What drugs cause mydriasis? An in-depth pharmacological review

October 10, 2025 •

5 min read

According to a 2023 press release regarding FDA approval for a drug reversing pharmacologically induced mydriasis, over 100 million thorough eye examinations involving dilating drops are performed in the United States each year. This common procedure, which intentionally causes mydriasis, highlights the significant role that various medications and substances play in affecting pupil size. Beyond clinical settings, a wide array of prescription, over-the-counter, and recreational drugs can also lead to dilated pupils.

Quick Summary

A diverse range of medications and illicit substances can cause pupil dilation, known as mydriasis, by affecting the eye's involuntary muscles through the autonomic nervous system. Key pharmacological classes include anticholinergics, sympathomimetics, and hallucinogens, with mechanisms varying from blocking constriction to stimulating dilation. The effect is often a side effect but is intentionally induced for medical exams.

Key Points

Drug Classes: The primary drug classes causing mydriasis are anticholinergics and sympathomimetics, which respectively block pupil constriction and stimulate dilation.
Recreational Drugs: Stimulants like cocaine and amphetamines, along with hallucinogens such as LSD and psilocybin, commonly cause mydriasis due to their effects on neurotransmitter systems.
Clinical Use: Mydriatic eye drops containing agents like atropine and tropicamide are used by ophthalmologists to intentionally dilate pupils for eye examinations.
Mechanism: Mydriasis occurs when drugs disrupt the balance of the autonomic nervous system by either exciting the sympathetic pathway or inhibiting the parasympathetic pathway.
Side Effects: Consequences of drug-induced mydriasis include light sensitivity, blurred vision, headaches, and an increased risk of angle-closure glaucoma in predisposed individuals.
Reversal: For pharmacologically-induced dilation in a clinical setting, newer treatments like phentolamine ophthalmic solution (Ryzumvi) are available to accelerate pupil constriction.

Mydriasis, or the dilation of the pupils, is a physiological process controlled by two opposing sets of muscles within the iris: the constrictor muscle, which makes the pupil smaller, and the dilator muscle, which makes it larger. These muscles are regulated by the autonomic nervous system, specifically the parasympathetic and sympathetic branches. The parasympathetic system causes the pupils to constrict, while the sympathetic system causes them to dilate. Drugs can interfere with this delicate balance in several ways, either by stimulating the sympathetic response or by inhibiting the parasympathetic response, leading to mydriasis.

Anticholinergic Agents

Anticholinergic drugs, also known as parasympatholytic drugs, are a common cause of drug-induced mydriasis. Their mechanism involves blocking the action of acetylcholine, the neurotransmitter responsible for stimulating the iris sphincter muscle to constrict. By inhibiting this constriction pathway, the pupil dilates. This effect is often sought by ophthalmologists during a dilated eye exam to provide an unobstructed view of the retina and other internal structures.

Examples of anticholinergic drugs causing mydriasis:

Atropine: A potent mydriatic and cycloplegic (paralyzes the ciliary muscle) agent, frequently used in ophthalmic procedures and sometimes systemically to treat a slow heart rate.
Tropicamide: A short-acting mydriatic eye drop used for routine eye examinations, with effects that typically last several hours.
Scopolamine: Used to prevent motion sickness and post-operative nausea, it can cause mydriasis as a systemic side effect.
Tricyclic Antidepressants (TCAs): Older antidepressants like amitriptyline have anticholinergic properties that can lead to dilated pupils.
Antihistamines: Certain first-generation antihistamines, such as diphenhydramine (Benadryl), possess anticholinergic effects that can cause mydriasis.

Sympathomimetic Agents

Sympathomimetic drugs mimic the effects of the sympathetic nervous system, the body's 'fight or flight' response. They cause mydriasis by directly stimulating the alpha-adrenergic receptors on the iris dilator muscle, causing it to contract and widen the pupil.

Examples of sympathomimetic drugs causing mydriasis:

Phenylephrine: A topical agent used during eye exams and as a decongestant, it directly stimulates alpha-adrenergic receptors.
Cocaine: As a powerful central nervous system stimulant, cocaine blocks the reuptake of norepinephrine, leading to increased sympathetic activity and pronounced mydriasis.
Amphetamines and Methamphetamines: These stimulants increase the release of norepinephrine and other neurotransmitters, causing a significant sympathetic response that includes pupil dilation.
MDMA (Ecstasy/Molly): This illicit substance affects serotonin, norepinephrine, and dopamine systems, resulting in an intense emotional and sensory experience that includes mydriasis.

Hallucinogens

Hallucinogenic drugs alter sensory perception and mood, often by acting on the serotonin system in the brain. This interference can lead to an increase in sympathetic nervous system activity and the resulting pupil dilation.

Examples of hallucinogens causing mydriasis:

LSD: A potent hallucinogen that primarily affects serotonin receptors, causing altered perceptions and dilated pupils.
Psilocybin (Magic Mushrooms): This psychedelic compound affects serotonin receptors, leading to hallucinogenic effects and pupil dilation.
Mescaline: Found in the peyote cactus, mescaline influences both serotonin and dopamine receptors, causing hallucinatory effects and mydriasis.

Other Medications and Substances

Beyond the primary classifications, several other medications and substances can cause mydriasis through various mechanisms:

Anticonvulsants: Certain anti-seizure medications, such as topiramate and oxcarbazepine, have been linked to mydriasis.
Botulinum Toxin (Botox): In cases of systemic exposure or local injection, botulinum toxin can inhibit acetylcholine release, leading to pupil dilation.
Selective Serotonin Reuptake Inhibitors (SSRIs): Some antidepressants in this class can also cause mydriasis, though the mechanism is not as direct as with TCAs.
Benzodiazepines: Although often associated with a sedative effect, these anti-anxiety medications can cause dilated pupils, especially in cases of misuse.
Certain Plants: Some plants, like Jimson weed and belladonna, contain anticholinergic alkaloids that can cause mydriasis if inhaled or touched.

Comparison Table of Mydriatic Drugs


Drug Type	Examples	Mechanism of Action	Context	Notes
Anticholinergic Agents	Atropine, Tropicamide	Blocks parasympathetic response (acetylcholine) causing relaxation of constrictor muscle	Therapeutic (eye exams), Systemic side effects	Can cause blurred vision and light sensitivity for hours.
Sympathomimetic Agents	Phenylephrine, Cocaine, Meth	Activates sympathetic response (alpha-adrenergic receptors) causing contraction of dilator muscle	Therapeutic (eye exams, decongestants), Recreational	Effects can be rapid and pronounced.
Hallucinogens	LSD, Psilocybin	Affects serotonin receptors, leading to sympathetic stimulation	Recreational	Associated with altered perception and other systemic effects.
SSRIs	Sertraline, Fluoxetine	Increases serotonin levels, indirect effect on autonomic system	Therapeutic (antidepressants)	Mydriasis is a less common side effect compared to others.
Benzodiazepines	Alprazolam, Clonazepam	Acts on GABA receptors, can affect autonomic balance	Therapeutic (anxiety), Recreational	Often a symptom in overdose or misuse situations.

Side Effects and Risks Associated with Drug-Induced Mydriasis

While medically-induced mydriasis from an eye exam is temporary, prolonged or frequent dilation, especially from recreational drug use, can lead to several complications. The most immediate side effect is photosensitivity, as the pupils can no longer constrict to regulate light entering the eye. This can also cause blurred vision, making tasks like driving and reading difficult.

For individuals with anatomically narrow angles in their eyes, drug-induced mydriasis can trigger a dangerous condition called angle-closure glaucoma. This occurs when the iris bulges and blocks the drainage angle of the eye, causing a rapid increase in intraocular pressure that can lead to vision loss. Symptoms include sudden eye pain, headache, blurred vision, and seeing halos around lights. It is a medical emergency requiring immediate attention.

Repeated or prolonged drug misuse can also cause long-term vision problems. For example, chronic cocaine use is associated with inflammation of the cornea (keratitis) and macular degeneration, while chronic alcohol abuse can lead to dry eye syndrome. Furthermore, significant, unexplained pupil dilation, especially if accompanied by other neurological symptoms like headache or confusion, could indicate a serious medical condition such as a head injury or stroke and warrants urgent medical evaluation.

Conclusion

Mydriasis is a visible sign of a complex pharmacological effect on the autonomic nervous system. A wide range of drugs, from standard ophthalmic drops to recreational substances, can cause the pupils to dilate by either enhancing the sympathetic 'fight or flight' response or blocking the parasympathetic 'rest and digest' response. While a controlled, temporary mydriasis during a medical procedure is routine, unexplained or prolonged pupil dilation can be a sign of a substance use issue or an underlying medical problem that requires investigation. Understanding which drugs cause mydriasis and their different mechanisms is crucial for both healthcare professionals and the public, helping to identify potential substance misuse or recognize symptoms of a more serious health concern.

For further information on the mechanism of action for specific mydriatic agents, including the newly approved reversing agent phentolamine ophthalmic solution, one can consult articles published by the National Institutes of Health (NIH).

Frequently Asked Questions

Normal pupil dilation is a physiological response to dim lighting and reverses when exposed to light. Drug-induced mydriasis is often prolonged, excessive, and the pupils may not constrict properly even in bright light.

The duration of drug-induced mydriasis varies significantly depending on the drug, dosage, and individual metabolism. Effects from eye exam drops can last several hours, while some recreational drugs can cause dilation lasting much longer.

Yes. Certain OTC medications, such as decongestants containing pseudoephedrine and older antihistamines like diphenhydramine, can have systemic effects that lead to mydriasis.

While temporary dilation from a medical exam is generally safe, prolonged or unexplained mydriasis can cause light sensitivity, blurry vision, and increase the risk of angle-closure glaucoma in some people. It can also be a symptom of a more serious medical issue.

If medically necessary, treatment depends on the cause. For post-examination mydriasis, drops like phentolamine ophthalmic solution (Ryzumvi) can be used for reversal. For recreational drug use, the pupils will return to normal as the drug's effects wear off.

Routine eye exam drops are generally safe and cause temporary mydriasis. However, prolonged exposure to certain drugs, especially with misuse, can potentially cause long-term vision problems.

Unequal pupil dilation (anisocoria) or sudden, unexplained dilation can be a sign of a serious condition, such as a head injury or stroke. You should seek immediate medical attention if this occurs.