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Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Thursday, December 22, 2011

Amphetamines Vault

Amphetamine:

Basic:

The term amphetamine in a general sense, can be used to describe a family of exogenous, usually synthetic, pharmaceuticals classified as "sympathomimetic amines" - which are similar in structure and pharmacology to the endogenous catecholamines or monoamines - specifically dopamine, norepinephrine, and phenylalanine. Compounds of the amphetamine family are built off of a phenethylamine skeleton. Phenethylamines are alternatively described as phenylpropylamines. Amphetamine is the alpha-methyl analogue of phenethylamine.

Amphetamine itself is a widely used psychostimulant drug and is the prototype off of which a series of amphetamine analogues have been built. It is a schedule 2 controlled substance in the US and is therefore used medicinally & illicitly. It is one of the most widely prescribed drugs in psychiatry practice. Amphetamine itself was first synthesized in 1887 Germany.

Use:

In the United States (and elsewhere), Amphetamine is used clinically for the following indications:

30mg prescription amphetamine tablets
Treatment of attention deficit disorder (ADD) & attention deficit hyperactivity disorder (ADHD).

Treatment of resistant cases of major depression.

Treatment of chronic fatigue syndrome & narcolepsy.

Emergency treatment of cardiac arrest & other types of acute cardiac failure.

As a nasal decongestant much like ephedrine or pseudoephedrine.

As an appetite suppressant, typically in obese individuals.

Chemistry:

Amphetamine is an analogue of the phenethylamine class and occurs as a racemic mixture. It is similar in structure to ephedrine & pseudoephedrine. Many analogues of amphetamine have been synthesized. 

Pharmacology:

Amphetamine acts as a traditional stimulant, by producing sympathomimesis - i.e. arousing the fight or flight response of the sympathetic nervous system by promoting the release of catecholamine neurotransmitters such as adrenaline, noradrenaline, and dopamine. Amphetamine increases alertness, energy, and mood, as well as vital functions such as breathing & cardiac output. Blood vessels in these areas dilate while blood vessels in non vital areas constrict - sympathetic arousal entails parasympathetic inhibition. These two systems operate in contrast to each other, maintaining a balanced system whereby the body's resources are mobilized according to current needs.

Sympathomimetic agents act by either directly activating post synaptic receptor sites and mimicking neurotransmitters, or by enhancing the actions of the neurotransmitters themselves.

Amphetamine works by the latter mechanism, specifically targeting reuptake of norepinephrine, dopamine, and serotonin by the following means:

Dopamine & Serotonin: Multiple theories have been proposed as to its exact mechanism. It is generally believed that amphetamine targets DAT and SERT - the presynaptic reuptake pumps for dopamine & serotonin; triggering a series of cellular changes which causes the transporter to function in reverse - i.e. rather than collecting excess dopamine from the synapse like a vaccum, it spits more dopamine or serotonin out into the synapse, basically flooding the synaptic cleft with the neurotransmitter. 

The dopaminergic actions of amphetamine take place throughout the mesolimbic & mesocortical reward pathways of the brain - key areas of these pathways include the striatum, ventral striatum, ventral tegmentum, and the nucleus accumbens. The serotonergic actions of amphetamine seem to be limited to key areas of the brain - for instance, projections of serotonergic neurons which run from the VTA to the prefrontal cortex; in addition to other corticolimbic projections.

Norepinephrine: Amphetamine increases extrecellular concentrations of norepinephrine (i.e. noradrenaline). In this case it is believed to act as a norepinephrine reuptake inhibitor. NE activity is heavily associated with arousal of the sympathetic nervous system - i.e. the fight or flight response, and possibly to a lesser extent, reward.

Effects:

Excitement, euphoria, increased energy, alertness, wakefullness, insomnia.

Amphetamine & amphetamine type drugs tend to produce paradoxial effects in those with behavioral disorders such as ADHD - rather than causing excitation, they produce calmness, concentration, and promote pragmatism over a racing thought process.

Amphetamine is a precursor to countless
other psychostimulants just as morphine
is to other narcotics 
 
Side effects include jitteriness, anxiety, agitation, fight or flight mode (adrenaline rush), hypertension, vasodilation, mydriasis (dilated pupils), bowel stimulation, diuresis. Overdose symptoms include irregular heartbeat, psychotic breaks, extreme confusion, slurred speech, aphasia (inability to speak), lazy eye or crossed-eyes, fear & panic, heart attack, stroke, cardiac arrest & death.

Methamphetamine:

Methamphetamine is the N-methyl analogue of amphetamine. It is one of the most potent psychostimulants in use.

Illicit methamphetamine as it commonly appears
Methamphetamine has a history of medicinal use and is available in the US under the trade name Desoxyn; which is used in the treatment of narcolepsy, chronic fatique, severe depression and obesity.

In the medical setting, the drug is given orally in tablet form. The effective therapeutic dosage for methamphetamine is much lower than dosages reported in the recreational setting, single doses beginning at 5 mg  and daily doses up to 20 mg. When used outside the medical setting, dosages vary depending on the route of administration and user experience. Naive users often attain pleasant and lasting effects with doses of 10-20 mg intranasally, while habitual users may easily exceed 100 mg in a single dose. Many report exceeding 1 gram of methamphetamine daily, while for non tolerant users these doses will surely be toxic. Keep in mind, these figures represent pure methamphetamine intake, they do not reflect variations in cut, bulk & purity.

When used casually or recreationally, methamphetamine is administered by various routes and in various forms. It can be snorted as a powder, injected as a solution, heated to vaporize and smoked in its crystallized form (known as ice or crystal meth), or taken orally. Both insufflation and inhalation are effective as alternatives to injection, they allow good absorbtion and a fairly rapid onset.


The N-methyl substitution of this compound is responsible for the potentiation of its effects, as compared to amphetamine, as it renders the compound more lipophilic, more brain penetrable, and more resistant to destruction by monoamine oxidase enzymes.

Methamphetamine, and its major metabolite amphetamine, bind with dopamine, NE, and serotonin (5HT) reuptake transporters and reverse their direction of flow, thus increasing the overall cellular flow of monoamine transmitters.


Methamphetamine has a plasma half life of around 4-6 hours and may be detected in urine for up to 2 days following a single use. Its effects can endure a few to several hours, depending on the dose and route of administration - 4 to 8 hours is common. Habitual or heavy users may stay awake for days at a time.

Side effects of this drug are the same as those of amphetamine. They include jitteriness, anxiety, agitation, hypertension, vasodilation, mydriasis (dilated pupils), bowel stimulation, diuresis. Overdose symptoms include irregular heartbeat, psychotic breaks, extreme confusion, slurred speech, aphasia (inability to speak), lazy eye or crossed-eyes, fear & panic, heart attack, stroke, cardiac arrest & death.

Long term habitual methamphetamine use is known to have toxic effects on dopaminergic neurons. This often leads to an extended state of depression, fatigue and anhedonia which can last for weeks to months while dopaminergic systems are restored to their original state.

Illicitly produced methamphetamine often contains a large amount of toxic impurities, due to the limited skills  and resources of those who produce the drug themselves. Methamphetamine produced using the new "one bottle" or "shake and bake" method has the potential to be particularly toxic and should be avoided.


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