alcohol abuse case study

Case Report

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• Published: 08 November 2022

Alcohol use disorder with comorbid anxiety disorder: a case report and focused literature review

• Victor Mocanu 1 , 2 &
• Evan Wood   ORCID: orcid.org/0000-0001-9412-6699 1 , 2  

Addiction Science & Clinical Practice volume  17 , Article number:  62 ( 2022 ) Cite this article

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Alcohol use disorder (AUD) and anxiety disorders (AnxD) are prevalent health concerns in clinical practice which frequently co-occur (AUD-AnxD) and compound one another. Concurrent AUD-AnxD poses a challenge for clinical management as approaches to treatment of one disorder may be ineffective or potentially counterproductive for the other disorder.

Case Presentation

We present the case of a middle-aged man with anxiety disorder, AUD, chronic pain, and gamma-hydroxybutyrate use in context of tapering prescribed benzodiazepines who experienced severe alcohol withdrawal episodes during a complicated course of repeated inpatient withdrawal management. After medical stabilization, the patient found significant improvement in symptoms and no return to alcohol use with a regimen of naltrexone targeting his AUD, gabapentin targeting both his AUD and AnxD, and engagement with integrated psychotherapy, Alcoholics Anonymous, and addictions medicine follow-up.

Proper recognition and interventions for AUD and AnxD, ideally with overlapping efficacy, can benefit individuals with comorbid AUD-AnxD. Gabapentin, tobacco cessation, and integrated psychotherapy have preliminary evidence of synergistic effects in AUD-AnxD. Meta-analysis evidence does not support serotoninergic medications (e.g. selective serotonin reuptake inhibitors) which are commonly prescribed in AnxD and mood disorders as their use has not been associated with improved outcomes for AUD-AnxD. Additionally, several double-blind placebo-controlled randomized trials have suggested that serotonergic medications may worsen alcohol-related outcomes in some individuals with AUD. Areas for future investigation are highlighted.

Introduction

Alcohol use disorder (AUD) is a prevalent health concern with a recent epidemiologic survey of the United States indicating a lifetime AUD prevalence of 29.1% and previous 12 month prevalence of 13.9% [ 1 ]. AUD portends an increased risk for diagnosis of a primary anxiety disorder (AnxD) [ 1 ], the definition of which, for the purposes of this case report, aligns with the most recent Canadian clinical practice guidelines for treatment of AnxD to include the DSM-IV umbrella of generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder, specific phobia, obsessive-compulsive disorder, and post-traumatic stress disorder (PTSD) [ 2 ]. A quarter or more of individuals with AUD qualify for dual diagnosis with a concurrent primary AnxD in cross-sectional studies [ 3 ]. Furthermore, individuals with comorbid AUD-AnxD fare worse in terms of severity, treatment response, and rate of relapse for both conditions [ 3 ]. Alcohol intoxication, withdrawal, and biopsychosocial consequences of AUD may all contribute to AnxD symptomatology and vice versa, some individuals with a primary AnxD may use alcohol as self-medication. Alternatively, these conditions may share a common neuropathophysiology influenced by environmental factors at the level of brain structures such as the amygdala and neurotransmitters including gamma aminobutyric acid (GABA), endogenous opioids, dopamine, and serotonin, with implications for clinical management [ 3 ].

We present a case report of an individual with comorbid AUD-AnxD and review literature for treatment options to aid clinicians in applying best current evidence for such individuals. Literature review consisted of relevant published studies extracted from author collections and PubMed search with no language or date restrictions for combinations of the following terms: alcohol, alcohol use disorder, anxiety, anxiety disorder, comorbidity, dual diagnosis. In addition, reference lists of selected articles were reviewed for eligible and relevant studies. We find that commonly used treatment options for either AUD or AnxD can have a range of positive and potentially negative impacts for AUD-AnxD which requires accurate understanding of evidence-based care in this area.

A middle-aged man with a longstanding but reportedly well managed history of anxiety disorder dating back to childhood presented for medicalized alcohol withdrawal management services. The individual had a workplace injury approximately 10 years prior that resulted in several spine fractures after which his anxiety deteriorated and he developed AUD. Around this time, an SSRI was trialed for AnxD over several months without benefit and ultimately discontinued. He did not endorse a history for a mood disorder, nor had he received a diagnosis as such. He went on to live with chronic pain and AUD-AnxD for half a decade at which point he had an accidental caustic ingestion resulting in an esophagectomy and jejunostomy tube feeding for one year. His AUD-AnxD subsequently deteriorated further resulting in a prescription of benzodiazepines which were taken for approximately one month until the patient experienced rebound anxiety, worsening of his AUD, and the emergence of gamma-hydroxybutyrate (GHB) use in the context of attempting to discontinue benzodiazepines. The individual sought care through an inpatient withdrawal management program where he had a number of repeated admissions complicated by alcohol withdrawal seizures. He was fortunately stabilized and benzodiazepines were tapered off at which point he was taking no other prescribed medications regularly. Prior to discharge, he was informed of AUD and AnxD treatment options. He was keen to engage with psychosocial supports while starting naltrexone 50 mg once daily and gabapentin 600 mg three times daily.

Eighteen months since discharge, he has found success engaging regularly with substance counselling, Alcoholics Anonymous, and outpatient addictions medicine as well as continuing with naltrexone and gabapentin, the majority of which were intended as synergistic treatments for AUD-AnxD (Fig.  1 ). He reports good health and no alcohol use, and although experiencing cravings, he describes feeling a shift from the sensation of “premeditated” or inevitable relapse as he had in previous attempts at reducing alcohol use.

Venn diagram of current evidence-based interventions reviewed for alcohol use and anxiety disorders

AUD-AnxD indicates comorbid alcohol use disorder and anxiety disorder

* Caution to be exercised with serotoninergic agents given evidence for potential worsening of alcohol outcomes in comorbid AUD-AnxD

Patient perspective

Hi, I’m here to share with you a little bit of the trial and tribulations endured over the many years of addiction. I was an individual who had a seemingly normal life, but under this was a person with undiagnosed mental problems. I was always a drinker who could take or leave drugs, and kept steady employment and had a very loving partner, it wasn’t until an injury in 2009 when my pace with alcohol quickened and I noticed that my consumption was now an everyday affair. Slowly I developed shakes and my day would start with vomiting until I had alcohol of some variety introduced, this continued on for many years and I was now a product of full-blown alcoholism. There now was no job, no partner and very few things that resembled a person who was still an active part of society. I was in and out of hospitals for experiencing multiple seizures and would go weeks with no food or water and begun isolating. I would become so weak physically that I could not move, and would some days awake in with bruises and cuts from either sizing or pass out, I was never sure which. Then I would begin my process of detox recovery house or treatment only to get home and start the vicious cycle again, some time I could stay sober longer if I was using GHB. Nothing would stop my craving and I no longer felt human. I wanted to die… I am proud to inform you that of Dec 12 2020 I have been living a life of sobriety but continue to struggle with cravings, but I use Alcoholics Anonymous as a support and by surrounding like minded people I find myself sober today.

Alcohol use disorder and anxiety

AUD and AnxD are common clinical concerns with evidence-based treatment options. Clinicians should recognize that when two conditions such as AUD and AnxD co-occur, clinical management may require nuance and differ from an approach taken in the context of an individual disorder. As we discuss below, research specifically concerning concurrent AUD-AnxD is still rare despite its high prevalence so data must often be extrapolated. The best available evidence indicates that approaches for treating one disorder may be efficacious, ineffective, or in fact counterproductive for comorbid AUD-AnxD.

AUD treatments

It is critical to recognize and offer proper treatment for AUD even when the primary presenting concern of a client may be an AnxD and vice versa. Whether sequential treatment of AUD and then AnxD, or vice versa, could reduce polypharmacy and iatrogenic harms versus their concurrent treatment remains largely unexplored. Unhealthy alcohol use and AUD are associated with more severe AnxD and conversely abstinence from alcohol is associated with improvement of AnxD [ 3 , 4 ]. To that effect, longitudinal strategies to address AUD may improve AnxD by extension. As conveyed by the reflections of the individual described in the present report, motivational enhancement, formal psychotherapy, mutual self-help interventions such as Alcoholics Anonymous, and supportive settings such as residential treatment facilities, all highlighting the health benefits of reduction or cessation of alcohol use, can serve an important psychosocial role alongside appropriate evidence-based AUD pharmacotherapy [ 5 ]. Nevertheless, the question remains whether certain interventions have additional efficacy in AnxD beyond their efficacy for AUD.

Naltrexone and Acamprosate

Naltrexone is a first-line evidence-based pharmacotherapy which functions as a non-selective opioid antagonist, reducing the rewarding effects of alcohol use mediated by endogenous opioids and downstream neurotransmitters. Studies have demonstrated efficacy for reducing binge drinking (number needed to treat [NNT] = 12) as well as relapse to any alcohol use (NNT = 20) [ 5 ], which motivated our use of naltrexone in the case strongly featuring AUD. To our knowledge, no clinical trial has yet effectively addressed whether naltrexone treatment for AUD can improve a comorbid AnxD, nor an AnxD disorder in isolation.

Acamprosate, which modulates glutamate and GABA signaling disrupted by chronic alcohol use, is another first-line AUD medication effective in preventing relapse to any alcohol use (NNT = 12) [ 5 ]. In terms of comorbid AnxD, some preliminary data suggests benefit of acamprosate for augmentation in various AnxD at doses equivalent or lower than those used in AUD [ 6 ]. However, as with naltrexone, there is a paucity of data to confidently gauge the effect of these first-line AUD medications on a comorbid AnxD and further research would be valuable in this area.

Gabapentinoids

Gabapentinoids such as gabapentin and pregabalin also modulate glutamate and GABA signaling implicated in AnxD and AUD specifically by antagonism of voltage-gated calcium channels. For AUD, gabapentin can be used in the short-term to treat alcohol withdrawal symptoms and in the longer-term to reduce heavy drinking days although efficacy for other endpoints such as reduction in cravings is debated [ 7 ]. Importantly, the data suggest that a key element of clinical efficacy of gabapentin is appropriate patient selection, specifically those with more severe AUD and alcohol withdrawal symptoms. For example, a recent positive randomized clinical trial (RCT) of gabapentin in AUD, which excluded any major psychiatric condition besides PTSD, found that patients with less severe withdrawal tended to fare worse numerically on all indices of alcohol use compared to placebo, although not statistically significant [ 8 ]. To date, some literature exists to support using pregabalin during alcohol withdrawal but data for longer-term treatment of AUD is very limited [ 5 ]. Interestingly, a RCT comparing pregabalin versus naltrexone in subjects with AUD (approximately 15% with comorbid AnxD in each arm) suggested pregabalin was about as effective as naltrexone in terms of AUD outcomes and more effective in reducing phobic anxiety, a subscale of the particular psychiatric questionnaire used in the study [ 9 ]. Further research is needed in this area to better characterize the efficacy of gabapentinoids for treating AnxD specifically in individuals with AUD-AnxD.

The available evidence more strongly supports efficacy of gabapentinoids in treatment of isolated primary AnxD. Gabapentin may be effective for several types of AnxD, [ 2 ] although to our knowledge there is no high-quality data yet available to support gabapentin for treatment of GAD which is frequently encountered in clinical practice. On the other hand, pregabalin has extensive data demonstrating efficacy for GAD as well as SAD, so much so that national practice guidelines currently view pregabalin as a first-line agent for these two conditions [ 2 ].

In sum, the current evidence indicates gabapentinoids have a role in the treatment of both AUD and AnxD and this class of medications may hold promise for treatment of comorbid AUD-AnxD. This emerging evidence supported the prescription of gabapentin in the above case which we believe ultimately contributed to the substantial benefit the individual found with the regimen described. In the interim while further evidence accumulates, a pertinent consideration in the application of gabapentinoids remains the risk of misuse. Gabapentin misuse occurs in the general population, particularly those with substance use disorders, for a variety of reasons including self-medication (e.g. anxiety, pain, and drug withdrawal symptoms) as well as documented recreational use or self-harm [ 10 ]. Even in context of supportive evidence, clinicians should nevertheless be aware of these reports and potential for gabapentinoids to be misused or diverted in treatment of AUD, AnxD, or overlap AUD-AnxD.

Other studied AUD medications

Other medications which have received research attention for AUD include baclofen, topiramate, antipsychotics, and benzodiazepines [ 5 ]. The evidence base for these agents is even more limited and inconclusive in the realm of AUD and comorbid AUD-AnxD. For example, baclofen is a GABA-B agonist medication with a Cochrane systematic review finding conflicting evidence for AUD, comorbid anxiety, and lack of high-quality evidence for use in alcohol withdrawal [ 11 ].

AnxD pharmacotherapies

Psychotropics.

Regarding selective serotonin reuptake inhibitors (SSRIs), the prevalent pharmacologic treatment for AnxD [ 2 ], a Cochrane systematic review of RCTs for comorbid AUD-AnxD found modest improvements in anxiety measures but unreliable or even unhelpful effects on comorbid AUD [ 12 ]. At this juncture, we acknowledge SSRIs are also frequently prescribed according to clinical practice guidelines for treatment of mood disorders that can be challenging to distinguish clinically from AUD and AnxD, which are commonly comorbid [ 13 ]. Nevertheless, meta-analyses demonstrate a lack of benefit of SSRIs in the context of AUD with mood disorder with similar concerns of worsening outcomes [ 14 , 15 , 16 ]. Given the common co-presentation of anxiety and depression among individuals with AUD, the following discussion instead explores the literature from the perspective of AUD outcomes for individuals with any exposure to SSRI or other serotoninergic medications, such as the individual in our case report, regardless of the primary indication for their use. Notably, comorbid mood and anxiety disorders are frequently reported in the available studies and often served as the primary indication for SSRI use.

We note with interest the underappreciated phenomenon of enhanced serotoninergic neurotransmission exacerbating AUD for certain individuals. For example, a secondary analysis of a RCT studying naltrexone for individuals with AUD and comorbid mood and anxiety disorders found prescriptions for SSRI outside of study protocol during follow-up to be associated with worse drinking outcomes for participants randomized to placebo, an effect which was attenuated if participants received naltrexone [ 17 ]. More convincing evidence supporting the potential for harm also exists in several RCTs. In an RCT of the SSRI citalopram for AUD in which mood, AnxD, and both disorders were highly comorbid, participants consumed more alcohol on more days compared to placebo regardless of mood or anxiety measures [ 16 ]. Several trials have also evaluated sertraline in AUD and found that younger participants with more severe AUD in particular tend to fare worse when prescribed an SSRI [ 18 ], moderated in part by the presence of an allele of the serotonin transporter gene favoring greater serotonergic tone [ 18 ]. However, these data are complicated to apply in clinical practice since the predisposing allele may also be found in older participants who happen to develop AUD later in life. Based on allele prevalence in the general US population, Kranzler et al. extrapolated that approximately double the number of individuals with AUD on a population level would be adversely affected by unselected SSRI treatment rather than find benefit [ 18 ]. One small trial comparing combinations of venlafaxine and cognitive behavioral therapy (CBT) for AUD found the only effective treatment for reducing heavy drinking days to be CBT alone with placebo medication, suggesting that selective serotonin and norepinephrine reuptake inhibitors such as venlafaxine may likewise be unhelpful for AUD outcomes [ 19 ].

Trazodone, another psychotropic medication which modulates serotonin transmission, although used for mood disorders and insomnia rather than AnxD, should be addressed in context of AUD. Trazodone is occasionally prescribed with intent as an antidepressant and sleep aid for individuals with AUD but one RCT found a minimal short-term improvement in sleep quality, while also reporting reduced abstinent days, and increased severity of alcohol consumption following withdrawl of trazodone [ 20 ].

In sum, despite the evidence for first-line treatment of isolated AnxD or mood disorders with serotoninergic agents such as SSRIs, clinicians should reconsider and exercise caution in prescribing these medications for patients with comorbid AUD given current observational, RCT, and meta-analysis evidence demonstrating lack of benefit and potential of harm to alcohol use outcomes. In the interim, further investigation is needed to clarify which selected subpopulations in clinical practice would benefit from step-wise approach later involving serotoninergic agents or conversely serotonin antagonists [ 21 ]. Careful use of pharmacologic agents targeting AnxD, such as pregabalin or gabapentin, in tandem with other biopsychosocial strategies may have more of an evidence-based role to play since AnxD are frequently comorbid, have been reported to more frequently precede rather than follow AUD [ 3 ], and are associated with worsening of AUD [ 22 ], suggesting that effective treatment of AnxD may prevent AUD deterioration.

Tobacco cessation

Although not directly relevant to the individual described in our case report, tobacco use may impact clinical outcomes for individuals with AUD-AnxD. Research indicates that weekly smoking in youth is a risk factor for worsening of AUD [ 22 ], and tobacco cessation has been shown to improve anxiety symptoms for both individuals with and without psychiatric disorders [ 23 ]. For instance, a recent meta-analysis demonstrated that the nicotinic receptor partial agonist varenicline was safe and conferred a 25% lower risk of anxiety compared to placebo - likely a result of reduction and cessation in tobacco use [ 24 ]. However, data specific to AUD-AnxD clinical outcomes after tobacco cessation interventions is still limited and inconclusive to date [ 25 ]. In addition to other known broad health benefits such as reduced incidence of cardiovascular disease and cancer, the cessation of tobacco use may also play a synergistic role in treatment of AUD-AnxD.

Psychotherapies

Formal psychotherapy holds promise for addressing the propagating psychosocial factors of AUD and AnxD alone or in addition to pharmacotherapy. In the realm of AnxD, CBT can be equally or more effective than medication alone [ 2 ]. For comorbid AUD-AnxD, motivational interviewing and CBT are effective for both conditions, especially as longer-term modalities with more durable efficacy [ 26 ]. Such targeted and integrated psychotherapy might be particularly effective for individuals with AnxD attempting to self-medicate anxiety symptoms by using alcohol.

Teaching points

AnxD and AUD are prevalent health concerns which frequently co-occur and can compound one another as demonstrated in our report. Their co-occurrence requires a thoughtful approach to treatment given the evidence that treatments of one disorder have been shown to be ineffective or counterproductive for the other disorder (Fig.  1 ). Although evidence is scarce for synergistic treatments of comorbid AUD-AnxD, the literature supports overlapping efficacy of tobacco cessation, use of gabapentinoids, and integrated psychotherapy, the latter two of which were applied with success for the individual in this case report. While the first-line AUD pharmacotherapies naltrexone and acamprosate do not yet have evidence of concurrent benefit for AnxD, effectively treating AUD may yield downstream benefit for AnxD as suggested by treatment response in this report. Lastly, caution should be exercised with serotoninergic medications such as SSRIs as there appears to be underappreciated evidence suggesting that SSRIs are not of benefit in the context of AUD [ 12 ], and may actually worsen alcohol related outcomes for certain individuals [ 16 ]. Further investigation is needed to understand synergistic versus step-wise approaches to treatment of comorbid AUD-AnxD and identification of specific population subgroups which may derive benefit with serotoninergic agonists versus antagonists.

Data availability

Not applicable to case report.

Abbreviations

anxiety disorder

alcohol use disorder

comorbid alcohol use disorder and anxiety disorder

cognitive Behavioral Therapy

gamma aminobutyric acid

generalized anxiety disorder

gamma-hydroxybutyrate

post-traumatic stress disorder

randomized clinical trial

social anxiety disorder

selective serotonin reuptake inhibitors

Grant BF, Goldstein RB, Saha TD, et al. Epidemiology of DSM-5 Alcohol Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry Aug. 2015;72(8):757–66. doi: https://doi.org/10.1001/jamapsychiatry.2015.0584 .

Article   CAS   Google Scholar  

Katzman MA, Bleau P, Blier P, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14(Suppl 1):1. doi: https://doi.org/10.1186/1471-244X-14-S1-S1 .

Article   Google Scholar  

Anker JJ, Kushner MG. Co-Occurring Alcohol Use Disorder and Anxiety: Bridging Psychiatric, Psychological, and Neurobiological Perspectives. Alcohol Res. 2019;40(1)doi: https://doi.org/10.35946/arcr.v40.1.03 .

Driessen M, Meier S, Hill A, Wetterling T, Lange W, Junghanns K. The course of anxiety, depression and drinking behaviours after completed detoxification in alcoholics with and without comorbid anxiety and depressive disorders. Alcohol Alcohol . 2001 May-Jun. 2001;36(3):249–55. doi: https://doi.org/10.1093/alcalc/36.3.249 .

British Columbia Centre on Substance Use (BCCSU), B.C. Ministry of Health, B.C. Ministry of Mental Health and Addictions. Provincial Guideline for the Clinical Management of High-Risk Drinking and Alcohol Use Disorder. BCCSU; 2019. https://www.bccsu.ca/wp-content/uploads/2021/01/AUD-Guideline.pdf .

Hertzman M, Patt IS, Spielman LA. Open-label trial of acamprosate as a treatment for anxiety. Prim Care Companion J Clin Psychiatry. 2009;11(5):267. doi: https://doi.org/10.4088/PCC.08l00714 .

Article   PubMed   PubMed Central   Google Scholar  

Kranzler HR, Feinn R, Morris P, Hartwell EE. A meta-analysis of the efficacy of gabapentin for treating alcohol use disorder. Addiction. 2019;09(9):1547–55. doi: https://doi.org/10.1111/add.14655 . 114 ) .

Anton RF, Latham P, Voronin K, et al. Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial. JAMA Intern Med. Mar 2020. doi: https://doi.org/10.1001/jamainternmed.2020.0249 .

Martinotti G, Di Nicola M, Tedeschi D, et al. Pregabalin versus naltrexone in alcohol dependence: a randomised, double-blind, comparison trial. J Psychopharmacol Sep. 2010;24(9):1367–74. doi: https://doi.org/10.1177/0269881109102623 .

Smith RV, Havens JR, Walsh SL. Gabapentin misuse, abuse and diversion: a systematic review. Addict 07. 2016;111(7):1160–74. doi: https://doi.org/10.1111/add.13324 .

Minozzi S, Saulle R, Rösner S. Baclofen for alcohol use disorder. Cochrane Database Syst Rev Nov. 2018;11:CD012557. doi: https://doi.org/10.1002/14651858.CD012557.pub2 .

Ipser JC, Wilson D, Akindipe TO, Sager C, Stein DJ. Pharmacotherapy for anxiety and comorbid alcohol use disorders. Cochrane Database Syst Rev Jan. 2015;1:CD007505. doi: https://doi.org/10.1002/14651858.CD007505.pub2 .

Beaulieu S, Saury S, Sareen J, et al. The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid substance use disorders. Ann Clin Psychiatry Feb. 2012;24(1):38–55.

Google Scholar  

Agabio R, Trogu E, Pani PP. Antidepressants for the treatment of people with co-occurring depression and alcohol dependence. Cochrane Database Syst Rev. 2018;04:4:CD008581. doi: https://doi.org/10.1002/14651858.CD008581.pub2 .

Grant S, Azhar G, Han E, et al. Clinical interventions for adults with comorbid alcohol use and depressive disorders: A systematic review and network meta-analysis. PLoS Med. 2021;10(10):e1003822. doi: https://doi.org/10.1371/journal.pmed.1003822 . 18 ) .

Charney DA, Heath LM, Zikos E, Palacios-Boix J, Gill KJ. Poorer Drinking Outcomes with Citalopram Treatment for Alcohol Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial. Alcohol Clin Exp Res Sep. 2015;39(9):1756–65. doi: https://doi.org/10.1111/acer.12802 .

Krystal JH, Gueorguieva R, Cramer J, Collins J, Rosenheck R, Team VCNS. Naltrexone is associated with reduced drinking by alcohol dependent patients receiving antidepressants for mood and anxiety symptoms: results from VA Cooperative Study No. 425, “Naltrexone in the treatment of alcoholism”. Alcohol Clin Exp Res Jan. 2008;32(1):85–91. doi: https://doi.org/10.1111/j.1530-0277.2007.00555.x .

Kranzler HR, Armeli S, Tennen H, et al. A double-blind, randomized trial of sertraline for alcohol dependence: moderation by age of onset [corrected] and 5-hydroxytryptamine transporter-linked promoter region genotype. J Clin Psychopharmacol Feb. 2011;31(1):22–30. doi: https://doi.org/10.1097/JCP.0b013e31820465fa .

Ciraulo DA, Barlow DH, Gulliver SB, et al. The effects of venlafaxine and cognitive behavioral therapy alone and combined in the treatment of co-morbid alcohol use-anxiety disorders. Behav Res Ther Nov. 2013;51(11):729–35. doi: https://doi.org/10.1016/j.brat.2013.08.003 .

Stein MD, Kurth ME, Sharkey KM, Anderson BJ, Corso RP, Millman RP. Trazodone for sleep disturbance during methadone maintenance: a double-blind, placebo-controlled trial. Drug Alcohol Depend Jan. 2012;120(1–3):65–73. doi: https://doi.org/10.1016/j.drugalcdep.2011.06.026 .

Johnson BA, Roache JD, Javors MA, et al. Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: A randomized controlled trial. JAMA . 2000 Aug 23–30 2000;284(8):963 – 71. doi: https://doi.org/10.1001/jama.284.8.963 .

Conway KP, Swendsen J, Husky MM, He JP, Merikangas KR. Association of Lifetime Mental Disorders and Subsequent Alcohol and Illicit Drug Use: Results From the National Comorbidity Survey-Adolescent Supplement. J Am Acad Child Adolesc Psychiatry Apr. 2016;55(4):280–8. doi: https://doi.org/10.1016/j.jaac.2016.01.006 .

Taylor G, McNeill A, Girling A, Farley A, Lindson-Hawley N, Aveyard P. Change in mental health after smoking cessation: systematic review and meta-analysis. BMJ (Clinical research ed) Feb 13. 2014;348:g1151. doi: https://doi.org/10.1136/bmj.g1151 .

Thomas KH, Martin RM, Knipe DW, Higgins JP, Gunnell D. Risk of neuropsychiatric adverse events associated with varenicline: systematic review and meta-analysis. BMJ Mar. 2015;12:350:h1109. doi: https://doi.org/10.1136/bmj.h1109 .

Kodl M, Fu SS, Joseph AM. Tobacco cessation treatment for alcohol-dependent smokers: when is the best time? Alcohol Res Health. 2006;29(3):203–7.

PubMed   PubMed Central   Google Scholar  

Baker AL, Thornton LK, Hiles S, Hides L, Lubman DI. Psychological interventions for alcohol misuse among people with co-occurring depression or anxiety disorders: a systematic review. J Affect Disord Aug. 2012;139(3):217–29. doi: https://doi.org/10.1016/j.jad.2011.08.004 .

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EW served as the Chief Medical Officer at Numinus Wellness, a Canadian company interested in medical application of psychedelic substances. Numinus Wellness was not involved in the conception, planning, writing or decision to submit this manuscript for publication. EW is supported by the Canadian Institutes of Health Research through the Canada Research Chairs Program. No other competing interests were declared.

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Mocanu, V., Wood, E. Alcohol use disorder with comorbid anxiety disorder: a case report and focused literature review. Addict Sci Clin Pract 17 , 62 (2022). https://doi.org/10.1186/s13722-022-00344-z

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Understanding alcohol use disorder.

Alcohol use disorder (AUD) is a medical condition characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences. It encompasses the conditions that some people refer to as alcohol abuse, alcohol dependence, alcohol addiction, and the colloquial term, alcoholism. Considered a brain disorder, AUD can be mild, moderate, or severe. Lasting changes in the brain caused by alcohol misuse perpetuate AUD and make individuals vulnerable to relapse. The good news is that no matter how severe the problem may seem, evidence-based treatment with behavioral therapies, mutual-support groups, and/or medications can help people with AUD achieve and maintain recovery. According to the 2022 National Survey on Drug Use and Health, 28.8 million adults ages 18 and older (11.2% in this age group) had AUD in 2021. 1,2 Among youth, an estimated 753,000 adolescents ages 12 to 17 (2.9% of this age group) had AUD during this time frame. 1,2

What Increases the Risk for Alcohol Use Disorder?

A person’s risk for developing AUD depends in part on how much, how often, and how quickly they consume alcohol. Alcohol misuse—defined as drinking in a manner, situation, amount, or frequency that could cause harm to the person who drinks or to those around them—over time increases the risk of AUD. Alcohol misuse includes binge drinking  and heavy alcohol use . Other factors also increase the risk of AUD, such as:

• Drinking at an early age. A recent national survey found that among people ages 26 and older, those who began drinking before age 15 were more than three times as likely to report having AUD in the past year as those who waited until age 21 or later to begin drinking. 3 The risk for females in this group is higher than that of males.
• Genetics and family history of alcohol problems. Genetics play a role, with hereditability accounting for approximately 60%; however, like other chronic health conditions, AUD risk is influenced by the interplay between a person’s genes and their environment. Parents’ drinking patterns may also influence the likelihood that a child will one day develop AUD.
• Mental health conditions and a history of trauma. A wide range of psychiatric conditions—including depression, post-traumatic stress disorder, and attention deficit hyperactivity disorder—are comorbid with AUD and are associated with an increased risk of AUD. People with a history of childhood trauma are also vulnerable to AUD.

What Are the Symptoms of Alcohol Use Disorder?

Health care professionals use criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), to assess whether a person has AUD and to determine the severity, if the disorder is present. Severity is based on the number of criteria a person meets based on their symptoms—mild (2–3 criteria), moderate (4–5 criteria), or severe (6 or more criteria).

A health care provider might ask the following questions to assess a person’s symptoms.

In the past year, have you:

• Had times when you ended up drinking more, or longer, than you intended?
• More than once wanted to cut down or stop drinking, or tried to, but couldn’t?
• Spent a lot of time drinking, being sick from drinking, or getting over other aftereffects?
• Wanted a drink so badly you couldn’t think of anything else?
• Found that drinking—or being sick from drinking—often interfered with taking care of your home or family? Or caused job troubles? Or school problems?
• Continued to drink even though it was causing trouble with your family or friends?
• Given up or cut back on activities you found important, interesting, or pleasurable so you could drink?
• More than once gotten into situations while or after drinking that increased your chances of getting hurt (such as driving, swimming, using machinery, walking in a dangerous area, or unsafe sexual behavior)?
• Continued to drink even though it was making you feel depressed or anxious or adding to another health problem? Or after having had an alcohol-related memory blackout?
• Had to drink much more than you once did to get the effect you want? Or found that your usual number of drinks had much less effect than before?
• Found that when the effects of alcohol were wearing off, you had withdrawal symptoms, such as trouble sleeping, shakiness, restlessness, nausea, sweating, a racing heart, dysphoria (feeling uneasy or unhappy), malaise (general sense of being unwell), feeling low, or a seizure? Or sensed things that were not there?

Any of these symptoms may be cause for concern. The more symptoms, the more urgent the need for change.

What Are the Types of Treatment for Alcohol Use Disorder?

Several evidence-based treatment approaches are available for AUD. One size does not fit all and a treatment approach that may work for one person may not work for another. Treatment can be outpatient and/or inpatient and be provided by specialty programs, therapists, and health care providers.

Medications

Three medications are currently approved by the U.S. Food and Drug Administration to help people stop or reduce their drinking and prevent a return to drinking: naltrexone (oral and long-acting injectable), acamprosate, and disulfiram. All these medications are nonaddictive, and they may be used alone or combined with behavioral treatments or mutual-support groups.

Behavioral Treatments

Behavioral treatments—also known as alcohol counseling, or talk therapy, and provided by licensed therapists—are aimed at changing drinking behavior. Examples of behavioral treatments are brief interventions and reinforcement approaches, treatments that build motivation and teach skills for coping and preventing a return to drinking, and mindfulness-based therapies.

Mutual-Support Groups

Mutual-support groups provide peer support for stopping or reducing drinking. Group meetings are available in most communities at low or no cost, and at convenient times and locations—including an increasing presence online. This means they can be especially helpful to individuals at risk for relapse to drinking. Combined with medications and behavioral treatment provided by health care professionals, mutual-support groups can offer a valuable added layer of support.

Please note: People with severe AUD may need medical help to avoid alcohol withdrawal if they decide to stop drinking. Alcohol withdrawal is a potentially life-threatening process that can occur when someone who has been drinking heavily for a prolonged period of time suddenly stops drinking. Doctors can prescribe medications to address these symptoms and make the process safer and less distressing.

Can People With Alcohol Use Disorder Recover?

Many people with AUD do recover, but setbacks are common among people in treatment. Seeking professional help early can prevent a return to drinking. Behavioral therapies can help people develop skills to avoid and overcome triggers, such as stress, that might lead to drinking. Medications also can help deter drinking during times when individuals may be at greater risk of a return to drinking (e.g., divorce, death of a family member).

If you are concerned about your alcohol use and would like to explore whether you might have AUD, please visit the Rethinking Drinking website .

To learn more about alcohol treatment options and search for quality care near you, please visit the NIAAA Alcohol Treatment Navigator .

For more information about alcohol and your health, please visit: niaaa.nih.gov

1  SAMHSA, Center for Behavioral Health Statistics and Quality. 2022 National Survey on Drug Use and Health. Table 5.1A—Substance use disorder for specific substances in past year: among people aged 12 or older; by age group, numbers in thousands, 2021 and 2022 [cited 2023 Dec 29]. Available from:  https://www.samhsa.gov/data/sites/default/files/reports/rpt42728/NSDUHDetailedTabs2022/NSDUHDetailedTabs2022/NSDUHDetTabsSect5pe2022.htm#tab5.1a  

2 SAMHSA, Center for Behavioral Health Statistics and Quality. 2022 National Survey on Drug Use and Health. Table 5.1B—Substance use disorder for specific substances in past year: among people aged 12 or older; by age group, percentages, 2021 and 2022 [cited 2023 Dec 29]. Available from: https://www.samhsa.gov/data/sites/default/files/reports/rpt42728/NSDUHDetailedTabs2022/NSDUHDetailedTabs2022/NSDUHDetTabsSect5pe2022.htm#tab5.1b

3  Age at drinking onset: age when first drank a beverage containing alcohol (a can or bottle of beer, a glass of wine or a wine cooler, a shot of distilled spirits, or a mixed drink with distilled spirits in it), not counting a sip or two from a drink. AUD: having met two or more of the 11 AUD diagnostic criteria in the past-year according to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) AUD risk across different ages at drinking onset is compared using the prevalence ratio weighted by the person-level analysis weight. Derived from the Center for Behavioral Health Statistics and Quality 2022 National Survey on Drug Use and Health (NSDUH-2022-DS0001) public-use file. [cited 2024 Jan 12]. Available from: https://www.datafiles.samhsa.gov/dataset/national-survey-drug-use-and-health-2022-nsduh-2022-ds0001

niaaa.nih.gov

An official website of the National Institutes of Health and the National Institute on Alcohol Abuse and Alcoholism

• Open access
• Published: 06 September 2024

Lifetime exposure to smoking and substance abuse may be associated with late-onset multiple sclerosis: a population-based case-control study

• Naghmeh Abbasi Kasbi 1 ,
• Sajjad Ghane Ezabadi 1 ,
• Kosar Kohandel 1 ,
• Faezeh Khodaie 1 ,
• Amir Hossein Sahraian 1 ,
• Sahar Nikkhah Bahrami 1 , 3 ,
• Mahsa Mohammadi 1 ,
• Amir Almasi-Hashiani 2 ,
• Sharareh Eskandarieh 1 &
• Mohammad Ali Sahraian 1  

BMC Neurology volume  24 , Article number:  327 ( 2024 ) Cite this article

Metrics details

Late-onset multiple sclerosis (LOMS), defined as the development of MS after the age of 50, has shown a substantial surge in incidence rates and is associated with more rapid progression of disability. Besides, studies have linked tobacco smoking to a higher chance of MS progression. However, the role of smoking on the risk of developing LOMS remains unclear. This study aims to evaluate the possible association between lifetime exposure to cigarette and waterpipe smoking, drug abuse, and alcohol consumption and the risk of LOMS.

This population-based case-control study involved LOMS cases and healthy sex and age-matched controls from the general population in Tehran, Iran. The primary data for confirmed LOMS cases were obtained from the nationwide MS registry of Iran (NMSRI), while supplementary data were collected through telephone and on-site interviews. Predesigned questionnaire for multinational case-control studies of MS environmental risk factors was used to evaluate the LOMS risk factors. The study employed Likelihood ratio chi-square test to compare qualitative variables between the two groups and utilized two independent sample t-test to compare quantitative data. Adjusted odds ratio (AOR) for age along with 95% confidence intervals (CI) were calculated using matched logistic regression analysis in SPSS 23.

Totally, 83 LOMS cases and 207 controls were included in the analysis. The female to male ratio in the cases was 1.5: 1. The mean ± SD age of 83 cases and 207 controls was 61.14 ± 5.38) and 61.51 ± 7.67 years, respectively. The mean ± SD expanded disability status scale (EDSS) score was 3.68 ± 2.1. Although the results of waterpipe exposure had no significant effect on LOMS development (P-value: 0.066), ever cigarette-smoked participants had a significantly higher risk of developing LOMS than those who never smoked (AOR: 2.57, 95% CI: 1.44–4.60). Furthermore, people with a history of smoking for more than 20 years had 3.45 times the odds of developing MS than non-smokers. Drug and alcohol abuse were both associated with LOMS in our study; of which opioids (AOR: 5.67, 95% CI: 2.05–15.7), wine (AOR: 3.30, 95% CI: 1.41–7.71), and beer (AOR: 3.12, 95% CI: 1.45–6.69) were found to pose the greatest risk of LOMS, respectively.

For the first time, we identified smoking, drug, and alcohol use as potential risk factors for LOMS development. According to the global increase in cigarette smoking and alcohol use, these findings highlight the importance of conducting interventional approaches for prevention.

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Introduction

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease that affects the central nervous system by infiltration of immune cells and inflammatory demyelination of white matter [ 1 ]. Considered the most common chronic demyelinating disorder, MS leads to disability and a significant decline in quality of life, especially in young individuals [ 2 ]. Although the exact etiology is still unclear, research has increasingly focused on identifying potential risk factors that may contribute to its development and progression. Factors such as previous EBV infection, vitamin D deficiency, obesity, and smoking have been proposed as potential risk factors for MS development [ 3 ].

The onset of MS usually occurs during the third to fourth decade of life [ 4 ]. However, some patients may experience symptoms beyond the age of 50 [ 5 ]. Recent studies have indicated that late-onset multiple sclerosis (LOMS) is more prevalent than previously believed, with estimates ranging between 4% and 9.4%. These findings challenge the notion that LOMS is of rare occurrence [ 6 , 7 ]. In light of existing literature, progressive patterns of MS are more common in LOMS patients [ 8 , 9 ]. Moreover, the diagnosis of LOMS can be challenging for clinicians, as many diseases in the elderly may present with similar characteristics [ 10 ]. This highlights the importance of early diagnosis, understanding the disease characteristics, and identifying its associated risk factors.

In the past few years, emerging epidemiological research has suggested a possible link between smoking and MS. Cigarette smoking amplifies inflammatory responses, diminishes specific components of the immune system, and enhances the propensity for infection [ 11 ]. Previous studies have also hinted at a possible connection between smoking and MS through the presence of low serum vitamin D levels and inadequate dietary vitamin D intake among smokers [ 12 ]. The duration and intensity of smoking play significant roles in the dose-dependent risks associated with MS, and the adverse effects gradually decline upon smoking cessation [ 13 , 14 ]. Waterpipe smoking has also been recognized as a risk factor for the development of MS [ 15 ]. Notably, the role of alcohol consumption in MS remains debated, with studies supporting both risk and protective viewpoints [ 12 , 16 ]. Some recent studies have also mentioned substance use as a potential risk factor for MS, although specific details are not provided [ 15 ]. However, there is limited evidence regarding the risk factors associated with LOMS.

This study aims to explore the potential effect of tobacco smoking, alcohol consumption, and substance abuse as risk factors for LOMS.

Materials and methods

Study design.

A population-based case-control study was carried out during 9 months from November 2022 to July 2023 in Tehran to investigate the potential risk factors of late-onset MS. The study employed a hybrid approach, combining both in-person and remote data collection methods.

Participants

The source population of our study was all residents aged 50 years and above residing in one of the 22 districts within the Tehran municipality for a minimum of two years. Cases were defined as confirmed LOMS patients according to the 2017 McDonald criteria, registered at our official MS registry, the nationwide MS registry of Iran (NMSRI) [ 17 , 18 ]. Besides, controls were healthy individuals within the source population with no history of MS, selected randomly through an age-matched randomization method from various areas of Tehran. Overall, 97 registered cases and 230 matched controls were contacted for further investigations and interview. Individuals with cognitive impairment or a lack of willingness to participate in the interview were excluded. Controls who presented any form of other neurological disease were also excluded.

Data collection

Clinical characteristics of LOMS cases were extracted from NMSRI to complete a structured questionnaire, designed specifically for multinational case-control research on environmental risk factors associated with MS [ 19 ]. Telephone interviews were also performed by four well-trained interviewers to gather supplementary data on the cases. Moreover, two interviewers conducted a face-to-face interview with the general population as the control group, using the same questionnaire.

Exposure assessment

Participants were asked to fill out the study questionnaire comprising demographic items such as age, sex, marital status, the highest level of education, and self-rated health status - scored from 1 (the lowest) to 5 (the highest)-, and their history of cigarette and waterpipe smoking, substance (opioids, cannabis, stimulants, hallucinogen) use, and alcohol (whisky/vodka, beer, and wine) consumption across the life course.

The history of cigarette smoking was considered positive if the participant smoked cigarettes for at least 6 months or more than 180 cigarettes in total. Substance use and alcohol consumption were positive if participants used them at least once per month for more than 6 months, while for waterpipe it was considered at least once per week for more than 6 months [ 13 , 20 ].

Statistical analysis

Quantitative data was described using mean and standard deviation, whereas qualitative data was described using number and percentage. Likelihood ratio chi-square test was utilized to compare qualitative variables between two groups and two independent sample t-test was employed to compare quantitative data. Crude and adjusted odds ratio (OR) and 95% confidence interval (CI) were also used to check the effect size of independent variables on dependent variables. All analyses were performed using Stata software version 14 and at a significance level of 0.05.

Ethical considerations

Each participant was thoroughly informed about his/her role in the study as well as the purpose of the research, and their probable questions about the study were answered. All participants were required to give verbal consent to be informed that their personal information is kept secure. Those who were unwilling to take part in our study were excluded. The ethics committee at Tehran University of Medical Sciences approved the current study by the code: IR.TUMS.NI.REC.1402.028. Furthermore, all the steps taken in this study adhere to the principles outlined in the Declaration of Helsinki.

Overall, 83 cases with LOMS and 207 controls were included. The demographic variables are compared between the two groups in Table  1 . The mean ± SD expanded disability status scale (EDSS) score was 3.68 ± 2.1 in cases. The results indicate that there was no significant difference between the two groups concerning marital status ( p  = 0.444). Compared to the controls, the cases had less education ( p  = 0.030) and a lower mean self-rated health score ( p  = 0.001).

The frequency distribution of cigarette and waterpipe smoking is shown in Table  2 . There was no significant difference in the frequency of waterpipe use between the two groups (6.0% vs. 4.3%). The frequency of ever cigarette smoking in the case group was significantly higher than in the control group (36.1% vs. 18.8%), and after adjusting for age, the odds of MS in smokers were 2.57 (95% CI: 1.44–4.60, p  = 0.001) times that of non-smokers. In addition, the odds of developing MS in current smokers were 4.33 (95% CI: 2.06–9.09, p  = 0.001) times that of non-smokers, while those who quit smoking had no higher odds of developing MS compared to non-smokers (OR = 1.40, 95% CI: 0.62–3.17, p  = 0.417). Subjects who had a history of smoking for more than 20 years had 3.45 times higher odds of developing MS than non-smokers (95% CI: 1.82–6.90, p  = 0.001). Passive smoking and its duration showed no significant difference between the two groups.

Table  3 depicts the association between substance and alcohol use and LOMS development. The prevalence of opium use in patients with LOMS was significantly higher than in the control group (14.5% vs. 2.9%), and after adjusting for age, the odds of developing MS in people with a history of opium use was 5.67 (95% CI: 2.05–15.7, p  = 0.001) times higher than those without a history. On the other hand, the prevalence of cannabis use in patients with LOMS were significantly lower (p-value = 0.025). There were no reports by any of our participants regarding the use of stimulants or hallucinogens.

The prevalence of alcohol consumption was significantly higher in the LOMS cases (24.1% vs. 11.6%). After adjusting for age, the results showed that the odds of developing MS in people with a history of alcohol consumption were significantly higher than that of those without a history of alcohol consumption (OR = 2.45, 95% CI: 1.26–4.76, p  = 0.008). Specifically, wine (OR = 3.30, 95%CI: 1.41–7.71, P  = 0.006) and beer consumption (OR = 3.12, 95%CI: 1.45–6.69, P  = 0.003) were associated with an increased LOMS risk ( Table 4 and 5 ).

The present population-based case-control study reported the characteristics of 83 LOMS patients and 207 healthy controls in an Iranian population and assessed the possible role of exposure to cigarette and waterpipe smoking, drug abuse, and alcohol consumption in the risk of LOMS development. Since various risk factors can influence the age of onset and differ across various age groups, as well as different populations, we have undertaken to explore the potential influence of tobacco smoking, alcohol consumption, and substance abuse as risk factors for LOMS. For all we know, this is the first research to examine these factors in a relatively large-scale Iranian population, which makes it stand out from other national studies. Besides, the inclusion of a large control group adds to the robustness of the analysis, enhancing the reliability of the results.

The mean ± SD EDSS score was 3.68 ± 2.1 in cases, indicating a moderate level of disability. Interestingly, there was no significant difference between the two groups concerning marital status which aligns with the findings of Alsharie et al. [ 1 ] who examined PPMS cases and controls, where they also found no significant differences in marital status ( P  = 0.02). Moreover, in our study, we observed that the LOMS cases had significantly lower levels of education and self-rated health compared to the control group. This finding echoes the results of studies on PPMS [ 1 ] and NMOSD [ 4 ], which reported a higher self-rated health score in controls compared to NMOSD cases. These results collectively suggest that educational attainment and self-perceived health may have an impact on various neurologic diseases, including LOMS, PPMS, and NMOSD. The differences in education levels and self-rated health between cases and controls highlight the potential influence of social and quality-of-life factors in the development and progression of neurologic conditions.

The current study also confirms the correlation between smoking cigarettes and increased odds for LOMS. The age-adjusted OR of developing LOMS was 2.57 in ever smokers and 4.33 in current smokers. However, the results could not show an association between ex-smokers and the risk of LOMS. Smoking for more than 20 years had 3.45 times the odds of developing LOMS. Although passive smoking was more prevalent in LOMS with OR of 1.79, the statistical analysis was unable to demonstrate a significant difference between the two groups. These findings broadly support the study on individuals with MS aged 40 to 69 years who reported increased OR of current smoking but not passive smoking [ 21 ]. Conversely, in a prospective cohort, current or former smoking was not significantly linked with the risk of LOMS [ 22 ].

Evidence on the risk factors of LOMS is limited. However, several studies have established that smoking is a risk factor for developing, and adverse prognosis of MS [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Duration and intensity of smoking contribute dose-dependent to the hazards of MS and the harmful effects slowly subside after smoking cessation [ 32 ]. The attributed effects of smoking might be due to interaction with some genetic variants and subsequent activation of T cells [ 33 ]. Smoking enhances inflammatory responses, reduces some immune defenses, and increase vulnerability to infection [ 11 ]. Furthermore, smoking acts synergistically with Epstein-Barr virus antibody levels to increases MS risk [ 34 ]. In addition, components in cigarette smoke might cause direct toxic effects on neurons [ 35 ].

Despite the strong evidence, some studies using Mendelian randomization manifested no clear confirmation of smoking as environmental risk factor for MS susceptibility [ 36 , 37 ]. In contrast to our findings, some studies have reported that passive smoking and prior smoking increased the risk of MS [ 13 , 20 , 38 , 39 , 40 , 41 ]. The frequency of ever waterpipe smoking in the LOMS group was slightly more than the control group; however, the difference was not significant. This limitation is attributed to the small sample size of patients who smoked water pipes and participated in the study. The limited number of participants who engaged in this smoking method precludes definitive conclusions regarding its potential association with the outcome of interest. Contrary to the current results, some studies have reported that waterpipe smoking increases the risk of MS [ 42 , 43 , 44 ].

We also observed a significant correlation between opium use and the onset of LOMS. The odds of developing MS in people with a history of opium use was 5.67 times higher than those without a history after adjusting for age.

No study had ever assessed the effect of drugs on the LOMS. However, evaluating the impact of recreational drugs on MS revealed a significant link between drug abuse and MS onset which is in line with our findings for LOMS [ 45 , 46 ]. Conversely, no connection was observed between the abuse of opium and the onset of MS in a study, and current or past use of marijuana and MS in another study [ 47 , 48 ].

It seems that alterations in the endogenous opioid system contribute to the onset and severity of symptoms in MS patients [ 49 ]. Studies detected all three Delta opioid receptors (DOR), Mu-opioid receptors (MOR), and Kappa-opioid receptors (KOR) in T cells, B cells, and macrophages [ 50 , 51 ]. Disruptions in the balance of the T helper cells, especially decreasing the Th1/Th2 ratio are established to play a major role in the immunopathogenesis of MS [ 52 , 53 ]. Morphine can cause an alteration in Th1/Th2 ratio, cytokine expression, T cell apoptosis, and differentiation [ 54 ]. Opium addict patients have higher EDSS scores, increased fatigue severity scale, and memory impairments [ 55 ].

In our study, the prevalence of alcohol consumption was significantly higher in LOMS patients compared to healthy subjects. In addition, drinking alcohol, especially wine and beer, during adolescence and young adulthood increased the risk of LOMS. In a large cohort study conducted in England between 1999 and 2011, the risk of developing MS in any type of alcohol use, such as alcohol consumption, alcohol abuse, and dependence, was significantly increased. This investigation supported a noteworthy positive relationship between alcohol use disorders and the risk of MS [ 56 ]. However, some population-based studies, have indicated that there is a dose-dependent inverse relationship between MS and alcohol consumption [ 57 ].

In previous studies, it has been mentioned that long-term high alcohol consumption has harmful effects on the humoral and cellular immune systems [ 58 ]. Furthermore, it seems that alcohol consumption can reduce the frequency of lymphocytes, and this reduction is more pronounced in people with alcohol use disorder (AUD) [ 59 ]. Also, alcohol abuse can cause a shift in T cell phenotype by changing the surface antigens and receptors [ 59 ]. In addition, due to the augmentation in hematopoietic proliferation, the number of memory T cells may increase and the accumulation of memory T cells in different tissues increases the incidence of chronic inflammatory diseases [ 60 ]. Taken together, studies have shown that chronic T-cell lymphopenia following heavy and long-term alcohol consumption leads to increased hemostatic proliferation and activation of T cells, thereby increasing the ratio of memory T cells to naïve T cells, in contrast, moderate alcohol consumption increases the number of lymphocytes [ 59 ]. Some studies have suggested that smoking and alcohol consumption can cause increasing immunoglobulin (Ig) levels, and affect the function of microglia and astrocytes, which leads to strengthening the immunogenicity of self-proteins and finally the beginning of autoimmune responses and autoimmune diseases such as MS [ 61 , 62 ].

Because alcoholic beverages are high in energy and are considered a source of energy for consumers, most AUD suffer from malnutrition such as vitamins deficiency [ 63 ]. Likewise, vitamin D deficiency is one of the known risk factors for developing MS [ 64 ]. Hence, in AUD the immune system suffers from various methods, such as malnutrition with vitamin deficiency, immune cells (B and T lymphocyte) dysfunction, and barrier defects that can increase the occurrence of chronic diseases such as MS and Alzheimer’s [ 59 ].

However, there is considerable evidence that low to moderate consumption of alcoholic beverages such as beer and wine, which contain polyphenols, have beneficial effects on health and the immune system [ 65 ]. It was reported that neither all alcohol consumption nor wine or beer drinking, was linked to the risk of developing MS [ 66 ]. This contrast seems to be due to the difference in alcohol consumption definition in these studies (at least once per month for more than 6 months in our research versus several categories of alcohol consumption in the mentioned study).

As far as we know, the current study was the first to investigate the risk factors of LOMS in a relatively large population in the region with well-matched controls; however, it should be noted that due to the retrospective nature of case-control studies and the possibility of recall bias, no causation can be made and further studies are needed to address these limitations, to confirm the findings and to provide additional information on the topic.

It is critical to identify the risk factors contributing to the development of LOMS. In our study, cigarette smoking, alcohol consumption, and substance abuse have been recognized as possible risk factors for LOMS. However, waterpipe smoking did not demonstrate any association with LOMS. Individuals who have smoked cigarettes for more than 20 years face an elevated risk of developing LOMS. Furthermore, the consumption of alcohol, particularly wine and beer, during adolescence and young adulthood has been linked to higher odds of experiencing LOMS. According to the global increase in cigarette smoking and alcohol use, these results highlight the need for interventional preventive programs.

Data availability

No datasets were generated or analysed during the current study.

Piggott T, Nonino F, Baldin E, Filippini G, Rijke N, Schünemann H, Laurson-Doube J. Multiple Sclerosis International Federation guideline methodology for off-label treatments for multiple sclerosis. Multiple Scler J - Experimental Translational Clin. 2021;7(4):20552173211051855.

Google Scholar  

Chwastiak LA, Ehde DM. Psychiatric issues in multiple sclerosis. Psychiatr Clin North Am. 2007;30(4):803–17.

Article   PubMed   PubMed Central   Google Scholar  

Maroufi H, Mortazavi SH, Sahraian MA, Eskandarieh S. Environmental risk factors of multiple sclerosis in the Middle East and North Africa region: a systematic review. Curr J Neurol. 2021;20(3):166–84.

PubMed   PubMed Central   Google Scholar  

Hellwig K, Verdun di Cantogno E, Sabidó M. A systematic review of relapse rates during pregnancy and postpartum in patients with relapsing multiple sclerosis. Ther Adv Neurol Disord. 2021;14:17562864211051012.

Ghadiri F, Sahraian MA, Razazian N, Ashtari F, Poursadeghfard M, Nabavi SM, et al. Late-onset multiple sclerosis in Iran: a report on demographic and disease characteristics. Mult Scler Relat Disord. 2023;70:104493.

Article   PubMed   Google Scholar  

Confavreux C, Vukusic S, Moreau T, Adeleine P. Relapses and progression of disability in multiple sclerosis. N Engl J Med. 2000;343(20):1430–8.

Article   CAS   PubMed   Google Scholar  

Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168–71.

Correia I, Marques I, Sousa L. História Natural Da Esclerose Múltipla–Revisão Natural History of multiple sclerosis–review. Sinapse ® . 2014:38.

Lotti CBC, Oliveira ASB, Bichuetti DB, Castro Id, Oliveira EML. Late onset multiple sclerosis: concerns in aging patients. Arq Neuropsiquiatr. 2017;75:451–6.

Martinelli V, Rodegher M, Moiola L, Comi G. Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis. Neurol Sci. 2004;25:s350–5.

Alrouji M, Manouchehrinia A, Gran B, Constantinescu CS. Effects of cigarette smoke on immunity, neuroinflammation and multiple sclerosis. J Neuroimmunol. 2019;329:24–34.

Morabia A, Bernstein M, Antonini S. Smoking, dietary calcium and vitamin D deficiency in women: a population-based study. Eur J Clin Nutr. 2000;54(9):684–9.

Mortazavi SH, Naser Moghadasi A, Almasi-Hashiani A, Sahraian MA, Goudarzi H, Eskandarieh S. Waterpipe and cigarette smoking and drug and alcohol consumption, and the risk of primary progressive multiple sclerosis: a population-based case-control study. Curr J Neurol. 2023;22(2):72–81.

Manouchehrinia A, Tench CR, Maxted J, Bibani RH, Britton J, Constantinescu CS. Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study. Brain. 2013;136(Pt 7):2298–304.

Abdollahpour I, Nedjat S, Mansournia MA, Sahraian MA, van der Mei I. Lifestyle factors and multiple sclerosis: a population-based incident case-control study. Multiple Scler Relat Disorders. 2018;22:128–33.

Article   Google Scholar  

Song J, Westerlind H, McKay KA, Almqvist C, Stridh P, Kockum I, et al. Familial risk of early-and late-onset multiple sclerosis: a Swedish nationwide study. J Neurol. 2019;266:481–6.

Ayoubi S, Asadigandomani H, Bafrani MA, Shirkoohi A, Nasiri M, Sahraian MA, Eskandarieh S. The National multiple sclerosis Registry System of Iran (NMSRI): aspects and methodological dimensions. Mult Scler Relat Disord. 2023;72:104610.

Ezabadi SG, Sahraian MA, Maroufi H, Shahrbaf MA, Eskandarieh S. Global assessment of characteristics of multiple sclerosis registries; a systematic review. Mult Scler Relat Disord. 2022;63:103928.

Pugliatti M, Casetta I, Drulovic J, Granieri E, Holmøy T, Kampman MT et al. A questionnaire for multinational case-control studies of environmental risk factors in multiple sclerosis (EnvIMS-Q). Acta Neurol Scand Suppl. 2012(195):43–50.

Abdollahpour I, Nedjat S, Mansournia MA, Sahraian MA, van der Mei I. Lifestyle factors and multiple sclerosis: a population-based incident case-control study. Mult Scler Relat Disord. 2018;22:128–33.

Kleerekooper I, Chua S, Foster PJ, Trip SA, Plant GT, Petzold A, Patel P. Associations of Alcohol Consumption and Smoking with Disease Risk and Neurodegeneration in individuals with multiple sclerosis in the United Kingdom. JAMA Netw open. 2022;5(3):e220902.

Pommerich UM, Nielsen R, Overvad K, Dahm CC, Tjønneland A, Olsen A, Dalgas U. Diet quality is not associated with late-onset multiple sclerosis risk- A Danish cohort study. Mult Scler Relat Disord. 2020;40:101968.

Manouchehrinia A, Huang J, Hillert J, Alfredsson L, Olsson T, Kockum I, Constantinescu CS. Smoking attributable risk in multiple sclerosis. Front Immunol. 2022;13:840158.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Poorolajal J, Bahrami M, Karami M, Hooshmand E. Effect of smoking on multiple sclerosis: a meta-analysis. J Public Health (Oxf). 2017;39(2):312–20.

PubMed   Google Scholar  

Degelman ML, Herman KM. Smoking and multiple sclerosis: a systematic review and meta-analysis using the Bradford Hill criteria for causation. Mult Scler Relat Disord. 2017;17:207–16.

O’Gorman C, Broadley SA. Smoking and multiple sclerosis: evidence for latitudinal and temporal variation. J Neurol. 2014;261(9):1677–83.

Nishanth K, Tariq E, Nzvere FP, Miqdad M, Cancarevic I. Role of smoking in the pathogenesis of multiple sclerosis: a review article. Cureus. 2020;12(8):e9564.

Arneth B. Multiple sclerosis and smoking. Am J Med. 2020;133(7):783–8.

Handel AE, Williamson AJ, Disanto G, Dobson R, Giovannoni G, Ramagopalan SV. Smoking and multiple sclerosis: an updated meta-analysis. PLoS ONE. 2011;6(1):e16149.

Asadollahi S, Fakhri M, Heidari K, Zandieh A, Vafaee R, Mansouri B. Cigarette smoking and associated risk of multiple sclerosis in the Iranian population. J Clin Neurosci. 2013;20(12):1747–50.

O’Gorman C, Bukhari W, Todd A, Freeman S, Broadley SA. Smoking increases the risk of multiple sclerosis in Queensland, Australia. J Clin Neurosci. 2014;21(10):1730–3.

Hedström AK, Hillert J, Olsson T, Alfredsson L. Smoking and multiple sclerosis susceptibility. Eur J Epidemiol. 2013;28(11):867–74.

Jacobs BM, Noyce AJ, Bestwick J, Belete D, Giovannoni G, Dobson R. Gene-environment interactions in multiple sclerosis: a UK Biobank Study. Neurol Neuroimmunol Neuroinflamm. 2021;8(4).

Hedström AK, Huang J, Brenner N, Butt J, Hillert J, Waterboer T, et al. Smoking and Epstein-Barr virus infection in multiple sclerosis development. Sci Rep. 2020;10(1):10960.

Rosso M, Chitnis T. Association between cigarette smoking and multiple sclerosis: a review. JAMA Neurol. 2020;77(2):245–53.

Mitchell RE, Bates K, Wootton RE, Harroud A, Richards JB, Davey Smith G, Munafò MR. Little evidence for an effect of smoking on multiple sclerosis risk: a mendelian randomization study. PLoS Biol. 2020;18(11):e3000973.

Vandebergh M, Goris A. Smoking and multiple sclerosis risk: a mendelian randomization study. J Neurol. 2020;267(10):3083–91.

Oturai DB, Bach Søndergaard H, Koch-Henriksen N, Andersen C, Laursen JH, Gustavsen S, et al. Exposure to passive smoking during adolescence is associated with an increased risk of developing multiple sclerosis. Mult Scler. 2021;27(2):188–97.

Sakoda A, Matsushita T, Nakamura Y, Watanabe M, Shinoda K, Masaki K, et al. Environmental risk factors for multiple sclerosis in Japanese people. Mult Scler Relat Disord. 2020;38:101872.

Hedström AK, Bäärnhielm M, Olsson T, Alfredsson L. Exposure to environmental tobacco smoke is associated with increased risk for multiple sclerosis. Mult Scler. 2011;17(7):788–93.

Zhang P, Wang R, Li Z, Wang Y, Gao C, Lv X, et al. The risk of smoking on multiple sclerosis: a meta-analysis based on 20,626 cases from case-control and cohort studies. PeerJ. 2016;4:e1797.

Alkhawajah NM, Aljarallah S, Hussain-Alkhateeb L, Almohaini MO, Muayqil TA. Waterpipe Tobacco Smoking and other multiple sclerosis environmental risk factors. Neuroepidemiology. 2022;56(2):97–103.

Abdollahpour I, Nedjat S, Almasi-Hashiani A, Nazemipour M, Mansournia MA, Luque-Fernandez MA. Estimating the marginal Causal Effect and potential impact of Waterpipe smoking on risk of multiple sclerosis using the targeted maximum likelihood estimation method: a large, Population-Based Incident Case-Control Study. Am J Epidemiol. 2021;190(7):1332–40.

Abdollahpour I, Nedjat S, Sahraian MA, Mansournia MA, Otahal P, van der Mei I. Waterpipe smoking associated with multiple sclerosis: a population-based incident case-control study. Mult Scler. 2017;23(10):1328–35.

Brosseau L, Philippe P, Méthot G, Duquette P, Haraoui B. Drug abuse as a risk factor of multiple sclerosis: case-control analysis and a study of heterogeneity. Neuroepidemiology. 1993;12(1):6–14.

Hawkes CH, Boniface D. Risk associated behavior in premorbid multiple sclerosis: a case-control study. Multiple Scler Relat Disorders. 2014;3(1):40–7.

Dehghan M, Ghaedi-Heidari F. Environmental risk factors for multiple sclerosis: a case-control study in Kerman. Iran Iran J Nurs Midwifery Res. 2018;23(6):431.

Ponsonby A-L, Lucas RM, Dear K, van der Mei I, Taylor B, Chapman C, et al. The physical anthropometry, lifestyle habits and blood pressure of people presenting with a first clinical demyelinating event compared to controls: the Ausimmune study. Multiple Scler J. 2013;19(13):1717–25.

Ludwig MD, Zagon IS, McLaughlin PJ. Featured article: serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone. Experimental Biology Med. 2017;242(15):1524–33.

Article   CAS   Google Scholar  

Ninković J, Roy S. Role of the mu-opioid receptor in opioid modulation of immune function. Amino Acids. 2013;45:9–24.

Bidlack JM. Detection and function of opioid receptors on cells from the immune system. Clin Diagn Lab Immunol. 2000;7(5):719–23.

Van Langelaar J, van der Vuurst RM, Janssen M, Wierenga-Wolf AF, Spilt IM, Siepman TA, et al. T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention. Brain. 2018;141(5):1334–49.

Kunkl M, Frascolla S, Amormino C, Volpe E, Tuosto L. T helper cells: the modulators of inflammation in multiple sclerosis. Cells. 2020;9(2):482.

Gao M, Sun J, Jin W, Qian Y. Morphine, but not ketamine, decreases the ratio of Th1/Th2 in CD4-positive cells through T-bet and GATA3. Inflammation. 2012;35:1069–77.

Ayoobi F, Bidaki R, Shamsizadeh A, Moghadam-Ahmadi A, Amiri H. Impact of opium dependency on clinical and neuropsychological indices of multiple sclerosis patients. Neurol Sci. 2019;40:2501–7.

Pakpoor J, Goldacre R, Disanto G, Giovannoni G, Goldacre MJ. Alcohol misuse disorders and multiple sclerosis risk. JAMA Neurol. 2014;71(9):1188–9.

Andersen C, Søndergaard HB, Bang Oturai D, Laursen JH, Gustavsen S, Larsen NK, et al. Alcohol consumption in adolescence is associated with a lower risk of multiple sclerosis in a Danish cohort. Multiple Scler J. 2019;25(12):1572–9.

Budeč M, Ćirić O, Koko V, Ašanin R. The possible mechanism of action of ethanol on rat thymus. Drug Alcohol Depend. 1992;30(2):181–5.

Barr T, Helms C, Grant K, Messaoudi I. Opposing effects of alcohol on the immune system. Prog Neuropsychopharmacol Biol Psychiatry. 2016;65:242–51.

Chou P, Effros JB. T cell replicative senescence in human aging. Curr Pharm Design. 2013;19(9):1680–98.

CAS   Google Scholar  

Thameem Dheen S, Kaur C, Ling E-A. Microglial activation and its implications in the brain diseases. Curr Med Chem. 2007;14(11):1189–97.

Eskandarieh S, Moghadasi AN, Sahraiain MA, Azimi AR, Molazadeh N. Association of cigarette smoking with neuromyelitis optica-immunoglobulin G sero-positivity in neuromyelitis optica spectrum disorder. Iran J Neurol. 2019;18(3):93–8.

Manari A, Preedy V, Peters T. Nutritional intake of hazardous drinkers and dependent alcoholics in the UK. Addict Biol. 2003;8(2):201–10.

Kočovská E, Gaughran F, Krivoy A, Meier U-C. Vitamin-D deficiency as a potential environmental risk factor in multiple sclerosis, schizophrenia, and autism. Front Psychiatry. 2017;8:47.

Diaz L, Montero A, Gonzalez-Gross M, Vallejo A, Romeo J, Marcos A. Influence of alcohol consumption on immunological status: a review. Eur J Clin Nutr. 2002;56(3):S50–3.

Massa J, O’reilly E, Munger K, Ascherio A. Caffeine and alcohol intakes have no association with risk of multiple sclerosis. Multiple Scler J. 2013;19(1):53–8.

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Naghmeh Abbasi Kasbi, Sajjad Ghane Ezabadi, Kosar Kohandel, Faezeh Khodaie, Amir Hossein Sahraian, Sahar Nikkhah Bahrami, Mahsa Mohammadi, Sharareh Eskandarieh & Mohammad Ali Sahraian

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Naghmeh Abbasi Kasbi: Data curation, Investigation, Writing – original draft, Writing – review & editing, Validation. Sajjad Ghane Ezabadi: Data curation, Investigation, Writing – original draft, Writing – review & editing. Kosar Kohandel: Data curation, Investigation, Writing – original draft, Writing – review & editing. Faezeh Khodaie: Data curation, Investigation, Writing – original draft, Writing – review & editing. Amir Hossein Sahraian: Data curation, Investigation, Writing – original draft. Sahar Nikkhah Bahrami: Writing- revision, review & editing. Mahsa Mohammadi: Data curation, Investigation, Writing – original draft. Amir Almasi-Hashiani: Methodology, Formal analysis, Writing – review & editing. Sharareh Eskandarieh: Project administration, Resources, Supervision, Validation, Writing – review & editing. Mohammad Ali Sahraian: Conceptualization, Project administration, Resources, Supervision, Validation, Writing – review & editing.

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Abbasi Kasbi, N., Ghane Ezabadi, S., Kohandel, K. et al. Lifetime exposure to smoking and substance abuse may be associated with late-onset multiple sclerosis: a population-based case-control study. BMC Neurol 24 , 327 (2024). https://doi.org/10.1186/s12883-024-03815-9

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Effects of Alcohol Consumption on Various Systems of the Human Body: A Systematic Review

Jerin varghese.

1 Medical School, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, IND

Sarika Dakhode

2 Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, IND

Prolonged alcohol intake for many years has been known to cause serious ailments in human beings since time memorial. Even after knowing that this dangerous addiction paves the way to one’s own grave, there isn’t much difference in the way the community sees this deadly habit. Time and again history has proven that this fatal addiction could make the life of those who consume it terrible. Also, the lives of the dear ones of alcoholic people are affected as alcohol not only affects those who consume them but also kin and friends. Various research studies conducted over many years clearly show the association of prolonged alcohol intake in the causation, aggravation, worsening, and deterioration of the health of its consumers. Moreover, chronic alcohol intake single-handedly is one of the major etiological factors in various serious diseases.

Introduction and background

Through the ages, alcoholism has been undisputedly maintaining its position in the list of risk factors for preventable diseases in the world. According to a WHO report, 5.3% of all deaths that occurred worldwide in the year 2016 were because of harmful alcohol use [ 1 ]. It is the main culprit behind the advancing nature of many chronic diseases. It drastically increases the severity of diseases and also makes the treatments less effective. Alcohol not only affects the person physiologically, but it has many adverse effects psychologically and socially too. Also, the habit of alcoholism leads to huge expenses [ 2 ]. Apart from systemic involvement, which causes various clinical manifestations, there are certain signs and symptoms that are most of the times non-specific and that as such don’t point out or say lead to a particular diagnosis, such as nausea, agitation, vomiting, anxiety, diaphoresis, tremors, headache, visual hallucinations, tachycardia, seizures, delirium, temperature elevation, etc. It is not always necessary that these mentioned signs and symptoms are compulsorily linked with disease conditions.

Alcohol clearly plays a very important role in making many other diseases progress to their advanced stages. It has been also noted that alcohol intake and its related disorders are often associated with many other manifestations; for example, patients with alcoholic neuropathy often have associated nutritional deficiencies. Recent studies have clearly proved that alcoholism is associated with many types of cancers too and this understanding of alcoholism has spurred research minds all over the globe to find out the exact pathophysiology behind the same. Alcohol is a very easily available source of addiction, which is one of the main reasons why it remains a serious threat to the community. There is a huge variety that is available as far as alcoholic drinks are concerned. Alcohol is also one of the cheaply accessible means of addiction; this explains why alcoholism is so prevalent. A person may initially start consuming alcohol in very low amounts most probably with just a desire to try it, but once he or she gets addicted, then getting rid of the habit becomes extremely difficult. Even if a person is mentally resolute enough to quit alcoholism, his or her body, which has been modified because of the chronic use of alcohol, won’t be up to the challenge anytime soon; he or she has to overcome many hurdles put forward by the body, which could in an umbrella term be referred to as alcohol withdrawal syndrome.

There are many social stigmas associated with alcohol intake. Most people get into this addiction by getting inspired by the people whom they admire, like actors, celebrities, role models, etc. Also, exposure to the sight of family members, relatives and friends drinking alcohol has a huge impact on one’s mindset as he or she may take it to be something that is normal. In the long run, most of the time, even without their realization, people get pathetically trapped in this dangerous fatal habit of alcoholism, which eventually makes their lives pitiful in almost all aspects. Studies have shown that alcohol is also a key player in many other domains too like accidents, suicide, depression, hallucinations, violence, memory disturbances, etc.

The main purpose of this review article is to enable any person reading this article to get a comprehensive insight into the effects of alcohol on the various systems of the human body, and for the same, many recognized research articles published in numerous well-acknowledged journals across the globe are reviewed. The article is written using very basic and simple terminologies so that even a layperson who reads it would be able to understand it. For the easy acceptability and understanding of the reader, the discussion is written in such a way that almost every major system is reviewed one by one and the effect of alcohol on these systems put forward in very simple language. The strategies used for the establishment of this review article are summarised in Figure ​ Figure1; 1 ; these include considering research articles that have been published in journals with are indexed in reputed platforms, segregating articles according to the different systems, framing the review like a discussion section of an article where details are explained in simple and straight forward sentences, etc.

Impact of alcohol on the central nervous system (CNS)

Alcohol exerts various effects on our CNS in various ways, the common ones being depression of the CNS, destruction of the brain cells, contraction of the tissues of the brain, suppression of the excitatory nerve pathway activity, neuronal injury, etc [ 3 ]. Alcohol’s impact on the functioning of the brain ranges from mild and anxiolytic disinhibitory effects, motor incoordination, sedation, emesis, amnesia, hypnosis and ultimately unconsciousness [ 4 ]. The synaptic transmission is heavily disturbed and altered by ethanol, and the intrinsic excitability in various areas of the brain is also compromised. The effects of ethanol may be pre-synaptic, post-synaptic, and at times, non-synaptic too. Alcohol being a psychotropic depressant of the CNS exerts a deeply profound impact on the neurons, which alters the biological and behavioural well-being of the one who consumes it by the promotion of interference in various neuronal pathways [ 5 ]. The treatments of many disorders of the CNS are shown to be affected by the consumption of alcohol, and thus, it is generally advised to keep oneself away from alcohol if one is undergoing treatment for any CNS manifestations, like anxiety or mood disorders [ 6 ].

Alcohol use disorder (AUD) is chronic in nature and is characterized by uncontrolled drinking and also a preoccupation with alcohol. The severity of AUD is a crucial factor in how it is going to affect the human body. AUD can be mild, moderate, or severe according to the symptoms a person experiences. The clinical manifestations of AUD include signs and symptoms such as inability to control the amount of alcohol intake, spending a lot of time drinking, feeling an uncontrollable craving for alcohol, loss of interest in social activities, failure to fulfil tasks within the time provided, etc. Most of the time, along with the person who consumes alcohol, several other factors are also to be taken care of in order to effectively manage alcohol-related health conditions. These factors can be social, environmental, genetic, psychological, etc, which make a considerable impact on how alcohol affects the behaviour and body of those consuming it. Binge drinking, i.e., drinking to such an extent on a single occasion that the blood alcohol concentration level becomes 0.08% or more, is a very relevant aspect of alcohol intake, which has to be dealt with, with utmost urgency. Certain research studies suggest that mild to moderate alcohol intake provides a certain sort of protection against a few CNS disorders like dementia, ischemia of neurons, etc, but this in no way should encourage the community in promoting alcohol intake as in reality, it is very difficult to remain within the limits of mild to moderate alcohol intake, and thus, eventually, people do end up as full-time severe alcohol abusers. Epilepsy, a seizure disorder caused by disturbed nerve cell activity in the brain, aggravates on excessive alcohol intake as alcohol increases the frequency of seizures in patients of epilepsy [ 7 ]. The issue becomes more severe in those epileptic patients who have refractory forms of epilepsy. As far as comorbidities are concerned, a valid history of abuse of substances or alcohol dependence is believed to be strongly associated with a high risk of sudden unexpected death in epilepsy (SUDEP) [ 8 ]. Heavy alcohol drinking over a long period of time has been found to have an intensely negative undesirable effect on the autonomic nervous system too.

Impact of alcohol on the cardiovascular system (CVS)

Chronic alcohol intake is undoubtedly a very important risk factor as far as cardiovascular diseases are concerned and several clinical trials do point out this fact. The results of several research studies conducted in various settings clearly indicate that increased intake of alcohol has increased adverse effects on our heart and its vasculature. Alcohol exerts its action on the cardiovascular system both directly and indirectly. Blood pressure, a very vital player in the domain of cardiovascular diseases, is in turn itself affected by increased alcohol consumption. Blood pressure gets increased on regular consumption of alcohol in a manner which is dose-dependent, which in turn increases the risk of hypertension and eventually leads to various cardiovascular complications. How exactly alcohol causes hypertension is still unclear with many pathophysiological theories out there. Atrial fibrillation, one of the most common causes of arrhythmia, is associated with the high-volume chronic intake of alcohol and above 14 g alcohol/day, the relative risk dramatically increases by 10% for each extra standard drink (14 g ethanol) [ 9 ].

Cerebrovascular accidents are increased to a great extent at almost all levels of alcohol intake [ 10 ]. Alcohol intake leads to both acute (depresses the cardiac function and also alters the blood flow of the involved region) and chronic cardiovascular manifestations [ 11 ]. Alcohol abuse along with other associated factors is one of the leading causes of secondary cardiomyopathy [ 12 ]. Cardiac arrhythmias get precipitated by alcohol consumption, be it acute or chronic. Heavy alcohol drinking is shown to impact the cardiovascular system in many ways, one of the most important among them being rebound hypertension [ 13 ]. Apart from congenital disorders of the cardiovascular system, it indeed is a very well-evident fact, which could be understood from the history of most of the patients diagnosed with cardiovascular disorders, that they used to consume a lot of alcohol for many years.

Impact of alcohol on the digestive system

Chronic alcoholism is found to have a very strong relationship with both acute pancreatitis and chronic pancreatitis. Chronic alcohol intake impairs the repair ability of the structures of the exocrine pancreas, thereby leading to pancreatic dysfunctioning [ 14 ]. Most of the patients diagnosed with pancreatitis have a strong history of chronic intake of alcohol. Liver diseases related to alcohol intake are known to humankind from the very beginning and probably are one of the oldest known forms of injury to the liver [ 15 ]. In liver diseases linked with alcohol, liver cirrhosis is a major concern. Statistics show that liver cirrhosis is one of the top 10 causes of death worldwide and this in itself indicates the severity of the same [ 16 ]. The changing lifestyle and also many people turning to prolonged alcohol intake for many years are contributing to the increased number of liver cirrhosis patients in the modern world. In liver cirrhosis patients, there occurs an increased severity of fibrosis due to the loss of parenchyma and fibrous scar proliferation [ 17 ]. Alcoholic liver disease (ALD) is an umbrella term which incorporates a wide range of injuries of the liver, spanning from simple steatosis to cirrhosis, and this also includes alcohol-related fatty liver disease (AFLD) and also alcoholic hepatitis [ 18 ]. Advancements in the diagnostic modalities have helped to diagnose ALD at an early phase and there is no doubt that newer and better investigations that have helped to detect more cases have led to a surge in the number of ALD patients on whole. Alcohol intake has a prominently bigger impact on the mortality of liver cirrhosis when compared with the morbidity [ 19 ]. A systemic review and meta-analysis suggests that women might be at a higher risk as far as developing liver cirrhosis is concerned even with little consumption of alcohol, as compared to men [ 20 ].

Impact of alcohol on the causation of cancer

Alcohol has much to do with cancers too and continuous research studies are conducted in order to find out the relationship between the two in detail. In a meta-analysis, it was found that women consuming alcohol had a later menopause onset, which is found to be associated with reduced cardiovascular disease risk and also all-cause mortality, but unfortunately, the happiness of this advantage gets compromised by the ironic fact that it has an increased risk of cancer (including ovarian and breast cancers) [ 21 , 22 ]. Large cohort studies, many meta-analyses, experimental research studies, etc are suggestive of the fact that the chronic intake of alcohol clearly increases colon and gastric cancer risk [ 23 ]. A causal association is also found between alcohol intake and cancers of the rectum, colon, liver, oesophagus, larynx, pharynx and oral cavity [ 24 ]. There are various theories put forward so as to understand the role of the consumption of alcohol in the development of cancer; there is suspicion that the rise in the number of alcohol users worldwide may be one of the reasons why the number of cancer patients is increasing at a global level. Chronic intake of alcohol may promote the genesis of cancer in many ways, some of the most notable ones being acetaldehyde (weak mutagen and carcinogen) production, cytochrome P450 2E1 induction associated oxidative stress, S-adenosylmethionine depletion/ which leads to global DNA hypomethylation induction, iron induction associated oxidative stress, retinoic acid metabolism impairment, etc [ 25 ].

Impact of alcohol on other systems

Apart from the systemic manifestations which do affect a particular system of the body, there are various disorders in which alcohol indirectly provides its crucial contribution. It is a common finding that one could perceive that alcohol is most of the time in the list of risk factors for various diseases. Alcohol has been found to adversely affect our immune system and the matter of concern as far as this issue is concerned is that immune responses are influenced by even moderate amounts of alcohol intake [ 26 ]. Alcohol affects innate immunity and also interferes with almost all the various aspects of the adaptive immune response. Alcohol is a key player in impairing anti-inflammatory cytokines and also promotes proinflammatory immune responses. The gastrointestinal biome is severely manipulated by the use of alcohol over a long period of time, which in turn is found to have a link with the establishment of various complications [ 27 ]. Alcohol and its metabolites are found to promote inflammation in the intestines and they do so through varied pathways [ 28 ]. Alcohol being a teratogen is documented to cause abnormalities of the brain, limbs, etc [ 29 ]. Multiple studies have been conducted across the globe to understand the effect of alcohol on humans; implications from certain such studies are put forth in Table ​ Table1 1 . 

Conclusions

Alcohol seldom leaves any system untouched as far as leaving its impression is concerned, spanning from single tissue involvement to complex organ system manifestations. Almost all the major organs that make up a human’s physiological being are dramatically affected by the overconsumption of alcohol. There is an enormous overall economic cost that is paid for alcohol abuse all over the world.

The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.

The authors have declared that no competing interests exist.