Methamphetamine use allows users of both sexes to engage in prolonged sexual activity, which may cause genital sores and abrasions as well as priapism in men. Methamphetamine may also cause sores and abrasions in the mouth via bruxism, increasing the risk of sexually transmitted infection.Besides the sexual transmission of HIV, it may also be transmitted between users who share a common needle. The level of needle sharing among methamphetamine users is similar to that among other drug injection users. Fatal
Doses of 200 mg or more of methamphetamine are considered fatal. Psychological
The psychological effects of methamphetamine can include euphoria, dysphoria, changes in libido, alertness, apprehension and concentration, decreased sense of fatigue, insomnia or wakefulness, self-confidence, sociability, irritability, restlessness, grandiosity and repetitive and obsessive behaviors. Peculiar to methamphetamine and related stimulants is "punding", persistent non-goal-directed repetitive activity. Methamphetamine use also has a high association with anxiety, depression, amphetamine psychosis, suicide, and violent behaviors. Neurotoxic and neuroimmunological
Methamphetamine is directly neurotoxic to dopaminergic neurons in both lab animals and humans. Excitotoxicity, oxidative stress, metabolic compromise, UPS dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression and other processes contributed to this neurotoxicity. In line with its dopaminergic neurotoxicity, methamphetamine use is associated with a higher risk of Parkinsons disease. In addition to its dopaminergic neurotoxicity, a review of evidence in humans indicated that high-dose methamphetamine use can also be neurotoxic to serotonergic neurons. It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine.
Methamphetamine may decrease the effects of sedatives and depressants and increase the effects of antidepressants and other stimulants as well. Methamphetamine may counteract the effects of antihypertensives and antipsychotics due to its effects on the cardiovascular system and cognition respectively. The pH of gastrointestinal content and urine affects the absorption and excretion of methamphetamine. Specifically, acidic substances will reduce the absorption of methamphetamine and increase urinary excretion, while alkaline substances do the opposite. Due to the effect pH has on absorption, proton pump inhibitors, which reduce gastric acid, are known to interact with methamphetamine. Pharmacology
Pharmacodynamics
Methamphetamine has been identified as a potent full agonist of trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor (GPCR) that regulates brain catecholamine systems. Activation of TAAR1 increases cyclic adenosine monophosphate (cAMP) production and either completely inhibits or reverses the transport direction of the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT). When methamphetamine binds to TAAR1, it triggers transporter phosphorylation via protein kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting in the internalization or reverse function of monoamine transporters. Methamphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent signaling pathway, in turn producing dopamine efflux. TAAR1 has been shown to reduce the firing rate of neurons through direct activation of G protein-coupled inwardly-rectifying potassium channels.