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Anticholinergics: Uses, Side Effects, Risks & Natural Sources

Written by Joe Cohen, BS | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Joe Cohen, BS | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Anticholinergics are drugs that have a long history of use for breathing and other respiratory problems, dating as far back as the ancient Egyptian and Greek physicians. In various forms, both natural and synthetic, their use expanded to mental, bladder, and gastrointestinal health.

Disclaimer: By writing this post, we are not recommending these drugs. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific and clinical literature. Please discuss your medications with your doctor.

What Are Anticholinergics?

Anticholinergics refer to medications or compounds that block the activity of the neurotransmitter acetylcholine. They bind to the same structures (known as receptors) as acetylcholine throughout the body, making it impossible for this neurotransmitter to achieve its usual effect [1, 2].

Some anticholinergics, such as hyoscamine, are derived from plants and other natural sources. The fruit and leaves of the plant Atropa Belladonna (atropine), or Deadly Nightshade, are also known to have anticholinergic effects [3, 4].

Other synthetic anticholinergic agents include ipratropium bromide (Atrovent), doxepin, tadalafil, and diphenhydramine. These anticholinergics can help treat breathing disorders (asthma & bronchitis), depression, insomnia, irritable bowel syndrome, and motion sickness. Some can even help relieve symptoms of Parkinson’s disease and overactive bladder [5, 6, 7, 8, 9, 10, 11].

The use of anticholinergics also comes with certain risks, especially if taken in excess. These include a range of effects from increased heart rate and blood pressure, blurred vision, impaired digestion, to delirium, dementia, and even coma. They can also cause redness, heating up, and dryness [12, 13].

Mechanism of Action

Acetylcholine can activate two different receptors in the body: nicotinic and muscarinic. Nicotinic receptors got their name because nicotine activates them, whereas a poison from mushrooms — called muscarinic acid — activates muscarinic receptors. Anticholinergics function in the opposite way, by blocking both [14, 2].

Acetylcholine acts in various important ways in the body. It serves as the final messenger for the parasympathetic system, which counteracts the fight-or-flight response. Acetylcholine can help to keep the body in a state of rest, digestion, and regeneration using the muscarinic pathway, which has five main receptor subtypes (M1-M5). Excess acetylcholine can also cause overactivation of the muscarinic system and worsen inflammation in some diseases, such as in asthma. This is why drugs that block muscarinic receptors in the lungs are used to relax the airways [15, 15].

Other antimuscarinic medications, such as those for overactive bladder, block specific muscarinic receptors (mostly M2 and M3). However, this can cause side effects elsewhere, such as dry mouth or headaches [16, 16].

Acetylcholine is also used to activate muscles using the nicotinic pathway, so drugs that block this pathway can cause paralysis and are sometimes used during anesthesia [17].

Types of Anticholinergics


Muscarinic receptors are mainly located along the brain and spinal cord, as well as in the muscles controlled by the parasympathetic system, including the bladder, heart, lungs, and airway muscles [14, 18, 19].

Ipratropium, scopolamine, glycopyrrolate are examples of muscarinic anticholinergics (antimuscarinics) [20, 21, 22].

Antimuscarinics treat bronchitis, asthma, motion sickness, and anxiety. Additionally, they act as antidepressants and prevent the toxic effects of nerve agents [20, 23, 24, 10, 23].

***Muscarinic anticholinergics can also be referred to as antimuscarinics, muscarinic antagonists, muscarinic cholinergic antagonists.


Nicotinic receptors are mainly located at the place where nerves connect with skeletal muscles. Curare, a natural nicotinic anticholinergic, was used in hunting for centuries. Scientists began to research its effects and first used it to stop muscle contractions during surgery. Curare allowed for the development of synthetic alternatives with similar activity [14, 25].

Pancuronium and mecamylamine are examples of nicotinic receptor blockers [21, 26].

Pancuronium a muscle relaxant used with anesthesia. Mecamylamine subdues the effects of alcohol and helps fight alcohol and cigarette addiction. It may even have antidepressive effects [26, 27, 28, 29].

Mecamylamine was once widely used to reduce blood pressure. However, that is rarely the case now due to the high rate of side effects of the required dosage [30].

***Nicotinic anticholinergics can also be referred to as antinicotinics, nicotinic antagonists.

Uses of Anticholinergics

1) Improve Respiratory Diseases and Conditions

Anticholinergics may improve respiratory diseases


In one study, tiotropium inhaler improved the amount and rate of exhalation in 470 patients with Chronic Obstructive Pulmonary Disease (COPD). It also reduced symptoms of wheezing and shortness of breath [31].

In another study, different anticholinergic compounds, including ipratropium, flutropium, and oxitropium bromide, relaxed the breathing pathways of 20 elderly men with COPD. Subjects experienced easier breathing from all treatments, but oxitropium bromide was the most effective [32].

Muscarinic anticholinergics, compared to steroid treatment, are most commonly used in COPD since they have longer lasting effects when opening the breathing channels and usually require a single daily dose to improve symptoms [20, 33].


Long-acting muscarinic anticholinergics help with asthma when inhaled with corticosteroids as shown in 15 clinical trials of 7122 patients. Their use as an add-on therapy reduces the risk of asthma attacks [6, 34].


Similar to asthma treatment, inhaled muscarinic anticholinergics ease breathing in bronchitis patients and double their breathing capacity. In recent years, muscarinic anticholinergics such as ipratropium bromide (Atrovent) have been used to help manage the daily symptoms of bronchitis [35, 36].

2) Antidepressants

Tricyclic antidepressants (TCAs) are one class of drugs used in depression, and they show some anticholinergic activity. Among 5 studies, 56-60% of patients responded positively to TCAs, which reduced depression scores and side effects [37, 38].

Scopolamine (at a dosage of 4.0 µg/kg) reduced symptoms of depression in 52 subjects (31 male, 21 female) with depression or bipolar disorder at a rapid rate. In a study, scopolamine had a lasting effect (over 2 weeks after treatment), and women experienced greater improvements than men [39].

The nicotinic anticholinergic mecamylamine, along with SSRIs antidepressants, improved treatment-resistant depression in two Phase II clinical trials [29].

In one case, the anticholinergic benztropine (at small doses) improved motor function and mood of a patient with Parkinson’s disease [24, 40].

3) Anesthesia

Pancuronium is a muscle relaxant used with anesthesia. When injected, pancuronium did not cause any major changes in heart rate or blood pressure in 90 patients compared to other muscle relaxants, such as vecuronium and pipecuronium. This makes it useful for heart surgeries [26, 41].

Anticholinergic drugs, such as glycopyrrolate, are important and can be given before surgery. It is much stronger than other anticholinergics, such as atropine, and leads to less irregular heartbeats and complications [22, 42].

4) Irritable Bowel Syndrome

In 3 studies in a total of 426 patients, the anticholinergic hyoscine reduced symptoms of irritable bowel syndrome compared to a placebo. Patients either improved or the abdominal pain went away completely [7].

Hyoscine/scopolamine butylbromide reduces cramping pain by relaxing the muscles of the stomach and intestines. It is useful for reducing abdominal pain, according to 10 clinical studies [43].

5) Quitting Smoking

The combination of mecamylamine and nicotine patches was better than just patches for smoking cessation. In a study of 48 subjects, about 40% of the patients on the combination stopped, compared to only about 4% of those using only patches. In another study of 80 patients, 40% of patients abstained for a year compared to 20% for alternative methods [28].

Both the combination therapy and mecamylamine alone reduced the reinforcing effects of smoking. Two weeks of treatment reduced feelings of personal reward from cigarettes [44].

6) Overactive Bladder and Abdominal Pain

Anticholinergics are often the first choice of drugs for treating overactive bladder. In 32 trials of 6800 participants with overactive bladder, anticholinergics produced significant improvements in symptoms compared to placebos (review) [45].

Anticholinergics partially improve symptoms of an overactive bladder according to a review of 50 clinical trials including 27000 patients, but their effects are not enough to make them the sole treatment method [46].

Anticholinergics, in combination with other drugs (alpha-adrenergic antagonist therapy), are a safe and effective method for treating overactive bladder and abdominal pain (review). The therapy helps relax bladder muscles [47].

7) Reduce the Effects of Alcohol

The anticholinergic mecamylamine reduced the breath alcohol levels (BAL) in 20 healthy subjects compared to placebo. Treatment before consuming 3 alcoholic beverages reduced the effects of alcohol and even the sense of reward felt through alcohol consumption [27].

8) Vertigo

Anticholinergics, specifically hyoscine/scopolamine butylbromide, suppress the symptoms of vertigo. They are able to reduce the sensation of motion in the ear’s sensor for motion and balance. Eliminating the hallucination of motion is the first step in treating vertigo. However, the clinical studies on antivertigo medication are limited by difficulties in following experimental guidelines [48].

9) Insomnia

In one study, doxepin, a TCA with anticholinergic effects, improved sleep patterns and quality of life in 130 elderly adults with chronic insomnia. It enhanced sleep duration, sleep quality, and sleep maintenance in these patients [5].

In a controlled study, a 50 mg dosage of diphenhydramine significantly reduced the amount of time needed to fall asleep in 110 subjects with mild to moderate insomnia. It also enhanced sensations of restfulness [49].

10) Can Reduce the Side Effects of Antipsychotics

In 4 studies, diphenhydramine reduced the movement disorders caused by antipsychotic medications in 737 subjects (review) [9].

Antipsychotic medications can cause muscles to repetitively contract or stiffen. Anticholinergic agents, such as diphenhydramine, are the primary treatment recommendation for such movement disorders (especially dystonia) [50, 51, 52, 53].

11) Enlarged Prostate

In a single-blind control study, the anticholinergic tadalafil improved the condition of 281 men with benign enlargement of the prostate. Sexually active men with fewer urinary tract symptoms also showed improved erectile function [11].

12) May Help Prevent Motion Sickness

Scopolamine effectively prevented motion sickness, compared to a placebo, in 1025 subjects enrolled in 14 different clinical studies (review) [10].

13) Can Reduce Nausea

In a randomized control study, dimenhydrinate, also known as the over-the-counter medication Dramamine, reduced sensations of nausea and vomiting in 70 women in the early stages of pregnancy. It was a more effective treatment than Vitamin B6 in 70 other pregnant women [54].

14) Help Manage Parkinson’s Disease

221 patients with Parkinson’s Disease (PD) engaged in anticholinergic trials to combat various symptoms of PD (review). Anticholinergics, in conjunction with other anti-PD medications, are more effective in improving motor function than placebos [8].

15) Prevent Excessive Sweating in Anxiety

In a controlled trial, glycopyrrolate reduced excessive sweating in 36 patients. Excessive sweating is linked to anxiety, and glycopyrrolate also reduced anxiety and improved the patients’ quality of life [55].

16) Are an Antidote for Nerve Agents

In rats, three anticholinergic drugs (benactyzine, biperiden, scopolamine) protected from toxic effects of the nerve agent tabun. Both 24 hours and 7 days after injection, these drugs significantly slowed down poisoning in the body better than atropine (another anticholinergic drug) [23].

The anticholinergics atropine and homatropine improved vision and reduced the toxic effects of the nerve agents sarin and VX in rat eyes. These agents are used in war and can cause excessive pupil constriction and impair visual function. Soldiers can use these to reverse the damage caused by such exposure [56, 57].

In rats, the anticholinergic tropicamide eye drops effectively reversed the toxic effects of sarin gas exposure. Within 4 hours, the visual impairment was completely reversed as the pupils widened and eyesight returned as tested in the visual task [58].

Doxylamine succinate vs Diphenhydramine


Diphenhydramine is an older antihistamine that also has anticholinergic effects. It is the main ingredient of the over-the-counter medication Benadryl, a sedating allergy medication [59].

Diphenhydramine provides rapid relief of acute food allergy reactions. In a study, diphenhydramine (1 mg/kg) relieved the symptoms of an allergic reaction in 70 patients at the same speed as the newer antihistamine cetirizine (0.25 mg/kg). However, cetirizine does not cause the side effects of drowsiness, sedation, and impaired movement [60, 61].

In a study, 50 mg of diphenhydramine reduced the number of nightly awakenings in elderly insomnia subjects compared to placebo. However, it does not affect sleep onset or sleep quality very much [62, 63].

Doxylamine Succinate

Doxylamine succinate (DS) is an antihistamine available over-the-counter, and an ingredient in many sleep aids, such as Noctyl, Nytol, Restaid, and in decongestant medications [64].

Doxylamine succinate is used in the treatment of the common cold. In a study of 688 sick patients, 4 daily dosages of 7.5 mg DS successfully reduced the cold symptoms of sneezing and runny nose. The incidence of sedative side effects was lower than earlier antihistamine studies on the common cold [65].

The OTC medication Diclegis (doxylamine succinate) combined with Vitamin B6 improves nausea and vomiting symptoms in 131 pregnant subjects. In the randomized control trial, its effects were noticeable on the 3rd day of treatment [66].

Both doxylamine succinate (25 mg) alone or in combination with acetaminophen improved sleep, sensations of rest, and reduced pain in comparison to placebo for 2931 post-surgery patients. However, the combination therapy led to the greatest improvement in sleep [67].

Side Effects of Diphenhydramine & Doxylamine

Over-the-counter medications containing diphenhydramine or doxylamine can be unsafe to use for elderly individuals (review). They can impair memory and information processing, cause dizziness or impaired vision [68, 69].

In a study, diphenhydramine led to drowsiness, reduced alertness, and had sedative effects on 16 male subjects [70].

Side Effects and Toxicity

Anticholinergic Syndrome

The anticholinergic syndrome refers to toxic effects produced by exceeding the maximum dose of anticholinergics, Symptoms include accelerated heartbeat, overheating, drowsiness, blurred vision, dry skin and mouth, and can even cause hallucinations and seizures. These symptoms do not appear in a well-defined manner [71].

The anticholinergic syndrome was common after surgical procedures involving general anesthesia with atropine and scopolamine. The symptoms include difficulty breathing, slowing down brain function, and altered cognition [72].

The side effects of muscarinic agents are broad and can include dry mouth, difficulty urinating, redness, blurry vision, dizziness, and cognitive impairment (memory loss and information processing) [73].

Can Worsen Brain Functions in the Elderly

The use of multiple anticholinergics at once increases the risk of dementia according to a study of 7 years and 3434 elderly (65 or older) participants [74].

In a study comparing 12 young and 15 elderly adults, the anticholinergic mecamylamine led to slower information processing and lower performance on memory-based tasks in the elderly group but not in the younger group [75].

In another longitudinal study of 1780 elderly individuals, anticholinergics reduced cognitive performances on certain tests evaluating visual memory and verbal fluency [76].

Anticholinergic toxicity leads to an increase in heart rate, blurred vision, impaired digestion, impaired cognitive function and memory processing, and heat intolerance, which can be especially dangerous for older patients [13, 77].

Mecamylamine (at 10 mg) causes impairment in learning and memory tasks amongst the elderly, but not in younger subjects. In a study, pancuronium with high-dose fentanyl anesthesia increased the heart rate and blood pressure of 12 patients undergoing heart surgery [75, 78].

Side Effects in Children and Adolescents

In a clinical study, 912 patients between the ages of 3-12 were observed for adverse reactions following single and double dosages of eye drops containing cyclopentolate. Adverse reactions, such as drowsiness, were common, but other side effects such as redness, dizziness, and irritability also occurred at a lower rate [79].

Several cases of anticholinergic toxicity in infants have been reported, with irritation, quickened heart rate, and inflammation [3].

Side Effects in Psychiatric Treatment

In a study 104 patients with schizophrenia, antipsychotics with anticholinergic effects impaired cognitive performance, information processing, and memory compared to non-anticholinergic medications [80].

An increase in anticholinergic levels in the blood caused decreased performance in memory tasks for 24 stabilized schizophrenic patients [81].

Anticholinergic Burden, which measures the effects of increased dosage, increases the risk of dementia according to a case-controlled review. The greatest risk came from antidepressants, bladder-focused, and antiparkinson drugs [82].

Side Effects on The Heart

An initial dosage (10 µg) and constant infusion of the anticholinergic atropine increased the resting heart rate of 9 adult males by 25-30 beats per minute. Additionally, the subjects had a subtle but prolonged increase in blood pressure after infusion [83].

The anticholinergic muscle relaxants used in anesthesia (pancuronium, vecuronium, and mivacurium) increase heart rate with an increased dosage in rat hearts [84].

Anticholinergic Poisoning

Anticholinergics, such as atropine, can cause toxic effects at dosages above 75-100 mg. However, the most severe cases occur at 450mg per person (review) [85].

Quinuclidinyl benzilate (BZ) is a far more potent anticholinergic and dangerous agent of chemical warfare. Restricted dosages of BZ led to exaggerated side effects of common anticholinergics in 36 subjects, including severe disorientation, delirium, and hallucination [85].

Uncontrolled consumption of the plant Atropa Belladonna, or Deadly Nightshade, can lead to anticholinergic poisoning. As seen in 50 patients, symptoms include meaningless speech, hallucinations, flushing, memory loss, increased heart rate, irregular breathing, and even coma [4, 86].

High tricyclic antidepressant (TCA) levels in the blood can cause anticholinergic poisoning, including the previously mentioned symptoms. However, there are 19 documented cases of overdose that led to comas, 16 of which required respiratory support, and 2 of these patients had died [87].

The following mnemonic is used to summarize the side effects of anticholinergics [13, 12]:

Blind as a bat (dilated pupils)

Red as a beet (redness/flushing)

Hot as a hare (hyperthermia)

Dry as a bone (dry skin)

Mad as a hatter (hallucinations/agitation)

Bloated as a toad (retaining urine)

The heart runs alone (tachycardia)

An antidote to Anticholinergic Poisoning

Physostigmine Salicylate is often used as an antidote to anticholinergic poisoning, as a 2mg dosage can reverse the side effects of breathing difficulty, hallucinations, heartbeat variations, dry skin, and coma [88, 89].

Physostigmine reversed the symptoms of antimuscarinic poisoning after a 13-year old overdosed on diphenhydramine along with other medications [90].

Drug Interactions

Anticholinergic medications react with a wide variety of drugs, and the effects are specific to the type of anticholinergic and other medication, including anti-dementia drugs and other anticholinergics [91, 92].

Anticholinergics and Antipsychotic Medications

The combination of antipsychotic medications and anticholinergics reduced cognitive function, such as information processing and verbal memory in 104 schizophrenic patients. As the anticholinergic dose increased, the effect was more evident [80].

Individuals taking donepezil, or other anti-dementia medications, commonly take anticholinergics as an antidote for exceeding dosage. However, the anticholinergics interact with the drug and increases the risk of dementia in elderly patients [93, 94, 91].

Anticholinergics and Cholinesterase Inhibitors

Cholinesterase inhibitors prevent the action of the enzyme cholinesterase, which breaks down acetylcholine. They are used to treat symptoms of Alzheimer’s disease. Anticholinergics act in opposing ways and can reduce the effects of these drugs by blocking the receptors for acetylcholine [95].

Anticholinergics and Diabetes Medication

Anticholinergics react with the diabetes medication metformin and can increase the levels of sugar in the blood, countering the effect of the drug [96].

Additive Effects of Anticholinergics

The chronic use of anticholinergic drugs increases the risk of dementia (review). Anticholinergics acting on the central nervous system (brain and spinal cord) accelerate inflammation in the brain and carry the highest risk [92].

In a study (longitudinal), combined anticholinergics reduced verbal fluency, visual memory, and self-regulation in 6912 participants. Over the 4 year period, continuous users faced an increased risk of side effects [97].


Genetic variants in the nicotinic receptor lead to a greater risk of contracting COPD. The specific variant, rs1051730 (identified in 3460 subjects with COPD compared to 11437 controls) is associated with increased risk of COPD regardless of smoking history [98].

The epsilon4 allele (APOE) carriers experience worse cognitive function after receiving anticholinergic medication. Over 3 weeks, 12 carriers scored lower on memory and information processing tests after 2.0 mg of an anticholinergic (trihexyphenidyl) [99]. 

Natural Anticholinergics

A lot of compounds can affect acetylcholine, either by imitating it or blocking its effects [100].

Compounds that Boost the Effects of Acetylcholine

  • Nicotine binds to the nicotinic receptors, increases their number, and the release of acetylcholine. However, continuous exposure to nicotine can slow down the effects, which explains tolerance and need for increasing amounts of nicotine in smokers [101, 102103].
  • Lipoic Acid increased the level of acetylcholine and improved memory in rats with dementia. It also reduced the number of reactive oxygen species that can cause inflammation in the brain [104].
  • In 19 clinical studies, Piracetam improved memory and cognitive function in the elderly. It also improved memory in 123 children post-anesthesia [105, 106].

Compounds that Block the Effects of Acetylcholine

  • Forskolin, from the Coleus plant, desensitized the acetylcholine receptors and blocks their function in rats [107].
  • Kava, a flower from the Pacific islands, reduced muscle contraction and activity in rats. It also partially blocks nerve signals that cause muscle action in frogs [108].
  • Mercury compounds reduce the activity of choline acetyltransferase, an enzyme that makes acetylcholine. They also directly block the activity of acetylcholine (via binding to receptors) [109, 110, 111].
  • Botulin, a bacterial toxin, blocks the release of acetylcholine from nerve endings. This is how Botox injections work in low doses, by temporarily freezing the surrounding muscles to reduce wrinkles [112].
  • Curare, traditionally made by South American indigenous tribes from diverse plants, binds to the nicotinic receptors and reduces acetylcholine levels. It can completely paralyze muscles by blocking nerve signals, which eventually can lead to death due to the inability to breathe [25, 113].
  • Leaves from the plant Atropa Belladonna, or Deadly Nightshade, brewed in tea are used as a remedy for bowel issues in certain cultures. Flowers of the Datura species and the Mandrakes are also used as remedies for asthma and bronchitis. When ingested excessively, they can cause be toxic [4, 114].
  • Glycine increased the amount of acetylcholinesterase in mouse spinal cords, which causes more acetylcholine to be broken down. However, too much can lead to excess stimulation and nerve exhaustion [115, 116].

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About the Author

Joe Cohen, BS

Joe Cohen won the genetic lottery of bad genes. As a kid, he suffered from inflammation, brain fog, fatigue, digestive problems, anxiety, depression, and other issues that were poorly understood in both conventional and alternative medicine.Frustrated by the lack of good information and tools, Joe decided to embark on a journey of self-experimentation and self-learning to improve his health--something that has since become known as “biohacking”. With thousands of experiments and pubmed articles under his belt, Joe founded SelfHacked, the resource that was missing when he needed it. SelfHacked now gets millions of monthly readers.Joe is a thriving entrepreneur, author and speaker. He is the CEO of SelfHacked, SelfDecode and LabTestAnalyzer.His mission is to help people gain access to the most up-to-date, unbiased, and science-based ways to optimize their health.
Joe has been studying health sciences for 17 years and has read over 30,000 PubMed articles. He's given consultations to over 1000 people who have sought his health advice. After completing the pre-med requirements at university, he founded SelfHacked because he wanted to make a big impact in improving global health. He's written hundreds of science posts, multiple books on improving health, and speaks at various health conferences. He's keen on building a brain-trust of top scientists who will improve the level of accuracy of health content on the web. He's also founded SelfDecode and LabTestAnalyzer, popular genetic and lab software tools to improve health.

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