Farbenkonzern at the Farbwerke Hoechst were confiscated by the U.S. Department of Commerce Intelligence, investigated by a Technical Industrial Committee of the U.S. Department of State and then brought to the US. The report published by the committee noted that while methadone itself was potentially addictive, it produced “considerably” less euphoria, sedation, and respiratory depression than morphine at equianalgesic doses and was thus interesting as a commercial drug. The same report also compared methadone to pethidine. German researchers reported that methadone was capable of producing strong morphine-like physical dependence, which is characterized by opioid withdrawal symptoms which are lesser in severity and intensity compared to morphine, but methadone was associated with a considerably prolonged or protracted withdrawal syndrome when compared to morphine. Morphine produced higher rates of self-administration and reinforcing behaviour in both human and animal subjects when compared to both methadone and pethidine. In comparison to equianalgesic doses of pethidine (DemerolTM), methadone was shown to produce less euphoria, but higher rates of constipation, and roughly equal levels of respiratory depression and sedation.In the early 1950s, methadone (most times the racemic HCl salts mixture) was also investigated for use as an antitussive.Isomethadone, noracymethadol, LAAM, and normethadone were first developed in Germany, United Kingdom, Belgium, Austria, Canada, and the United States in the thirty or so years after the 1937 discovery of pethidine, the first synthetic opioid used in medicine.
Adverse effects
Adverse effects of methadone include:
Sedation
Constipation
Flushing
Perspiration
Heat intolerance
Dizziness or fainting
Weakness
Chronic fatigue, sleepiness and exhaustion
Sleep problems such as drowsiness,
Insomnia
Constricted pupils
Dry mouth
Nausea and vomiting
Low blood pressure
Headache
Heart problems such as chest pain or fast/pounding heartbeat
Abnormal heart rhythms
Respiratory problems such as trouble breathing, slow or shallow breathing (hypoventilation), light-headedness, or fainting
weight gain
Memory loss
Itching
Difficulty urinating
Swelling of the hands, arms, feet, and legs
Mood changes, euphoria, disorientation
Blurred vision
Decreased libido, difficulty in reaching orgasm, or impotence
Missed menstrual periods,
Skin rash
Central sleep apnea

Withdrawal symptoms
Physical symptoms

Lightheadedness
Tearing of the eyes
Mydriasis (dilated pupils)
Photophobia (sensitivity to light)
Hyperventilation syndrome (breathing that is too fast/deep)
Runny nose
Yawning
Sneezing
Nausea, vomiting, and diarrhea
Fever
Sweating
Chills
Tremors
Akathisia (restlessness)
Tachycardia (fast heartbeat)
Aches and pains, often in the joints or legs
Elevated pain sensitivity
Blood pressure that is too high (hypertension, may cause a stroke)Cognitive symptoms

Suicidal ideation
Susceptibility to cravings
Depression
Spontaneous orgasm
Prolonged insomnia
Delirium
Auditory hallucinations
Visual hallucinations
Increased perception of odors (olfaction), real or imagined
Marked increase in sex drive
Agitation
Anxiety
Panic disorder
Nervousness
Paranoia
Delusions
Apathy
Anorexia (symptom)Methadone withdrawal symptoms are reported as being significantly more protracted than withdrawal from opioids with shorter half-lives. When used for opioid maintenance therapy, Methadone is generally administered as an oral liquid. Methadone has been implicated in contributing to significant tooth decay. Methadone causes dry mouth, reducing the protective role of saliva in preventing decay. Other putative mechanisms of methadone-related tooth decay include craving for carbohydrates related to opioids, poor dental care, and general decrease in personal hygiene. These factors, combined with sedation, have been linked to the causation of extensive dental damage.