Due to the relative rarity of dextromethorphan addiction and withdrawal, there have not been many studies done into the duration of dextromethorphan withdrawal symptoms. That being said, we can look to a few case studies to illustrate a rough, generalized timeline. Due to the short half-life of dextromethorphan of roughly 3 hours in most people, the symptoms of dextromethorphan withdrawal usually begin fairly soon after the last use, commonly within 6 hours.
When used in very large doses, dextromethorphan produces effects akin to those produced by dissociative anesthetics such as ketamine or PCP. Similarly, the symptoms of dextromethorphan withdrawal resemble withdrawal symptoms from these dissociatives. The symptoms of dextromethorphan withdrawal can also vary in both intensity and duration, sometimes substantially, between different people.
While the half-life of dextromethorphan is fairly short in the vast majority of people, there are genetic and metabolic differences that may substantially prolong this half-life. In particular, people of northern European ancestry may have genetic factors that can increase this half-life to around 30 hours, so in these individuals, the withdrawal timeline will be significantly longer, although this also means that the symptoms of dextromethorphan withdrawal will be less intense.
A general overview of the dextromethorphan withdrawal timeline may look like this:
Within hours of the last use, dextromethorphan withdrawal symptoms will begin to appear. These symptoms are very rarely deadly, although they can certainly be quite uncomfortable. These symptoms will begin fairly soon after the last time someone uses dextromethorphan and commonly persist at fairly intense levels for at least a week. By the beginning of the second week, most of the physical symptoms may still be present, but they will be on their way to resolution.
Some of the symptoms of dextromethorphan withdrawal that may be experienced during the first week include:
With the physical symptoms reducing during the second week and stomach issues resolving, being able to eat and sleep more may help improve the subjective experience of other symptoms.
The third week is often much improved from a physical standpoint, with almost all physical symptoms as well as insomnia frequently being resolved or very close to it. The psychological symptoms, however, may seem more intense. This is often a subjective intensification since as the physical symptoms resolve, they are no longer able to distract from the psychological symptoms, therefore they may seem more intense. While the direct physical discomfort and possible dangers may have passed, there are still risks. By the fourth week, someone may be close to their usual selves again. That being said, the post-acute symptoms may still be present, sometimes at a fairly high level.
While the most physically uncomfortable time may be passed by this point, there is still work to be done. Support and guidance are often needed if someone wants the best possible chance at achieving long-term recovery.
The post-acute withdrawal symptoms are the longer-lasting, but less intense, symptoms that commonly linger for weeks or months after the acute withdrawal phase has ended. These are strictly psychological in nature, but they can still be present significant challenges to someone’s continued sobriety and health.
Some of the post-acute symptoms of dextromethorphan withdrawal include:
These symptoms have been known to persist for weeks, months, or rarely even years after the last time someone used dextromethorphan. While they are less intense than the acute symptoms, they often fade gradually over time. Even though they do not pose direct, physical risks, deep depression can lead to thoughts of suicide, and even suicide attempts. This requires effective psychiatric and therapeutic care if dangerous outcomes are to be avoided. Both medication and clinical therapy can be very effective at reducing the risks and the severity of these symptoms.
Dextromethorphan, also known as DXM, is a common ingredient in cough medications such as Robitussin, and until recently, there were no regulations regarding the sale of dextromethorphan in America. While no federal regulations exist currently, there are state-level bills and laws being passed to prohibit or otherwise regulate the sale of dextromethorphan to people under the age of 18, but these vary by state. Dextromethorphan, even though it is derived from morphine, does not have appreciable interactions with opioid receptors. The exact way that dextromethorphan works is still unclear, although it is known to interact with NMDA glutamate receptors as an antagonist, a σ (Sigma) receptor agonist, and an inhibitor of serotonin and norepinephrine reuptake.
Glutamate is a major excitatory neurotransmitter in the brain that has a multitude of roles, and the fact that dextromethorphan acts as an antagonist at NMDA glutamate receptors means that it can reduce the excitatory impact produced by glutamate. These glutamate interactions, among other somewhat mysterious mechanisms, is one of the ways it acts as a cough suppressant. The effects of dextromethorphan are also dose-dependent, with small amounts producing depressive effects and large amounts producing dissociative and hallucinogenic effects. The exact way this works is unclear, although it most likely has to do with the combination of NMDA antagonism, σ-1 receptor stimulation, and serotonin reuptake inhibition, somewhat similar to more classic hallucinogens.
Through long-term and heavy use of dextromethorphan, the systems that were affected will undergo changes. Alternatively known as upregulation (in the case of glutamate) and downregulation (in the case of serotonin and norepinephrine), these are regulatory processes performed by the brain in an attempt to maintain neurotransmitter balance. Since dextromethorphan reduces the impact of glutamate at NMDA receptors, the brain will “upregulate” these receptors, or turn up their sensitivity. With serotonin and norepinephrine, receptors were experiencing more stimulation due to dextromethorphan’s inhibition of their reuptake transporters. These neurotransmitter systems will undergo an opposite but similar process of “downregulation” where the brain reduces the sensitivity of their receptors. Once these upregulation and downregulation processes have begun to occur, someone will begin to feel unwell when they go too long without dextromethorphan. These are the symptoms of dextromethorphan withdrawal, and depending on someone’s use habits, they may range from a little uncomfortable, to potentially life-threatening.
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