Stimulants And Understanding Their Effects

[SpunkySkunk347]

NOTE: The information in this thread is not verified by medical professionals (and as of right now, not even peers have verified any of it) and this information SHOULD NOT BE TAKEN AS FACT in the event of a medical emergency or any medical conditions regarding the use of stimulants. If an emergency is speculated, contact emergency services right away (i.e., 911) Taking more than the prescribed/recommended daily dose of any medicine may result in consequences detrimental to your health. The diagnosis done by a professional doctor or health-care professional should be valued above all other opinions when regarding safety, dangers, and possible medical conditions regarding the use of medicine.

I am creating this thread essentially to serve as an advanced discussion of the use of stimulants (particularily amphetamine and similar chemicals) and the side effects on the human body/mind of these chemicals. I hope to cover what particular mechanisms of action are for the perceived side effects in both an advanced-pharmacological talk and also brief summaries for the layman to understand. This differentiates from any "FAQ" type threads in the fact that these are not proven answers necessarily and are open for discussion. I hope that by the time this thread reaches a significant amount of information, all of our understanding of the pharmacology (and indeed psychology) involved with stimulants can be improved greatly.

Amphetamine (alpha-methylphenethylamine, beta-phenyl-isopropylamine) achieves its effects in the human body/mind, in very basic terms, by reversing the reuptake of neurotransmitters (Notably dopamine and norepinephrine, and to a lesser extent serotonin) mainly in the limbic system and frontal lobe regions of the brain. This leads to perceived effects of stimulation (increased concentration, euphoria, etc) but also comes at a cost. The peripheral nervous system is also stimulated as well, causing many side effects.

I would like to first discuss the cause, effects, and possible solutions to certain side effects.

A very pronounced side-effect for people (and yet barely noticeable if at all for others) is dizziness, numbness, racing heart, feelings of tightness in the chest, and other symptoms associated with high blood pressure. These effects seem to be caused by amphetamine's (and many other stimulants such as cocaine, Ritalin, caffeine, and nicotine) properties as a vasoconstrictor (constricting the blood vessels). However, treating the high blood pressure can be quite a dilemna. It would seem at a first glance the using beta-blockers such as "Propranolol" would be effective, however this is still controversial, as blocking of beta-adrenaline receptors would increase activation of alpha-adrenaline receptors, and would cause possibly dangerous side effects of its own. From wikipedia:

Beta blockers must not be used in the treatment of cocaine, amphetamine, or other alpha adrenergic stimulant overdose. The blockade of only beta receptors increases hypertension, reduces coronary blood flow, left ventricular function, and cardiac output and tissue perfusion by means of leaving the alpha adrenergic system stimulation unopposed. The appropriate antihypertensive drugs to administer during hypertensive crisis resulting from stimulant abuse are vasodilators like nitroglycerin, diuretics like furosemide and alpha blockers like phentolamine.

This would seem to recommend certain vasodilators for the treatment of a stimulant overdose, which is the case. However those medications can cause many undesirable side effects of their own, and may outweigh the side-effects one was originally trying to relieve - For a person simply trying to relieve unwanted stimulant side-effects, I myself wouldn't recommend self-medication with vasodilators.
It seems there is a general consensus which agrees that benzodiazepines can be used successfully (and often are used in emergency room visits when a patient is panicking from stimulant side-effects). Benzodiazepines are GABAnergic, and reduce the overall stimulation in the brain particularily in the areas which some amphetamine side-effects are caused. Possible benzodiazepines that would treat side-effects include diazepam (Valium), alprazolam (Xanax), Lorazepam (Ativan), or Clonazepam (Klonopin). Benzodiazepines are generally safe to use if the only drug a person is experiencing side effects from are stimulants such as amphetamine, however this is not always the case. Is it agreed upon by you pharmacology-enthusiasts here, that benzodiazepines are a relatively safe medication to use in treatment of stimulant side effects?

In the case of amphetamine-related psychosis and anxiety, I am curious as to the effectiveness of carbamazepine. I had once used a dose of carbamazepine to self-treat a possible amphetamine-psychosis, and most of the anxious thoughts were relieved, but I was left with agonizing neurological pain (a pounding, nearly unbareable headache).

What is the effectiveness of using anti-psychotics to treat amphetamine anxiety/psychosis if amphetamine is still in active effect?
How exactly does amphetamine increase norepinephrine levels, is it direct reversal of reuptake, or more related to dopamine?
I assume that vasoconstriction occurs due to increased norepinephrine levels, what are your opinions?
What are possible risks (I'm mostly looking at possible neurotoxicity) of taking amphetamines while also being prescribed SSRIs (particularily Zoloft)?

Thank you for reading, and thank you for any feedback you wish to give.

 

[SpunkySkunk347]

NOTE: The information in this thread is not verified by medical professionals (and as of right now, not even peers have verified any of it) and this information SHOULD NOT BE TAKEN AS FACT in the event of a medical emergency or any medical conditions regarding the use of stimulants. If an emergency is speculated, contact emergency services right away (i.e., 911) Taking more than the prescribed/recommended daily dose of any medicine may result in consequences detrimental to your health. The diagnosis done by a professional doctor or health-care professional should be valued above all other opinions when regarding safety, dangers, and possible medical conditions regarding the use of medicine.

lmfao, tweaked out poster wrote a disclaimer, in this thread 8)

I have another question..
Would a blood thinner (such as aspirin) cause blood pressure to increase, decrease, or stay the same while on amphetamine?
I guess I do not really grasp the mechanics of how blood pressure works. Wouldn't thinning of the blood make it easier for outside pressure from muscle tension to push inwards on the blood vessels, causing an increase increased vasoconstriction?
For me I guess it somehow seems synonymous in my mind that Vasoconstriction = High Blood Pressure, and Vasodilation = Low Blood Pressure. But is this not always the case?

Yet another question that came to mind. If a person were say, in a circumstance where they chose not to/weren't able to treat undesirable side effects with other substances, what would be simple things that could help reduce side effects? Usually anti-anxiety techniques are fairly effective, but sometimes the problem might be physical pain related. Usually, if my muscles are painfully tense from the comedown of a stimulant, a hot (and sometimes turning it to cold) shower works. I think maybe this helps somehow to balance out constriction of the blood vessels? Another thing which seems to help is making sure my extremities (feet and hands) are warm and getting adequate circulation. I think maybe a possible thing to help "balance out constriction/dilation" is to keep your outside warm and also if you can cool off your inside. Perhaps stay under a blanket (as long as it lets you stay not hot, but just warm) and drink cool (not ice cold) water. Or to just pour lukewarm water on areas of your body that ache to help move the heat from that area of the body. I suppose if you were really bothered by side effects, taking your temperature with a thermometer and drinking fluids (juice will help your body to metabolise amphetamine quicker and help it get out of your system) to balance out your temperature to normal body temperature.
Would acetaminophen, aspirin, and/or ibuprofen be effective in safely/sufficiently relieving any headaches or muscle pain on the crash?

 

[Hammilton]

Um.. Not 1:1 but I would imagine that vasoconstriction will always RAISE blood pressure, and dilation will always lower it. But not neccessarily create clinically high pressure.

 

[shibireru]

Why would you even think to use propranolol, metoprolol or any other beta blocker? Amphetamines reverse the process of reuptake of norepinephrine, increasing its concentrations within the synapse; norepinephrine has a much higher affinity for the alpha adrenergic receptors than the beta. Personally, I would use (and I know I've been perseverating on these lately. I repeat myself an awful lot) an alpha-2 adrenergic agonist (e.g. clonidine, dexmedetomidine, tizanidine, lofexidine, etc...) The alpha-2 mediates feedback inhibition, so to produce agonism of it is to reduce the degree of stimulation of all other adrenoreceptors. Even better perhaps would be a combination of an alpha and beta blocker.

What is the effectiveness of using anti-psychotics to treat amphetamine anxiety/psychosis if amphetamine is still in active effect?

Certain atypical antipsychotics, because they act as alpha blockers, might seem like a good idea, but I would be willing to bet than the combination of ziprasidone or quetiapine with amphetamine would be vastly more likely to produce akathisia - and a severe form of it at that - than either ziprasidone or quetiapine administered alone. I say this because clonidine and propranolol have been demonstrated to be very effective remedies for ziprasidone-induced akathisia (benzodiazepines are minimally effective in the treatment of severe akathisia, by the way).

I actually have a bit of experience with this (very recent, too). Allow me to share a little anecdote here:

Recently I was admitted to a near-by hospital because I was having a severe panic attack (caused probably by a combination of PTSD, hypoglycemia, and caffeine). Long story short, I was admitted to a psychiatric hospital because my mother is a mentally retarded bint who deserves no less than to die in a fire. While in the psych ward I requested some clonidine for my PTSD and anxiety, which I found to be quite effective, but the next day they refused to treat me with it further and insisted that I try some ziprasidone for the condition. Well, I tried it and experienced some of the most severe akathisia possible for about 4-6 hours, which was pure hell, agony, and terror (*); I surely would have killed myself by any means possible if thoughts of suicide had produced even the tiniest bit of anticipatory pleasure (quite the contrary: for some reason when I'm in my worst states of mind, suicidal ideation makes me more depressed, whereas in my less depressed states it is pleasant for me to think of death). Keeping in mind that my baseline noradrenergia and/or adrenergia are very high by default because I have PTSD and I was suffering mild rebound effects from clonidine discontinuation, and that alpha 2 agonists and beta antagonists are tremendously effective treatments for akathisia, one should perhaps suppose that administration of certain atypical antipsychotics (such as ziprasidone) to a person suffering from amphetamine-induced anxiety and troubling sympathomimetic activity would be liable only to produce akathisia, since the beta component isn't being rectified.

By the bye, does anyone have a precise understanding of the pharmacodynamics of clonidine? I have been having a bit of difficulty eliciting that information. I wonder because it felt a bit like it had some rather strong anticholinergic activity and I am interested in trying a "purer" alpha 2 agonist to treat my PTSD.

*Karma hath remunerated me: following my release from the psych ward a doctor gave me a prescription for fentanyl that I hadn't even requested and didn't expect to receive in my wildest dreams. So, all that suffering that was needlessly and fruitlessly inflicted upon me over those five days will soon be made up for.... if the fentanyl doesn't kill me (I have zero opioid tolerance).

 

[SpunkySkunk347]

Why would you even think to use propranolol, metoprolol or any other beta blocker? Amphetamines reverse the process of reuptake of norepinephrine, increasing its concentrations within the synapse; norepinephrine has a much higher affinity for the alpha adrenergic receptors than the beta. Personally, I would use (and I know I've been perseverating on these lately. I repeat myself an awful lot) an alpha-2 adrenergic agonist (e.g. clonidine, dexmedetomidine, tizanidine, lofexidine, etc...) The alpha-2 mediates feedback inhibition, so to produce agonism of it is to reduce the degree of stimulation of all other adrenoreceptors. Even better perhaps would be a combination of an alpha and beta blocker.

Certain atypical antipsychotics, because they act as alpha blockers, might seem like a good idea, but I would be willing to bet than the combination of ziprasidone or quetiapine with amphetamine would be vastly more likely to produce akathisia - and a severe form of it at that - than either ziprasidone or quetiapine administered alone. I say this because clonidine and propranolol have been demonstrated to be very effective remedies for ziprasidone-induced akathisia (benzodiazepines are minimally effective in the treatment of severe akathisia, by the way).

Makes sense, thanks. I am mostly bummed out because I have plenty of beta-blockers and anti-psychotics in my home pharmaceutical collection, but no alpha-blockers. I would simply go to the doctor and ask for an alpha-blocker to help me get to sleep (during the crash of amphetamine, anxiety and post-stimulation keep me awake), they aren't very abuseable substances from what I know. But, unfortunately, EVERY doctor I know has an overinflated ego and the moment I go into their office with my own "suggestions" they take offense to it as if I had just insulted their mother.

I actually have a bit of experience with this (very recent, too). Allow me to share a little anecdote here:

Recently I was admitted to a near-by hospital because I was having a severe panic attack (caused probably by a combination of PTSD, hypoglycemia, and caffeine). Long story short, I was admitted to a psychiatric hospital because my mother is a mentally retarded bint who deserves no less than to die in a fire. While in the psych ward I requested some clonidine for my PTSD and anxiety, which I found to be quite effective, but the next day they refused to treat me with it further and insisted that I try some ziprasidone for the condition. Well, I tried it and experienced some of the most severe akathisia possible for about 4-6 hours, which was pure hell, agony, and terror (*); I surely would have killed myself by any means possible if thoughts of suicide had produced even the tiniest bit of anticipatory pleasure (quite the contrary: for some reason when I'm in my worst states of mind, suicidal ideation makes me more depressed, whereas in my less depressed states it is pleasant for me to think of death). Keeping in mind that my baseline noradrenergia and/or adrenergia are very high by default because I have PTSD and I was suffering mild rebound effects from clonidine discontinuation, and that alpha 2 agonists and beta antagonists are tremendously effective treatments for akathisia, one should perhaps suppose that administration of certain atypical antipsychotics (such as ziprasidone) to a person suffering from amphetamine-induced anxiety and troubling sympathomimetic activity would be liable only to produce akathisia, since the beta component isn't being rectified.

By the bye, does anyone have a precise understanding of the pharmacodynamics of clonidine? I have been having a bit of difficulty eliciting that information. I wonder because it felt a bit like it had some rather strong anticholinergic activity and I am interested in trying a "purer" alpha 2 agonist to treat my PTSD.

*Karma hath remunerated me: following my release from the psych ward a doctor gave me a prescription for fentanyl that I hadn't even requested and didn't expect to receive in my wildest dreams. So, all that suffering that was needlessly and fruitlessly inflicted upon me over those five days will soon be made up for.... if the fentanyl doesn't kill me (I have zero opioid tolerance).

Ha I have had a very similar experience myself! Last October I was in a psychiatric hospital for 2 fucking months, held in against my will by my mother, and then upon discharge, the psych doctor sent me on my way with a prescription to zoloft and Adderall 30mgx2 daily. I was like That doctor was very understanding though, and was actually quite open to suggestions I had. Other crazy-ass psyche ward experiences I've had, was once I was in an inpatient for a week/outpatient for a week type of deal in a psyche ward, and they really didn't do dick. Then I went back AGAIN as an inpatient, at the end of that stay the doctor was like "JESUS you're an asshole kid, FINE you want benzos? Well we aren't going to give you valium or xanax, but we'll give you klonopin!" 8) I was trying to tell them that the half-life of klonopin was way too fucking long, and I just needed a short acting benzo to take care of a panic attack whenever they came along. I took the klonopin, but needless to say, it not only got rid of my panic attacks but left me in a zombified dream state for the next 2 days after taking it.

I seriously would pay money to have some of these doctors be locked in a state of extreme panic, akathisia, and an "all too enjoyable" sense of impending death. Then while they are crying on the floor screaming in agony, I would throw pills of zoloft, seroquel, and abilify at them while laughing my ass off and telling them "You're just drug seeking you little bastard!"

Anyways, I experienced some notable akathisia while trying to use carbamazepine to treat an amphetamine comedown, and I also experienced a milder case of akathisia while using seroquel to treat an amphetamine comedown.

 

[bubbbble]

has anyone used nitrogycerin, in conjunction to stimulants? how bout on the regular? has anyone used it to offset angsty feelings regularly associated with stim use, by dosing routinely, using it as something of a counterpart to the drug?

I have a bottle of the stuff here....and am trying to figure out whether it's safe to assume that I'll feel less like my entire body is pulsating CONSTANTLY, and at a rate I deem TOO FAST (I'm thinking >110/20 bpm, mind you, a rate i've never to my knowledge reached), if I were to take a tiny little taste of nitro while high? how about using it on an occasional basis in an attempt to offset extreme paranoia stemming from heart rate, at least?

I should add- the stim that comes to mind here is MDPV.

I mean, sure, it's no doubt probably plenty stoopid to consider dosing with both a vaso dilator AND constrictor on the frequent.....buuuuut...whaatiff?? and with that question out of mind, what if used when needed only to counteract paranoid feelings regarding your heartbeat?

thanks yall