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Discussion => Drug safety => Topic started by: Beastie on February 26, 2012, 05:05 am

Title: Safe? Valium after Methamphetamine=YES + Prevents Neurotoxicity
Post by: Beastie on February 26, 2012, 05:05 am
Read Post #10
That is the real deal and life saving information if you or anyone you know uses an Amphetamine.

---
Hello,

I can't seem too find a whole lot of data on this.  I know Meth releases a lot of serotonin, and when combined with a drug like Opioids witch release a load of dopamine the combo can/is be deadly.

However, it seems Diazepam aka Valium dose not release dopamine or serotonin. Instead it produces raised levels of a neurotransmitter called GABA. The effect of this neurotransmitter is inhibit the neuro activity of nearly all other neurotransmitters, such as, serotonin, dopamine, norepinephrine i.e. it makes neurons stop firing so much.

<<<
side note, this is why one REALLY dose not want to use Valium vary often because the physical withdrawals are extremely bad and can be permanent. Cold turkey quitting of Diazepam can be deadly. One should vary slowly decrease dosage to stop. Like cut down 1mg/day for one week. Then cut by 1mg/day again the next week and so on really slow i.e. if you have a 20mg/day addiction for the first week take 19mg/day week-2 take 18mg/day.
then when you get down to like 10mg/day only cut off like 0.5mg/day. When you get to 5mg/day only cut down like 0.25mg/day
>>>

Anyway back to the point.
Seeing as how Diazepam dose not release dopamine, but instead increases GABA who's action is to inhibit the action of other neurotransmitters including the serotonin that the Methamphetamine is releasing. Am I correct that there is probably no life threatening interaction between Methamphetamine and Diazepam aka Valium?

I would pose the hypothesis that Diazepam's action of increasing GABA activity would serve to nullify the large amounts of serotonin the Methamphetamine is releasing in a biologically normal way i.e. the body normally uses GABA to slow down the activity of neurons.  So, I would conclude that as long as one dose not shock the body by taking large amounts of Diazepam and/or directly after taking Methamphetamine. Say, if one waits at least 4-6hr's after taking the last dose of Methamphetamine. Then takes 5 to 15mg of Diazepam, depending upon tolerance, one would experience a relatively safe come down from the Methamphetamine.  I would also stress that one would never want to develop a Diazepam aka Valium addiction, so Diazepam's use should be limited.

What are your thoughts on the Safety of using Diazepam aka Valium to come down form Methamphetamine? I read that rehab clinics will proscribe Diazepam to recovering Methamphetamine addicts, however I am guessing that they wait until the Methamphetamine has worn off. My question is whether is safe when one is in the after-effects stage of Methamphetamine i.e. after 4-6hr's according to erowid.org.

----------
Personally, I have use Diazepam in this way. I have found that it dose Not Kill the Meth High, but when I take 10mg of "Roche Valium" 6hr's after the last hit of Methamphetamine from a pipe, it kills the cravings for more Methamphetamine and allows me to fall asleep. Some times, I'll take another 5mg of Diazepam 1hr after the first dose of Diazepam if I feel I need a little more. However, if I 'snorted' meth then it may kill cravings but, because it seems small amounts of Methamphetamine in the snot keeps getting released into the bloodstream for a long time, so I still can not sleep.
Title: Re: Safe? Valium after Methamphetamine
Post by: microRNA on February 26, 2012, 08:23 am
You are on the right track, however some of your assumptions or background are incorrect. I honestly have a fair amount of psychopharmacological background yet I certainly still have tons to learn, but will do my best. Its so complicated I will likely still do an injustice to the actual beauty that is the tangled labyrinth of neural circuitry. In an attempt to summarize I may likely also provide some not quite accurate info.

i am stoned and lazy an dont feel like looking up sources but if there is something specific you are interested in I will find info on that, just ask or if you think I made an error please let me know so I can look it up and correct the mistake.

First, downers and stimulants are some of the most loved combos, yet also some of the most dangerous for the two opposing forces, often acting on the heart.

Given (meth)amphetamine's structure, it actually more closely resembles nor(epinephrine) and dopamine. Meth has a the capability to reverse the action of the re-uptake transporters, literally dumping the intracellular store of serotonin, dopamine, and norepinephrine which essentially exerts its effects. Dopamine from the ventral tegmental area innervates the nucleus accumbens and is associated (mostly) with MOTIVATION not euphoria (this is why coke, which merely is a dopamine releasing agent, has the main effect of wanting to do more coke)!!! this is the largest misconception among drug users, but studies indicate dopamine is released during reward seeking, but once the actual reward is obtained, the dopamine drastically cuts off and is followed downstream by an effect of the dopamine, causing serotonin release from the raphe nuclei which is for a large part responsible for the general elevation of mood. Norepinephrine is largely related to the process of attention and the epinephrine effects are responsible for the peripheral sympathetic response. Most of these effects target G-protein couples receptors, increasing rates of the second messenger cAMP, which activates (sodium) ion channels directly as well as protein kinases (PKA) that result in transcription factors such as CREB being disinhibited. Inositol triphosphate and diacylglycerol also cause calcium release from the endoplasmic reticulum activating protein kinase C as well. Sorry, basically all this results in depolarization of the neuron and a greater likelihood of the cell firing, and thus overall stimulation of the CNS.

Benzos do not cause GABA release (this is actually what opiates do in some areas if I remember correctly), but they allosterically modify the activity of the GABA receptor, which means the same level of GABA causes an exaggerated effect. GABA receptors are chloride ion channels, and so benzos essentially cause more chloride ions to flow into the cell which hyperpolarizes the cell and drastically reduces the likelihood an action potential will fire. Toning down the activity in neural circuits globally.

It is not so clear cut that GABA inhibits the actions of other neurotransmitters. Even the same neurotransmitter can oppose its own action in a circuit depending on the receptor subtypes, either stimulatory or inhibitory,  that are present and activated. GABA may actually inhibit an inhibitory circuit, which causes disinhibition and thus actually stimulates the target circuit. Also, remember the conscious effects are not the result of simple neuron firing, yet the synchronized and patterned sequence of firing is what actually encodes the process generally. Tripping is from a very slight effect by 5ht2a stimulation which disrupts this ordered arrangement of neural activation and the brain no longer can interpret the information being conveyed cause the pattern is all out of whack.

Back in the day benzos and coke were one of my favorite combinations, provides an awesome euphoria without the jittery tweaked out feeling. After tripping on lsd my favorite thing is to take a benzo and a very similar relaxed enjoyable inebriation results and I can easily sleep. Basically taking meth and a benzo would be similar, it will just reduce some of the stimulatory properties but not negate the effects those neurotransmitters are having disrupting the normal activity of the circuit. I may even take the benzo then use the amp for euphoria and to stay awake, but I am a downer kinda guy so I would do it backward. Just do not abuse this combination frequently, given the crazy long half life and subsequent metabolism to amphetamine, I assume you would be stressing your heart so just be careful.

Let me know if you have any questions or need to clarify.
- microRiboNucleicAcid
Title: Re: Safe? Valium after Methamphetamine
Post by: Beastie on February 26, 2012, 01:43 pm
Thank you for your vary detailed response. I too have a psychopharmacology, as well as, an organic chemistry background. However, you seem to be markedly farther along in your studies them I. Plus, I have scents moved into computer programming, and networking, so I have forgotten many things.

Anyway so, I was vary incorrect about the effect of Methamphetamine. I had the nagging feeling that I was wrong. I did know that Valium did not exactly release GABA but merely potentiates the effects of it. I should have been more clear about that. Thank you for pointing that out and concurring that is what Diazepam dose.

So, I gather from what you have said that taking Diazepam while under the influence of Methamphetamine can in fact be a dangerous combo. The danger being the effects the drugs have on the hart i.e. one will speed it up a lot, and the other wants to slow it down a lot. Furthermore, the mode of operation for Diazepam dose not necessary protect one from the potentially deadly effects a downer plus an upper combo is known to have. You also reminded me that not all neurotransmitter sites are the same, which results in say one dopamine agonist may have a different effect then another dopamine agonist, because not all dopamine sites are exactly the same. <is that wrong?>
Therefore, to determine the potential negative effects the combo could produce will take a fair amount of research, and probably the only way to prove any hypothesis would be to conduct scientific studies. If anyone knows of any studies of any Amphetamine in combination with any Benzo please post a link.   

I will continue to have a healthy respect for the use of Valium to come down from Methamphetamine. Even though the combo is not like 100% deadly, one never knows with these things, and while under the influence of the drugs one may take too much with out even realizing. Until I can obtain more information, I will limit the use of Valium to come down from Methamphetamine i.e. not make it a regular thing, and continue with my rule of waiting 6hr's after the last Methamphetamine hit before I take any Valium in an effort to reduce the shock my body and certainly my hart. Luckily, I do not use Methamphetamine nor Valium too often. I have a fairly strong respect for any addictive drug, and even more so with vary strong drugs like these. I allow that respect to manifest itself in the form of moderation, making a schedule of usage before I start, and never braking my schedule i.e. if I am suppose to take no more then 250mg of Meth and take the last hit no later then 2pm Sunday I stick to that schedule no madder how much my high mind can rationalize braking the schedule. Generality, I also reserve Methamphetamine use for when I have a lot of work to do, like a 10 page paper to write. This helps me stop when my schedule says too, because I have already completed the goal i.e. I think it is harder to stop when the only goal is to have fun, because that goal is never over.

I would still like to hear what others have to say, or more from you microRNA.
Title: Re: Safe? Valium after Methamphetamine
Post by: Angelology on February 26, 2012, 03:47 pm
Hello,

I can't seem too find a whole lot of data on this.  I know Meth releases a lot of serotonin, and when combined with a drug like Opioids witch release a load of dopamine the combo can/is be deadly.

However, it seems Diazepam aka Valium dose not release dopamine or serotonin. Instead it produces raised levels of a neurotransmitter called GABA. The effect of this neurotransmitter is inhibit the neuro activity of nearly all other neurotransmitters, such as, serotonin, dopamine, norepinephrine i.e. it makes neurons stop firing so much.

<<<
side note, this is why one REALLY dose not want to use Valium vary often because the physical withdrawals are extremely bad and can be permanent. Cold turkey quitting of Diazepam can be deadly. One should vary slowly decrease dosage to stop. Like cut down 1mg/day for one week. Then cut by 1mg/day again the next week and so on really slow i.e. if you have a 20mg/day addiction for the first week take 19mg/day week-2 take 18mg/day.
then when you get down to like 10mg/day only cut off like 0.5mg/day. When you get to 5mg/day only cut down like 0.25mg/day
>>>

Anyway back to the point.
Seeing as how Diazepam dose not release dopamine, but instead increases GABA who's action is to inhibit the action of other neurotransmitters including the serotonin that the Methamphetamine is releasing. Am I correct that there is probably no life threatening interaction between Methamphetamine and Diazepam aka Valium?

I would pose the hypothesis that Diazepam's action of increasing GABA activity would serve to nullify the large amounts of serotonin the Methamphetamine is releasing in a biologically normal way i.e. the body normally uses GABA to slow down the activity of neurons.  So, I would conclude that as long as one dose not shock the body by taking large amounts of Diazepam and/or directly after taking Methamphetamine. Say, if one waits at least 4-6hr's after taking the last dose of Methamphetamine. Then takes 5 to 15mg of Diazepam, depending upon tolerance, one would experience a relatively safe come down from the Methamphetamine.  I would also stress that one would never want to develop a Diazepam aka Valium addiction, so Diazepam's use should be limited.

What are your thoughts on the Safety of using Diazepam aka Valium to come down form Methamphetamine? I read that rehab clinics will proscribe Diazepam to recovering Methamphetamine addicts, however I am guessing that they wait until the Methamphetamine has worn off. My question is whether is safe when one is in the after-effects stage of Methamphetamine i.e. after 4-6hr's according to erowid.org.

----------
Personally, I have use Diazepam in this way. I have found that it dose Not Kill the Meth High, but when I take 10mg of "Roche Valium" 6hr's after the last hit of Methamphetamine from a pipe, it kills the cravings for more Methamphetamine and allows me to fall asleep. Some times, I'll take another 5mg of Diazepam 1hr after the first dose of Diazepam if I feel I need a little more. However, if I 'snorted' meth then it may kill cravings but, because it seems small amounts of Methamphetamine in the snot keeps getting released into the bloodstream for a long time, so I still can not sleep.
So meth isn't enough for you?
Title: Re: Safe? Valium after Methamphetamine
Post by: Beastie on February 26, 2012, 05:02 pm
nope, I like my nicotine, weed, alcohol now and then,  caffeine, every once in a while LSD or some other psychedelic.

This thread was talking about two drugs, because I would like to learn the safety of using one drug to counteract the unwanted effects of the other.
Title: Re: Safe? Valium after Methamphetamine
Post by: randomovdbuser on February 26, 2012, 06:48 pm
hmh. Standard ER treatment of amphetamine-intoxication is... tumdum... diazepam.
Preferably IM or rectally. The combo is "relatively" safe. As long as you don't drink alcohol while on it.
Or you could end up like Amy and Whitney, and hopefuly Britttney in the not-so-distant future.
Title: Re: Safe? Valium after Methamphetamine
Post by: sedgeandbee on February 26, 2012, 06:56 pm
microRNA is quite right.

However, I would like to point out that combining methamphetamine and opioids is not unsafe because this results in excess dopamine release. Rather, the danger arises from methamphetamine cloaking some of the effects of opioids, which can result in dosing problems for the opioid. Essentially, there is a risk that individuals will take too high of a dose of an opioid, especially in the case of heroin when the strength is often gauged by subjective effects. This makes it very easy for the individual to overdose or become unconscious without notice.
Title: Re: Safe? Valium after Methamphetamine
Post by: jewfro on February 26, 2012, 07:30 pm
nope, I like my nicotine, weed, alcohol now and then,  caffeine, every once in a while LSD or some other psychedelic.

This thread was talking about two drugs, because I would like to learn the safety of using one drug to counteract the unwanted effects of the other.

valium, xanax, ativan, klonopin, etc are all used to come down off uppers....

although i never heard that opioids release dopamine... good too know  :o
Title: Re: Safe? Valium after Methamphetamine
Post by: Beastie on February 26, 2012, 09:38 pm
Thank all of you for your input. I really appreciate it :)

Well, after reading that Valium is given for Amphetamine overdose in the ER, I have had much more luck with my google searches. Thank you so much for saying that.

It seems that it is quite common for a doctor to prescribe Adderall and Valium or Xanax at the same time. It seems normally the prescription calls for the use of Adderall in the morning and a Benzo at night. One person is prescribed 30mg XR once a day, 10mg IR in the afternoon, and 1mg Kpins twice a day by his doctor. Another guy who is on a Adderall + Benzo combo is insistent that the two drugs are not contraindicative. There is one guy on the drug-forms that is also saying, "On a side note, SWIM read somewhere that benzos are used in the ER (IV) in cases of amphetamine overdose." Although, maybe that is where you got that info from. If so, then really it only counts as one person suggesting that. However, every post on wiki.answers.com about Adderall and Benzo's is reporting that there is no negative interaction. Here is one such statement, "The simple answer is absolutely, yes. There is no evidence that shows mixing benzodiazepines with a amphetamine causes a negative interaction."

Adderall is simply Amphetamine, and correct me if I am wrong, but Methamphetamine basically has the same effects as Amphetamine but is simply stronger. I think now it is looking like my original hypothesis was correct (even though my memory about the effects of Methamphetamine was way off), which was, because of the way Diazepam slows the CN it dose not create the 'speed ball' deadly effects in combination with Methampetamine, at least not to a worrisome degree if the Diazepam is taken after the brunt of the Methampetamine effects have worn off and at normal dosages.

Certainly no alcohol with Valium, that is one combo that most certainly can be deadly, because they potentate each-other which can result in a major depression of the CN and cause the user to fall asleep and stop breathing.

I'll keep myself safe for now, and keep looking for more concrete evidence that the use of Diazepam to comedown from Methampetamine is relatively safe. I think the ER Amphetamine overdose lead is a good one to follow to the end. If that is true, I would consider the question answered.
Title: Re: Safe? Valium after Methamphetamine
Post by: randomovdbuser on February 27, 2012, 02:28 pm
I did not read that, that's how we treat amphetamine-intoxications at our ER department.
Week after week. After week. After week.

/edit:
nice paper describing treatment: hxxp://jrd.consultantlive.com/display/article/1145425/1372099
Title: Re: Safe? Valium after Methamphetamine
Post by: Beastie on February 29, 2012, 02:00 am
Thank you randomovdbuser for explaining that is vary good to know.

--

I found a proper scientific research paper on amphetamine/methamphetamine. It covers everything from physiological/neurological effects to physiological and behavioural effects of amphetamine/methamphetamine usage and poisoning. It is based on proper scientific studies and provides references.

It shows that Diazepam dose not induce a negative interaction when taken in combination with amphetamines or cocaine. Diazepam dose have cardiovascular effects but only vary slightly. Diazepam is in fact suggested to treat stimulant overdose. In fact, Diazepam not only is safe to take with Amphetamine it is recommended. Diazepam protects from DA depletion caused by neurtoxic effects of Amphetamine poisoning.

Here is part of it
hxxp://www.acnp.org/g4/gn401000166/ch162.htm
...
Sustained high-dose administration of amphetamines (especially methamphetamine) to experimental animals produces a persistent depletion of DA which is associated with terminal degeneration (62, 182, 195), as well as neuronal chromatolysis in the brain stem, cortex and striatum (42, 182). In contrast, continuous dosing with extremely high doses of cocaine (100–250 mg/kg/day i.v.) did not induce terminal degeneration in frontal cortex and striatum (62, 183). Recently, Cubellis et al. (36) presented evidence that amphetamine, in contrast to cocaine, induces redistribution of DA from the vesicles into the cytosol; thus, the loss of the protection of the vesicles' relatively reducing environment results in cytosolic oxidative stress that may initiate amphetamine neurotoxicity. The DA depletion is reported to be permanent in the caudate of monkeys (196). The main hypotheses for underlying mechanisms have included 1) the conversion of DA into a hydroxy oxidative metabolite (195, 196); and 2) glutaminergic stimulation of toxicity, which can be inhibited by N-methyl-D-aspartate antagonist MK-801 (200).

Methamphetamine toxicity is inhibited by a variety of drug treatments, including: 1) DA synthesis inhibitor alpha-methyl-para-tyrosine; 2) DA receptor antagonists; 3) NMDA receptor antagonists, e.g., MK-801; 4) DA and serotonergic reuptake inhibitors protecting against DA and serotonin toxicity respectively (195). Even though most studies have found that serotonergic and DA reuptake inhibitors specifically protect these two sites, certain reuptake blockers (such as benztropine) do not (195). On the other hand, mazindol, a non-specific blocker, protects against both DA and serotonergic neurotoxicity. Ali et al. (1994) have further demonstrated in mice that a major factor for neurotoxicity is hyperthermia which is highly correlated with the degree of long-term DA depletion (21). Furthermore, haloperidol, diazepam and MK-801, all of which can reduce methamphetamine-induced hyperthermia, protect rats against DA depletion (4). They also demonstrated that reducing the ambient temperature (4°C) reduced neurotoxicity to the same levels found when phenobarbital, diazepam and MK-801 were present to protect the cell. Tolerance to methamphetamine induced by increasing doses also reduces the hyperthermic response and as well protects against neurotoxicity (89, 188).
An important caveat is that not all protective mechanisms act by preventing the hyperthermic effect; the monoamine uptake blockers inhibit neurotoxicity in the absence of inhibition of hyperthermia, e.g., fluoxetine blocks methamphetamine serotonin toxicity without reducing temperature (140). The monoamine protection from neurotoxicity by reuptake inhibition is emphasized by the unexpected discovery that even massive and 24-hour continuous dosing of cocaine, e.g., 100 mg/kg/day, does not result in DA system neurotoxicity (119, 182, 183). Hyperthermia has been well documented to increase amphetamine stereotypy (93, 220). Hyperthermia alone is well known to result in neuronal chromatolysis and has been previously proposed as a significant contributor to amphetamine-induced DA depletion and neuronal damage in clinical as well as experimental animal histopathology (52). Hyperthermia may have been one of the factors resulting in deaths among athletes taking moderate doses of amphetamine in the 1960s and 70s (145). Even in mild hyperthermia, increased body temperature induces a linear decrease in the inhibitory feedback of stimulants on somatodendritic autoreceptors (130). Thus, body temperature changes induced by amphetamine should be considered as one of the contributors to toxicity.
One of the hallmarks of amphetamine-induced neurotoxicity is the loss of DA uptake sites in the striatum and accumbens. These studies of transporters after chronic amphetamine have reported decreases in the range of 30–40% (158). Recently, Silvia et al. (198) addressed the functional significance of changes in transporters on amphetamine's behavioral effects. After seven days of infusion of transporter RNA antisense ODN into the SN/VTA nuclei, mazindol binding was reduced 32% in the caudate. Administration of 2 mg/kg of amphetamine at this time resulted in robust contralateral turning (an increase of 400%); in contrast, 10 mg/kg of cocaine induced no changes in the turning response. The lack of turning response to cocaine after transporter reduction contrasts with the substantial cocaine-induced contralateral turning after unilateral SN/VTA D2 ODN to reduce D2 autoreceptors in the striatum (199). Thus, the amphetamine-induced loss of DA uptake sites could have two consequences: 1) a protective mechanism reducing further neurotoxicity, and 2) reverse tolerance to subsequent amphetamine administration, perhaps resulting in adverse symptoms such as paranoid psychosis (see also the discussion on neurotoxicity in the habenular interpeduncular track and its possible relationship to augmentation amphetamine-induced adverse effects).
...

Test results and reports have shown that Diazepam also greatly alleviates symptoms of Amphetamine Psychosis brought on by high or prolonged doses of Amphetamine or Methamphetamine. It is also noted that Diazepam's effects are much shorter acting then Methamphetamine, so re-administration of Diazepam may be needed if the symptoms of Amphetamine Psychosis comeback. Studies have shown that Diazepam also markedly reduces Amphetamine withdraw symptoms. This action is likely do to be the result of Diazepam helping to stabilize Dopamine in the body.
Title: Re: Safe? Valium after Methamphetamine=YES + Prevents Neurotoxicity
Post by: randomovdbuser on February 29, 2012, 07:41 pm
np, feel free to send me some btc ;S
Ow no wait, this forum is a hobby, not a job. Glad to be of service :-)