Effect of Δ-9-Tetrahydrocannabinol and Cannabidiol on Nocturnal Sleep and Early-Morning Behavior in Young Adults

Abstract

The effects of cannabis extracts on nocturnal sleep, early-morning performance, memory, and sleepiness were studied in 8 healthy volunteers (4 males, 4 females; 21 to 34 years). The study was double-blind and placebo-controlled with a 4-way crossover design. The 4 treatments were placebo, 15 mg Delta-9-tetrahydrocannabinol (THC), 5 mg THC combined with 5 mg cannabidiol (CBD), and 15 mg THC combined with 15 mg CBD. These were formulated in 50:50 ethanol to propylene glycol and administered using an oromucosal spray during a 30-minute period from 10 pm. The electroencephalogram was recorded during the sleep period (11 pm to 7 am). Performance, sleep latency, and subjective assessments of sleepiness and mood were measured from 8:30 am (10 hours after drug administration). There were no effects of 15 mg THC on nocturnal sleep. With the concomitant administration of the drugs (5 mg THC and 5 mg CBD to 15 mg THC and 15 mg CBD), there was a decrease in stage 3 sleep, and with the higher dose combination, wakefulness was increased. The next day, with 15 mg THC, memory was impaired, sleep latency was reduced, and the subjects reported increased sleepiness and changes in mood. With the lower dose combination, reaction time was faster on the digit recall task, and with the higher dose combination, subjects reported increased sleepiness and changes in mood. Fifteen milligrams THC would appear to be sedative, while 15 mg CBD appears to have alerting properties as it increased awake activity during sleep and counteracted the residual sedative activity of 15 mg THC.

High-Potency Marijuana Impairs Executive Function and Inhibitory Motor Control

“…All were heavy marijuana users who smoked marijuana on a daily basis and might have developed tolerance to many marijuana related cognitive effects. In the present study, heavy daily users of marijuana were not included in order to exclude confounding by residual impairment of recent THC use shown to persist in abstinent marijuana users (Fried et al, 2005;Haney et al, 1999;Nicholson et al, 2004;Pope et al, 2001). Subjects in the present study, thus, were light marijuana users that may have been more sensitive to THC effects as compared to the heavy daily users.…”

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action

“…44 This effect of CBD may be biphasic, since in low doses (15 mg) the cannabinoid appears to have alerting properties in healthy volunteers, as it increases wakefulness during sleep and counteracts the residual sedative activity of 15 mg THC. 45 Previous reports of subjective feelings by healthy volunteers after CBD (1 mg/Kg) showed a significant increase in "clear minded" and "quick-witted" feelings, in contrast with THC (0.5 mg/Kg) that induced an increase in "muzzy" 46 feelings. In agreement with the two last observations, intracerebroventricular administration of CBD in rats during the lights-on period increased wakefulness (W) and decreased rapid eye movement sleep (REMS), probably through increased dopamine release.…”

Sleep Disturbances: Implications for Cannabis Use, Cannabis Use Cessation, and Cannabis Use Treatment

“…Specifically, CBD administration has been shown to have sleep-inducing (with a 20 mg/kg dose) and sleepmaintenance (with a 40 mg/kg dose) qualities in rats, with tolerance to these effects developing after long-term administration [8]. However, among humans, administration of CBD (i.e., 15 mg) has been shown to have an alerting affect, which can counter the sedating qualities of Δ 9 -THC [17]. Despite the disparate findings regarding the individual effects of Δ 9 -THC and CBD, when combined, Δ 9 -THC and CBD appear to have an antagonistic effect on each other in terms of the sleep-wake cycle [8,18].…”