Tolerance, methamphetamine

Tolerance is characterized by reduced responsiveness to the initial effects of a drug after repeated exposure or reduced responsiveness to a related compound (i.e., cross-tolerance). Animal studies have not provided conclusive evidence of tolerance to the effects of the centrally active compounds in toluene or trichloroethane (Moser and Balster 1981 Moser et al. 1985). Observations in humans, on the other hand, have documented pronounced tolerance among subjects who chronically inhale substances with high concentrations of toluene (Glaser and Massengale 1962 Press and Done 1967) and butane (Evans and Raistrick 1987). Kono et al. (2001) showed that tolerance to the reinforcing effects of solvents is comparable to that conditioned by nicotine but less intense than that reported with alcohol or methamphetamine use. 

Seiden, L.S. Fischman, M.W. and Schuster, C.R. Long-term methamphetamine induced changes in brain catecholamine in tolerant rhesus monkeys. Drug Alcohol Depend 1 215-219, 1975-76. 

Fischman, M.W., Schuster, C.R. Tolerance development to chronic methamphetamine intoxication in the rhesus monkey. Pharmacol. Biochem. Behav. 2 503, 1974. 

GHB taken in combination with ecstasy or methamphetamine can lead to the impression in users that their tolerance for the drug has increased far beyond what it actually has. Individuals who report consuming up to five times the normal dose when on speed or ecstasy acknowledge that their average high dose landed them in the hospital when taken alone. 

Ritalin is a mild stimulant. On the contrary, the studies found that Ritalin, although effective in treating the symptoms of ADHD, shows no clear long-term improvement on users and can have dangerous effects on health, including death. Because the effects of Ritalin on humans are virtually identical to those produced by cocaine, amphetamine, and methamphetamine (speed), the researchers noted that its abuse liability is high and can lead to marked tolerance and psychological dependence. 

Other Side-Chain Substitutions. Limited substitution of the side chain is tolerated. A J3-hydroxy group on methamphetamine... 

Methamphetamine Increase in blood pressure Narcolepsy Tremor Marked tolerance occurs... 

PO. Well absorbed, enters CNS, excreted without undergoing metabolism, half-life = 4-6 hrs. Elimination is slowed by alkalination of urine. Often abused. Severe tolerance and dependence. Methamphetamine ( Speed") acts similarly, but is very addictive and often abused. MAO inhibitors hypertensive crisis, CNS overstimulation. Barbiturates supraadditive mood elevation. Tricyclic Antidepressants potentiate CNS stimulation, inhibit metabolism of amphetamine. Overdose treatment Acidify urine. Give chlorpromazine to treat CNS symptoms and alpha-receptor blocker to lower blood pressure. 

Kim, H.S. "Blockade by GinsengTotal Saponin of the Development of Methamphetamine Reverse Tolerance and Dopamine Receptor Supersensitivity in Mice, Plania Medica, 1995, vol. 61, pp. 22-25. 

Methamphetamine also acts as a dopaminergic and adrenergic reuptake inhibitor and as a monamine oxidase inhibitor. It results in stimulation of the mesolimbic reward neuronal network, causing euphoria and excitement. The responses of the brain diminish the effects of cocaine or meth, which results in a "craving to take more and more of the drug to overcome the tolerance and recreate the high. Addiction is the result. 

Evidence has been reported suggesting that the role of catecholamines in analgesia may depend mainly on dopamine or dopamlne/noreplnephrlne ratios.Strong cross tolerance between the analgesic effects of methamphetamine and morphine develops after 5 days administration. ... 

Seiden, L. S., Fishman, M. W. and Schuster C. R. (1976) Long-term methamphetamine induced changes in brain catecholamines in tolerant Rhesus monkeys. Drug Alcohol Dependence, 1, 215. 

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