Dexamfetamine - extremely tired and no positive effects?

[chris106]

Hey everybody,

I'm relatively new here, and please excuse my bad english...

I started taking prescribed dexamfetamine about a week ago. Before that, I had been taking DL-Amfetamine (also prescribed) for about 2 Months. Now before even that about 4 years MPH, on and off.

MPH as well as DL-Amf had good, though slightly different positive effects on my ADD-Symptoms. But because both also had side effects like dry mouth and "stiff muscles", I wanted to try Dexamfetamine. I thought since it doesn't effect the noradrenaline-system (right word in english?) as much, it should have the positive effects without the side effects.

Now here's the thing: Even after a week-long med pause before starting Dexamf, the first minimal dose of 2mg made me so extremely tired, that I had the urge to lay down in my bed and take a nap, which I did. It has more or less been the same since.
I varied the dose up to 8 mg, but it's allways the same. I also sleep enough, drink enough, and keep an eye on good nutritioun.
I don't even feel like that when I don't take meds at all. Even though I'm also often somewhat tired and unfocused with no meds, it's not even close to the extreme drowsiness I feel when under Dexamfetamine. It's instantly, too - like 30 minutes after taking it. Might as well just knock myself out.

Does anyone have an explanation for that, or maybe even had the same experience? I mean, I was planning to up the dose to 10 mg, to see if it will change in the opposite direction at some point. But frankly, I'm almost too scared now, and I just don't feel well at all when I take it. I didn't get any shit done this week. Under DL-Amf before, it was actually going really well in that regard, minus the minor side-effects it had.

I will definetely stop taking Dexamf in a couple of days, and maybe after a pause go back to DL-Amf. I would just like to now if this odd and atypical effect of Dexamf on me could possibly be a clue as to ADD not actually being the cause of my ADD-Symptoms, but maybe some other disorder?

Thanx in advance, would love to hear from you guys!

 

[hatrix]

Your dose of dextroamphetamine is incredibly low. An average therapeutic dose is more around 20mg. I wouldn't even think you could feel anything from 2mg.

Benzedrine doesn't really seem like anything that would be good for an ADD medication. I'm not sure where you live though it's clearly not in the united states because of the way you spell amphetamine and the fact you're prescribed benzedrine. Do they have Adderall as a prescription medication where you live ? It's a combination of dextroamphetamine and levoamphetamine 75%/25% respectively. It's the probably the best medication for ADD.

 

[chris106]

First of all, thanks for your answer!
Well, you guessed right

I'm from germany, and typically you can just get various forms of MPH as prescription here.
Dl-Amphetamine ( 50% / 50% dextroamphetamine and levoamphetamine, I guess that's what "benzendrine" is?) and "pure" 100% Dextroamphetamine can only be prescribed "off-label", meaning health ensurance won't cover one bit and doctors are often hesitant to prescribe it at all. I get mine as some kind of a water-based mixture that has to be made in the drug-store every time.

Amphetamine has somewhat of a stigma to it here in general, people being worried about neurotoxicity and addiction and all that. I know that's not the case in the US, where it is seen equal to MPH.

However, we sadly don't have Adderall here. We might get "Vyvanse" sometime soon, but that's just a Dextroamphetamine prodrug as well, as far as I know.

By the way, except some minor side-effects DL-Amphetamine (Benzedrine?) worked quite well for me, in even lower comparable doses ( 8mg). It was my understanding that pure Dextroamphetamine is at least twice as potent, so 4mg of that should at least work equally well, which is what confuses me so much....

Why should DL-Amphetamine (Benzedrine?) not be good as ADD medication?

 

[pasha]

Many studies show that insomnia and many other sleep disorders are directly related to dopamine depletion in some cortex's of the brain. If your dopamine receptors are down-regulated/de-sensitized and you abruptly pause use of amphetamines, then dopaminergic transmission will be extremely low causing disruptions in sleep. Once you start your use of amphetamine again dopaminergic transmission returns to 'normal' causing drowsiness and inducing sleep.

Many insomniacs/narcoleptics such as myself can benefit from a low dose stimulant before sleep. At root the cause of your problem, much like me, is caused by dopaminergic abuse. Opioids in my case, and stimulants in yours. The only way to resolve the issue is abstain from dopaminergic use in order for down-regulation/de-sensitization to reverse so when you do use stimulants, you aren't feeding your brain something that it requires in order for you to sleep properly.

If you would like some studies regarding dopamine and sleep I have about a dozen of them I'd be happy to provide.

 

[chris106]

Thank you!

So what you're saying is, I should stop the Amphetamine for some time because I overdid it, so my receptors can downregulate, and then lower doses will work properly again as they are supposed to? Or do you mean that I have to stay away from this stuff alltogether, because it will allways fuel my possible sleeping-disorder?

I've also suspected that I might have some kind of sleep disorder. Me and my doc actually plan to get me tested later this year in an institution where they monitor your sleep and run some tests for about a week ( hell if I know what these are called in english ). So the stimulants where just to "hold me over" till then. Because even to MPH I never quite reacted in a way that someone with actuall ADD would long term, even though I definetely had some good effects from it.

Thanks for you offer too. If you can provide the links, then by any means
However, what I would really be interested in, is if this sleep-dopamine relation works vise-versa, too. I'm asking because I was allways told that i have "breathing pauses" while sleeping (again, don't know the english medical-term). And I've also had those since i was a teen, so way before i was taking MPH or even knew about ADD.
The reason for those could be a physical one, my chin (or lower jaw) is quite far back, and therefore my tongue might block the "breathing-pathways". So could it be, that my sleep disorder causes my ADD symptoms and dopamine dysfunction in the daytime, and not the other way around?

 

[Jabberwocky]

I completely understand why you're sleepy at 2mg - thats not a dose that people with ADHD/ADD should be taking for theraputic benefits as it will do exactly that: put you to sleep!

Personally I take dexamphetamine twice a day, at 20mg in the morning and 20mg in the afternoon. I don't think that you're suffering from overdoing the amphetamines as you have been using it therapeutically i'm assuming and you weren't abusing the medication. Some people will take less, some more. You have to titrate a dose upwards until you find your ideal dose. I suggest you up your dose to around 10-15mg and see how you go with that, and depending on how long it's duration is on yourself, twice a day is the ideal (if you wake up early, say 8am that is).

If i take 5mg of dexamphetamine I get very sleepy and tired. In fact sometimes I even take this dose before I go to bed and I fall asleep much more quickly and easily, and my mind is no longer racing so I also am able to concentrate on sleeping too. I don't find myself wondering off in my mind and all these thoughts racing through my head.

 

[chris106]

Thanx

Sleep-Disorder or no, that's exatly what i will try tonight. ( Or in a few minutes, since it's allready night here overseas )
Maybe I will wake up relaxed for the first time in a long time... Guess I will go with 2,5mg for starters though....
And in the morning I'll take 11 mg and see what that does. Will post results tomorrow, thank you guys so much!
Well, have a nice day everyone, and good night! ^_^

 

[pasha]

Thank you!

So what you're saying is, I should stop the Amphetamine for some time because I overdid it, so my receptors can downregulate, and then lower doses will work properly again as they are supposed to? Or do you mean that I have to stay away from this stuff alltogether, because it will allways fuel my possible sleeping-disorder?

You need to cease amphetamine use so your receptors can up-regulate.

Basically what I'm saying is your brain is lacking a major hormone when you don't have amphetamine, or when I don't have opioids, which is dopamine, which regulates normal sleep. When you give your brain the dopamine via amphetamine, you induce sleep because the lack dopamine that's causing you sleep dysfunction is back in your brain.

The treatment if you do have a sleeping disorder can be chosen by you. You can either abstain from dopamine releasers (stimulants) so your dopamine function can return to normal, causing your sleep to return to normal or you can feed your brain the dopamine via stimulants which is the case in many people with sleeping disorders. You must note though that people with natural sleeping disorders that are not drug induced don't have the luxury of the first option, they're stuck with dopamine dysfunction for life, so you might want to take that into account.

Here are the studies:

[Look at bottom post]

If you need anymore clarification since I'm not the best at explaining let me know and I'll try my best.

 

[Swimmingdancer]

When you give your brain the dopamine via amphetamine, you induce sleep because the lack dopamine that's causing you sleep dysfunction is back in your brain.

A second area of research is into the role dopamine may play in narcolepsy. Administration of L-dopa, a precursor molecules of dopamine, to narcoleptic patients has been shown to improve their vigilance (Boivin & Montplaisir, 1991). Administration of the amino acid L-tyrosine, also a precursor to dopamine, has in preliminary investigation shown similar results (Roufs, 1990). If these findings are confirmed, researchers may conclude that dopamine levels are involved in the disorder.

Haven't had time to read all the links you posted, but that study you posted seems to say the opposite of what you're saying, that raising the dopamine levels decreased sleepiness. Also dopamine antagonists are known to be sedatives. So I am confused. But would like to understand more, as someone with insomnia.

 

[pasha]

If I read most of them properly I'm pretty sure they corroborate what I'm saying.

If a particular study does not, than that's entirely possible as it's dose dependent. For narcoleptics with daytime sleepiness/drowsiness a higher dose of amphetamine will certainly induce wakefulness, for someone with insomnia that's dopamine related such as an ex-opioid/methamphetamine addict a low dose amphetamine will put them to sleep as it will induce dopaminergic activity but not enough adrenergic/dopaminergic activity to cause wakefulness. Decreased daytime drowsiness also allows narcoleptics to sleep at night as that's one of the major issues they face in that sleep during the day causes less sleep at night and vice-versa.

Several opioid/stimulant addicts on this site and many that I know outside of this site tend to experience the exact same thing, there are many threads about amphetamine causing drowsiness in which several users PM'd me for more data, hence why I conjured up all those studies then and now once more. I myself cannot sleep on benzodiazepines but only 5-10 milligrams of adderall.

This is also why sleepiness is mentioned as a side effect on datasheets of many stimulants. You'll find the same connection with most dopaminergic euphoriants such as cannabis. There are definitely other mechanisms that are involved in their drowsiness but dopamine seems to be a major link.

Some of the links are broken, ill keep updating with data:

The debate resides on the demonstration that DA is a substance dramatically related to sleep processes, and not associated exclusively with wakefulness events. In this sense, recent data from literature reveal that REM sleep neural pathways are triggered when D2 dopaminergic receptors are activated on a background of reduced mesolimbic glutamatergic and serotonergic tone. Furthermore, selective lesion of the substantia nigra pars compacta (SNpc) neurons elicits a remarkable disruption of REM sleep. Additionally, the overall mean firing rate of the ventral tegmental area (VTA) neurons, present a large increase in the burst firing during REM sleep episodes. Such evidence prompts us to speculate that dopaminergic neurons present at SNpc and VTA could be consider essential for sleep regulation, in particular for triggering and maintenance of REM sleep, respectively. A clinical corroboration of this hypothesis concerned a study of motor restoration control, observed during REM sleep in Parkinson's disease (PD) patients. We propose that the paradigm of DA is being involved with wakefulness and not sleep regulation is not fully accurate. The premise stated in the current manuscript allegates that DA could present an important participation in both sleep and wake states, and each state may be accounted by differential degrees of dopaminergic modulation. The conclusion drawn from these findings is that DA has significant implications in the sleep regulation, and that particular condition has to be fully considered in respect of treatment and management of PD patients.

Dopamine Antagonists inducing wakefulness:

The effects of the putative dopamine (DA) autoreceptor antagonists cis-(+)-5-methoxy-1-methyl-2-(di-n- propylamino)tetralin, (+)-UH 232, and cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76, on sleep-wake activity, EEG, and motor activity in the rat were studied. Both drugs induced a dose-dependent increase in wakefulness

Dopamine in parkinsons:

l-DOPA medication improved the quality of sleep. Delta sleep was most visibly improved. Also, post-treatment enhancement of the mean delta power over the parkinsonian hemisphere was supported statistically.

The role of dopamine in slow wave sleep control and mechanism of contralateral hemisphere involvement are discussed.

Dopamine agonists in narcoleptics causing dose dependent sleepiness:

Dopamine (DA) traditionally has not been considered a modulator of sleep/wake state in part because of claims that endogenous DA transmission varies little between sleep/wake states. Thus, recent clinical recognition of daytime sleepiness in PD has been met with surprise and has prompted a search for its cause(s).2,3⇓ A decades-long debate as to whether DA participates in behavioral state control—and if it does, what its role(s) might be—has been rekindled. This issue of Neurology includes one study documenting daytime sleepiness with the D2–D3 receptor agonist ropinirole in drug-naïve control subjects4 and three investigating the pathophysiologic basis of like decrements seen in the face of DA deficiency accompanying PD.5-7⇓⇓ In an upcoming issue, a fifth work reports on physiologically defined sleepiness in patients with PD who reported sleepiness, as well as its clinicoetiologic correlates.8 That sleepiness is common not only with D2–D3 agonist use but also with endogenous DA loss is seemingly paradoxical, and this highlights the complexity of the influences of DA on the sleep/wake state.

Anatomy and state-related function of midbrain DA neurons:

The mesocortical, mesolimbic, and mesostriatal systems are the most conspicuous of central dopaminergic pathways,9 and govern cognitive, emotive, and motor behaviors. Midbrain DA neurons have the potential to modulate normal and pathologic thalamocortical neuron excitability and, by inference, the sleep/wake state

Dopamine and circadian rhythms:

These interrelationships are consistent with a common regulatory mechanism governing the sleep/wake and/or rest/activity in plasma catecholamine levels.

Apomorphine induced sleep:

Sleep induction has been studied in humans after the administration of apomorphine, a direct stimulant of the central dopaminergic system. The drug induced sleep and vomiting in healthy volunteers while it had no significant effect on 10 Parkinsonism patients treated for a long period with L-dopa. Apomorphine given to a group of Parkinsonism patients not receiving any specific treatment, and with a lower degree of disease severity, induced vomiting and sleep with a pattern similar to that in healthy subjects. A relationship between the dopaminergic system and sleep induction is suggested.

Dopamine in Mice:

Neuroscientists at Duke University Medical Center working with genetically engineered mice have found that the brain chemical dopamine plays a critical role in regulating sleep and brain activity associated with dreaming.

When dopamine levels were dramatically reduced, the mice could no longer sleep, the scientists said. When dopamine levels were increased, the mice exhibited brain activity associated with dreaming during wakefulness.

The same processes likely occur in humans, according to the researchers. They said the findings give insight into the sleep problems common among patients suffering from Parkinson's disease, a neurodegenerative disorder in which brain cells containing dopamine die or become impaired.

A new study suggests that destruction of significantly fewer dopamine-producing cells could result in sleep problems long before the motor problems become apparent, the researchers said.

Dopamine is a "neurotransmitter" that carries signals from one neuron to another. It is known to control movement, balance, emotion and the sense of pleasure.

Normally, when a signal needs to travel through the brain, neurons release dopamine to transport the signal across the gap, or synapse, between neurons. A kind of protein pump, called a transporter, recycles dopamine back to the neurons to prepare for the next burst of signal.

In studies 10 years ago, Marc Caron, Ph.D., James B. Duke professor of cell biology and a co-investigator in the current study, used the techniques of genetic engineering to produce a strain of mice that lacked this protein transporter. In such transgenic mice, dopamine lingers outside brain cells, stimulating surrounding neurons hundreds of times longer than normal. Caron and colleagues found that when they placed the mice in an unfamiliar environment, such as a new cage, the animals groomed themselves excessively and ran around the cage, mirroring the bizarre behaviors experienced by people with schizophrenia.

The researchers used this same strain of transgenic mice in the current study. They reasoned that both schizophrenia and Parkinson's disease are characterized by imbalances of dopamine in the brain, and that patients with both diseases experience sleep disturbances. So the researchers sought to further manipulate the mice to study the role of dopamine in the sleep cycle.

First, the researchers treated the mice with a chemical that stops the production of dopamine entirely. In fairly short order, the mice had used up their initial supply of dopamine and were running on empty.

The mice became rigid, immobile, and unable to sleep or dream, displaying symptoms similar to those experienced by patients with Parkinson's disease, the researchers said.

The researchers then measured the electrical activity in each animal's hippocampus, the region of the brain known to be involved in emotion and memory, during three major brain states: wakefulness, quiet sleep and dreaming (also known as rapid eye movement sleep). Using electrodes finer than a human hair implanted into individual neurons, the researchers could monitor signals passed among hundreds of neurons in the treated mice. They found a lack of dopamine completely suppressed brain activity and behaviors associated with quiet sleep and dreaming.

To verify that the sleep disturbances were caused by a lack of dopamine, the researchers gave the mice L-dopa, a drug used to increase the levels of dopamine in Parkinson's disease patients. The treated animals regained the brain patterns and behaviors associated with sleep and dreaming, demonstrating the critical role dopamine plays in the sleep-wake cycle, according to the researchers. Further pharmacological testing revealed that L-dopa exerted its effects by docking at a specific site, called the D2 receptor, on the surface of the neurons.

"Sleep disorders may be the first sign of Parkinson's disease," said lead study investigator Kafui Dzirasa, an M.D.-Ph.D. student working in Nicolelis's laboratory.

 

[chris106]

Thanx for the interesting information, chromophobia!

Took 2,5 mg of Dexamphetamine yesterday right before sleep and had no trouble falling asleep. In the morning however, my sleep became uncalm again, but I'm used to that.
I took 11mg after getting up and had a healthy breakfast.

Now I feel somewhat good, definetely not as drowsy as with lower doses. I still feel somewhat weird and sedatet though, as if I'm not quite there. I think the balance of the dopaminergic/ adrenergic system you mentioned above is a key-part, as under MPH as well as under DL-Amphetmaine, which tend to affect both systems, I had much better results. Problem there is that I can't go too high with the doses, since then adrenergic side-effects will become too much. ( My doc says I'm the only one of his ADD Patients who gets these adrenergic side effects when under such comparably low doses of mph)

Maybe some other medication specifically for people with sleep disorder may be better for me, but first I'll have to whait to get my sleeping tested ( speaking of which, what are these institutions where they do that called in english? It's like a special kind of hospital, in german they are called "sleeping-laboratory", that's a rough translation, though )

 

[pasha]

^ In English it's called a sleep study conducted by a sleep technician in a sleep laboratory. I hope you get the issue resolved.

Good luck.

 

[chris106]

Thanx!

 

[Swimmingdancer]

Thanks for explaining more Chromophobia. If I understand correctly, what you are actually saying is that dopamine needs to be in the right balance for proper sleep, not simply that too little dopamine = insomnia and dopamine = sedation; it's more complicated than that; correct?

If I read most of them properly I'm pretty sure they corroborate what I'm saying.

If a particular study does not, than that's entirely possible as it's dose dependent. For narcoleptics with daytime sleepiness/drowsiness a higher dose of amphetamine will certainly induce wakefulness, for someone with insomnia that's dopamine related such as an ex-opioid/methamphetamine addict a low dose amphetamine will put them to sleep as it will induce dopaminergic activity but not enough adrenergic/dopaminergic activity to cause wakefulness. Decreased daytime drowsiness also allows narcoleptics to sleep at night as that's one of the major issues they face in that sleep during the day causes less sleep at night and vice-versa.

What confused me was that the one study you originally quoted simply said dopamine precursors promoted wakefulness in narcoleptics, and I didn't understand how that supported what you were saying about dopamine causing the OP to get sleepy. It seems like too much OR too little dopamine can both cause insomnia?

This is all very interesting to me because I have sleep issues and I'm quite certain I have low dopamine levels, but the conventional wisdom is just that dopamine antagonists cause sedation.

My doc says I'm the only one of his ADD Patients who gets these adrenergic side effects when under such comparably low doses of mph

If by mph you mean methylphenidate, I get nasty side effects at very low doses too.

 

[pasha]

Thanks for explaining more Chromophobia. If I understand correctly, what you are actually saying is that dopamine needs to be in the right balance for proper sleep, not simply that too little dopamine = insomnia and dopamine = sedation; it's more complicated than that; correct?

No problem, your absolutely spot on, its nowhere near as simple as that.

What confused me was that the one study you originally quoted simply said dopamine precursors promoted wakefulness in narcoleptics, and I didn't understand how that supported what you were saying about dopamine causing the OP to get sleepy. It seems like too much OR too little dopamine can both cause insomnia?

This is all very interesting to me because I have sleep issues and I'm quite certain I have low dopamine levels, but the conventional wisdom is just that dopamine antagonists cause sedation.

To be honest with you I could have sworn I've reviewed those studies before, so when the OP asked for them I didn't bother reviewing them thoroughly again. I skimmed the ones that are relevant to my point and quoted them even though I think it's all interrelated.

In either case dopamine agonists can promote wakefulness and stop excessive daytime sleep and micro-sleeping, this is one of the many reasons why narcoleptics are prescribed amphetamines because the belief is if they sleep less throughout the day-they'll sleep better at night-sleep less throughout the day etc. You can also reverse that in which GHB (Xyrem) is prescribed for narcolepsy with insomnia. Stimulant addicts are also notorious micro-sleepers.

Insomnia (drug or non drug induced), parkinsons disease, cataplexy, narcolepsy and several other neurological disorders are all not fully understood, but the most promising evidence all has ties to dopamine, but it hasn't been exactly tied up just yet.

but the conventional wisdom is just that dopamine antagonists cause sedation.

That's a very good point, one that crossed my mind, but it's not as simple as D1 antagonism causing sleep. When receptors are antagonized others become saturated. Even if they didn't the mechanism behind dopamine antagonists can be attributed to their histamine antagonism more so than anything else.

What's really interesting is that schizophrenics receiving anti-psychotic treatment had sleep stage abnormalities, REM disturbances, and other sleep dysfunctions which makes sense in a dopamine stand point according to some of the studies I presented.

 

[Swimmingdancer]

What's really interesting is that schizophrenics receiving anti-psychotic treatment had sleep stage abnormalities, REM disturbances, and other sleep dysfunctions which makes sense in a dopamine stand point according to some of the studies I presented.

Makes sense to me too, and I'm not schizophrenic I've just tried them for sleep and found that, while I fell asleep faster, my sleep was really poor and I woke up a lot (not to mention the unpleasant side effects).

 

[chris106]

If by mph you mean methylphenidate, I get nasty side effects at very low doses too.

Yes, Methylphenidate is what I mean. My doc told me that it is very uncommon for someone who REALLY has ADD or ADHD to react that strongly to the side effects of MPH.
My muscles, especially my neck, get all stiff and my mouth gets very dry. Also my voice starts to sound monotone, and fine motoric movement becomes worse. All known side effects, but actually in much higher doses!
If that's like how you react to it, it could be a hint that you indeed have some kind of sleepdisorder,too.
There are special medications for that as well, some of wich also influence the dopaminergic system, but from a completely different angle...

 

[Toz]

I am really tired so I'm sorry but this is TLDR at the moment for me, I will answer this question according to the first post. I find that you really need to fine tune your dose of these pills, too much will end up with negative effects, too little do the same. There is a "sweet spot" that should have minimal side effects. Trick is also to keep a steady amount in you at all times (well obviously not before bed). Can take a while to find your way there, but I think your dose is riddiculously low and I would not want to beon that dose, then I'd rather not take anything at all. Needs upping I'd bet. 8mg day seems riddiculously low and would make me feel worse only.

Also I had horrible side effects from MPH, fuck MPH, it's like trying to use a crappy version of crack for medicine. My life was just rollercoaster up and down on these + physical symptoms oh boy did they suck nausea stomach cramps muscle cramps etc
Was prescribed up to 120mg / day then gave up on it.

 

[chris106]

With Mph I can kind of relate
However Dl-Amphetamine worked pretty well for, actually it was the only one where I didn't feel like I was "on drugs", minor side effects aside.
Dexamphetamine - I still have to see abou that. As you said, it seems difficult to find the sweet-spot in dosing and keep a steady level at all times. I don't wanna feel like I'm a slave to a drug and have to plan my whole day accordingly...

Howerver, did I get this right - you stopped medication alltogether now? Or did you find something that works for you?

PS: As you see, you were right, my dose really just needed upping

 

[Swimmingdancer]

Yes, Methylphenidate is what I mean. My doc told me that it is very uncommon for someone who REALLY has ADD or ADHD to react that strongly to the side effects of MPH.

I disagree with your doctor and I think there are a lot of other people with ADHD who would too. It's rather well-known for it's side effects. Maybe your doctor just happened to not have had other patients of their's mention strong side effects at low doses, that doesn't mean it doesn't happen.