Methamphetamine

Article Author:
Rama Yasaei
Article Editor:
Abdolreza Saadabadi
Updated:
5/6/2020 4:30:15 PM
PubMed Link:
Methamphetamine

Indications

Methamphetamine is one of the powerful stimulants of the central nervous system (CNS). It is sometimes used as a second-line treatment for attention deficit hyperactivity disorder and obesity; however, methamphetamine is better known as a recreational drug.

Methamphetamine was first discovered in 1893 from two chemical subgroups: dextromethamphetamine and levomethamphetamine. After two decades, in 1919, methamphetamine originated from amphetamine in Japan. Later in the 1930s, the drug was introduced to the United States as a bronchial inhaler and a nasal decongestant. Later, it was used to treat obesity. Overall, the use of the term methamphetamine refers to an equal mixture of dextromethamphetamine and levomethamphetamine in their pure amine forms. Prescribing this medication is limited due to its neurotoxic potential and risk of recreational use as a euphoriant. Today, there are safer medications of choice with the same treatment efficacy, and hence, the use of methamphetamines in the United States is very limited.[1]

Due to illicit trafficking and recreational use of racemic methamphetamine, levomethamphetamine, and dextromethamphetamine, the agent is a schedule II controlled substance in the United States and the United Nations Convention on Psychotropic Substances.[2]

Because of the relatively simple chemical process to synthesize methamphetamine, it can be produced illicitly in meth-labs nationwide.[3] Illegal laboratories and larger super-labs across the United States, particularly in California (Central Valley), Arizona, Utah, and Texas, have surfaced over the past three decades. The growth of Mexico-based traffickers and the expansion of independent illegal labs, methamphetamine is mass manufactured in many places today in the Pacific Northwest, Midwest, and some parts of the southeast and the northeast United States.[3]

The use of methamphetamine triggers elevated mood, alertness, increase concentration, energy, decreased appetite and causes weight loss, and increased sexual libido (recreational methamphetamine).

The use of methamphetamine in higher doses can induce psychosis, bleeding in the brain, skeletal muscle breakdown, and seizures. Moreover, when used chronically, it can cause violent behavior, mood swings, and psychosis such as paranoia, delirium, auditory and visual hallucination, and delusions.

Chronic long-term methamphetamine use can be highly addictive, and if it discontinued abruptly, it might lead to withdrawal symptoms that can be persistent for months after use.

Street Terms for Methamphetamine

Meth, crystal meth, crystal, speed, scootie, yellow powder, crank, ice, spoosh, glass, chalk, redneck cocaine, yellow barn, tina, tick-tick

Street Terms for Smokable Methamphetamine

Hot ice, L.A. glass, hiropon, super Ice, L.A. ice, Batu, quartz, hanyak[1]

Mechanism of Action

Methamphetamine affects the central nervous system (CNS)  by enhancing the release of monoamine neurotransmitters such as serotonin, dopamine, and norepinephrine.[4] The use of methamphetamine can lead to many pharmacological effects because of its ability to use various molecular processes. Methamphetamine causes the levels of monoamines to be increased by:

  • Discharging the monoamines out of their storage and freeing them into the synaptic space by making reversal action of the dopamine transporters
  • Obstructing the reuptake of monoamines by preventing the activity of transporters of monoamine[6]
  • Methamphetamine can increase the expression of CRE-Luc by TAAR1 in transfected cells. Methamphetamine interacts with TAAR1 which triggers a definite inhibition in dopamine uptake dependent on TAAR1 in transfected cells. Methamphetamine has a similar effect on brain striatal synaptosomes.[5][6]
  • Reducing the dopamine transporters expressions at the cell surface
  • The proliferation of the cytosolic levels of monoamines by inhibiting the monoamine oxidase activity
  • Enhancing the expression and activity of the dopamine-synthesizing enzyme tyrosine hydroxylase[7]

Methamphetamine is highly lipid-soluble which helps to be transferred relatively fast across the blood-brain barrier and has an immediate effect on the CNS.[2]

Administration

Methamphetamine can be ingested orally, through intravenous injection, smoked, and snorted.

Adverse Effects

People who use methamphetamine feel an acute, powerful short rush for about 5 to 30 minutes, which varies based on different routes of use. The drug also causes an enhanced energy level, decreases appetite, and creates euphoria for a range of 6 to 12 hours.

 Short-Term Effects

  • Decreased appetite
  • Nausea
  • Psychosis
  • Tachycardia
  • Hypertension
  • Increased body temperature  
  • Panic attack
  • Mydriasis (dilation of pupils)
  • Disturbed sleep patterns
  • Violent, bizarre, and erratic behavior
  • Hallucinations and irritability
  • Seizures, convulsions, and death from high doses

Long-Term Effects

  • Long-lasting damage to the blood vessel of heart and brain
  • Lung, liver, and kidney damage
  • Hypertension that can lead to heart attacks, strokes, and death
  • Severe tooth degeneration
  • In cases where the drug was sniffed, destruction of soft-tissues in the nose
  • In cases where the drug was smoked, respiratory problems
  • In cases where the drug was injected, infectious diseases, cellulitis, and abscesses
  • Weight loss and malnutrition
  • Disorientation, apathy, confusion, and exhaustion
  • Severe psychological dependence
  • Psychosis
  • Depression
  • Damage to the brain structure similar to Alzheimer disease, epilepsy, and stroke

Tweaking

The last stage of methamphetamine misuse happens when the person who inappropriately uses methamphetamine becomes paranoid and irritable because of a lack of sleep for about 3 to 15 days. This behavior is called "tweaking," and the person with this behavior is known as the "tweaker." Usually, tweakers continue to require more methamphetamine to get to the original high.[8] This effect is difficult to achieve, which causes frustration and irritability and unsteady behavior in the tweaker. Because tweakers are unpredictable, they can behave violently, can get involved in domestic arguments, spur-of-the-moment offenses, and become a danger to others or themselves.[9] A tweaker can behave normally and have clear eyes, concise speech, and brisk movements; however, careful observation will indicate that the person's eye movement is much faster than normal (up to 10 times), and they have a minor quiver voice and jerky movements. Some tweakers minimize or cover these physical symptoms by using a depressant like alcohol or opioids; however, the use of a depressant by the tweaker increases his or her negative feelings of paranoia, irritability, and frustration significantly. Other people around these users should use extreme caution because of their unpredictable behaviors.[10]

Contraindications

  • Having thoughts of suicide
  • Tourette syndrome
  • Hyperthyroidism
  • Bipolar disorder
  • Psychotic disorder
  • Drug abuse
  • Behaving with excessive cheerfulness or activity
  • Chronic muscle twitches or movements
  • Aggressive behavior
  • Increased ophthalmic pressure
  • Hypertension
  • History of a heart attack
  • Coronary artery disease
  • Cardiomyopathy
  • Arrhythmia
  • Chronic heart failure
  • Stroke
  • Atherosclerosis
  • Numbness
  • Prickling
  • Tingling of fingers and toes
  • Seizures
  • Loss of appetite
  • Weight loss
  • Breastfeeding mothers
  • Increased cardiovascular event risk
  • Structural disorder of the heart
  • Chronic kidney disease stage 4 (severe) or 5 (failure)
  • Kidney disease with a likely reduction in kidney function
  • Allergic reaction to sympathomimetic agents or amphetamine analogs

Monitoring

Methamphetamine users have different symptoms that can be recognized, for example, lack of sleep (insomnia), acute anxiety, agitation, and psychotic or violent behavior. If these types of behavior develop after using the methamphetamine, the meth use may have developed dependency. Chronic meth users also usually show poor personal hygiene and sores on their bodies from picking at "crank bugs," unhealthy complexion, a pale, and tactile hallucination that often seen in tweakers. Methamphetamine users may develop cracked teeth because of extreme clenching of their jaw during the time being high on methamphetamine.

Toxicity

The use of methamphetamine can cause physical and psychological dependence and increased tolerance. Because of the rapid development of tolerance, methamphetamine users frequently need to increase the dose to get to the satisfying "high," which can be very dangerous because the administration of too much methamphetamine also increases the risk of an overdose.[11] Based on the reports from 2011, more than 102,000 emergency department visits in the United States were related to methamphetamine use, with over 50% of users also using a combination of other drugs such as alcohol and marijuana, thus producing a synergistic effect. Knowing the physical and behavioral symptoms of the methamphetamine overdose, and diagnosis of the toxicity is essential for saving the patient's life.[12]

  • Acute: When methamphetamine users experience an adverse reaction due to use a large amount of methamphetamine one time, it can sometimes be fatal.
  • Chronic: Result of many adverse health effects of chronic methamphetamine abuse

Signs and symptoms of methamphetamine toxicity:

  • Mydriasis (dilated pupils)
  • Bradycardia or tachycardia
  • Irregular heart rhythm (arrhythmia)
  • Chest pains
  • Shortness of breath
  • Increased body temperature
  • Heart attack
  • Hypertension
  • Kidney damage
  • Altered mental status. 
  • Gastrointestinal distress
  • Agitation, violent, psychotic behaviors 

Patients who experience methamphetamine toxicity usually present with an altered mental status that can show as psychotic episodes, irritability, suicidal ideation, and rarely coma or seizures.

Some patients present with psychotic symptoms, including tactile hallucinations and severe paranoia.

Chronic long-term methamphetamine use can also cause dental complications, significant weight loss, and skin problems such as sores and abscesses.[3]

Enhancing Healthcare Team Outcomes

Due to the unpredictable behaviors, irritability, and the possibility of psychotic behavior of methamphetamine users, especially during the hospital visit due to the overdose or complication, the safety of medical and security staff is important. Hence, the advice is always to use precautions when dealing with these patients. Another healthcare worker or security personnel should always accompany these patients. The triage nurse should be fully aware of the adverse effects of amphetamine and ensure that the emergency department is fully aware of the individual admitted.


References

[1] Radfar SR,Rawson RA, Current research on methamphetamine: epidemiology, medical and psychiatric effects, treatment, and harm reduction efforts. Addiction & health. 2014 Summer-Autumn     [PubMed PMID: 25984282]
[2] Cisneros IE,Ghorpade A, Methamphetamine and HIV-1-induced neurotoxicity: role of trace amine associated receptor 1 cAMP signaling in astrocytes. Neuropharmacology. 2014 Oct     [PubMed PMID: 24950453]
[3] Krasnova IN,Cadet JL, Methamphetamine toxicity and messengers of death. Brain research reviews. 2009 May     [PubMed PMID: 19328213]
[4] Der-Ghazarian TS,Charmchi D,Noudali SN,Scott SN,Holter MC,Newbern JM,Neisewander JL, Neural Circuits Associated with 5-HT{sub}1B{/sub} Receptor Agonist Inhibition of Methamphetamine Seeking in the Conditioned Place Preference Model. ACS chemical neuroscience. 2019 Jul 17     [PubMed PMID: 31042352]
[5] Shi X,Swanson TL,Miner NB,Eshleman AJ,Janowsky A, Activation of Trace Amine-Associated Receptor 1 Stimulates an Antiapoptotic Signal Cascade via Extracellular Signal-Regulated Kinase 1/2. Molecular pharmacology. 2019 Oct     [PubMed PMID: 31409621]
[6] Miner NB,Phillips TJ,Janowsky A, The Role of Biogenic Amine Transporters in Trace Amine-Associated Receptor 1 Regulation of Methamphetamine-Induced Neurotoxicity. The Journal of pharmacology and experimental therapeutics. 2019 Oct     [PubMed PMID: 31320495]
[7] Huang WS,Chen GJ,Tsai TH,Cheng CY,Shiue CY,Ma KH,Yeh SH, In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine. EJNMMI research. 2019 Sep 18     [PubMed PMID: 31535286]
[8] Hauw F,Meppiel E,Steichen O,Conan PL,Capron J,de Broucker T, Isolated persistent acute global amnesia after acute abuse of 3,4-methylenedioxy-methamphetamine (MDMA). Journal of the neurological sciences. 2018 Mar 15     [PubMed PMID: 29406963]
[9] Hoffman WF,Jacobs MB,Dennis LE,McCready HD,Hickok AW,Smith SB,Kohno M, Psychopathy and Corticostriatal Connectivity: The Link to Criminal Behavior in Methamphetamine Dependence. Frontiers in psychiatry. 2020     [PubMed PMID: 32180738]
[10] Kaushal N,Matsumoto RR, Role of sigma receptors in methamphetamine-induced neurotoxicity. Current neuropharmacology. 2011 Mar     [PubMed PMID: 21886562]
[11] Nie L,Zhaom Z,Wen X,Luo W,Ju T,Ren A,Wu B,London ED,Li J, Factors affecting the occurrence of psychotic symptoms in chronic methamphetamine users. Journal of addictive diseases. 2018 Jul-Dec     [PubMed PMID: 31682200]
[12] Weng TI,Chen LY,Chen JY,Chen PS,Hwa HL,Fang CC, Characteristics of analytically confirmed illicit substance-using patients in the Emergency Department. Journal of the Formosan Medical Association = Taiwan yi zhi. 2020 Feb 6     [PubMed PMID: 32037264]