Anticholinergic effects are side effects that occur when a drug blocks the neurotransmitter acetylcholine from binding to its receptors throughout the body. Because acetylcholine is involved in everything from saliva production and bladder control to memory and attention, blocking it produces a wide and sometimes surprising range of problems. Dry mouth, constipation, and blurred vision are the most recognizable short-term effects, but the picture gets more concerning with long-term use, particularly in older adults, where cumulative anticholinergic exposure has been linked to increased dementia risk.
What Happens in Your Body
Acetylcholine drives the parasympathetic nervous system, which handles the “rest and digest” functions you rarely think about. When a drug blocks those receptors, many of those quiet processes stall. Saliva production drops, gut movement slows, the bladder has trouble emptying, sweat glands dial back, and the pupils widen. The result is a cluster of symptoms that anyone on these medications may recognize: a persistently dry mouth, difficulty urinating, constipation, overheating more easily, and sensitivity to bright light.
Dry mouth is the single most commonly reported anticholinergic side effect, showing up in roughly one in five to one in three people taking these drugs. That figure has been confirmed across randomized trials and a large worldwide placebo-controlled trial.1PubMed Central. Anticholinergic medication: Related dry mouth and effects on the salivary glands It sounds trivial, but chronic dry mouth raises the risk of tooth decay, gum disease, and oral infections because saliva protects the mouth from bacteria. If you have been on one of these medications for years and your dentist keeps finding cavities, the drug may be a contributing factor.
The peripheral effects are dose-dependent and generally reversible once the drug is stopped or reduced. But they are not always recognized as side effects. A person taking an antidepressant who develops constipation may blame diet. Someone on an antihistamine who notices blurred vision may assume they need new glasses. The anticholinergic origin of these symptoms often goes unnoticed because the drugs causing them were prescribed for something entirely unrelated.
How the Brain Is Affected
Acetylcholine is also a major signaling molecule in the brain, where it supports attention, memory formation, and arousal. Blocking it centrally produces cognitive effects that range from mild fogginess to full-blown delirium, depending on the dose, the person’s age, and how many anticholinergic drugs they are taking at once.
Delirium is the most dramatic acute cognitive consequence. It occurs in roughly 11 to 26 percent of elderly medical inpatients even without anticholinergic drugs, but exposure to medications with anticholinergic properties independently increases delirium severity in older patients already experiencing it.2JAMA Internal Medicine. Use of Medications With Anticholinergic Effect Predicts Clinical Severity of Delirium Symptoms in Older Medical Inpatients In the elderly, delirium linked to anticholinergic drug toxicity can be a serious warning sign of underlying disease.3JAMA. Delirium (Acute Confusional States)
One nuance worth noting: the relationship between anticholinergic drugs and delirium appears to be partly cumulative and partly confounded by other factors. In one study of hospitalized older patients, the link between anticholinergic drug burden and delirium was no longer statistically significant after accounting for pre-existing dementia and malnutrition.4PubMed. Relation Between Delirium and Anticholinergic Drug Burden in a Cohort of Hospitalized Older Patients: An Observational Study That does not mean the drugs are safe for the brain. It means delirium is complicated, and anticholinergic exposure is one piece of a larger puzzle that includes frailty, nutrition, and baseline cognitive health.
Which Drugs Have Anticholinergic Properties
This is where many people are caught off guard. Anticholinergic effects are not limited to a single drug class. They show up across a surprisingly wide range of medications, many of which are prescribed for conditions that have nothing to do with the nervous system. An analysis of Brazil’s national essential medicines list found that about 15 percent of the drugs on it had anticholinergic activity. Roughly half of those were central nervous system drugs, mainly antipsychotics, but cardiovascular medications, especially beta-blockers, made up the next largest group.5Revista Brasileira de Farmácia Hospitalar e Serviços de Saúde. Identification of anticholinergic activity of drugs of the Brazilian National List of Essential Drugs
Common drug classes with anticholinergic properties include:
- Antihistamines: especially first-generation ones like diphenhydramine (Benadryl) and hydroxyzine
- Antidepressants: particularly older tricyclics like amitriptyline and nortriptyline
- Antipsychotics: both older (chlorpromazine) and some newer agents (olanzapine, quetiapine)
- Bladder medications: oxybutynin, tolterodine, and similar drugs for overactive bladder
- Muscle relaxants: cyclobenzaprine
- Gastrointestinal drugs: some antispasmodics like dicyclomine
- Parkinson’s treatments: anticholinergics like benztropine and trihexyphenidyl
The problem compounds when a person takes several of these at once, each contributing a small anticholinergic load that adds up to a significant total. A patient on a low-dose tricyclic antidepressant for chronic pain, an antihistamine for allergies, and oxybutynin for bladder symptoms might not be on a “high dose” of any single anticholinergic, yet the combined burden could be substantial.
The Cumulative Burden Problem
Researchers have developed scoring tools to quantify a person’s total anticholinergic exposure, because the risk appears to be cumulative. The most widely studied is the Anticholinergic Cognitive Burden (ACB) scale, which assigns each drug a score of 1, 2, or 3 based on how strong its anticholinergic properties are. The scores from all medications a person takes are added together to give a total burden score.
A systematic review identified 19 different anticholinergic burden scales, but the ACB scale and the German Anticholinergic Burden Scale scored highest for quality.6PubMed Central. Quality of anticholinergic burden scales and their impact on clinical outcomes: a systematic review In practice, the ACB scale has shown the strongest dose-response relationship with real-world problems. Among adults aged 65 to 74, moving from an ACB score of 1 to a score of 4 or higher was associated with a jump from about 1.4 times the odds of an emergency department visit to about 2.3 times the odds. For incident dementia in that same age group, the increase was even steeper, from about three times the odds at a score of 1 to roughly ten times the odds at a score of 4 or higher.7The Annals of Family Medicine. Comparative Associations Between Measures of Anti-cholinergic Burden and Adverse Clinical Outcomes
Hospitalized elderly patients taking anticholinergic drugs showed worse cognitive test performance compared to those not taking them, and this followed a dose-response pattern: higher total burden scores meant worse cognition.8PubMed. Association of anticholinergic burden with cognitive and functional status in a cohort of hospitalized elderly The evidence is consistent enough that most geriatric guidelines now recommend checking a patient’s total anticholinergic burden before adding any new medication.
Long-Term Use and Dementia Risk
The most alarming evidence concerns the association between years of anticholinergic drug use and the risk of developing dementia. A large prospective study tracked over 3,400 older adults for an average of about seven years and found a clear dose-response relationship. People with the highest cumulative anticholinergic exposure, equivalent to taking a strong anticholinergic daily for three or more years, had about a 54 percent higher risk of dementia and a 63 percent higher risk of Alzheimer’s disease compared to non-users.9PubMed Central. Cumulative Use of Strong Anticholinergic Medications and Incident Dementia
A nested case-control study in the United Kingdom, drawing on medical records from hundreds of thousands of patients, found a similar pattern. The highest category of anticholinergic exposure was associated with about a 49 percent increased odds of dementia compared to no exposure.10JAMA Internal Medicine. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study Importantly, the risk was not driven by one drug class alone. Antidepressants, bladder medications, and antipsychotics all contributed.
These are observational studies, so they cannot prove causation. It is possible that the conditions being treated with anticholinergics, such as depression or incontinence, are themselves early markers of dementia rather than the drugs causing it. Researchers have tried to address this by excluding the years immediately before diagnosis and by adjusting for pre-existing conditions, and the association persists, but it cannot be completely ruled out as confounding.
What Brain Imaging Reveals
Some of the most unsettling data comes from neuroimaging studies comparing the brains of anticholinergic users to non-users. In one study of cognitively normal older adults, those taking anticholinergic medications had smaller total cortical volume, thinner temporal lobes, and larger ventricles, which is a sign that the brain has lost tissue. Their brains also showed reduced glucose metabolism in the hippocampus, a region critical for forming new memories.11PubMed Central. Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults
A population-based study across a broad adult age range found that higher anticholinergic burden was associated with smaller hippocampus volume, with effects visible in imaging of the temporal and parietal regions of the brain.12PubMed Central. Inverse association between the anticholinergic burden and hippocampus volume in a population-based cohort across the entire adult age range Another study tracked brain changes over time and found that anticholinergic users had faster rates of cortical thinning, particularly in the posterior cingulate and frontal regions.13Alzheimer’s & Dementia: Translational Research & Clinical Interventions. Midlife anticholinergic drug use, risk of Alzheimer’s disease, and brain atrophy in community-dwelling older adults
Again, cross-sectional imaging cannot prove causation. But the convergence of findings across multiple studies, showing both structural brain changes and metabolic changes in regions tied to memory, strengthens the biological plausibility of a real drug-induced effect.
Mortality and Cardiovascular Risk
The risks are not limited to the brain. A 10-year follow-up of over 21,000 middle-aged and older adults in the EPIC-Norfolk study found that those with a high anticholinergic burden had roughly double the risk of both death and cardiovascular disease compared to those with no anticholinergic exposure, even after adjusting for confounders.14PubMed Central. Total anticholinergic burden and risk of mortality and cardiovascular disease over 10 years in 21,636 middle and older aged men and women of EPIC-Norfolk prospective population study A systematic review and meta-analysis confirmed that anticholinergic exposure was consistently linked to higher mortality across multiple studies and scoring tools.15PubMed Central. The Prognostic Value of Anticholinergic Burden Measures in Relation to Mortality in Older Individuals: A Systematic Review and Meta-Analysis
This makes sense pharmacologically. Acetylcholine is involved in heart rate regulation, and blocking it can increase heart rate and affect blood pressure. But the mortality association likely also reflects the broader frailty and polypharmacy common in high-burden patients, so the numbers should be read as risk signals rather than precise causal estimates.
Why Older Adults Are Especially Vulnerable
Several things change with aging that amplify anticholinergic harm. The blood-brain barrier becomes more permeable, allowing drugs that might stay peripheral in younger people to reach the brain more easily. The brain’s baseline acetylcholine production declines with age, so blocking what remains has a proportionally larger effect. Kidney and liver function slow down, meaning drugs stay in the body longer. And older adults tend to be on more medications, compounding the cumulative burden.
In the very oldest patients, the cholinergic pathways running from the basal forebrain to the cortex and hippocampus are already under strain. When these patients develop infections or other acute illnesses, the blood-brain barrier can become even more permeable, letting inflammatory molecules into the central nervous system. Combined with pharmacological blockade of muscarinic receptors, this can precipitate acute cognitive failure more readily than in younger patients.16Adv Geriatr Med Res. Dynamic Changes in Anticholinergic Burden and Its Association with Multidimensional Vulnerability in Hospitalized Oldest-Old Patients
Overactive Bladder Drugs as a Case Study
Bladder medications deserve special attention because they are among the most commonly prescribed anticholinergics in older adults, and alternatives exist. Drugs like oxybutynin and tolterodine work by blocking the muscarinic receptors that cause bladder muscle contractions, but they also block those receptors everywhere else in the body, including the brain.
A population-based cohort study compared patients with overactive bladder who were treated with anticholinergic medications to those treated with a beta-3 agonist (mirabegron), which works through a different mechanism entirely. Anticholinergic users had about a 23 percent higher risk of developing dementia, with the effect most pronounced in men and those aged 75 or younger.17PubMed. Increased risk of dementia among patients with overactive bladder treated with an anticholinergic medication compared to a beta-3 agonist: a population-based cohort study A similar finding emerged from a Japanese population study, reinforcing that the association holds across different countries and healthcare systems.18PubMed. Risks of Dementia Associated With Anticholinergic Medication Compared to Beta-3 Agonist Among Older Patients With Overactive Bladder in Japan: The LIFE Study
This comparison is valuable because it addresses a common rebuttal: maybe people who develop bladder problems are simply at higher risk for dementia regardless of treatment. By comparing two drug treatments for the same condition, these studies control for the underlying disease and still find excess risk in the anticholinergic group.
First-Generation Versus Second-Generation Antihistamines
If you have ever felt drowsy after taking Benadryl (diphenhydramine), you have experienced a central anticholinergic effect. First-generation antihistamines cross the blood-brain barrier freely because they are not recognized by the pumps that keep many drugs out of the brain. Research in animal models has shown that sedating antihistamines like diphenhydramine, hydroxyzine, and triprolidine are not substrates of P-glycoprotein, a transporter protein at the blood-brain barrier that acts as a gatekeeper.19Drug Metabolism and Disposition. P-Glycoprotein Limits the Brain Penetration of Nonsedating but not Sedating H1-Antagonists
Second-generation antihistamines like cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra) are recognized and actively pumped back out, which is why they cause far less drowsiness and fewer cognitive effects.20PubMed. Assessment of the first and second generation antihistamines brain penetration and role of P-glycoprotein The practical takeaway is straightforward: if you are taking a first-generation antihistamine regularly, especially for something like sleep or chronic allergies, switching to a second-generation option removes a significant source of anticholinergic brain exposure without sacrificing allergy relief.
Anticholinergic Toxidrome
At high enough doses, anticholinergic effects become an acute medical emergency known as anticholinergic toxidrome. Medical students learn the classic presentation through a mnemonic: “blind as a bat (dilated pupils), dry as a bone (no sweating), red as a beet (flushed skin), mad as a hatter (delirium), hot as a hare (hyperthermia), and full as a flask (urinary retention).” This describes a person in serious toxicity, and it can happen with overdoses of diphenhydramine, antipsychotics, or tricyclic antidepressants, among others.
One case report described a 43-year-old woman who ingested roughly 150 diphenhydramine tablets in a suicide attempt. Benzodiazepines had minimal effect, and she was heading toward intubation before being treated with physostigmine, a drug that boosts acetylcholine levels by preventing its breakdown.21PubMed Central. Physostigmine in Anticholinergic Poisoning: An Old Antidote With Resurgence In another case involving olanzapine overdose, a single dose of physostigmine produced dramatic improvement within five minutes, restoring the patient’s orientation and resolving his rapid heart rate, dilated pupils, and dry mucous membranes.22Journal of the Academy of Consultation-Liaison Psychiatry. The Use of Physostigmine in the Diagnosis and Treatment of Anticholinergic Toxicity After Olanzapine Overdose
A randomized trial comparing physostigmine to lorazepam for anticholinergic toxidrome, mostly from diphenhydramine, found that physostigmine was far more effective. After the initial dose, all patients in the lorazepam group still had delirium, compared to less than half in the physostigmine group. By four hours, only about a fifth of physostigmine-treated patients still had delirium, versus all of the lorazepam-treated patients. No serious complications like seizures or dangerous heart rhythms occurred.23PubMed. A randomized trial comparing physostigmine vs lorazepam for treatment of antimuscarinic (anticholinergic) toxidrome This is relevant because physostigmine fell out of favor in emergency medicine for decades over safety concerns, and its rehabilitation as a treatment option is a relatively recent development.
Can Stopping the Drugs Reverse the Damage?
This is the question everyone wants answered, and the honest answer is that we do not know for certain. A systematic review found that only observational cohort studies, not randomized trials, showed cognitive improvement after discontinuing anticholinergic medications.24PubMed. Impact of anticholinergic discontinuation on cognitive outcomes in older people: a systematic review The randomized trial evidence is thin and contradictory.
A Cochrane review examining whether reducing anticholinergic burden improves cognitive outcomes found very low certainty evidence overall. One trial showed improvement on a specific cognitive test in the intervention group, but no actual difference in anticholinergic burden between groups. Two trials that successfully reduced the burden produced mixed results: one showed no clear cognitive difference, and the other found improvement on a working memory test but no change on several other cognitive measures. The review concluded that there is simply not enough evidence to support or refute the idea that deprescribing anticholinergics improves cognition.25PubMed Central. Anticholinergic deprescribing interventions for reducing risk of cognitive decline or dementia in older adults with and without prior cognitive impairment Nor was there evidence for benefit on mortality, quality of life, falls, or physical function.26Cochrane Database of Systematic Reviews. Anticholinergic burden reduction interventions versus usual care for cognitive outcomes in older adults
The lack of randomized evidence does not mean deprescribing is pointless. It means the trials have been small, short, and few. The peripheral side effects like dry mouth, constipation, and urinary retention typically improve promptly after stopping a drug. Whether long-term structural brain changes are reversible remains an open and urgent question.
Anticholinergics in Parkinson’s Disease and Movement Disorders
Anticholinergic drugs have a long history in neurology, where they are used to treat tremor in Parkinson’s disease and to manage movement disorders caused by antipsychotic medications. Benztropine and trihexyphenidyl remain in use for these conditions, but the cognitive trade-off is real. In a cohort of Egyptian Parkinson’s patients, those treated with benztropine showed lower cognitive performance than those treated with amantadine, a dopaminergic alternative. Cognitive dysfunction was present in about 78 percent of the Parkinson’s patients studied, and chronic disease combined with anticholinergic treatment was the factor most associated with lower cognition.27PubMed. The effect of anticholinergic drugs on cognition of patients with Parkinson’s disease: a cohort study from the Egyptian population
A recent evidence review clarified that anticholinergics have a supported role in drug-induced parkinsonism and dystonia, but are not recommended for tardive dyskinesia, akathisia, or neuroleptic malignant syndrome. Nor is there good evidence for routine preventive use in most patients starting antipsychotics, except those at high risk for acute dystonic reactions.28PubMed Central. An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders In older adults especially, the cognitive and peripheral harms can outweigh the benefits for movement symptoms that might be managed through dose adjustment or alternative agents.
Contradictory Prescribing in Dementia Patients
One of the more troubling patterns in clinical practice involves patients already diagnosed with dementia being prescribed anticholinergic drugs at the same time as cholinesterase inhibitors, the medications designed to boost the acetylcholine that anticholinergics block. This amounts to pressing the gas and the brake at the same time. A study of nursing home residents found that this co-prescribing pattern was common, with women more likely to receive both drug types simultaneously. Interestingly, minority populations including Black and Hispanic residents were less likely to be co-prescribed anticholinergics alongside cholinesterase inhibitors.29PubMed Central. Anticholinergic co-prescribing in nursing home residents using cholinesterase inhibitors: potential deprescribing cascade
This kind of pharmacological contradiction highlights a systemic problem: different specialists prescribing for different conditions without coordinating the overall medication picture. A urologist prescribes oxybutynin for incontinence. A psychiatrist prescribes a cholinesterase inhibitor for dementia. Neither may check whether the other’s drug is undermining their treatment. Identifying and resolving these conflicts is one of the clearest practical benefits of anticholinergic burden screening.
The Ancient Pharmacology of Nightshades
The anticholinergic properties of certain plants were exploited long before anyone understood the receptor pharmacology behind them. Tropane alkaloids found in plants of the nightshade family, including belladonna, henbane, jimsonweed, and mandrake, have been used for thousands of years as poisons, hallucinogens, and medicines.30PubMed Central. Beauty of the beast: anticholinergic tropane alkaloids in therapeutics Atropine, derived from belladonna, is still used today to dilate pupils during eye exams and to treat certain heart rhythm problems. Scopolamine, from the same chemical family, is the active ingredient in motion sickness patches. Both are muscarinic receptor antagonists, which is another way of saying they produce anticholinergic effects by design. The difference between a therapeutic dose and a toxic one with these compounds has always been narrow, a fact that Renaissance poisoners understood intuitively and that modern pharmacology has quantified.