Physical effects of amphetamine overdose include hypertensive emergency, tachycardia, and cerebrovascular accident (stroke). The cocaine-induced surge in synaptic levels of norepinephrine results in increased activation of postsynaptic alpha-adrenergic receptors in the brain. This gives rise to objective central effects of cocaine, including increased wakefulness, increased respiration, and decreased appetite (upper panel of the figure below). A buildup in synaptic levels of dopamine causes increased activation of postsynaptic dopamine receptors. This will result in subjective central effects of cocaine, including a sense of well-being (euphoria), increased sense of energy, increased sense of confidence, and, at high doses, psychotic behavior (lower panel of the figure below). Another effect of increased dopamine is the activation of the brain’s reward center which contributes to the development of physical dependence.

IV. Part 4. Psychotherapeutic Drugs

• Methylphenidate (0.4 mg/kg i.m.) was also injected into newborn infants with “depression,” describing poor breathing, resulting in a “marked increase in respiratory activity” and “increased crying and bodily activity” (Gale, 1959).
• In addition, licit dextroamphetamine is a substrate for manufacture of illicit methamphetamine, which can then be smoked or injected.
• The actual amount of coca leaves per glass was described by Coca-Cola in an editorial letter as 0.11 g (Candler, 1891), or enough to produce about 0.5 mg of cocaine, less than 0.01 mg/kg in an adult (Jenkins et al., 1995).
• Interestingly, the effects of methylphenidate on the blood-oxygen level–dependent signal varied based on the cognitive requirements of specific parts of the task.
• Additionally, understanding how these Parkinsonian symptoms develop may reveal additional pathways for treatment of the condition and MA use disorder.
• Peripheral vasodilators like nitroglycerin and nicardipine may be effective in lowering blood pressure.

Modafinil (Provigil, Modiodal, Nuvigil) is a psychostimulant that was developed to treat narcolepsy (Bastuji and Jouvet, 1988), and has emerged as the leading therapeutic used to treat sleep disorders. Modafinil is also approved for use with obstructive sleep apnea/hypopnea disorder and shift-work sleep disorder. Recently, numerous off-label applications have been tested, including the treatment of ADHD, Alzheimer’s disease, Parkinson’s disease, depression, and cocaine addiction. In a review of 40 articles on methylphenidate’s effects on ADHD published between 1993 and 2006, 63.5% of the studies identified improvements in cognitive function due to immediate-release methylphenidate (Pietrzak et al., 2006). Measures of planning/cognitive flexibility, attention/vigilance, saccadic eye movement, and inhibitory control showed improvement in roughly 70–83% of the studies. There is some evidence that these benefits may be seen exclusively when neural resources need to be recruited.

Public Health

Ten participants with schizophrenia, currently taking antipsychotics, were administered 0.25 mg/kg d-amphetamine before a series of cognitive tasks. D-Amphetamine improved reaction time on spatial working memory and Stroop tasks in both participants with schizophrenia and controls, and increased language production and improved working memory accuracy in those with schizophrenia (Barch and Carter, 2005). By contrast, an earlier study found either no difference or minor impairments on a range of cognitive tasks (e.g., symbol copy, digit symbol) when those with schizophrenia were administered d-amphetamine (10 or 20 mg; Kornetsky, 1976).

Psychiatric Disorders

Twenty milligrams of amphetamine improved IQ in mentally ill patients by almost a full standard deviation. Scores here (drawn from their Table 1) have been adjusted to a scale of 100, and the Benzedrine group includes subjects tested 90 or 150 minutes after administration (both groups performed similarly). In addition, methamphetamine also results in an increased production of a lipid molecule, ceramide, which speeds up cell metabolism and results in earlier cell death and faster aging (see Fig. 8.7 below). Amphetamine was initially marketed under the name Benzedrine® as a treatment for narcolepsy, obesity, mild depression, and various other medical conditions. Amphetamines were soon seen as being capable of enhancing cognition, which led to their widespread use in academics in the late 1930s. It was also given to World War II bomber pilots and sentries as energy pills to increase wakefulness and reduce fatigue and appetite.

This underscores the importance of providing people who use stimulants access to and education about naloxone (the opioid overdose reversal drug). Other factors in the preference for smokable forms of cocaine and MA include availability and price. Crack is generally less expensive and more available than powdered cocaine hydrochloride and produces, in the initial smoker, a very intense but brief rush (Drug Enforcement Administration, Diversion Control Division, 2019a).

• In an early study of the effects of methylphenidate on “hyperkinetic” children (Sprague and Sleator, 1977), cognitive improvement was found on a difficult test, but not an easy test of short-term memory after methylphenidate administration at a low dose (0.3 mg/kg p.o.).
• At low doses, stimulants produce an increase in wakefulness, attention, and confidence and vigor.
• At this stage, the adverse consequences of cocaine use disorder have probably affected all aspects of the person’s life.
• Long-term use can lead to stimulant use disorder, tolerance, and, upon cessation of use, withdrawal (UNODC, 2019b).

Interestingly, another study in mice found that doses of 10, 30, and 100 mg/kg administered 30 minutes before training impaired learning, whereas doses of 1, 3, 10, and 30 mg/kg i.p., administered immediately following training enhanced learning (Angelucci et al., 1999). It is worth noting that the study by Kopf et al. (1999) found no increase in learning with a 3.0 mg/kg dose of caffeine administered immediately after training, whereas Angelucci et al. (1999) (who used weaker training) did find a significant enhancement in learning with this dose. These findings demonstrate that, although rodent studies are able avoid confounds such as caffeine pre-exposure, attention to the details of the experimental design is still necessary when comparing results. Human PET studies agree with the animal literature in implicating both dopamine and norepinephrine as critical to the mechanism of action of methylphenidate. Oral methylphenidate was shown to block dopamine transporters (DAT) in the human brain, with only approximately 0.25 mg/kg methylphenidate leading to 50% blockage of dopamine transporters (Volkow et al., 1998). Oral methylphenidate, still within the therapeutic range (0.8 mg/kg, on average), dramatically increased extracellular dopamine concentration, with the effect more pronounced in younger participants (Volkow et al., 2001).

General Effects of Stimulants

However, ingestion of some amphetamines, including 3,4-methylenedioxymethamphetamine, will not reliably result in a positive test for the presence of amphetamines.1920 Conversely, some non-amphetamine medications may cause false-positive results for the presence of amphetamines. These drugs include pseudoephedrine,21 mebeverine,22 metoprolol,23 tetracaine,24 dimethylamylamine,25 aripiprazole,26 and ranitidine.27 Thus, clinicians should not rely on drug metabolite testing alone to make a diagnosis of amphetamine toxicity. Obtaining an accurate medication history for how long do amphetamines stay in urine the patient may allow a diagnosis to be made independently of drug metabolite testing. Therefore, obtaining medication histories should always be a focus during the evaluation of patients who are intoxicated. Amphetamine abuse remains prevalent in the United States (US), with significant implications for public health and individual well-being.