Sprout
Bluelight Crew
- Joined
- Oct 13, 2009
- Messages
- 7,377
What Is It?
Methamphetamine is perhaps the pinnacle of a stimulant psychotropic and infamous in almost every corner of the world where it is equally prohibited, controlled and demonised. Existing as the N-Methyl analogue of Amphetamine, its genesis began with the creation of its predecessor, the quintessential phenethylamine stimulant that is, Amphetamine in 1887 - the evolution to Methamphetamine came in 1893 by Dr. Nagayoshi who produced the racemic form. In 1919 the world was introduced to the enantiomerically pure D-Methamphetamine via the work of Dr. Ogata using the very same RP/I reduction of Ephedrine still used today in clandestine laboratories.
Methamphetamine was largely ignored for decades until it was utilised mainly by the Axis forces of WWII in oral capsules designed to keep soldiers fighting through the exhaustion, malnutrition and sheer terror they were exposed to daily under the name "Pervitin".
Methamphetamine Pharmacology
Acting as the prototypical Triple Releasing Agent, Meth causes floods of Dopamine (DA) to be released from pre- to post-neuronal receptors across the synaptic space, a similar action takes place with Serotonin being released from vesicles in a reversal of the usual gradient through VMAT2 and TAAR1 activity. These two functions are responsible for the "rush" and euphoria associated with rapid administration of Meth, alongside permeating the blood brain barrier with ease. The physical stimulation, and subsequently the cardiopulmonary overexertion that leads to death via hypoxia, cerebral aneurysms, myocardial inarctions results from the effect of the innate excitatory impulse molecules of Norepinephrine and from there - Acetychloline, which controls the dilation, relaxation, contraction and function of muscle and vascular walls. The long term use of Meth, and any powerful stimulation, leads to progressive death of heart muscle and tissue along with impairing the functionality of large portions of the heart anatomy - right-sided heart failure and damaged valves induce hypoxic anaemia and symptotology of Heart Failure (weakness, fatigue, arrythmia, bradycardia, fainting, cyanosis).
Methamphetamine Neurotoxicity
Methamphetamine is widely and predictably considered the most inherently neurotoxic recreational drug, inducing cell death via signalling cascades, oxygen deprivation, acidosis, dehydration, and most importantly: blockade of the Ca2+ channels in the endoplasmic reticulum (ER) of cells. The Calcium gradient in the ER is used to begin the process of the apoptotic pathway - both through self-degradation of the membrane structure and massive secretion of lytic enzymes by lysozomes to decompose into waste to be recycled.
Anatomical Neurotoxicity
Post-exposure rats display marked destruction of the striatum, Ventral Tegumental Area and large swathes of the Mesolimbic System connectome due to the synthesis and massive concentration and activity of DA in these brain regions. The Amygdala and Hippocampus suffer massive damage again due to unmediated Calcium efflux and it is this impairment that interferes with perceived risk-reward processing and the relative value of experiences and the motivation to perform them.
Chronic exposure in addiction has a cumulative deleterious effect on the Prefrontal Cortex associated with a loss of impulse control once the dendritic pruning and apotptosis impairs the connectivity of the rPFC and the Midbrain (mesolimbic system as above) causing increases in risk-taking behaviours and reactivity to social and environmental cues (paranoid delusional psychotic states occur readily).
Molecular Neurobiology of Toxicity
Mediation of the incredibly destructive force of Methamphetamine on the neurological system has been shown to occur via the action of Neuropeptide Y (NPY) - "In physiology, neuropeptide Y (NPY) is a peptide chemical messenger secreted by the hypothalamus, that portion of the brain that controls hunger, thirst, fatigue, and body temperature. NPY plays a role in various basic processes in the brain, including energy regulation, memory formation, and seizure activity. The main effect of NPY is to promote increased food intake and decreased physical activity in response to a plummeting blood sugar level. In addition to increasing food intake, it increases the percentage of calories stored as fat and blocks pain receptor signals to the brain. NPY also increases constriction of blood vessels."
NPY gene transcription is massively amplified during Meth exposure as a defensive mechanism against reactive oxidation of neuronal bodies via Y1 binding leading to improved Ca2+ regulation and transport in the Mitochondria (Mt) and S/RER. A downstream effect is the suppression of pain signals, physical discomfort, regulated metabolism and antagonism of the toxic mechanics Meth induces.
Neuropeptide S also plays a major role in toxicty, regulating wakefulness, thirst, energy and reduces excitotoxic cellular damage in a complimentary relationship with NPY. The combined effect of NPY/S and Substance P can be contrasted in the formers' reduction and increase in the latter of Reactive Nitrogen Species and oxidative by-products.
Interestingly, NPS actually prevents the Parkinsonian Dopaminergic destruction induced by MPP+.
An increase in transcription of VMAT2 is associated with massive reductions in many mechanisms of neurotoxicity but with an unexpected increase in basal DA concentration, alongside reducing innate inflammation and retaining immunological function via compartmentalisation of the biogenic amines NE, SE, DA and Histamine into sealed vesicles, thus preventing their deleterious impact in excess.
Methamphetamine is perhaps the pinnacle of a stimulant psychotropic and infamous in almost every corner of the world where it is equally prohibited, controlled and demonised. Existing as the N-Methyl analogue of Amphetamine, its genesis began with the creation of its predecessor, the quintessential phenethylamine stimulant that is, Amphetamine in 1887 - the evolution to Methamphetamine came in 1893 by Dr. Nagayoshi who produced the racemic form. In 1919 the world was introduced to the enantiomerically pure D-Methamphetamine via the work of Dr. Ogata using the very same RP/I reduction of Ephedrine still used today in clandestine laboratories.
Methamphetamine was largely ignored for decades until it was utilised mainly by the Axis forces of WWII in oral capsules designed to keep soldiers fighting through the exhaustion, malnutrition and sheer terror they were exposed to daily under the name "Pervitin".
Methamphetamine Pharmacology
Acting as the prototypical Triple Releasing Agent, Meth causes floods of Dopamine (DA) to be released from pre- to post-neuronal receptors across the synaptic space, a similar action takes place with Serotonin being released from vesicles in a reversal of the usual gradient through VMAT2 and TAAR1 activity. These two functions are responsible for the "rush" and euphoria associated with rapid administration of Meth, alongside permeating the blood brain barrier with ease. The physical stimulation, and subsequently the cardiopulmonary overexertion that leads to death via hypoxia, cerebral aneurysms, myocardial inarctions results from the effect of the innate excitatory impulse molecules of Norepinephrine and from there - Acetychloline, which controls the dilation, relaxation, contraction and function of muscle and vascular walls. The long term use of Meth, and any powerful stimulation, leads to progressive death of heart muscle and tissue along with impairing the functionality of large portions of the heart anatomy - right-sided heart failure and damaged valves induce hypoxic anaemia and symptotology of Heart Failure (weakness, fatigue, arrythmia, bradycardia, fainting, cyanosis).
Methamphetamine Neurotoxicity
Methamphetamine is widely and predictably considered the most inherently neurotoxic recreational drug, inducing cell death via signalling cascades, oxygen deprivation, acidosis, dehydration, and most importantly: blockade of the Ca2+ channels in the endoplasmic reticulum (ER) of cells. The Calcium gradient in the ER is used to begin the process of the apoptotic pathway - both through self-degradation of the membrane structure and massive secretion of lytic enzymes by lysozomes to decompose into waste to be recycled.
Anatomical Neurotoxicity
Post-exposure rats display marked destruction of the striatum, Ventral Tegumental Area and large swathes of the Mesolimbic System connectome due to the synthesis and massive concentration and activity of DA in these brain regions. The Amygdala and Hippocampus suffer massive damage again due to unmediated Calcium efflux and it is this impairment that interferes with perceived risk-reward processing and the relative value of experiences and the motivation to perform them.
Chronic exposure in addiction has a cumulative deleterious effect on the Prefrontal Cortex associated with a loss of impulse control once the dendritic pruning and apotptosis impairs the connectivity of the rPFC and the Midbrain (mesolimbic system as above) causing increases in risk-taking behaviours and reactivity to social and environmental cues (paranoid delusional psychotic states occur readily).
Molecular Neurobiology of Toxicity
Mediation of the incredibly destructive force of Methamphetamine on the neurological system has been shown to occur via the action of Neuropeptide Y (NPY) - "In physiology, neuropeptide Y (NPY) is a peptide chemical messenger secreted by the hypothalamus, that portion of the brain that controls hunger, thirst, fatigue, and body temperature. NPY plays a role in various basic processes in the brain, including energy regulation, memory formation, and seizure activity. The main effect of NPY is to promote increased food intake and decreased physical activity in response to a plummeting blood sugar level. In addition to increasing food intake, it increases the percentage of calories stored as fat and blocks pain receptor signals to the brain. NPY also increases constriction of blood vessels."
NPY gene transcription is massively amplified during Meth exposure as a defensive mechanism against reactive oxidation of neuronal bodies via Y1 binding leading to improved Ca2+ regulation and transport in the Mitochondria (Mt) and S/RER. A downstream effect is the suppression of pain signals, physical discomfort, regulated metabolism and antagonism of the toxic mechanics Meth induces.
Neuropeptide S also plays a major role in toxicty, regulating wakefulness, thirst, energy and reduces excitotoxic cellular damage in a complimentary relationship with NPY. The combined effect of NPY/S and Substance P can be contrasted in the formers' reduction and increase in the latter of Reactive Nitrogen Species and oxidative by-products.
Interestingly, NPS actually prevents the Parkinsonian Dopaminergic destruction induced by MPP+.
An increase in transcription of VMAT2 is associated with massive reductions in many mechanisms of neurotoxicity but with an unexpected increase in basal DA concentration, alongside reducing innate inflammation and retaining immunological function via compartmentalisation of the biogenic amines NE, SE, DA and Histamine into sealed vesicles, thus preventing their deleterious impact in excess.
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