The acute effects of methamphetamine include increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), pupil dilation and hyperglycemia (increased blood sugar). A person who ingests meth will experience an increased focus and mental alertness, the elimination of the subjective effects of fatigue and a decrease in appetite. Continued high doses of methamphetamine produce anxiety reactions during which the person is fearful, tremulous and concerned about his well-being; an amphetamine psychosis in which the person misinterprets others' actions, hallucinates and becomes unrealistically suspicious; an exhaustion syndrome, involving intense fatigue and need for sleep after the stimulation phase; and a prolonged depression, during which suicide is possible.

Crystal meth is reported to attack the immune system, so meth users are often prone to infections of different kinds, one being an MRSA infection. This may simply be a result of long-term sleep deprivation and/or malnutrition.

Other side effects include twitching, jitteriness, repetitive behavior (known as "tweaking") and jaw clenching or teeth grinding. It has been noted that methamphetamine addicts lose their teeth abnormally fast; this may be due to jaw clenching, although heavy meth users also tend to neglect personal hygiene, such as brushing teeth. It is often claimed that smoking crystal meth speeds this process by leaving a crystalline residue on the teeth and while this is apparently confirmed by dentists, no clinical studies have been done to investigate.

Methamphetamine is commonly smoked in glass pipes or in aluminum foil heated by a flame underneath. The latter is known as "chasing the dragon". Meth must be heated (not burned) to cause the desired smoke. Smoking meth is probably the most impure form of ingestion. In addition to the possible effects on teeth, it is very damaging to the lungs. Methamphetamine users who smoke it sometimes experience mild asthma. Another problem with smoking meth is the potential presence of oxidation byproducts created when the heated drug comes in contact with air. Even if the initial drug is pure methamphetamine, the act of smoking it produces other chemicals, some of which may be toxic.

Methamphetamine is a powerful nasal decongestant, so methamphetamine users who snort it often have very clear nasal cavities. However, there have been rare cases of people snorting so much meth that their nose cartilage deteriorates, though snorting cocaine is far more likely to cause nasal degeneration, due to its vasoconstrictive properties. Snorting crystal meth may also cause tooth decay, since the nasal passages are directly connected to the mouth region, and it is theorized that damaging crystalline particles can still attach to the teeth. Another theory is that meth directly affects calcium balance in the body. Crystal Meth has also been shown to decrease the production of saliva, the lack of which causes tooth decay.

Injection is a popular method for use, but potentially carries quite serious risks. The hydrochloride salt of methamphetamine is soluble in water; injection users may use any dose from 200mg to over a gram in one I.V. dose using a small needle. In methamphetamine research, injection users often do not experience severe tooth decay, presumably because there is no residue left as there is through smoking it. But injection users experience greater jaw-clenching than users who snort or smoke it, since injecting methamphetamine has a much more powerful effect. This can cause loose teeth, so injection users still do lose their teeth. Also, this method of ingestion brings the risk of infection; injection users often experience skin rashes (sometimes called "speed bumps") and all kinds of infections due to the methamphetamine damage to the skin. As with any injected drug, if a group of users shares a common needle without sterilization procedures, very grave blood-borne diseases such as HIV or hepatitis can be transmitted as well.

The least-detrimental method of taking crystal meth may be oral administration. The effects are moderated over time to a greater degree, and neither teeth, skin, nor nasal passages are directly exposed to potentially harmful chemicals (assuming the user is careful not to allow pure crystal meth to come in contact with these parts of the body during ingestion). The less-intense "hit" may make this a less popular current choice for administration.