Methamphetamine: Ephedrine-based and P2P-based

Methamphetamine paraphernalia. Spoon with residue, needles, cotton balls, small baggies, cut straw (tooter), and a band of rubber for tourniquet.

Methamphetamine is a popular recreational drug and following the recent introduction of P2P meth it is now less expensive and more available than ever before. Meth is a central nervous system stimulant. It may be in powder or crystalline form (crystal meth). The powder may be white, tan, pink, red or brown depending on the method used to produce the drug. Meth may be smoked, snorted, ingested or injected after dissolving the powder in water. 

From the 70’s to the mid-2020’s meth was most often produced in home-laboratories and in Mexico for shipment to the US using cold medications containing ephedrine to manufacture the meth. Eventually the sale of ephedrine was limited in the United States and outlawed in Mexico. As a result, meth producers re-invented the process for manufacturing meth using legally purchased phenyl-2-propanone (P2P) and other easily available chemicals. 

The vast majority of meth on the market today is derived from P2P. It is cheaper, less contaminated, purer and more potent than ephedrine-based meth (2020 National Drug Threat Assessment, March 2021, DEA-DCT-Dir-008-21), making the drug more dangerous. 

During production of methamphetamine, the chemical structure of the drug may “flip” creating 2 stable versions of the same compound. These versions are called isomers and each isomer, D-meth and L-meth, has different effects on the body. L-meth does not have psychotropic effects and was present in significant amounts in early P2P. However, by 2019 manufacturers learned to remove L-meth from P2P so that today’s P2P is about 97%-99% pure psychoactive D-meth.

Smoking or injecting meth produces an intense rush (flash). The “flash” is extremely pleasurable but lasts only a few minutes. Snorting or ingesting the drug results in euphoria without a flash, starting 3-5 minutes after taking the drug and lasting 15-20 minutes. Following the “flash” users experience an immediate euphoria and rush accompanied by increased alertness, wakefulness and physical activity. The “high” from the drug starts quickly and fades quickly inducing people to take repeated doses in a binge pattern, giving up food and sleep for several hours or several days resulting in a “crash” culminating in cognitive issues, depression, cravings, anxiety, and sleep problems. 

Various small bags containing a crystalline substance that is meth.

The increased levels of d-isomer in P2P induce an intense and prolonged euphoric high with severe physical repercussions including increased blood pressure and respiratory rate, increased body temperature, increased risk of liver failure and elevated risk of heart attacks or strokes. P2P meth may cause schizophrenia and other psychoses. Meth derived from ephedrine causes users to stay awake and act socially aggressive. In contrast, P2P users tend to stay isolated and experience hallucination or delusions (NIDA. 2023, October 9. References. Retrieved from https://nida.nih.gov/publications/research-reports/methamphetamine/references on 2024, February 19).

The physical and mental side effects of P2P are prolonged and sometimes irreversible. Users are at risk of organ failure and struggle with paranoid episodes, psychosis and, like users of ephedrine-meth, report the sensation of bugs crawling under their skin. P2P meth tends to be laced with other addictive drugs including fentanyl. As a result, users may require very prolonged detoxification. The other effects of P2P meth are similar to those of ephedrine-based meth. (S Quinones, Atlantic, November 2021. theatlantic.com)   

Effects on the brain

The effects of methamphetamine on the brain are related to its chemical effects resulting in the release of huge amounts of dopamine affecting the reward-region of the brain, creating extreme pleasure and reinforcing drug taking behavior. Repeated release of large amounts of dopamine is the basis for rapid addiction to this drug. As a result of the huge amount of dopamine released it is not unusual that one dose of methamphetamine may result in addiction. Besides addiction, prolonged use of the drug causes weight loss, anxiety and confusion, sleep problems, violent behavior, hallucinations and psychosis.” Meth mouth” is a common problem. Continued use of methamphetamine affects coordination, learning, emotions and memory. 

Short-term effects of methamphetamine

14 small bags of a blue crystalline substance that was meth

The short-term effects of the drug are increased wakefulness and increased physical activity, decreased appetite, increased libido, rapid heart rate, increased blood pressure and elevated body temperature. Users may have dilated pupils, profuse sweating, and panic. Death may occur as a result of high body temperature, convulsions or cardiac arrest. 

Long-term effects

Long-term effects are psychosis, paranoia, hallucinations, repetitive motor activity, loss of memory, aggressive or violent behavior, severe dental problems (meth mouth) and weight loss. Meth has become highly associated with risky sexual behavior, increasing the risk for contracting hepatitis B or C and HIV. Perhaps the most devastating effect on the addict and his/her friends/family is that the addict rarely returns to being the person he/she was before exposure to meth. 

Meth induced psychosis symptoms may last for months or years after a person has quit using methamphetamine. Stress may precipitate spontaneous recurrence of methamphetamine psychosis in people who had experienced psychosis before using meth (Glasner-Edwards S, CNS Drugs 2014;28:1115-26).

Significant changes occur in the user’s brain. Functional imaging studies of the brain have demonstrated alterations in the activity of the dopamine system that are associated with impaired motor activity and impaired verbal learning (Volkow ND.  Am J Psychiatry 158(3):377– 382, 2001). Studies in chronic methamphetamine users have also revealed severe structural and functional changes in areas of the brain associated with emotion and memory, which may account for many of the emotional and cognitive problems observed in these individuals (Chang L. Addiction 102(Suppl 1):16–32, 2007). 

Withdrawal 

Homeless man going through the symptoms of withdrawl.

The symptoms of methamphetamine withdrawal are primarily fatigue, depression, increased appetite, anxiety, irritability, headaches, agitation, excessive sleeping, vivid or lucid dreams, and suicidal ideations. Symptoms may last for days in occasional-users and weeks or months in chronic users. The severity is also dependent on the amount of methamphetamine used. 

Effects on the fetus, Infants and children 

Methamphetamines damages the fetus resulting in permanent brain abnormalities with subsequent delay in language skills and aggressive behavior. Prenatal exposure leads to future self-control problems in early school-age children, including poor attention, poor self-regulation skills, and poor problem-solving skills; all due to changes in the frontal cortex of the brain. Poor growth through 3 years of age has been documented. 

The newborn is often born premature and small for gestational age. At the time of birth there may be placental abruption or rupture of the uterus. Infants exposed to prenatal meth also have poor suck, smaller head size, shorter length and more often require intensive care. Laboratory studies have shown that meth impairs mineral uptake in the developing cartilage thus affecting growth.