It is important to note that the medical complications of MA may vary depending on the individual, frequency of use, amount of dosage, and/or prior medical attributes.
The “Crash”
When MA is administered in high doses and then discontinued, dysphoria or the “crash” sets in.[1] The crash is characterized by symptoms of depression, anxiety, agitation, and intense drug craving.[2] The symptoms are mild in instances when the dosage is lower. Higher doses and binges, however, can cause a crash that is similar to unipolar depression with melancholy and suicidal ideation. This can occur in individuals who do not have a history of depression, suicidal ideation, or suicide attempts.[1] These symptoms typically stop when the crash, which may last for a few days, is over.[1,3]
Clinical management of a crash occurs in two stages. First, the user is placed under observation to prevent self-harm and to recover from the depressed/agitated mood by getting some sleep. The second stage is to conduct an evaluation after sleep to make sure that neurovegetative symptoms and symptoms such as suicidal ideation have stopped. Usually, the clinical management can be done without hospital admission.[1]
Withdrawal
Following the crash, MA users who have developed a dependence on the drug will experience withdrawal symptoms. These symptoms are generally the opposite of those associated with MA intoxication, and they can include fatigue, craving for sleep, increased appetite, loss of physical and mental energy, depression, anhedonia (inability to experience pleasure), increased appetite, limited interest in one’s surroundings, and impaired social functioning. The symptoms may increase in intensity over the 12 to 96 hours immediately following the crash, or they may wax and wane over several weeks. A severe and persisting depression in this phase can result in suicidal ideation or suicide attempts and is a major concern for the user. In the protracted withdrawal phase, periods of drug craving may reemerge. These cravings are often triggered by conditioned environmental cues and can only be extinguished by sustained abstinence. Some authors have reported that the use of medications for treating MA withdrawal is generally of little value. And if any treatments are provided, they should be specific to the symptoms presented.[3,4]
Neurotoxic Effects
The physiological function of the striatal (nuclus accumbens, caudate, putamen) region of the brain may be highly impaired in long term MA users because there are reduced levels of dopamine and decreased dopamine receptor function linked to decreased stimulation of adenylyl cyclase activity in that part of the brain.[5] Such changes in the dopamine system of the brain can cause decreased motor speed and impaired verbal learning.[6]
Studies using Magnetic Resonance Imaging (MRI) of people with MA addiction have indicated structural changes in the brain. Loss of grey matter was seen in the cingulate, limbic, and paralimbic cortices of MA users, as well as a smaller hippocampi and white-matter hypertrophy.[5,7] In addition, those who were long-term MA abusers had enlarged striatum and slight alterations in their cerebral vasculature. Magnetic Resonance Spectroscopy (MRS) in MA users indicated that neuronal damage does occur in drug users, with damage to the frontal regions of the brain and the basal ganglia.[5]
Cognitive Effects
Neuropsychological deficits can be byproducts of long-term MA use. There has been repeated evidence indicating that specific impairments in working memory, attention, and executive functioning occur due to long-term abuse. Attention deficits seen in MA users may be related to cognitive inhibition and an inability to suppress irrelevant task information. The executive functions impaired by MA use include abstract reasoning, planning, and behavioral flexibility. These deficits mimic those observed in attention-deficit hyperactivity disorder (ADHD). Episodic memory is also hindered by continued MA use, as measured by impairments in word recall tasks.[5]
Pulmonary Arterial Hypertension
Recent evidence suggests an association between methamphetamine use and pulmonary arterial hypertension (PAH).[8] The pathogenic link between methamphetamine use and pulmonary vascular disease is not yet known, but various theories exist. Proposed mechanisms include toxic endothelial injury, hypoxic insult, direct spasm, vasculitis, and dysregulation of the mediators of vascular tone.[9.10]
Mental Health
MA psychosis can develop over time in regular users. Gradually, abnormal behaviors develop: for example, feelings of being watched evolve into paranoid delusions; visual hallucinations start with fleeting glimpses of just recognizable images in the peripheral vision, and later they become fully formed and stable; auditory hallucinations begin with hearing simple noises.[11-13] Research in Japan, where MA use has been prevalent for decades, indicated that between 36 and 64% of MA users who have had psychotic symptoms continue to present with those symptoms for more than 10 days after stopping MA use, even though the MA is eliminated from the bloodstream in less than 5 days. This work also indicated that users with MA psychosis are much more likely to experience psychotic symptoms again if they use MA and are also more likely to have a psychotic relapse when confronted with stressful situations.[5,14]
Self-injurious behavior can result after administration of high or repeated doses. These behaviors include self-biting, head banging, scratching, cutting, hair pulling, and other forms of tissue damage. In addition, chronic use of MA can cause users to scratch at “crack bugs” (delusion that bugs are crawling under the skin), resulting in sores and skin abscesses on the body. It has also been reported that some MA users have severely and repeatedly mutilated their own genitalia while on MA.[13]
Methamphetamine induced acute psychotic episodes and persistent paranoid psychoses are often treated with typical antipsychotics such as the dopamine D2 receptor antagonist haloperidol (HAL). This treatment strategy presumably counteracts the effects of acute meth-induced increases in dopamine release and a host of psychiatric symptoms typically associated with increased dopamine transmission. Recent research, however, has raised the possibility that the use of haloperidol may be contraindicated as it may dispose some individuals to the development of hyperkinetic movement disorders and seizures.[15]
Oral Health
Oral health problems are commonly associated with methamphetamine abuse. MA users are hyperactive and often limit eating and drinking during periods of acute drug use, leading to dehydration and dry mouth. MA also causes reduction in saliva secretion by stimulating the inhibitory α2 receptors. The saliva that is produced is high in protein, further exacerbating oral dryness. Compounding this problem further, when MA users do drink, they often consume caffeinated soft drinks high in sugar content. Additionally, when bingeing, MA users may not practice any oral hygiene.[16]
As a result, MA users often develop caries. Frank coronal lesions are preceded by decay involving the facial and cervical areas of the maxillary and mandibular teeth. Tooth wear can be further exacerbated by bruxism, as acute MA administration often causes users to grind their teeth and clench their jaws. Finally, the motivation to obtain dental care can be limited, as MA users sometimes do not report pain, even in the presence of severe caries.[16]
HIV/Sexually Transmitted Infections
MA is known to create effects that alter judgment and inhibitions, leading people to engage in unsafe behaviors, thus elevating the risk of HIV transmission.[6] The primary route of transmission for HIV and other infectious diseases among injection drug users is sharing contaminated needles, syringes, or other paraphernalia. Since MA alters judgment and inhibitions, MA users are more likely to share paraphernalia and instigate such transmission.[6]
MA abuse can elevate the transmission of HIV not only in individuals who inject the drug, but also in those who use other routes of administration [6], largely because MA users often experience an increase in their libido. Such an increase can lead to promiscuity, compulsive masturbation, or prolonged intercourse. Moreover, users who had abnormal sexual adjustment before their use of the drug may be at increased risk for promiscuity, prostitution, and sadomasochistic behavior.[13] Factors such as promiscuity and prostitution not only escalate the risk of sexually transmitted infections (STI) for MA users, but for their partners as well.[17]
On the other hand, MA abuse can sometimes become a partial substitute for or inhibit sexual activity. For example, some users report that the effects of MA may become more rewarding than sex or resemble sexual experiences such as an orgasm. In addition, some MA users have reported that they have a decreased interest in sex and sometimes experience impotence.[13]
The emergence of risky sexual behavior due to MA abuse has had substantial repercussions for the homosexual and bisexual communities of men.[6,17] HIV positive men who have sex with men and engage in MA-driven sexual activity report high rates of unprotected anal sex and low rates of condom use. Furthermore, they are more likely to have multiple sex partners, participate in sexual marathons, and engage in anonymous sex.[17] Heterosexual men and women are also endangered by MA use. They are more likely to engage in risky sexual behaviors such as having multiple sex partners, anonymous partners, and unprotected sex.[6]
HIV may cause more neuronal injury and cognitive impairment in MA abusers than in non-drug abusers.[6] Consequently, by using MA, persons who are HIV positive may worsen the progression of their HIV and its health effects.
Death
The two most common reasons for death due to MA use appear to be (1) when new users who have not developed a tolerance administer a dose as high as that used by an experienced user or (2) when a user takes a high dose after a period of withdrawal during which the user’s tolerance had decreased.[13] Mechanisms responsible for deaths include [18]: