Side Effects of dextromethorphan: A Synthesis of Findings from 26 Studies

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Original Abstract of the Article

Main Research Findings

Dextromethorphan is widely used as a cough suppressant, but abuse can lead to psychological side effects. 7 A study revealed that in Germany, dextromethorphan is sold over-the-counter (OTC), and adolescents are abusing it for its psychoactive effects. In particular, a product called Hustenstiller-ratiopharm has widely circulated information on abuse on the internet, making it a high-risk product for abuse.

Dextromethorphan is known to have NMDA receptor antagonist properties and is attracting attention as a treatment for neuropathic pain. 14 A study reported that NMDA receptor antagonists such as ketamine and dextromethorphan are effective in treating neuropathic pain. However, NMDA receptor antagonists are less effective for some types of neuropathic pain, such as postherpetic neuralgia.

Dextromethorphan is also being researched as a treatment for pseudobulbar affect (PBA). 11 A study reported that combination therapy with dextromethorphan and quinidine is effective in reducing PBA symptoms. However, various medications are used to treat PBA, and each has reported side effects. Combination therapy with dextromethorphan and quinidine has also been reported to have side effects such as dizziness, tachycardia, and QT prolongation.

Dextromethorphan has also shown potential as a treatment for nicotine-induced cancer. 3 A study reported that the combined use of dextromethorphan and metformin can suppress the development of nicotine-induced cancer. Metformin is used as a treatment for diabetes. Since both dextromethorphan and metformin are highly safe drugs, they are expected to be used as preventive or therapeutic agents for nicotine-induced cancer.

Dextromethorphan abuse can lead to psychological dependence and neurological and psychological side effects. 24 A study of 53 dextromethorphan abusers revealed that the most common side effects were neurological and psychological symptoms.

Reasons for Side Effects

Side effects of dextromethorphan are mainly due to its NMDA receptor antagonist properties. 14 The NMDA receptor is a receptor for the neurotransmitter glutamate, playing a role in regulating neuronal excitability. Dextromethorphan inhibits the NMDA receptor, suppressing neuronal excitability. This action is linked to dextromethorphan's analgesic and antitussive effects, but it also carries the potential for causing psychological side effects.

Common Side Effects

Psychological Side Effects

Abuse of dextromethorphan can lead to psychological dependence, hallucinations, delusions, anxiety, and manic episodes. 24 A study of 53 dextromethorphan abusers revealed that the most common side effects were neurological and psychological symptoms.

Neurological Side Effects

Abuse of dextromethorphan can lead to dizziness, unsteadiness, ataxia, and seizures. 24 A study of 53 dextromethorphan abusers revealed that the most common side effects were neurological and psychological symptoms.

Physical Side Effects

Abuse of dextromethorphan can lead to nausea, vomiting, constipation, and respiratory depression. It can also affect the heart, potentially causing QT prolongation and arrhythmias. 11 A study reported that combination therapy with dextromethorphan and quinidine is effective in reducing PBA symptoms, but side effects such as dizziness, tachycardia, and QT prolongation were reported.

Countermeasures for Side Effects

Psychological Side Effects

If psychological side effects occur, appropriate treatment such as drug therapy or psychotherapy is required. Stopping dextromethorphan abuse is the most effective way to reduce side effects. Support from family and friends can also aid in recovery.

Neurological Side Effects

If neurological side effects occur, appropriate treatment such as drug therapy or rehabilitation is required. Stopping dextromethorphan abuse is the most effective way to reduce side effects. It is also important to live in a safe environment.

Physical Side Effects

If physical side effects occur, it is necessary to consult with a healthcare professional and receive treatment to improve symptoms. Stopping dextromethorphan abuse is the most effective way to reduce side effects. It is also important to drink enough fluids.

Comparison between Studies

Commonalities among Studies

Many studies have shown that dextromethorphan has NMDA receptor antagonist properties. 14 , 2 Also, it is commonly reported that abuse of dextromethorphan can lead to psychological dependence and neurological and psychological side effects. 24

Differences among Studies

The effects of dextromethorphan vary depending on the study. For example, the therapeutic effects on neuropathic pain vary between studies, with some showing effectiveness while others do not. 14 , 16 , 20 Similarly, the therapeutic effects on PBA vary in effectiveness between studies, with some showing high effectiveness while others show lower effectiveness. 11 , 10 This is likely due to differences in the diseases and patient populations studied, as well as the administration methods and dosages of dextromethorphan.

Notes on Application to Real Life

Dextromethorphan is sold over-the-counter as a cough suppressant, but abuse can lead to psychological dependence and neurological and psychological side effects. 24 Therefore, it is crucial to take dextromethorphan as directed by a doctor. If you experience any changes in mood or behavior while taking dextromethorphan, consult your doctor immediately.

Limitations of Current Research

Research on the effects and side effects of dextromethorphan is still insufficient. In particular, further research is needed on the effects of long-term use and the impact on specific patient populations.

Future Research Directions

Various studies are needed to better understand the effects and side effects of dextromethorphan. For example, studies to investigate the effects of dextromethorphan on the brain, studies to investigate the interaction of dextromethorphan with other drugs, and studies to establish safe methods of using dextromethorphan.

Conclusion

Dextromethorphan is widely used as a cough suppressant, but abuse can lead to psychological dependence and neurological and psychological side effects. 24 It is crucial to take dextromethorphan as directed by a doctor. If you experience any changes in mood or behavior while taking dextromethorphan, consult your doctor immediately.

Literature analysis of 26 papers
Positive Content
21
Neutral Content
0
Negative Content
5
Article Type
1
0
1
12
25
1.

[Genetic and environmental effects on neuromodulation and the antinociceptive effect of dextromethorphan].

Author: OestreicherM K, DesmeulesJ, PiguetV, AllazA F, DayerP

Antinociceptive effect
Neuromodulatory effects
CYP2D6 phenotype

Dextromethorphan and its metabolite dextrophan were found to have antinociceptive and neuromodulatory effects. The effects were heavily dependent on the cytochrome P450 2D6 phenotype (CYP2D6).

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : French

2.

Central regulation of the cough reflex: therapeutic implications.

Author: CanningBrendan J

Cough relief

NMDA-type glutamate receptor antagonists and neurokinin receptor antagonists have shown antitussive effects in various species, including humans. These centrally acting antitussives offer advantages over peripherally acting drugs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

3.

Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling.

Author: WangLu, DuLiang, XiongXiao, LinYusheng, ZhuJianlin, YaoZhimeng, WangShuhong, GuoYi, ChenYuping, GearyKyla, PanYunlong, ZhouFuyou, GaoShegan, ZhangDianzheng, YeungSai-Ching Jim, ZhangHao

ESCC prevention
ESCC treatment

Nicotine, the major component of tobacco and e-cigarettes, was found to enhance ESCC cancer malignancy and tumor-initiating capacity by activating the JAK2/STAT3 signaling pathway through interaction with CHRNA7. The combination of dextromethorphan and metformin effectively repressed nicotine-enhanced cancer-initiating cell properties and inhibited ESCC progression, suggesting its potential as a preventive and/or therapeutic strategy against nicotine-promoted ESCC.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Peripherally active dextromethorphan derivatives lower blood glucose levels by targeting pancreatic islets.

Author: ScholzOkka, OtterSilke, WeltersAlena, WörmeyerLaura, DolenšekJurij, KlemenMaša Skelin, PohorecViljem, EberhardDaniel, MrugalaJessica, HamacherAnna, KochAngela, SanzMiguel, HoffmannTorsten, HogebackJens, HerebianDiran, KlöckerNikolaj, PiechotAlexander, MayatepekErtan, MeissnerThomas, StožerAndraž, LammertEckhard

Pancreatic islet protection
T2DM treatment
Central side effects

Dextromethorphan (DXM) is a cough suppressant with potential benefits for treating diabetes. However, it can cause side effects affecting the brain. This study investigated how to modify DXM to target the pancreas without affecting the brain. The researchers found that by changing the structure of the drug, they could eliminate central side effects while preserving the beneficial effects on pancreatic cells.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Treatment of the common cold.

Author: SimasekMadeline, BlandinoDavid A

cold symptom relief
cold med risks

This abstract discusses the common cold and its treatment options. It discusses the effectiveness and side effects of over-the-counter and prescription medications, as well as alternative remedies.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Glutamate-dependent regulation of cholinergic phenotype in hypothalamic neurons.

Author: BelousovAndrei B

Glutamate receptor antagonism
Cholinergic side effects

The study investigated the effects of glutamate NMDA receptor antagonists on cholinergic activity in rat hypothalamic cultures. Chronic treatment with dextromethorphan, amantadine, eliprodil, and lamotrigine induced acetylcholine activity and choline acetyltransferase immunoreactivity. These findings suggest a possible mechanism for some side effects of anti-glutamate drugs in the central nervous system.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

7.

[Dextromethorphan abuse in adolescents: what can the pharmacists do?].

Author: MüllerSandra, JaffanLinda, KloiberEdith, LäerStephanie

Abuse
Psychotropic side effects

Dextromethorphan (DXM) is an over-the-counter cough suppressant that is abused by adolescents. This study monitored DXM sales in German retail pharmacies and found that young buyers of Hustenstiller-ratiopharm, a product with instructions for DXM abuse online, shared characteristics with those identified by the German regulatory agency as abusers.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : German

9.

ALSUntangled #71: Nuedexta.

Author: SunYuyao, BenatarMichael, Mascías CadavidJavier, EnnistDave, WicksPaul, StaatsKim, BeauchampMorgan, JhootySartaj, PatteeGary, BrownAndrew, BertoriniTulio, BarkhausPaul, BrombergMark, CarterGreg, BedlackRichard, LiXiaoyan

Improved bulbar function
Mild to moderate side effects

This review supports the consideration of Nuedexta, a combination drug originally approved for pseudobulbar affect, as a potential treatment for bulbar dysfunction in ALS patients, with or without pseudobulbar affect.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

10.

Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect.

Author: SchoedelKerri A, MorrowSarah A, SellersEdward M

PBA treatment
Drug interactions
QT prolongation

Dextromethorphan/quinidine (DM/Q) is a combination product indicated for the treatment of pseudobulbar affect (PBA). Three studies have shown significant effects on the primary end point, the Center for Neurologic Study-Lability Scale, and secondary efficacy endpoints.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

Therapeutic use of dextromethorphan: key learnings from treatment of pseudobulbar affect.

Author: MillerAriel, PanitchHillel

PBA treatment

Pseudobulbar affect (PBA) is an emotional disorder characterized by uncontrollable laughing and crying. The combination of dextromethorphan (DM) and quinidine (Q) has been shown to be safe and effective in treating PBA symptoms in patients with multiple sclerosis and amyotrophic lateral sclerosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

12.

Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis.

Author: JamesEleanor, EllisCathy, BrassingtonRuth, SathasivamSivakumar, YoungCarolyn A

Dysphagia

This review updates the management of sialorrhea, or excessive salivation, in people with motor neuron disease (MND).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

13.

KCNT1-positive epilepsy of infancy with migrating focal seizures successfully treated with nonnarcotic antitussive drugs after treatment failure with quinidine: A case report.

Author: TakaseChihiro, ShiraiKentaro, MatsumuraYu, WatanabeTomohiro, WatanabeAkimitsu, Hirasawa-InoueAyaka, MizuguchiTakeshi, MatsumotoNaomichi, SugaiKenji, HayashiMasaharu

EIMFS treatment
Cardiac side effects

KCNT1 gene mutations cause epilepsy of infancy with migrating focal seizures (EIMFS), a severe epilepsy that is resistant to antiepileptic drugs. Quinidine, a partial antagonist of the K<sub>Ca</sub>4.1 channel encoded by KCNT1, is a potential targeted treatment for EIMFS but has variable efficacy and cardiac side effects.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

14.

Targeting N-methyl-D-aspartate receptors for treatment of neuropathic pain.

Author: ZhouHong-Yi, ChenShao-Rui, PanHui-Lin

Treat neuropathic pain
Side effects

This article reviews the role of N-methyl-d-aspartate receptors (NMDARs) in neuropathic pain and the potential of NMDAR antagonists for treatment. NMDAR antagonists have shown promise in reducing hyperalgesia and allodynia in animal models and in patients with complex regional pain syndrome and painful diabetic neuropathy. However, patients with postherpetic neuralgia respond poorly.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

15.

AXS-05: an investigational treatment for Alzheimer's disease-associated agitation.

Author: WardKristen, CitromeLeslie

Agitation treatment
Serious side effects

This study discusses the challenges of treating agitation in Alzheimer's disease (AD) patients, focusing on the limitations of existing medications and the potential benefits of AXS-05, a combination of dextromethorphan and bupropion, which is currently being investigated for this indication.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

16.

The intravenous ketamine test predicts subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients.

Author: CohenSteven P, VerdolinMichael H, ChangAudrey S, KuriharaConnie, MorlandoBennie J, MaoJianren

Fibromyalgia pain
Side effects

This study investigated whether a low-dose intravenous ketamine test could predict the response to treatment with the oral N-methyl-D-aspartate receptor antagonist, dextromethorphan (DX), in patients with fibromyalgia. A significant correlation was found between pain relief with ketamine and DX.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

Drugs used in the treatment of opioid tolerance and physical dependence: a review.

Author: RaithK, HochhausG

Pain relief
Reduced tolerance
Physical dependence
Respiratory depression

This study reviews the development of tolerance to opioid medications. The study discusses various mechanisms of tolerance and potential strategies to minimize its development.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

18.

N-Substituted-3-alkoxy-derivatives of dextromethorphan are functional NMDA receptor antagonists in vivo: Evidence from an NMDA-induced seizure model in rats.

Author: WitkinJeffrey M, CerneRok, NewmanAmy H, IzenwasserSari, SmithJodi L, TortellaFrank C

Anticonvulsant effects
Reduced side effects

This study found that N-substituted-3-alkoxy-substituted dextromethorphan analogs exhibited anticonvulsant effects through NMDA receptor blockade in rats. The anticonvulsant potency was positively associated with the affinity for the NMDA receptor ion channel, suggesting that these low-affinity NMDA receptor antagonists may be useful for developing new treatments for neurological and psychiatric disorders.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

19.

Levodropropizine for treating cough in adult and children: a meta-analysis of published studies.

Author: ZanasiAlessandro, LanataLuigi, FontanaGiovanni, SaibeneFederico, DicpinigaitisPeter, De BlasioFrancesco

Cough treatment

Levodropropizine is an effective and well-tolerated peripheral antitussive drug. It is a safe and effective alternative to central cough suppressants, which may be associated with side effects limiting their use.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

20.

An Insight into Potential Pharmacotherapeutic Agents for Painful Diabetic Neuropathy.

Author: QureshiZunaira, AliMurtaza Najabat, KhalidMinahil

PDN pain management
Side effects

Painful diabetic neuropathy (PDN) is a debilitating complication of diabetes. This review explores the pathways involved in PDN and discusses FDA-approved and commercially available medications for its treatment, including duloxetine, pregabalin, tapentadol extended release, capsaicin, and spinal cord stimulation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

21.

New morphinan derivatives with negligible psychotropic effects attenuate convulsions induced by maximal electroshock in mice.

Author: KimHyoung-Chun, ShinChan Young, SeoDong Ook, JhooJin Hyeong, JhooWang-Kee, KimWon-Ki, ShinEun-Joo, LeeYoung-Ho, LeePhil Ho, KoKwang Ho

Anticonvulsant effect
Neuroprotective effect
Reduced psychotropic effects

This study investigated the behavioral effects of a series of morphinan analogs, including dextromethorphan (DM) and dextrorphan (DX), in mice. The results suggest that some of these analogs may be promising anticonvulsants that are devoid of PCP-like behavioral side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

22.

Multidrug toxicity involving sumatriptan.

Author: KnittelJessica L, VorceShawn P, LevineBarry, HughesRhome L, BosyThomas Z

Acute mixed drug toxicity
Multidrug fatality

This report describes a multidrug fatality involving sumatriptan, highlighting the potential risks associated with high doses of the medication.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

23.

Attenuation of the stimulant and convulsant effects of cocaine by 17-substituted-3-hydroxy and 3-alkoxy derivatives of dextromethorphan.

Author: ZapataAgustin, GasiorMaciej, Geter-DouglassBeth, TortellaFrank C, NewmanAmy Hauck, WitkinJeffrey M

Cocaine blocker
Novel drug target

A series of dextromethorphan (DM) analogs were effective in blocking the stimulant and convulsant effects of cocaine in mice. These analogs blocked cocaine’s effects at doses that did not cause side effects like ataxia and sedation. This research suggests new strategies for blocking cocaine’s harmful effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

24.

Side effects of dextromethorphan abuse, a case series.

Author: ZiaeeVahid, Akbari HamedEhsan, HoshmandArezoo, AminiHomaioon, KebriaeizadehAbbas, SamanKeivan

Neurological side effects
Psychological side effects

This study investigates the side effects of Dextromethorphan (DXM) abuse in a group of volunteers. The study found that neurological and psychological symptoms were the most common side effects, with psychological dependency and recreational use being the main reasons for repeated DXM abuse.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

25.

Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications.

Author: HalmoLaurie Seidel, WangGeorge Sam, ReynoldsKate M, Delva-ClarkHeather, Rapp-OlssonMalin, BannerWilliam, BondG Randall, KauffmanRalph E, PalmerRobert B, PaulIan M, GreenJody L, DartRichard C

Fatalities

This study describes fatalities associated with exposures to over-the-counter cough and cold medications in children younger than 12 years old.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

26.

Involuntary emotional expression disorder: treating the untreated.

Author: BrooksBenjamin Rix

IEED treatment
Side effects

This abstract discusses treatment options for involuntary emotional expression disorder (IEED), including tricyclic antidepressants, selective serotonin reuptake inhibitors, and the combination of dextromethorphan and quinidine.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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