Alcohol & methamphetamine synergy

[Psychadelic_Paisly]

Hey hey.

The last 6 months or so I've REALLY enjoyed mixing meth with my alcohol. Whenver I go out for a big night, say a 21st B'day etc. I'll always take my point of speed with me. Mostly to keep that 'sobriety' thing happening, but the two together do it for me much more than one or the other.
Then again, I also enjoy relaxing at home with some drinks and a few lines watching movies, playing computer games etc.
The thing is, we all know how cocaine and alcohol actually has a synegy effect in the way that it produces that other chemical which is more cardiotoxic. I forget what it's called. P_D, this is basically for you....

Just wondering, what could be the cause, if any, that when I, mix speed with drinks, it is a much more euphoric, cruisy, yet still tweaked out ride. Even off just a glass or so, I feel almost kind of fuzzy.

Your thoughts???

 

[Pleonastic]

The chemical you're thinking of with coke and alcohol is cocaethylene. But unfortunatly other than that I don't have much to add that wouldn't be guessing.

 

[Cowboy Mac]

Methamphetamine and Alcohol Interactions.

Methamphetamine is often used in combination with ethanol. To investigate a possible drug interaction we performed a double blind placebo controlled study in eight regular methamphetamine users (*). Compared with methamphetamine alone, methamphetamine and ethanol increased heart rate, rate pressure product and total intoxication. We concluded the combined use of methamphetamine and ethanol has physiologic consequences which are distinct from the effects of ethanol or methamphetamine alone. The altered cardiovascular and subjective responses could not be explained by any simple alteration in methamphetamine pharmacokinetics.

*. Mendelson J; Jones RT; Upton R; Jacob P III. "Methamphetamine and ethanol interactions in humans" Clinical Pharmacology and Therapeutics, 1995, 57(5):559-68.

source

Clin Pharmacol Ther. 1995 May;57(5):559-68.

Methamphetamine and ethanol interactions in humans.

Mendelson J, Jones RT, Upton R, Jacob P 3rd.

Drug Dependence Research Center, Langley Porter Psychiatric Institute, University of California, San Francisco 94143-0984, USA.

OBJECTIVE: Methamphetamine and ethanol are commonly used together. We examined the effects of intravenous methamphetamine (30 mg), oral ethanol (1 gm/kg), and the combination of methamphetamine (30 mg) and ethanol (1 gm/kg).

METHODS: Eight methamphetamine and ethanol users were studied in a double-blind, double-placebo, within-subject, balanced Latin-square design. Ethanol was administered in six drinks over 30 minutes. Methamphetamine was injected 60 minutes after the first drink was begun. Cardiovascular, subjective, and neuropsychologic effects of the drug combinations were measured for 6 hours. Methamphetamine and amphetamine in plasma and urine were measured by capillary gas chromatography for 48 hours. Data were analyzed by repeated-measures ANOVA.

RESULTS: Compared with methamphetamine alone, the combination increased heart rate but decreased systolic blood pressure. The net cardiovascular effect was an increase in rate pressure product, an index of cardiac work and myocardial oxygen consumption. The combination diminished the subjective effects of ethanol while not affecting the subjective effects of methamphetamine.* Methamphetamine pharmacokinetics were not altered by the concurrent administration of ethanol, with the exception of lowering the apparent volume of distribution at steady state for methamphetamine.

CONCLUSIONS: As a potent sympathomimetic drug with alpha-agonist-like effects, methamphetamine increased systolic blood pressure, with minimal change in heart rate. The concurrent administration of methamphetamine and ethanol increased cardiac work, which could produce more adverse cardiovascular effects than either drug taken alone. The increased perceived global intoxication may explain the popularity of this drug combination.*

abstract source - I was unable to locate the full study.
*emphasis added myself.

Nippon Hoigaku Zasshi. 1992 Feb;46(1):32-48.

The effect of ethanol on the metabolism of methamphetamine

[Article in Japanese]

Ochiai T.

Department of Legal Medicine, Showa University School of Medicine, Tokyo, Japan.

In order to clarify the effects of ethanol (EtOH) on metabolism of methamphetamine hydrochloride (MA-HCl), the plasma and urine samples were taken from three groups of three male crab-eating monkeys (Macaca fascicularis). MA-HCl was given to the first group, both MA-HCl and EtOH were given once to the second group, the after consecutive administration of EtOH for four weeks, both MA-HCl and EtOH were given to the third group. Comparisons were made of the sequential change in the concentration of unchanged methamphetamine (MA) and its supposed metabolites, amphetamine (AP), p-hydroxymethamphetamine (p-HOMA), and p-hydroxyamphetamine (p-HOAP). Additional hematological and plasma-biochemical tests were performed to monitor the influences under the administration of MA-HCl and EtOH on the animals. For the extraction of MA and its metabolites from blood and urine, a solid phase extraction was carried out with which an excellent recovery was achieved. Gas chromatography mass spectrometry (GC-MS) was used to measure the metabolites after changing them to the form of TFA derivative, producing good results. EtOH concentration in the blood was measured by GC using a head-space method. The biological half-life (t1/2) of MA tended to be shortened slightly in the plasma when EtOH was given consecutively. The maximum concentration of AP obtained by administration of EtOH was half that obtained by single administration of MA-HCl and the detectable time was shortened.* A high concentration of p-hydroxy metabolites that the been almost undetectable when both MA-HCl and EtOH were administered once, was detected when EtOH was administered consecutively, compared with that when only MA-HCl was administered. Particularly, considerable amounts of p-HOAP was detected even after 72 hours. The trends seen in the excretion of MA and its metabolites into the urine were the same as seen in their plasma concentrations, although there was a difference in the detectable time. The urine collected in a metabolic cage for the monkey was contaminated with drinking water, so that the total amounts of metabolites, rather than sequential change as in the case of plasma, were considered to be of greater significance. When EtOH was administered consecutively, the excreted amounts of p-HOAP in the urine increased saliently and characteristically.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID: 1597931 [PubMed - indexed for MEDLINE]

abstract source - I was unable to locate the full study.
*emphasis added myself.


The duration of methamphetamine will be slightly reduced if you continue to administer successive alcohol doses.

 

[Psychadelic_Paisly]

Thanks CMB I could almost kiss you... if you know... I was that way inclined hehe

Now I guess the only thing to cap this thread off would be for P_D to throw in some cool organic chem pics and confusing diagrams! You got it in you P_D? That's right, I've given you a challange!!!! GO FOR IT MY SON!!!!!!!!!!!!


*excuse my retardedness.... currently on the concoction I'm disscussing...*

But that challange still stands P_D..... hey, that's kind of like that challange they have for that metal guy on JJJ..... well.... not really..... I'm going now............... I'm gonna regret this post tomorrow.........

 

[AndyzPsylocybes]

yeh... what the fuck are you talking about man ! haha :D

 

[Cowboy Mac]

You will need to read the post, and the bolded emphasis are parts I thought were pertinent to pp's question.

Just wondering, what could be the cause, if any, that when I, mix speed with drinks, it is a much more euphoric, cruisy, yet still tweaked out ride. Even off just a glass or so, I feel almost kind of fuzzy.

The first paper concludes that:

The increased perceived global intoxication may explain the popularity of this drug combination.

I couldn't find any interactions between them both, and it seems that it is simply the combined effects of both drugs rather than any specific interaction that explains the feeling.

The second paper deals with the effect of alcohol on methamphetamine regarding duration, and that if you administer multiple doses of alcohol after you have consumed methamphetamine it reduces the duration of the methamphetamine slightly. A full copy of the paper may detail more information on the pharmacokinetics and possible potentiations/contraindications.

Thanks CMB I could almost kiss you... if you know... I was that way inclined hehe

*raaaaawwww*

edit:

yeh... what the fuck are you talking about man ! haha

I just realised that the comment was about pp's triplej comment. /me hits forehead.

 

[phase_dancer]

Thanks for the excellent posts Mac.

OK Paisly, you are definitely going to regret this...


This paper outlines behavioral patterns in rats with meth and ethanol, and perhaps also explains some of the other......shall we say...er... tendencies associated with speed and booze.

Effects of methamphetamine and ethanol on learning and brain neurotransmitters in rats

Takehiko Yamamura, Shigeru Hishida, Katsuhiko Hatake, Tadaaki Taniguchi and Harumi Ouchi

Department of Legal Medicine, Hyogo College of Medicine 1-1, Mukogawa-Cho, Nishinomiya 663, Japan

Received 11 November 1991. Available online 7 November 2002.


Abstract

The interactions of methamphetamine (MAMP) and ethanol (EtOH) on multiple active/passive avoidance performance and neurotransmitters in different brain regions were examined. After the acquisition schedules, rats were retrained under the influence of MAMP (2 mg/kg/day, IP), EtOH (2 g/kg/day, IP), and in combination over 20 days in rats (n = 6 per group). As a function of progress of drug treatment, MAMP-EtOH mixtures disrupt the learned avoidance performance and produced severe impairment of discriminative behavior caused by enhancement of excitability induced by MAMP when compared with MAMP only.

At withdrawal, MAMP-EtOH-induced impairments of performance significantly persisted, whereas MAMP-only-induced impairments slightly recovered. At the eleventh day of drug withdrawal, MAMP-only-induced alterations of neurotransmitter levels at different regions were alleviated by EtOH, but these did not return to normal levels.

These data provide support for the direct antagonistic and indirect additive interactions following constant daily treatment with a combination of MAMP and EtOH. EtOH may be an important factor in MAMP abuse to MAMP-induced psychosis or neurotoxicity.

Although meth has a long half life - and in my opinion metabolites are also active cardio-vascular stimulants - large doses are rarely reported as fatal, perhaps because other pathways are activated at higher doses and the drug's effective half life is reduced. These could include more MAOB & oxidative enzymes, rate increases in hydroxylation and deamination routes of metabolism, receptor sequestration and other receptor activation as well as increased elimination of unchanged meth. It's fair to assume that any of these might be affected by ethanol - a reactive substance and one for which our body often prioritizes metabolism over other drugs/toxins.

These next papers discuss factors relating to metabolism, with the first paper, while failing to formally conclude much, does indicate the toxicity of meth is extended with ethanol. Both papers posted by Cowboy Mac indicate no change occurs in the pharmacokinetics except for "lowering the apparent volume of distribution at steady state for methamphetamine"

This "steady state" refers to the approximate kinetic rates of the reaction, or more specifically, to the overall rate of production of a product. "Steady State Approximation" assumes the intermediate compound remains constant in concentration throughout the process;

A--ENZYME 1-(rate maybe fast or slow)->Intermediate--ENZYME 2-(rate maybe fast or slow)-->B

In reality things don't quite work like this, particularly with enzyme systems where multiple intermediates may exist, or enzyme or cofactor availability is limited. However it suffices to say that meth distribution is limited when ethanol is present and so the meth remains circulating primarily within the central body. As blood plasma levels are likely to remain higher for longer, this would be expected to add to toxicity, as the level of meth becomes more concentrated in organs such as the liver and heart and perhaps [?] also the brain. [Dr's, please correct me if I'm wrong ].

But, there is some discrepancy regarding metabolism. CM's 3rd paper mentions;

The biological half-life (t1/2) of MA tended to be shortened slightly in the plasma when EtOH was given consecutively.

Yet the second paper below suggests ethanol slows down down metabolism. If this is so, then it also seems reasonable to assume a higher plasma concentration of meth remains active for longer, thereby both presenting a higher toxicity profile, while simultaneously producing less of a peripheral effect due to reduced distribution.

It does appear alcohol has very different actions on meth metabolism if taken together as compared to redosing with alcohol as many people tend to do.

Sudden death due presumably to internal use of methamphetamine

S. Katsumata , K. Sato , H. Kashiwade , S. Yamanami , H. Zhou , I. Yonemura , H. Nakajima and H. Hasekura

Department of Legal Medicine, Tokyo Ika Shika University School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113, Japan

Received 4 March 1993; Revised 4 May 1993; accepted 18 May 1993. Available online 22 March 2004.

DOI

Abstract

A 26-year-old male was found naked and excited in the backyard of his neighbor's house. He was carried to a nearby hospital, and returned home with his family, but took a sudden turn for the worse and died. In a judicial autopsy, the ethanol concentration of blood was found to be 0.58 g/l, and methamphetamine (MA) was detected in his blood by thin-layer chromatography.

The concentration of MA in his blood was 4.38 mol/dl, higher than the fatal level. The amount of MA in his stomach was 5.8 mg (34.58 mol/100 g), indicating that he ingested MA by internal use. Among the autopsy cases of acute MA poisoning reported in Japan, hypersthesia is known to last 1–3 h before death, whether the administration is by intravenous injection or orally. But the present case is quite unusual, as the death followed 6 h or more of hypersthesia. This was attributed to the patient's combined intake of alcohol with MA, as it is known to decrease the mortality in mice.

Urinary excretion of p-hydroxylated methamphetamine metabolites in man. II. Effect of alcohol intake on methamphetamine metabolism

Kazuaki Shimosato

Department of Legal Medicine, Kawasaki Medical School, Kurashiki, Okayama 701-01, Japan

Received 9 April 1987. Available online 7 November 2002.

DOI

Abstract

The effect of drinking alcoholic beverages on methamphetamine metabolism was investigated in man. The subjects, 97 males and 9 females, were divided into three groups by evaluation of their urinary pH; i.e., acidic, subacidic and neutral groups.

The subjects in each group were further divided into ethanol-positive subjects and ethanol-negative subjects, depending on the presence or absence of ethanol in their urine. Gas chromatographic analysis showed the urinary concentrations of methamphetamine in the ethanol-positive subjects to be higher than those in the ethanol-negative subjects in both the acidic and subacidic urinary pH groups.

Liquid chromatography, on the other hand, showed the urinary concentrations of p-hydroxymethamphetamine and p-hydroxyamphetamine for the ethanol-positive subjects to be lower than those for the ethanol-negative subjects in all three groups.

The relative proportions of p-hydroxylated metabolites to unchanged methamphetamine in urine, therefore, were severely reduced in the ethanol-positive subjects. These results suggest that drinking alcoholic beverages probably results in a suppression of methamphetamine metabolism in man.

The following paper examines the reduced sensitivity to meth when taken with ethanol (mice). It may in part also account for why some drinkers tend to consume more speed when partying - (although I also thought it was simply a mixture of greed and exuberance 8(

Decrease in d-methamphetamine sensitivity in mice due to ethanol: Apparent inhibitory and stimulatory effects of ethanol on d-methampheamine-induced locomotor activity

Hirofumi Kohda1, Masumi Funahashi, Ichiro Shikata and Hiroshi Kimura

Department of Legal Medicine, Faculty of Medicine Osaka University, Nakanoshima, Osaka 530, Japan

Received 5 May 1986. Available online 26 November 2002.

DOI

Abstract

The locomotor activity of mice was recorded after administration of d-methamphetamine-HCI (1.5, 2.5, 5.0 and 7.5 mg/kg body weight) and/or ethanol (0.8 and 1.6 g/kg body weight).

Mice injected with lower doses of d-methamphetamine (1.5 or 2.5 mg/kg) showed a marked increase in locomotor activity, while in those with higher doses of d-methamphetamine (5.0 or 7.5 mg/kg), locomotor activity was not further enhanced, but slightly decreased. Administration of ethanol inhibited the stimulated locomotor activity caused by low doses of d-methamphetamine (1.5 or 2.5 mg/kg), while the stimulation of motility after higher doses of d-methamphetamine (5.0 or 7.5 mg/kg) was potentiated by administering ethanol.

Although apparent inhibition and stimulation of d-methamphetamine-induced locomotor activity of mice due to ethanol was observed, it is suggested that mice administered ethanol showed the decreased sensitivity to d-methamphetamine by plotting total locomotor activity of mice against doses of d-methamphetamine administered.

The half maximum effective dose of d-methamphetamine for locomotor activity was increased from 1.5 mg/kg to 3.0 mg/kg by concomitant administration of 1.6 g/kg ethanol.

From the publications listed by CM and in this post, it would seem that metabolism plays a big part, possibly by 2 direct actions; prolonging metabolism and reducing sensitivity. Perhaps this sensitivity in humans relates mostly to the negative affects of meth, thereby allowing the user to increase intake of meth without feeling the usual "orange light" signals that would normally mean time to pull up.

All guesswork on my behalf... but Paisly, if you want pretty chemical pictures then you have to ask a more specific chemistry type question

Bold added for emphasis; p_d

 

[Psychadelic_Paisly]

That was awesome, thanks P_D. Makes for an intersting read that's for sure

*EDIT* As for pictures, I guess it doesn't really matter now since there doesn't appear to be any kind of chemical 'interference' persay between the two chemicals.
Cheers though

 

[Caviar]

a pointful of meth makes the alcohol, go down.

 

[Haki]

Regarding MDMA, I have always found that a slow alcohol administration throughout the night helps things stay grounded enough so you can dance with a bit of flair, move about and not be so knocked out on your ass in the event of a strong pill.

Beer I enjoy to keep you on your feet.

ya.

 

[Fry-d-]

I love a good bump

 

[Splatt]

Don't drink too much. Nothing worse than being awake for the hang over after 20 drinks that night.
Both drugs severley dehydrate you, so remember the water.

 

[lok1]

aallsssoo remeber that when your on any amphetamines (speed.meth.dextro) that you cant acuratly feel how drunk you are. so you may feel 100% sobre but will still blow above the limit.

 

[Haki]

aallsssoo remeber that when your on any amphetamines (speed.meth.dextro) that you cant acuratly feel how drunk you are. so you may feel 100% sobre but will still blow above the limit.

Yes... can't wait for the day when you can use 'I've just snorted a point of speed' is a good excuse for being a little bit over...

ya.

 

[Splatt]

For some strange reason friends and I have found that alcohol testers are actually less likely to pick you up after a medium night of drinking if you have had speed. Any reason for this or were the cops just being lazy?

 

[Caviar]

i loved this when i was meth head