Why Do People Abuse Benadryl? Risks and Dependency

People misuse Benadryl (diphenhydramine) for reasons that range from chasing its sedative and anxiety-dampening effects to deliberately pursuing the hallucinations it can produce at high doses. The drug is cheap, legal, and available without a prescription in virtually every pharmacy, which makes it easy to underestimate. But diphenhydramine at misuse-level doses acts less like a mild allergy pill and more like a potent anticholinergic drug, producing delirium, dangerous heart rhythms, seizures, and in some cases death.

What Draws People to Misuse an Allergy Pill

The motivations behind Benadryl misuse are not all the same, and understanding them matters because the risks scale differently depending on why someone is taking too much. At the most common end, people escalate their use gradually while trying to self-treat insomnia or anxiety. One well-documented case involved a 46-year-old woman who started taking diphenhydramine for trouble sleeping and anxiety, then over 15 years increased her daily dose to between 625 and 750 mg, far beyond the recommended maximum of 300 mg per day for adults. She developed severe physiologic dependence and a withdrawal syndrome when she finally stopped.¹ That pattern, starting with a legitimate reason and slowly losing control of dosing, is a recurring theme in the clinical literature.

At the other end of the spectrum are people who take very large amounts specifically to experience the drug’s hallucinogenic and dissociative effects. At high doses, diphenhydramine floods the brain’s muscarinic receptors, producing vivid (and often terrifying) hallucinations, confusion, and psychosis. A case report from the 1980s described a 24-year-old man who arrived at an emergency department with hallucinations and bizarre behavior after deliberately ingesting a large quantity of Benadryl.² These hallucinations are rarely described as pleasant by the people who experience them, yet curiosity and peer pressure continue to drive experimentation.

A third group consists of people already taking antipsychotic medications who find that diphenhydramine counteracts some of those drugs’ side effects, particularly tremors and restlessness. One reported patient was using up to thirty 50-mg tablets a day, describing the feeling as “good and calm” and saying the drug “stopped the tremors.” A review of published cases at that time found an apparent link between diphenhydramine abuse and antipsychotic use across multiple patients.³ That dose, 1,500 mg per day, is five times the maximum recommended amount and well into the range where life-threatening toxicity becomes likely.

The TikTok Challenge and Adolescent Misuse

Beginning around 2020, a social media trend encouraged teenagers to take large doses of Benadryl on camera to experience and record hallucinations. The so-called “Benadryl Challenge” spread across TikTok and similar platforms, leading to a measurable wave of emergency calls. One published case described a teenage girl who acknowledged she wanted to get high from Benadryl after learning about the challenge online. Her previous unsuccessful attempts with 200 mg and 300 mg prompted her to take a larger handful of pills, which triggered a seizure.⁴

The connection between online buzz and real-world harm was not just anecdotal. A study tracking web mentions of the Benadryl Challenge alongside calls to U.S. poison control centers found that spikes in online mentions were followed by a significantly elevated number of diphenhydramine overdose calls involving adolescents, with that increase persisting for more than 25 days after each spike.⁵ The lag and duration suggest that social media trends do not just reflect existing behavior but actively recruit new participants over a period of weeks.

What makes this particularly dangerous for adolescents is that the margin between a dose that produces odd sensations and a dose that causes seizures or cardiac arrest is narrow, unpredictable, and varies from person to person. A 13-year-old girl who intentionally ingested about 9.5 mg per kilogram of body weight developed a full anticholinergic toxidrome with severe agitation, psychosis, and hallucinations that persisted even after treatment with sedatives.⁶ Teenagers tend to have less body mass, which means a given number of pills produces higher blood concentrations than it would in an adult.

Why Tolerance Builds So Fast

One of the trickiest features of diphenhydramine is how quickly the body adapts to it. If you take it for a few nights to help with sleep, the drowsiness that knocked you out the first night fades remarkably fast. A controlled study comparing diphenhydramine to placebo found that the drug caused significantly higher sleepiness and worse cognitive performance on day one, but by day four, both sleepiness and performance impairment were indistinguishable from placebo. Tolerance to the sedative effect was essentially complete within three days.⁷

This rapid tolerance is a direct driver of escalating use. When the standard dose stops working, people take more. When the increased dose stops working, they take more again. Clinical reviews of antihistamines for insomnia treatment acknowledge that while these drugs have some role for short-term sleep problems, tolerance develops so quickly that their usefulness fades in days rather than weeks.⁸ The person who started with two pills for sleep and is now taking ten is not necessarily chasing a high; they are often chasing the same relief they got at the beginning, not realizing they have entered genuinely dangerous dosing territory.

What Happens to the Body at Toxic Doses

Diphenhydramine is an anticholinergic, meaning it blocks the neurotransmitter acetylcholine at receptor sites throughout the body. At therapeutic doses, this produces the familiar effects of reduced allergic symptoms and drowsiness. At toxic doses, the blockade becomes so widespread that nearly every organ system is affected. Emergency physicians learn the signs through a set of classic mnemonics:

• Delirium and hallucinations: blocking acetylcholine in the central nervous system produces confusion, agitation, and sometimes full psychosis. This is the most dangerous feature and marks severe toxicity.
• Dry skin and mouth: sweat glands are shut down, leaving the skin parched.
• Hyperthermia: without sweating, the body cannot cool itself and temperature rises, sometimes dangerously.
• Flushed skin: the body tries to compensate for the lost sweating by dilating blood vessels near the skin surface.
• Blurred vision: the pupils dilate and cannot focus properly.
• Urinary retention: the bladder muscles lose their normal control.
• Rapid heart rate and abnormal rhythms: diphenhydramine inhibits the vagus nerve’s calming effect on the heart and, at high doses, can also block sodium channels in cardiac tissue, widening the QRS interval and prolonging the QT interval on an electrocardiogram.

That last point about the heart is where misuse becomes acutely fatal. Diphenhydramine at high concentrations does not just speed the heart up; it disrupts the electrical conduction system that keeps the heartbeat organized. One fatal overdose case found a serum diphenhydramine concentration of 18.7 micrograms per milliliter at the time of arrival, a level associated with severe cardiotoxicity and death.⁹ The cardiac effects are what make diphenhydramine overdose genuinely life-threatening rather than merely unpleasant, and they can occur before the person or the people around them realize how much trouble they are in.¹⁰

Dependence and What Withdrawal Looks Like

For years, diphenhydramine was assumed to carry little to no dependence risk. The clinical evidence now paints a different picture, at least for people who use it heavily over time. Reported cases of true diphenhydramine dependence typically involve daily doses exceeding 1,000 mg taken over months or years. Withdrawal symptoms include craving, worsening insomnia, runny nose, nausea, irritability, restlessness, abdominal cramps, sweating, and diarrhea. The only described approach to managing withdrawal has been gradual tapering.¹¹

Several of these symptoms are cholinergic rebound effects, the body’s acetylcholine system surging back after being suppressed for so long. Early clinical discussions underestimated the scope of withdrawal, sometimes noting increased defecation as the only rebound effect. But closer examination of documented cases revealed additional features including marked irritability, restlessness, and severe insomnia with patients unable to stay still.¹² The 46-year-old woman mentioned earlier developed what clinicians described as a “classic amnestic-confusional withdrawal syndrome,” meaning she became confused and lost the ability to form new memories when the drug was removed.¹

The fact that dependence cases are individually documented in case reports rather than large studies does not mean the problem is rare; it more likely means it is underrecognized. People buying an over-the-counter allergy medication in escalating quantities are not flagged the way someone filling opioid prescriptions would be. The lack of systemic tracking is itself part of the problem.

Long-Term Cognitive Damage

Even beyond the acute poisoning risk, there is growing concern about what chronic anticholinergic exposure does to the brain over time. Acetylcholine is deeply involved in memory formation and cognitive function, and suppressing it repeatedly appears to leave lasting marks. A large population-based study examined the relationship between long-term anticholinergic use and the development of Alzheimer’s disease. People who used strong anticholinergics (a category that includes diphenhydramine) at moderate-to-high doses over nine or more years showed meaningfully elevated risk. Those in the highest exposure group had a roughly 40 percent greater risk of developing Alzheimer’s compared to the lowest-exposure group, and the association was even stronger among younger-old adults (aged 60 to 64), where the highest-exposure group faced about an 83 percent increase in risk.¹³

This does not prove that Benadryl causes Alzheimer’s; observational studies can identify associations but not prove causation. People with sleep problems or anxiety, the very conditions that drive long-term diphenhydramine use, may themselves have elevated dementia risk for other reasons. Still, the dose-response pattern (more use, more risk) and the biological plausibility (chronic acetylcholine suppression in brain regions critical for memory) are troubling enough that many geriatric guidelines now recommend against routine anticholinergic use in older adults.

Older Adults and Hidden Overuse

Benadryl misuse is not exclusively a young person’s problem. A study of older adults found that more than half, 59 percent, had used an over-the-counter product containing diphenhydramine or the closely related antihistamine doxylamine to improve sleep within the past 30 days. The same study found that those who were taking these products were significantly less likely to be aware of any safety risks compared to those who were not taking them (38 percent aware versus 49 percent).¹⁴

This is concerning because older adults are more vulnerable to anticholinergic side effects. Their bodies metabolize drugs more slowly, they are more likely to be taking other medications that interact, and they are at higher baseline risk for falls, confusion, and cognitive decline. The American Geriatrics Society’s Beers Criteria, a widely referenced list of medications considered potentially inappropriate for older adults, includes diphenhydramine. Yet many older adults do not realize that familiar brands marketed specifically as sleep aids often contain the same diphenhydramine found in Benadryl allergy tablets.

How Overdose Deaths Are Investigated

One of the more unsettling realities of diphenhydramine toxicity is how difficult it can be to pin down after death. A nine-year review from the Cook County Medical Examiner’s Office found that postmortem blood concentrations in fatal cases ranged enormously, from 3,300 to 228,000 nanograms per milliliter. A broader literature review spanning 1998 to 2024 confirmed this wide variability, with acute toxicity concentrations ranging from 14,640 to 285,000 nanograms per milliliter. The authors emphasized that diphenhydramine-only toxicity deserves careful consideration in death investigations because there are no specific autopsy findings that point to it, and the postmortem blood levels vary so widely that no single threshold reliably separates lethal from non-lethal cases.¹⁵

Another forensic study raised the same challenge from a different angle, noting that some fatal cases involved blood concentrations below the commonly cited 5 micrograms per milliliter cutoff traditionally used to distinguish “toxic” from “lethal” ranges. The authors argued that a strict lethal threshold cannot be universally applied and that each case requires individual interpretation, factoring in scene findings, medical history, and a thorough toxicological workup.¹⁶ In practical terms, this means some diphenhydramine deaths may go unrecognized or be attributed to other causes, particularly when the drug was taken alongside alcohol or other substances.

Treatment in the Emergency Room

When someone arrives at an emergency department with signs of severe diphenhydramine toxicity, treatment is primarily supportive: IV fluids, cooling measures for hyperthermia, benzodiazepines for agitation and seizures, and cardiac monitoring for arrhythmias. The specific antidote for anticholinergic poisoning is physostigmine, a drug that temporarily boosts acetylcholine levels to counteract the blockade. Its use has been debated for decades because of concerns about side effects, including the possibility of triggering seizures or a dangerous cholinergic overreaction.¹⁷

More recent data, however, suggests that physostigmine is both safer and more effective than its reputation implies. A study of anticholinergic toxicity cases found that patients who received physostigmine alone had a significantly lower rate of intubation, about 1.9 percent compared to 8.4 percent among those treated with other approaches.¹⁸ This matters because intubation means putting someone on a ventilator, which carries its own risks and extends hospital stays. Still, physostigmine is typically reserved for the most severe presentations and is given under careful monitoring.

Why Regulatory Fixes Are Complicated

Diphenhydramine has been available without a prescription for decades and is an ingredient in dozens of branded products beyond Benadryl itself, including many over-the-counter sleep aids and combination cold medicines. Restricting it the way pseudoephedrine was restricted (moved behind the pharmacy counter with purchase tracking) has been discussed but not implemented in most jurisdictions. A systematic review of over-the-counter drug misuse recommended a range of measures including scheduling amendments, better detection of misuse in pharmacy practice, and public health awareness campaigns.¹¹

The challenge is balancing access against harm. Millions of people use diphenhydramine safely every year for allergies and occasional sleeplessness. Making it harder to obtain penalizes the majority for the behavior of a relative few. At the same time, the drug’s perceived harmlessness is itself a risk factor. Most people who would never touch an illicit drug feel completely comfortable taking a handful of something they bought at a grocery store. Increased awareness among pharmacists, parents, and the public about what diphenhydramine actually does at high doses is probably a more realistic first step than major scheduling changes.

Pets and Accidental Exposure

Diphenhydramine is sometimes given to dogs and cats on veterinary advice for mild allergies or travel anxiety, but the margin of safety is narrower than many pet owners realize. A published case documented a fatal diphenhydramine poisoning in a 10-year-old dog that had pre-existing health conditions and likely co-ingested ethanol alongside the drug.¹⁹ Households where Benadryl is used casually or stockpiled in accessible locations create accidental ingestion risk for pets, particularly dogs, which are less discriminating about what they swallow. If you keep diphenhydramine in the house, store it the way you would any other medication, out of reach of both children and animals.