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
poster:Ame Sans Vie
thread:345604
URL: http://www.dr-bob.org/babble/20040510/msgs/345638.html