Soft contact lenses are more adherent to the corneal surface than hard lenses, which allows the Acanthamoeba organism to bind to mannosylated glycoproteins on the corneal surface. Expression of these proteins on the corneal surface is increased by contact lens use. This increase in glycoprotein content, along with microtrauma to the corneal epithelial surface due to contact lens use increases the risk for infection. Once the organism has gained access to the surface of the eye, it is able to invade through the epithelium and Bowmans layer. In some cases, the infection can then group around corneal nerves, producing radial deposits (radial keratoneuritis), and causing extreme pain. These are features also seen in viral and bacterial keratitis, and may be misleading. The organism is also capable of invading deeper into the cornea; using metalloproteases it is able to penetrate deep into the stroma of the cornea. As the disease progresses, it may penetrate through the cornea but very rarely causes infection inside the eye (endophthalmitis) due to a robust neutrophil response in the anterior chamber.While the vast majority of cases of Acanthamoeba keratitis occur in contact lens wearers, there have been many cases of Acanthamoeba described in those who do not wear contact lenses, especially outside the United States. In non-contact lens users, the greatest risks for developing Acanthamoeba infection are trauma and exposure to contaminated water. Further predisposing factors include contaminated home water supply, and low socioeconomic status.
Dependence and withdrawal
Drug tolerance develops rapidly in amphetamine abuse (i.e., recreational amphetamine use), so periods of extended abuse require increasingly larger doses of the drug in order to achieve the same effect. According to a Cochrane review on withdrawal in individuals who compulsively use amphetamine and methamphetamine, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose." This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in roughly 88% of cases, and persist for 3–4 weeks with a marked "crash" phase occurring during the first week. Amphetamine withdrawal symptoms can include anxiety, drug craving, depressed mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and lucid dreams. The review indicated that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence. Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose. Overdose
An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care. The severity of overdose symptoms increases with dosage and decreases with drug tolerance to amphetamine. Tolerant individuals have been known to take as much as 5 grams of amphetamine in a day, which is roughly 100 times the maximum daily therapeutic dose. Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves convulsions and coma.