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 up- 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. 1, 2, 3, 4, 5, 6
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.
Some of the symptoms of dextromethorphan withdrawal include:
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. 5, 6, 7, 8, 9, 10
The post-acute withdrawal symptoms are the longer-lasting, but less intense, symptoms that commonly linger for weeks or months after the initial, or 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, the sometimes 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. 7, 8, 9
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.
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. 10, 11, 12
For a generalized and speculative illustration of the first month of the dextromethorphan withdrawal symptoms, let’s take a week-by-week look:
Within hours of the last use, dextromethorphan withdrawal symptoms will begin to appear.
The first symptoms to appear are usually increased anxiety, constant sweating, tachycardia, and hypertension. During the second day, additional symptoms such as tremors, increased irritability, diarrhea, vomiting, muscle and stomach pain may arise, joined by insomnia that night. While tachycardia and hypertension may resolve fairly quickly, often within a few days, the rest of the symptoms typically persist throughout the first week. Depression, cravings for dextromethorphan, and decreasing energy levels may begin to appear as the week goes on, and these often intensify as time goes on. The rest of the symptoms often intensify, plateau, and begin to resolve over the course of the first week of withdrawal.
By the beginning of the second week, most of the physical symptoms have normally resolved, or are on their way to resolution. Muscle pain, stomach cramps, and vomiting usually resolve by this time, but diarrhea may still persist. Sweating may also be present, although it is usually reduced somewhat from the prior week. Insomnia should be expected to persist and depression, anxiety, fatigue, and lethargy are often still present. With the physical symptoms reducing and stomach issues resolving throughout the week, being able to eat more food 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 fully 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. The risks of relapse and suicidal ideation are very real, and great care should still be taken to monitor and treat these symptoms.
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. Again, there is substantial variability in the timeline of dextromethorphan withdrawal symptoms due to the individual metabolic differences in those who may use it. Because of this, some people may have fully recovered by now, while others may have persistent symptoms for many more weeks, months, or possibly even years longer. If treatment has not already been sought, it is highly recommended to do so now. The most physically uncomfortable time may be passed, but there is still work to be done, and support and guidance are often needed.
The physical effects of dextromethorphan detox are thought to be mostly due to glutamate, serotonin, and norepinephrine neurotransmitter dysregulation, and these can produce issues in two major systems: the gastrointestinal tract and the cardiovascular system. While these effects are very rarely dangerous on their own, if someone has an underlying health condition, then they may be at increased risk for dangerous complications.
The manifestation of diarrhea is very common during dextromethorphan detox, and there is a good reason for this. Since dextromethorphan inhibits serotonin reuptake, it is probable that the brain and body will downregulate serotonin receptors in an attempt to maintain balance. The reduced sensitivity at serotonin receptors means that this neurotransmitter will have reduced efficacy. This can cause issues in the brain, but also in the gastrointestinal tract. About 95% of the serotonin in the body is located in the gut where it helps facilitate effective digestion. In the intestines, serotonin is partially responsible for moderating and slowing intestinal muscle contractions to help food digest effectively and properly. Due to the reduced impact produced by serotonin due to downregulation, the gastrointestinal tract exhibits hyperactive symptoms and produce the uncomfortable effects of diarrhea, stomach cramps, and may contribute to vomiting. 13, 14
Increases in both heart rate and blood pressure are quite common effects of dextromethorphan detox although they often resolve fairly quickly. These effects are also due to both psychological and neurotransmitter imbalances, particularly with dysregulation of the neurotransmitter norepinephrine. Norepinephrine is both a neurotransmitter in the brain and a hormone in the blood. In the brain, it can indirectly affect heart function by modulating the brain’s output signals to the heart, while in the blood it can directly impact heart function by stimulating the release of adrenaline, thereby increasing heart rate, blood pressure, and blood sugar levels. Serotonin may also play a minor role as it can contribute to psychological factors such as anxiety that may, in turn, contribute to an increase in cardiovascular function. 14, 15, 16
The psychological effects of dextromethorphan detox might possibly present more of a risk than the physical effects. Dextromethorphan has a multifaceted mechanism of action that affects several neurotransmitter systems. While the functions of glutamate, serotonin, and norepinephrine receptors are fairly well understood in general, their influence and role in dextromethorphan withdrawal is not. Additionally, the exact function of the σ receptor is still not well understood. The psychological effects experienced during detox can vary between people, sometimes greatly, and the exact causes for some of these effects remain unclear.
Increased levels of anxiety is a very common effect of detoxing from many drugs, and dextromethorphan is no exception. The manifestation of anxiety, in this case, has both neurological and psychological causes that may contribute to varying degrees. This may also be a fairly long-lasting effect, with the intense and short-term anxiety levels probably due to neurotransmitter downregulation and the longer-term, less intense symptoms of anxiety being most likely due to a further process of neurological remodeling that occurs after downregulation. The psychological component can affect both the acute and post-acute experience of anxiety, with therapy and the development of new coping skills being very effective at reducing anxiety caused by behavioral issues.
Neurologically, several dysregulated neurotransmitter systems could contribute to increased anxiety. The neurotransmitters glutamate and serotonin may be large contributors to anxiety levels, with glutamate able to increase anxiety and serotonin able to reduce anxiety. During dextromethorphan detox, glutamate may have an increased effect, while serotonin may have a reduced effect due to neurotransmitter receptor dysregulation to both systems. Serotonin is also a mood elevator and regulator and has a very large impact on depressive states of mind. Norepinephrine may also contribute by contributing to states of hypervigilance and increased stress. The role of the σ neurotransmitter receptor regarding anxiety is uncertain, although current studies indicate that it seems to have an impact on depression and anxiety.
Psychologically, states of heightened anxiety can be due to the sudden loss of a powerful, although very unhealthy, coping mechanism. When someone begins using dextromethorphan, it is usually for fun. Through continued and increasingly frequent use, this can become a way to cope with the normal stresses of life. Once tolerance, and later physical dependence, develop the use of dextromethorphan can become psychologically necessary to relax and relieve stress. The potency with which dextromethorphan can produce relaxation and comfort often causes it to become the primary and only means of dealing with life, and when this is suddenly removed it can leave someone feeling helpless, hopeless, and afraid. Increased levels of anxiety and depression are common effects during early dextromethorphan detox, and these often persist until proper neurotransmitter function has been restored and, later, once someone is able to learn healthier, nondestructive ways to cope with stress. 17, 18, 19, 20
Entering a dextromethorphan detox center can be extremely helpful to someone’s chances of making it through detox successfully and, in some cases, safely. These facilities specialize in treating the effects of dextromethorphan detox and are staffed by trained medical professionals, clinical therapists, and addiction treatment experts whose goal is to help people complete the often difficult withdrawal and detox process. Not everyone may require or even desire to enter one of these facilities although, in certain situations, it may be especially beneficial or even necessary if they hope to achieve long-term sobriety.
Here, we will take a look at some circumstances that may indicate a dextromethorphan detox center is highly recommended:
If someone has made past attempts at quitting dextromethorphan use and subsequently relapsed, then a dextromethorphan detox center may provide a better chance of long-term recovery. Not only will these facilities be able to reduce the severity of dextromethorphan withdrawal symptoms through medications and therapy, but they can also provide referrals to continued treatment after detox has been completed. These centers also have connections with their local recovery communities and this can be helpful towards finding a sober living and getting into a recovery fellowship that is aligned closely with someone’s individual needs.
Getting help for dextromethorphan addiction can be a very scary prospect, but it is often necessary if someone wants to build a life free from active dextromethorphan addiction. People in active addiction often feel completely isolated and alone and recovery may seem hopeless or impossible at times. With treatment, help, and support recovery is possible and a new life can be built, often better than anything imaginable while actively using dextromethorphan. It takes courage to reach out for help and willingness to accept help when it arrives, but these are often all that is required to change one’s life and rediscover a life free from the bondage of dextromethorphan use.
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