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Methadone - PsychonautWiki

Fatal overdose may occur when opiates are combined with other depressants such as benzodiazepines , barbiturates , gabapentinoids , thienodiazepines , alcohol or other GABAergic substances. It is strongly discouraged to combine these substances, particularly in common to heavy doses. WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. It is not a recommendation and should be verified with other sources for accuracy. Methadone sold under trade names such as Dolophine and Methadose is a synthetic opioid analgesic used for the treatment of moderate to severe pain and for the treatment of opioid addiction. It is commonly used to treat and manage the symptoms of opioid addiction. The subjective effects are similar to those of other synthetic opioids such as fentanyl , however, most users note a significantly stronger euphoria. Like dextropropoxyphene , the use of methadone is associated with cardiac arrhythmia, however it is more common with dextropropoxyphene than it is with methadone. Methadone is an opioid of the diphenylpropylamine class, featuring two phenyl rings attached to carbon R 4 of the main 2-oxodimethylaminoheptane chain. It exists as a racemic mixture of both dextromethadone and levomethadone. It is also similar in structure to tapentadol and dextropropoxyphene. Methadone and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine EDDP , are often measured in urine as part of a drug abuse testing program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims, or in whole blood to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. Methadone usage history is considered in interpreting the results as a chronic user can develop tolerance to doses that would incapacitate an opioid-naive individual. Chronic users often have high methadone and EDDP baseline values. The protonated form of methadone takes on an extended conformation, while the free base is more compact. The way in which opioids structurally mimic these natural endorphins results in their euphoria , pain relief and anxiolytic effects. This is because endorphins are responsible for reducing pain, causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or general excitement. Methadone is metabolized by the cytochrome P system. Unlike most opioids, methadone is a weak serotonin reuptake inhibitor as well as a weak NMDA antagonist. Similarly to dextropropoxyphene , methadone is a nicotinic acetylcholine receptor antagonist. The metabolic half life of methadone differs from its duration of action. The metabolic half life is 8 to 59 hours approximately 24 hours for opioid-tolerant people, and 55 hours in opioid-naive people , as opposed to a half life of 1 to 5 hours for morphine. The length of the half life of methadone allows for exhibition of respiratory depressant effects for an extended duration of time in opioid-naive people. Methadone has been shown to reduce neuropathic pain, primarily through NMDA receptor antagonism. Glutamate is the primary excitatory neurotransmitter in the central nervous system. Acting as an NMDA antagonist may be one mechanism by which methadone decreases craving for opioids and tolerance, and has been proposed as a possible mechanism for its distinguished efficacy regarding the treatment of neuropathic pain. Disclaimer: The effects listed below cite the Subjective Effect Index SEI , an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism. It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:. Methadone has a moderate toxicity relative to dose. As with all opioids, long-term effects can vary but can include diminished libido, apathy and memory loss. It is also potentially lethal when mixed with depressants like alcohol or benzodiazepines and generally has a wider range of substances which it is dangerous to combine with in comparison to other opioids. Methadone is known to lower the seizure threshold. It should not be taken during benzodiazepine withdrawals as this can potentially cause seizures. It is strongly recommended that one use harm reduction practices when using this drug. As with other opioids , the chronic use of methadone can be considered extremely addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal symptoms may occur if a person suddenly stops their usage. Tolerance to many of the effects of methadone develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline in the absence of further consumption. Methadone presents cross-tolerance with all other opioids , meaning that after the consumption of methadone all opioids will have a reduced effect. The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse , largely because of reduced tolerance. It has also been found that the environment one is in can play a role in opioid tolerance. In one scientific study, rats with the same history of heroin administration were significantly more likely to die after receiving their dose in an environment not associated with the drug in contrast to a familiar environment. Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions although it is not guaranteed to include all of them. Always conduct independent research e. Google , DuckDuckGo , PubMed to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit. While methadone has been reported to occasionally cause serotonin syndrome when combined with certain substances such as those listed below , anecdotal reports suggests that it does so at a much lower rate than tramadol. Combinations with the following substances can cause dangerously high serotonin levels. Serotonin syndrome requires immediate medical attention and can be fatal if left untreated. As such, it may contain incomplete or wrong information. You can help by expanding it. Physical effects. Cognitive effects. March American Journal of Therapeutics. ISSN August Nature New Biology. Journal of Pharmacology and Experimental Therapeutics. Opioids in cancer pain 2nd ed ed. Oxford University Press. ISBN October The Journal of Pharmacology and Experimental Therapeutics. Cardiology Research and Practice. Journal of Addiction Medicine. British Journal of Anaesthesia. OCLC PMID Bundeskanzlei \\\\\\\\\\\\\\\[Federal Chancellery of Switzerland\\\\\\\\\\\\\\\]. Retrieved January 1, This legality section is a stub.

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