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Dextromethorphan Withdrawal Timeline

Medically Reviewed By: Benjamin Caleb Williams RN, BA, CEN

Written By: Phillippe Greenough

Article Updated: 01/22/2021

Number of References: 22 Sources

Dextromethorphan is a common ingredient in cough medicines and used for treating various neurological conditions, but when used in large amounts or for long periods, it can also be addictive. The symptoms of dextromethorphan withdrawal can sometimes be quite intense and may be dangerous in some circumstances, although this is very rare. In this article, we will look at how dextromethorphan works, the symptoms of withdrawal, the timeline involved, the physiological effects of dextromethorphan withdrawal, and some scenarios when a dextromethorphan detox center may be especially recommended.

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Dextromethorphan Withdrawal Symptoms

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:

Weeks 1 & 2

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:

  • Deep Depression
  • Increased Anxiety
  • Strong Cravings for Dextromethorphan
  • Diaphoresis (constant sweating)
  • Tremor or Shaking
  • Fatigue and Lethargy
  • Insomnia
  • Chills and Increased Sensitivity to Cold
  • Muscle Pain
  • Vomiting and Stomach Cramps
  • Diarrhea
  • Increased Irritability
  • Tachycardia (increased heart rate)
  • Hypertension (elevated blood pressure)
  • Myoclonus (muscle spasms)

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.

Weeks 3 & 4

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.

  • Depression
  • Anxiety
  • Cravings for Dextromethorphan
  • Mild Fatigue
  • Mild Insomnia
  • Irritability

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.

Post-Acute Withdrawal Symptoms

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:

  • Depression
  • Anxiety
  • Fatigue and Lethargy
  • Cravings for Dextromethorphan

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.

More About Dextromethorphan Addiction

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.

Article References (In Addition to 5 in-article references)

  1. 1 FDA AccessData: Neudexta (dextromethorphan hydrobromide and quinidine sulfate) Capsules Label
  2. 2 Pharmacology & Therapeutics: Pharmacology of Dextromethorphan - Relevance to Dextromethorphan/Quinidine (Nuedexta®) Clinical Use
  3. 3 Clinical Toxicology: Dextromethorphan Poisoning - An Evidence-Based Consensus Guideline for Out-of-Hospital Management
  4. 4 Addiction Biology: Dextromethorphan Psychosis, Dependence, and Physical Withdrawal
  5. 5 Psychopharmacology Bulletin: Dextromethorphan in Cough Syrup - The Poor Man’s Psychosis
  6. 6 Psychopharmacology: High Doses of Dextromethorphan, An NMDA Antagonist, Produce Effects Similar to Classic Hallucinogens
  7. 7 StatPearls: Dextromethorphan Toxicity
  8. 8 Current Opinion in Endocrinology, Diabetes, and Obesity: Serotonin in the Gastrointestinal Tract
  9. 9 Cardiovascular Research: Serotonin and Catecholamines in the Development and Progression of Heart Valve Diseases
  10. 10 American Journal of Physiology - Heart and Circulatory Physiology: Norepinephrine Transporter Function and Human Cardiovascular Disease
  11. 11 Neuroscience & Biobehavioral Reviews: The Brain Norepinephrine System, Stress and Cardiovascular Vulnerability
  12. 12 European Journal of Pharmacology: Hippocampal NMDA Receptors and Anxiety - At the Interface Between Cognition and Emotion
  13. 13 NeuroRx: Advances in the Treatment of Anxiety - Targeting Glutamate
  14. 14 Journal of Psychopharmacology: Serotonin and Brain Function - A Tale of Two Receptors
  15. 15 Pharmacology & Therapeutics: Sigma Receptors - Potential Targets for A New Class of Antidepressant Drug
  16. 16 The Journal of Transpersonal Psychology: Facilitating Transpersonal Experiences with Dextromethorphan - Potential, Cautions, and Caveats
  17. 17 Basic and Clinical Neuroscience: Effects of Dextromethorphan on Depressive-and Cognitive-Associated Behaviors - A Sexually Dimorphic Study

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