Humor Appreciation Increased by Psychostimulants During Sleep Deprivation

Certain psychostimulant drugs can enhance the ability of sleep deprived volunteers to detect humor, according to a study published in the aptly-named journal Sleep.

The study was conducted by William D.S. Killgore, Sharon A. McBride, Desiree B. Killgore, and Thomas J. Balkin of the Department of Behavioral Biology at the Walter Reed Army Institute of Research. It was published in 2006.

“Humor appreciation requires the confluence of multiple cognitive and affective processes, including simple attention, working memory, mental flexability, set shifting, long-term memory retrieval, verbal abstraction, and the integration of these cognitive components with affective and somatic state information – capacities that are unique to the heteromodal association regions of the prefrontal cortex,” as Killgore and his colleagues explain.

This area of the brain, the prefrontal cortex, is involved in a number of important executive functions, such as decision making, and is also very sensitive to sleep deprivation.

In the study, 29 male and 24 female volunteers between the ages of 18 to 36 were given a psychostimulant after 49 hours of sleep deprivation and then completed a number of tasks. These 54 volunteers received either 600 milligrams of caffeine, 400 milligrams of modafinil, 20 milligrams of dextroamphetamine, or a placebo.

Modafinil (brand name Provigil) is often used to treat conditions such as narcolepsy and similar disorders related to sleepiness. Dextroamphetamine (brand name Dexedrine) is often prescribed for the treatment of ADHD and is sometimes prescribed for treatment-resistant depression and obesity.

Five and a half hours after receiving one of the psychostimulants or placebo, the volunteers completed the University of Pennsylvania Humor Appreciation Test. This test is composed of a series of 40 pairs of images and sentences. Each pair contains either two images or two sentences that vary slightly from one another. One of these images or sentences is funny or humorous, while the other is not.

After being shown one of the pair of images or sentences, the volunteer was required to indicate which one was funnier.

The volunteers also completed psychomotor vigilance testing to assess their reaction time and the Stanford Sleepiness Scale to assess their subjective feeling of sleepiness.

“Interestingly, administration of modafinil, 400mg, significantly enhanced the ability to detect humor in cartoons, relative to placebo or caffeine 600mg, but did not enhance performance significantly beyond that of dextroamphetamine 20mg,” according to Killgore and his colleagues.

Although modafinil and dextroamphetamine enhanced the ability of volunteers to detect humor on the visual portion of the test, none of the psychostimulants appeared to improve the detection of humor on the verbal portion of the test.

Chemical structure of Modafinil
Chemical structure of Modafinil

The study also found that volunteers who were administered dextroamphetamine had the fastest response times, followed by the modafinil group and the caffeine group. Similarly, “those participants receiving dextroamphetamine 20mg reported significantly lower subjective sleepiness” and those administered caffeine reported lower levels of sleepiness as well.

“In contrast, the sleepiness rating of the modafinil group did not differ significantly from that of placebo.”

Although those administered modafinil showed the greatest ability to appreciate visual humor, this was not because they were more alert or less sleepy.

“These findings suggest that mere enhancement of alertness and vigilance was not itself sufficient to improve the complex cognitive processes involved in humor appreciation. Furthermore, as evidenced by the lack of an effect of modafinil on Stanford Sleepiness Scale scores relative to placebo, maintenance of subjective alertness was also neither necessary nor sufficient to produce improvement in the appreciation of humor.”


Killgore, W.D.S., McBride, S.A., Killgore, D.B. & Balkin, T.J. (2006). The effects of caffeine, dextroamphetamine, and modafinil on humor appreciation during sleep deprivation. Sleep, Vol 29, No 6: 841-847. Full text:

1 Comment

  1. Avatar

    Autism and self injurious behaviors with seizures is an area that is little understood by experts. However, it appears that careful use of both a combination of anti-convulsants and psychostimulants that would enhance the areas vulnerable to producing outbursts of SIB, would be indicated. Naturally, a sleep study and perhaps a SPECT scan would be needed to pinpoint where seizures are beginning, and thus target the types of seizures with proper AED first, then add psychostimulant, low dose. This would perhaps be the saving grace of many self injurious autistic patients with epilepsy, given the reluctance of doctors to treat them with psychostimulants, due to epilepsy. Research shows that judicious, careful use of BOTH anticonvulsant and psychostimulant would be of great benefit to autistics with intraccable treatment resistant, self injurious behaviors and seizures. Autism, especially the most severe cases, require comprehensive behavioral and medical management/treatment. Many autistics have ADHD type issues, but because they also have seizures, aren’t being prescribed the psychostimulants needed to enhance prefrontal cortex perfusion.