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looking for substitutes to dexedrine

gib65

Bluelighter
Joined
Apr 2, 2010
Messages
58
Hello,

I'm on dexedrine. I'm experiencing tolerance. My doctor an I are trying to work out a regimen that will reduce the tolerance as much as possible, including possibly trying different drugs. My current approach is to alternate between different drugs on different days of the week. I've found that if I take the dexedrine two days in a row, then give myself a 5 day rest, I seem to avoid the tolerance. However, 2 days a week is hardly enough to deal with my ADD symptoms, particularly at work where I need it the most. So as an example of alternating between drugs, I'll take caffeine pills on the remaining days of the week. Caffeine can help with ADD symptoms but it's not recommended by doctors (and I find it has mixed results). It also makes me feel like crap on the second and third day--jitters, feelings of uneasiness, feeling worn out--and the withdrawal on the weekend is just awful (tired and depressed). So I'm continuing to search for other substitutes.

Ephedrine seems to be a viable candidate. I just tried 8mg this morning. Didn't have an effect. Then I tried 16mg after lunch today. After an hour, I felt the onset--bit more alert, more focused--but didn't last long--started to come down after another hour. According to erowid, I should be able to bump it up to 24mg, maybe even 32mg, for the "common" dosage. Maybe I'll try that tomorrow.

In order to overcome tolerance to dexedrine, I would need a medication that acts as a stimulant in terms of concentration, sharp/quick thinking, alertness, and also mood enhancement (more on this below), and its mechanism of action would have to be something other than dopamine receptors (and most likely norepinephrine receptors as well). Dexedrine works by flooding the synaptic gap with dopamine (and to a lesser extent norepinephrine). Tolerance builds up from the dopamine receptors on the recipient neuron reducing in number in order to adjust for the excess amount of dopamine. Therefore, I would need a drug that works on different receptor types, thereby giving the dopamine receptors a break so that they can recuperate their numbers.

An example of a drug combination that DOESN'T work is alternating between dexedrine and methylphenidate (another ADD med). They both increase the amount of dopamine (and norepinephine to a lesser extent) in the synaptic gap but by different means, so it does no good to switch from one to the other in order to get around dopamine tolerance (I've tried it).

I'm going to talk to my doctor about atomoxetine. Atomoxetine works on norepinephrine receptors instead of dopamine receptors (but then again, dexedrine and methylphenidate also work on norepinephrine receptors but to a much lesser extent). However, atomoxetine takes time to have its effect (two to three weeks) so it may not be the kind of drug one can simply "swap out" when one becomes tolerant to another drug. And if one becomes tolerant to atomoxetine, one can take a break from it for 5 days to a week, but then would one have to start over again? Then again, maybe the fact that it requires so long to come into effect means that one would be much less likely to develop a tolerance.

I also want to note that what I'm looking for is not so much an ADD med, but a medication that targets at least these three symptoms: cognitive deficiencies (slowness, mistakes, non-responsiveness), fatigue, and depression. <-- These are the three struggles I deal with in my life. These are a common set of symptoms when it comes to ADD, but because ADD is so variegated, I don't want to put what I'm trying to accomplish in terms of ADD. Putting it in terms of cognitive deficiencies, fatigue, and depression narrows down the focus and makes it much less likely that people will misunderstand what exactly it is I'm trying to target. This also makes it clear that if there are drugs that work to ameliorate certain symptoms but not others (say atomoxetine helps with the cognitive deficiencies but not the fatigue or depression--I don't know, haven't tried it), then people can make suggestions on meds that target ONLY depression or fatigue (to be supplemented with the meds that work on cognitive deficiencies). Asking strictly for ADD meds might miss these. Dexedrine and methylphenidate have been the only drugs so far that have helped with all three of these symptoms. Caffeine helps put me in a better mood, but only the dexedrine and methylphenidate have actually made me feel confident, and given me a constructive attitude (as in I'm far more prone to react to problems constructively, believing that I can overcome them with the right effort and approach, rather than worrying and complaining about how my problems will be the end of me). The confidence also helps a lot with the social anxiety (which I kinda lump together with the depression because depression and anxiety tend to go together) whereas caffeine tends to heighten anxiety. I understand this to be a direct effect of an increase in dopamine (the "feel good" chemical). I'm told that atomoxetine heightens focus and attention by a different means--by stimulating the "danger" system in the brain, which can raise alertness and focus--which sounds to me like it might be an unpleasant experience (though if it acts on norepinephrine receptors, which act similar to dopamine receptors, this may not be true). But suppose atomoxetine worked for me--at least in terms of the cognitive deficiencies--then I might be able to supplement it with something like kratom, a mild opiate, in order to deal with my mood. That's sort of an example of what I mean by supplementary drugs that you might want to recommend.

Any suggestions and/or advice are welcome.
 

Perforated

Moderator: SLR, DC
Staff member
Joined
Sep 28, 2019
Messages
8,949
I cannot offer advice, but I am curious whether your presumed tolerance to Dexedrine diminishes its effectiveness for ADD symptoms specifically (I know you have two other categories of need). My psychiatrist insists that genuine ADHD patients do not become tolerant of Dexedrine or other stimulants (as far as lessening their ADHD symptoms goes. Most patients (he says) never go past the max dose of 30 mg per day for years.
 

negrogesic

Moderator: BDD, OD
Staff member
Joined
Jul 21, 2002
Messages
9,382
Location
Negronesia
For context could you first quantify what "building tolerance" means in terms of milligrams of d-amphetamine( ie, how much are you taking and how this tolerance is manifesting?
 

gib65

Bluelighter
Joined
Apr 2, 2010
Messages
58
I'll answer both of you at once. I've experienced tolerance effects after a week of taking 30mg of dexedrine a day (20mg in the morning, 10mg after lunch). Tolerance to me means I am no longer feeling any effects--like I feel exactly the same as I do when I'm not on any drugs at all. When I asked my GP how I can measure whether the meds are working or not, he said it's usually based on self reports--as in, you know it's working if it feels like it's working--and it don't feel like it's working.

I had a psychiatrist say the same thing your psychiatrist said, Atelier: he never heard of dexedrine not working. And he thought it was all in my mind, like I just believed it wasn't working. But when I'm depressed half the time and finding it difficult to stay awake in the afternoon, I gotta think those effects are real. Not to mention the fact that withdrawal symptoms start to come on later in the day.

I do get the impression I'm a really odd case. Almost no one I've come across reports the same difficulties with tolerance as what I'm experiencing. I experience the same thing with other drugs, caffeine in particular. After 3 days of drinking coffee, it completely looses its effect (to the point where not even drinking loads more coffee has any effect--like I've reached a tolerance ceiling). My best friend who's been drinking coffee for years says "I can still get a kick out of it."

One consideration I had was that it's not a receptor deficiency kind of tolerance, but a metabolism kind of tolerance. What I mean is, maybe it's my metabolism learning to be really, really efficient at cleansing my body so that after several days of taking dexedrine, it learns to remove it from my body almost immediately after I consume it. This is where my experiment with switching between dexedrine and methylphenidate comes in. I went on 70mg/day of methylphenidate for a week (35mg in morning, 35mg after lunch). It was great at first but then after a week, completely lost it's effect. Then I switched to dexedrine (20mg in morning), no effect even on the first day. Did that for a week, then went back on the methylphenidate. No effect. Knowing that it takes a week for me to get over the tolerance of either drug, one would think that if this was a metabolism thing, one week without dexedrine should force my body to have to get used to the dexedrine again before it develops a tolerance. Same with the methylphenidate. But if this is a receptor deficiency thing, the results of my experiment make perfect sense. Both drugs work by increasing the amount of dopamine in the brain, which would build up a dopamine receptor deficiency, and switching from one drug to the other wouldn't get around this. So for me, that eliminates the metabolism theory of tolerance. But I'm not a doctor so I don't know if I'm conducting or interpreting these experiments correctly.
 

falsifiedhypothesi

Moderator: BDD, OD, Music
Staff member
Joined
Feb 22, 2014
Messages
3,758
Location
Detroit MI
I only skimmed the post so apologies if this has been mentioned, but adrafinil seems to work decent for some people. Its kind of a novel stimulant.
 

gib65

Bluelighter
Joined
Apr 2, 2010
Messages
58
I only skimmed the post so apologies if this has been mentioned, but adrafinil seems to work decent for some people. Its kind of a novel stimulant.

Thanks for the suggestion, falsifiedhypothesi, but based on what I read on adrafinil, it's a dopamine reuptake inhibitor, which means it won't work as a substitute to the dexedrine:

gib65 said:
In order to overcome tolerance to dexedrine, I would need a medication that acts as a stimulant in terms of concentration, sharp/quick thinking, alertness, and also mood enhancement (more on this below), and its mechanism of action would have to be something other than dopamine receptors (and most likely norepinephrine receptors as well). Dexedrine works by flooding the synaptic gap with dopamine (and to a lesser extent norepinephrine). Tolerance builds up from the dopamine receptors on the recipient neuron reducing in number in order to adjust for the excess amount of dopamine. Therefore, I would need a drug that works on different receptor types, thereby giving the dopamine receptors a break so that they can recuperate their numbers. [/qoute]
 

necropolis

Bluelighter
Joined
Apr 10, 2020
Messages
41
Location
Colorado
Let me start off by saying that I am not qualified to offer medical advice, but I can say that your situation seems unusual to me (I have ADHD and take generic immediate-release Dexedrine at the exact same dose level you mentioned earlier [20mg AM / 10mg PM], and I have never had a complete loss of efficacy over almost a decade of use). Some tolerance may develop due to down-regulation of dopamine receptors, but as has been mentioned most ADHD patients do not lose effectiveness for focus and concentration when the medication is used at prescription-level dosages. I can understand loss of effect from taking hundreds of milligrams a day, but not at the standard 20-40mg most people are on. Since it sounds like you are not overusing the drug, I don't understand why you are experiencing such a loss of effect. It must be very frustrating.

Several years ago, I noticed a slight loss of effect - not being able to concentrate as well and not feeling as motivated as usual, and my psychiatrist decided to have me rotate the Dexedrine with 37.5mg of phentermine. I would take the phentermine for 2-3 days, then switch off for 2-3 days of amphetamine. This seemed to work well for me, but it sounds like another stimulant is not what you are looking for.

The only other drugs I can think of that might provide some relief are venlafaxine (Effexor) and milnacipran. Effexor can be problematic in terms of side-effects and withdrawal effects. Those two might provide some help with depression and energy level, but they could never replace a true stimulant in terms of effect.

Another possibility is to take an NMDA antagonist for a short time (1-2 weeks). Keep in mind that this is pure speculation on my part though - I know that NMDA antagonists reduce tolerance to opioids, but I'm not sure if the same applies for stimulants. I'm also not talking about tripping out here - only a fraction of the dissociative dose should be sufficient. In the case of dextromethorphan maybe 60-90 mg/day would be plenty. Like I said though, not sure whether this would work or not.

Hope that you get it resolved one way or another. I know firsthand how frustrating dealing with ADHD and depression can be.
 

negrogesic

Moderator: BDD, OD
Staff member
Joined
Jul 21, 2002
Messages
9,382
Location
Negronesia
Avoid atomoxetine, its awful stuff.

Cyclazodone by the way is an excellent alternative to d-amphetamine. In some ways I prefer it as it lacks that awful comedown than d-amphetamine has. It can be purchased online with some resourcefulness (don't ask how though).

Ephedrine could be used in a pinch, but you'll likely need 50mg/day (25mg BID).

I must say questions start forming in my mind when i hear someone took 20mg of d-amph with absolutely "no effect", particularly from someone without a significant tolerance. It had zero effect, really?
 

negrogesic

Moderator: BDD, OD
Staff member
Joined
Jul 21, 2002
Messages
9,382
Location
Negronesia
Ephedrine - just ordered some. It's OTC

Youll need alot. I used to 100mg a day for a while. Dont do that. 50mg is pretty strong. Avoid if you have had heart problems or heart disease. Has more peripheral side-effects than some amphetamines (ephedrine is one hydroxyl group away from methamphetamine, otherwise identical).

Methamphetamine is simply a product of the reduction of the hydroxyl group ephedrine. Some fat woman name ephedrine underwent gastric bypass surgery and had become the thin piece of ass named methamphetamine, and the before and after photos are amazing
 

gib65

Bluelighter
Joined
Apr 2, 2010
Messages
58
necropolis said:
Let me start off by saying that I am not qualified to offer medical advice, but I can say that your situation seems unusual to me (I have ADHD and take generic immediate-release Dexedrine at the exact same dose level you mentioned earlier [20mg AM / 10mg PM], and I have never had a complete loss of efficacy over almost a decade of use). Some tolerance may develop due to down-regulation of dopamine receptors, but as has been mentioned most ADHD patients do not lose effectiveness for focus and concentration when the medication is used at prescription-level dosages. I can understand loss of effect from taking hundreds of milligrams a day, but not at the standard 20-40mg most people are on. Since it sounds like you are not overusing the drug, I don't understand why you are experiencing such a loss of effect. It must be very frustrating.

Indeed it is. And I don't understand it either. I'm just going on theories. Like you, I'm not a doctor, and my theories could be all wrong. Might not be tolerance at all, but something else going on in my body. That's why I'm working with my doctor to figure this out. Might have to see a specialist.

necropolis said:
...my psychiatrist decided to have me rotate the Dexedrine with 37.5mg of phentermine...The only other drugs I can think of that might provide some relief are venlafaxine (Effexor) and milnacipran...Another possibility is to take an NMDA antagonist for a short time...In the case of dextromethorphan maybe 60-90 mg/day would be plenty...

That's a great list of meds, necropolis. I'll be sure to research them.

negrogesic said:
Avoid atomoxetine, its awful stuff.

Oh? Do tell.

negrogesic said:
Cyclazodone by the way is an excellent alternative to d-amphetamine.

Great! Another one to add to the list.

negrogesic said:
Ephedrine could be used in a pinch, but you'll likely need 50mg/day (25mg BID).

I've been trying ephedrine the past couple days. I tried 24mg this morning then again in the afternoon. Seems perfect for me. A nice steady pick-me-up that really helps me stay alert and engaged in my work. No jitters or nasty side effects (not yet anyway). The come down feels nice and easy too. Research tells me it works (indirectly) on specific norepinephrine receptors. While dexedrine also works on norepinephrine receptors, it's main mechanism of action is dopamine receptors, so ephedrine *might* still be a candidate for a substitute. It also works specifically on alpha and beta receptors. While I have no idea what that means, it sounds like it targets specific norepinephrine receptors only, and *maybe* not (all) the ones that dexedrine targets. We'll see.

negrogesic said:
I must say questions start forming in my mind when i hear someone took 20mg of d-amph with absolutely "no effect", particularly from someone without a significant tolerance. It had zero effect, really?

There were times when, yes, it really felt like zero effect. Other times, it felt like there was (maybe) a minor threshold effect... but these are times when I don't know if I'm really feeling something or I'm just telling myself I'm feeling something. If it is something, it sure doesn't last for more than an hour, which is still a problem. If it's not enough to at least get me out of the negative moods and the fatigue, it's still a problem. And the sharp, focused thinking is definitely not there either.

But look, negrogesic, I really don't feel like going on a tangent trying to convince anyone that I'm telling the truth. If you don't believe me, that's fine, but please let's not get side tracked. I do appreciate your recommendations in regards to alternative medications, but I'd prefer to stick to that. Not that I'm against tangents, just not that one. Thanks.
 

tweakerguy

Bluelighter
Joined
Aug 3, 2005
Messages
1,173
Location
Mobile Alabama
Methamphetamine is simply a product of the reduction of the hydroxyl group ephedrine. Some fat woman name ephedrine underwent gastric bypass surgery and had become the thin piece of ass named methamphetamine, and the before and after photos are amazing

She is one spicy latin lover 🥵
 
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