately but not surprisingly it causes nervousness. Furthermore, it brings on a *dull* or *flat* affect, but at the same time somewhat mood-elevating, that's hard to believe; I mean, it is a stimulant.
Yeah, Ritalin is an odd creature. I'm always hearing (mostly from the sensationalist media) that methylphenidate is nothing short of "kiddie-cocaine" as it operates in a very similar fassion. Well if that's true, then I guess the absolute euphoria I used to get from using coke was just placebo in response to doing an illicit drug, lol; I mean, my experience with Ritalin was *exactly* the same as you describe yours. The word "nervousness" so much more accurately describes the uneasy Ritalin feeling than "anxiety", which is how I used to refer to it. It really didn't cause me to be anxiety-laden, but rather I was rendered jittery, tense and more than a bit asocial. It just made me want to keep to myself and be in my own head constantly -- it was like chemically-induced autism.
Have you tried any amphetamine drugs? Since we both experienced methylphenidate in the same manner it seems, you may fare as well on the amphetamines as I have. They've given me my life back. As opposed to methylphenidate, they are true, well-rounded stimulants, IMHO. Not to mention the gentler comedown, ability to prevent tolerance via NMDA antagonism, and greater history of cardiovascular safety.
Keep me/us updated!
~Michael
Posted by chemist on May 14, 2004, at 23:58:18
In reply to Re: For AME and all benzo+stim users! » chemist, posted by Viridis on May 14, 2004, at 1:36:49
> What's the significance of the Sigma catalog? They'll send them to anyone (I have stacks of them and receive 2-3 a year). You can't order any controlled substance from them without extensive documentation. Sigma is extremely strict about this (believe me, I know!). They sell LSD, MDMA, PCP, cocaine, etc., but only to researchers with tons of goverment paperwork who keep meticulous records of every milligram used and are subject to regular inspections. This isn't a negative post, just a statement that reputable chemical companies are extremely careful about what they sell and to whom.
it was an inside joke....those of us who disdain organic synthesis as being a cookie-cutter discipline often refer to the organic texts as catalogues, be it sigma, fluka, etc....i apologize for the inside reference, and admire ame's insight....all the best, chemist
This is the end of the thread.
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