sauppers

Substance Abuse and Addiction
Uppers

INTRODUCTION -- OVERVIEW
CNS stimulants, or uppers, in general either mimic or directly increase the electrical activity of the CNS. If this stimulation continues or if the effect of the drug is particularly profound (as with using a very high dose) then the action may suddenly terminate. In abuse circles, this is called the "crash" and pharmacologically may be due to either neurotransmitter depletion or nerve fatigue.

The major side effects of stimulants involve

The CNS -- nervousness, irritability, restlessness, insomnia, anorexia, paranoia, and aggression

Note that chronic abusers will show weight loss while on uppers. This is a result of both the anorexiant properties of the drug (the feeling of hunger satisfied) and the choice of drug over food that is common with most abused drugs.

COCAINE
Cocaine is an alkaloid derived from Erythroxylon coca. The history of its use and abuse is long and varied. Modern use did not begin until the late 19th century, when it appeared as the hydrochloride salt in beverages (Vin Mariani®, Coca-Cola®) and patent medicines and was promoted by professionals such as Freud and Kohler. In addition to the oral dosage forms, it was also injected. During the 20th century, the salt form is snorted and, with the development of free base (not the salt) of the drug as "freebase" and "crack", and smoked.

Mechanistically, cocaine both blocks the re-uptake (re-storage) and stimulates the release of neurotransmitters, mediating the following effects:

Other effects of cocaine include local anaesthetic action that may numb the nasal mucosa when snorted and cause arrhythmias. Additionally, it will stimulate those nerves that mediate itch (an effect called formication). Cocaine addicts who experience these "cocaine bugs" have been observed to scratch themselves bloody in response to this effect.

Withdrawal with cocaine is associated with anhedonia (cannot feel pleasure), anergia (no energy, listless -- including sedation, reduced blood pressure and heart rate), euthymia (the good feeling described above in the cycle), and craving.

Cocaine may often be adulterated with fillers. These will often contribute non-sterile particular components (talc, baking powder) that could lead to infection, or a worsening of the side effects (local anaesthetics are sometimes used -- these increase the risk of life-threatening arrhythmias).

If the dose is high enough to be fatal, the user may die of convulsions, cardiac arrest, or respiratory depression. NOTE that at high doses cocaine will directly cause seizures by direct CNS stimulation. However, if the drug is taken at a dose lower than that required to produce seizures over a long period of time, seizure may appear anyway -- a process called pharmacological kindling. Cocaine use during pregnancy may cause stillbirth and/or abortion due to its stimulant effects. Additionally, the hypertension produced in the mother would predispose her to eclampsia and potential harm to both her and the child. Moreover, if the child is born during use, it may be physically addicted and suffer from withdrawal following removal of the drug source (the mother's womb).

The compulsive use of cocaine is encouraged by its euphoric effect. Other factors that often lead to use include boredom, attempts to achieve the intense rush produced by the first time use (rarely if ever achieved), attempts to avoid the crash, and other emotional/environmental factors previously discussed.

Smokable Cocaine -- although cocaine hydrochloride can be smoked, the temperatures needed to melt it are high enough that a large portion of the active cocaine is destroyed. The development and availability of the free base introduced a new route of absorption for cocaine (the free base melts at a lower temperature, preserving the integrity of cocaine). Inhalation of "freebase", "crack" or "rock" produces an extremely fast (absorbed faster) and intense rush compared to snorted cocaine. "Freebase" is typically more pure than "crack" cocaine ("crack" was developed as a cheaper shortcut in producing "freebase" and yielded smaller rocks or nuggets that could be sold as individual dosage units -- rather than a gram of "freebase" out of which the user could get more that one hit, he may buy one hit of "crack". It is called "crack" for the crackling sound that is made during is processing.) While on a gram per gram basis, "crack" is more expensive that "freebase", its sale in smaller one or two hit packs make it more affordable to young or poorer abusers.

Polydrug Abuse -- As noted above cocaine may be combined with other drugs for polydrug abuse (there are studies that support the view that if a person abuses one drug, then they are much more likely to abuse a second drug). Smokable cocaine is often combined with the following:

AMPHETAMINES
Mechanistically, amphetamines exert their effects by a different action that cocaine, but the result is the same. The reason for this is that they also stimulate the same CNS nervous systems as cocaine. However, amphetamines prompt the release of the NT and, except at high doses, do not directly stimulate the post-synaptic receptor. Additionally, they do not affect the cholinergic system (acetylcholine) to any great effect.

Historically, amphetamine was synthesised in 1887, but not used medically until the 1930s, when it was promoted to treat low blood pressure. In the 1950s and 1960s, its use as an anorexiant was widely promoted among physicians. From the 1960s on, abuse of amphetamines increased. Currently, crank is probably the most widely abused form of amphetamine.

Much of the street amphetamine is produced local to the area it is sold. Formerly, synthesis was complicated and usually emitted toxic, explosive, and noxious fumes, which predisposed the laboratory to fires and discovery by the law. Newer techniques in the manufacturing process have eliminated many of these problems. Synthesis of amphetamine analogues is high due to 1) potential profit, 2) ease of synthesis, and 3) attempts to synthesise compounds that are not controlled and therefore, not illegal.

The most common routes of amphetamine administration include snorting (which can cause permanent injury to the nasal septum), shooting (or injecting, which is painful due to the drug or vehicle), and smoking (which avoids the adverse effects of the first two and also results in a faster and more intense high). The duration of effect, regardless of route, is typically 4 to 6 hours (as opposed to 40 min to 1 ½ hrs for cocaine), although the effects of some smokable amphetamine is reported to last 8 to 12 hrs.

Physiologically, the effects of amphetamine include tachycardia, hyperpyrexia, elevated blood pressure, tachypnea, bronchodilatation, and CNS stimulation. Curiously, another effect often observed in amphetamine abusers is poor dental health. Tolerance develops rapidly to its effects. Among the CNS effects, euphoria and a sense of well-being often are replaced with aggression and paranoia with long-term use. (Ice is said to produce more euphoria with less risk of cardiovascular side effects, which may or may not be the case but would account for its popularity.)

AMPHETAMINE CONGENERS

Anorexiants -- these agents are used in medical practice to suppress appetite in weight loss programs. The drugs include fenfluramine (Pondimin®), dexfenfluramine (Redux®), and phentermine (Ionamin®, Adipex-P®). Again, there may be more abuse by the physicians overprescription than street use of these agents. Fenfluramine and dexfenfluramine are not currently available due to valvular effects leading to cardiovascular death. However, recent clinical evidence has shown that the risk of valvular defect may not be as great as previously thought and, consequently, the drugs may re-appear in the medical community.

LOOK ALIKES/OVER THE COUNTER PRODUCTS

Adrenergic agents, used primarily to treat nasal congestion and asthma or as diet aids, such as ephedrine, pseudoephedrine, phenylpropanolamine, and caffeine, may be abused by the public. Although the potential for euphoria/well-being or reward is not high for these agents, their ability to prevent sleep may predispose their abuse. (As seen especially with students and long-haul truckers.) Often their benefits are out-weighed by the potential danger of avoiding sleep and rest. NATURALLY OCCURRING STIMULANTS

Catha edulis

Betel nuts are commonly abused in the South Pacific and to some extent in this country. They are the seeds of Areca catechu and the active constituent is arecoline. Their action is very similar to nicotine in that they stimulate both the parasympathetic and sympathetic nervous systems. Betel nuts are often chewed with leaves of other plants such as mint or "limed" to improve their palatability. Chronic chewing may result in staining of teeth and an increased risk of oral carcinoma. The incidence of cancer is even greater in those who also use alcohol extensively and either smoke or chew tobacco.

Yohimbe, the common name for the African tree Pausinystolia yohimbe, yields the active constituent yohimbine. It is a mild stimulant but used and abused primarily for its purported efficacy in male impotence.

Ephedra or ma huang is a mild stimulant from the Chinese bush Ephedra sinica. The active constituent, ephedrine, produces mild CNS stimulation, decongestant, and bronchodilatory activity. Currently it is used among the American population as one-half of the herbal fen-phen combination to aid in weight loss. (The other half of herbal fen-phen is St. Johns Wort.)

Caffeine, perhaps the most widely abused stimulant in the world, is derived from numerous sources including coffee (Coffee arabica), tea (Thea sinensis), chocolate (Theobroma cocoa), and cola soft drinks (Cola nitida). Caffeine is a methylated xanthine alkaloid that produces mild CNS stimulation through the inhibition of the enzyme phosphodiesterase. This prolongs the effect of neurotransmitters (particular noradrenaline). Medically, caffeine is used primarily as an adjunct to analgesia (it increases the pain killing effect of aspirin). Side effects of caffeine include irritability, arrhythmia, and increase acid secretion in the stomach. High doses may decrease fertility and increase neonatal blood pressure, which could harm the foetus. There is also an unproven correlation between caffeine intake and breast cancer. Tolerance develops to the effect of caffeine and physical dependence will produce withdrawal symptoms upon discontinuation of the drug -- headache, fatigue, lethargy, depression -- up to one week following the last intake. Generally use of greater than 500 mg of caffeine will cause physical dependence. However, intake of as little as 100-200 mg/day over a long period of time may lead to dependence with physical withdrawal upon discontinuance of the source.

NICOTINE
Nicotine is derived primarily from Nicotinia tabacum, a new world plant. Although used since pre-history by American aboriginals, its used did not reach Europe until the import of tobacco following colonisation by Britain, France, and Spain. Cigar and pipe, as well as hand rolled cigarette, smoking, while popular all the way through the 19 century, was not the primary form of abuse. Smoking did not surpass chewing/dipping/snorting tobacco until after the Great War, when advances in technology allowed the mass production of pre-rolled cigarettes. Cigarette smoking then escalated and is currently to most popularly used form of tobacco.

Pharmacology of Nicotine
Nicotine acts as an agonist at cholinergic nicotinic sites, primarily in the brain and nervous system ganglia. This action fires the nerves, causing the release of other neurotransmitters such as

2) nicotine stays associated with the receptor longer than the endogenous ligand acetylcholine. This could prevent acetylcholine from binding to the receptor and preventing further stimulation. Hence, after the initial stimulation, the effect would be reduced stimulation and, therefore, a calming effect.

3) The calming effect could be psychological, due to the person feeling they had avoided withdrawal by taking a hit or by actually preventing nicotine withdrawal.

Tolerance develops relatively rapidly to the effects of nicotine. This may be (but is not always) accompanied by increased use (this will be discussed more below). Withdrawal is characterised by headache, nervousness, fatigue, hunger, irritability, decreased concentration, sleep disturbances, and craving.

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Severe acute toxicity is relatively rare and involves life-threatening cardiovascular effects (tachycardia, hypertensive crisis, arrhythmia).

The chronic toxic effects of nicotine use are relatively insidious, which is one of the dangers of prolonged tobacco use. The overall effect of chronic tobacco use in a decrease in longevity (on the average, about 8 years are taken off the life-expectancy of chronic smokers) with a decrease in quality of life, due to a higher incidence of medical problems, increased fatigue, and therefore decreased physical activity. With smoking tobacco, this overall effect is due to

Respiratory effects -- cancer (due more to the tar and other burned components that to the nicotine, although nicotine may be a co-carcinogen), emphysema, bronchitis, chronic obstructive pulmonary disease. (Note that while still a risk, lung cancer does not occur as often with cigars and pipes, because they do not burn as intensely as cigarettes. These forms of administration also have a high risk or mouth, oesophageal, and pharynx/larynx cancer.)

(NOTE that many of these effects, both cardiovascular and respiratory are due, not only to the nicotine and tar, but also to the gases produced upon burning, especially carbon monoxide, CO.)

(ALSO NOTE that these effects may be passed on to non-smokers via second-hand smoke. The potential for risk is, of course, due to level and frequency of exposure.)

Direct CV effects of nicotine -- tachycardia and hypertension which may lead to stroke, heart attack. and coronary/cerebral artery disease.

Sociological summary -- Tobacco use has a high level of publicity and public awareness. This is due to large personal interest groups, massive amounts of advertising and lobbying dollars laid out by the tobacco industry, and congressional and judicial intervention in regulation of tobacco use.