Amphetamines
Methamphetamine is a very addictive stimulant drug. It can be smoked, injected, inhaled or taken by mouth. It has many street names, such as speed, meth, and chalk. Methamphetamine hydrochloride, the crystal form inhaled by smoking, is referred to as ice, crystal, glass and tina.
Methamphetamine affects the brain and can create feelings of pleasure, increase energy and elevate mood. Abusers may become addicted quickly, needing higher doses more often. Adverse health effects include irregular heartbeat, increased blood pressure and a variety of psychological problems. Long-term effects may include severe mental disorders, memory loss and severe dental problems.
Physical effects of dextroamphetamine can include hyperactivity, dilated pupils, blood shot eyes, flushing, restlessness, dry mouth, bruxism, headache, tachycardia, bradycardia, tachypnea, hypertension, hypotension, fever, diaphoresis, diarrhoea, constipation, blurred vision, aphasia, dizziness, twitching, insomnia, numbness, palpitations, arrhythmias, tremors, dry and/or itchy skin, acne, pallor, convulsions, and with chronic and/or high doses, seizure, stroke, coma, heart attack and death can occur. There is also significant research which highlights the possible neurotoxic effects of amphetamine on the dopaminergic system, even in clinical doses.

Psychological effects
Psychological effects can include euphoria, anxiety, increased libido, alertness, concentration, energy, self-esteem, self-confidence, sociability, irritability, aggression, psychosomatic disorders, psychomotor agitation, grandiosity, excessive feelings of power and superiority, repetitive and obsessive behaviours, paranoia, and with chronic and/or high doses, amphetamine psychosis can occur.

Withdrawal effects
Withdrawal symptoms of amphetamine primarily consist of mental fatigue, mental depression and increased appetite. Symptoms may last for days with occasional use and weeks or months with chronic use, with severity dependent on the length of time and the amount of amphetamine used. Withdrawal symptoms may also include anxiety, agitation, excessive sleep, vivid or lucid dreams, deep REM sleep and suicidal ideation.
 
Side effects
Contraindications
Amphetamine elevates cardiac output and blood pressure making it dangerous for use by patients with a history of heart disease or hypertension. Amphetamine can cause a life-threatening complication in patients taking MAOI antidepressants. The use of amphetamine and amphetamine-like drugs is contraindicated in patients with narrow-angle glaucoma or anatomically narrow angles. Like other sympathomimetic amines, amphetamine can induce transient mydriasis. In patients with narrow angles, pupillary dilation can provoke an acute attack of angle-closure glaucoma. These agents should also be avoided in patients with other forms of glaucoma, as mydriasis may occasionally increase intraocular pressure.
Amphetamine has been shown to pass through into breast milk. Because of this, mothers taking amphetamine are advised to avoid breastfeeding during their course of treatment.

Dependence and addiction
Tolerance is developed rapidly in amphetamine abuse; therefore, periods of extended use require increasing amounts of the drug in order to achieve the same effect.
 
Overdose
An amphetamine overdose is rarely fatal but can lead to a number of different symptoms, including psychosis, chest pain, and hypertension.
 
Psychosis
Abuse of amphetamines can result in a stimulant psychosis that can present as a number of psychotic disorders (i.e. paranoia, hallucinations, delusions). The intensity and duration of symptoms may vary, but unlike true psychotic disorders (i.e. schizophrenia), stimulant psychoses are not considered to be permanent and will eventually resolve upon discontinuation of the drug's use.

Amphetamine exerts its behavioural effects by modulating several key neurotransmitters in the brain, including dopamine, serotonin, and norepinephrine. However, the activity of amphetamine throughout the brain appears to be specific; certain receptors that respond to amphetamine in some regions of the brain tend not to do so in other regions. For instance, dopamine D2 receptors in the hippocampus, a region of the brain associated with forming new memories, appear to be unaffected by the presence of amphetamine.
The major neural systems affected by amphetamine are largely implicated in the brain’s reward circuitry. Moreover, neurotransmitters involved in various reward pathways of the brain appear to be the primary targets of amphetamine. One such neurotransmitter is dopamine, a chemical messenger heavily active in the mesolimbic and mesocortical reward pathways. Not surprisingly, the anatomical components of these pathways—including the striatum, the nucleus accumbens, and the ventral striatum—have been found to be primary sites of amphetamine action.
The fact that amphetamine influences neurotransmitter activity specifically in regions implicated in reward provides insight into the behavioural consequences of the drug, such as the stereotyped onset of euphoria. A better understanding of the specific mechanisms by which amphetamine operates may increase our ability to treat amphetamine addiction, as the brain’s reward circuitry has been widely implicated in addictions of many types.

Endogenous amphetamines
Amphetamine has been found to have several endogenous analogues; that is, molecules of a similar structure found naturally in the brain. l-Phenylalanine and β-Phenethylamine are two examples, which are formed in the peripheral nervous system as well as in the brain itself. These molecules are thought to modulate levels of excitement and alertness, among other related affective states.
 
Dopamine
Perhaps the most widely studied neurotransmitter with regard to amphetamine action is dopamine, the “reward neurotransmitter” that is highly active in numerous reward pathways of the brain. Various studies have shown that in select regions, amphetamine increases the concentrations of dopamine in the synaptic cleft, thereby heightening the response of the post-synaptic neuron.[ This specific action hints at the hedonic response to the drug as well as to the drug’s addictive quality.
The specific mechanisms by which amphetamine affects dopamine concentrations have been studied extensively. Currently, two major hypotheses have been proposed, which are not mutually exclusive. One theory emphasizes amphetamine’s actions on the vesicular level, increasing concentrations of dopamine in the cytosol of the pre-synaptic neuron. The other focuses on the role of the dopamine transporter DAT, and proposes that amphetamine may interact with DAT to induce reverse transport of dopamine from the presynaptic neuron into the synaptic cleft.
The former hypothesis is backed by data demonstrating that injections of amphetamine result in rapid increases of cytosolic dopamine concentrations. Amphetamine is believed to interact with dopamine-containing synaptic vesicles in the axon terminal. Amphetamine is a substrate for a specific neuronal synaptic vesicle uptake transporter called VMAT2. When amphetamine is taken up by VMAT2, the vesicle releases dopamine molecules into the cytosol in exchange. The redistributed dopamine is then believed to interact with DAT to promote reverse transport. Calcium may be a key molecule involved in the interactions between amphetamine and VMATs.
The latter hypothesis postulates a direct interaction between amphetamine and the DAT. The activity of DAT is believed to depend on specific phosphorylating kinases, such as protein kinase c, specifically PKC-β. Upon phosphorylation, DAT undergoes a conformational change that results in the transportation of DAT-bound dopamine from the extracellular to the intracellular environment. In the presence of amphetamine, however, DAT has been observed to function in reverse, spitting dopamine out of the presynaptic neuron and into the synaptic cleft. Thus, beyond inhibiting reuptake of dopamine, amphetamine also stimulates the release of dopamine molecules into the synapse.
In support of the above hypothesis, it has been found that PKC-β inhibitors eliminate the effects of amphetamine on extracellular dopamine concentrations in the striatum of rats. This data suggests that the PKC-β kinase may represent a key point of interaction between amphetamine and the DAT transporter.

Serotonin
Amphetamine has been found to exert similar effects on serotonin as on dopamine. Like DAT, the serotonin transporter SERT can be induced to operate in reverse upon stimulation by amphetamine.[ This mechanism is thought to rely on the actions of calcium ions, as well as on the proximity of certain transporter proteins.
The interaction between amphetamine and serotonin is only apparent in particular regions of the brain, such as the mesocorticolimbic projection. Recent studies additionally postulate that amphetamine may indirectly alter the behavior of glutamatergic pathways extending from the ventral tegmental area to the prefrontal cortex. Glutamatergic pathways are strongly correlated with increased excitability at the level of the synapse. Increased extracellular concentrations of serotonin may thus modulate the excitatory activity of glutamatergic neurons.
The proposed ability of amphetamine to increase excitability of glutamatergic pathways may be of significance when considering serotonin-mediated addiction. An additional behavioural consequence may be the stereotyped loco motor stimulation that occurs in response to amphetamine exposure.