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Sleep
disorders
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Nicholson
AN, Turner C, Stone BM, Robson PJ. Effect
of Delta-9-tetrahydrocannabinol and cannabidiol
on nocturnal sleep and early-morning behavior
in young adults. J Clin Psychopharmacol.
2004 Jun;24(3):305-13. |
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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.
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Navarro
L, et al. Potential role of the cannabinoid
receptor CB1 in rapid eye movement sleep
rebound. Neuroscience. 2003;120(3):855-9.
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Sleep is an unavoidable activity of the brain.
The delay of the time to sleep (sleep deprivation),
induces an increase of slow-wave sleep and rapid-eye-movement
(REM) sleep (rebound) once the subject is allowed
to sleep. This drive to sleep has been hypothesized
to be dependent on the accumulation of sleep-inducing
molecules and on the high expression of these
molecule receptors. In this study we selectively
deprived rats of REM sleep for 24 h by using
the flowerpot technique. One group deprived
of REM sleep was treated with SR141716A, a cannabinoid
receptor 1 (CB1) receptor antagonist and then
allowed to sleep for the next 4 h. Two other
groups were killed, one immediately after the
REM sleep deprivation period and the other after
2 h of REM sleep rebound (REM sleep deprivation
plus
2 h of rebound). In both groups we determined
the expression of the CB1 receptor and its mRNA.
Results indicated that SR141716A prevents REM
sleep rebound and REM sleep deprivation does
not modify the expression of the CB1 protein
or mRNA. However, REM sleep deprivation plus
2 h of sleep rebound increased the CB1 receptor
protein and, slightly but significantly, decreased
mRNA expression. These results suggest that
endocannabinoids may be participating in the
expression of REM sleep rebound.
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Carley
DW, Paviovic S, Janelidze M, Radulovacki
M. Functional role for cannabinoids in respiratory
stability during sleep Sleep. 2002 Jun 15;25(4):
391-8. |
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STUDY OBJECTIVES: Serotonin,
acting in the peripheral nervous system, can
exacerbate sleep-related apnea, and systemically
administered serotonin antagonists reduce sleep-disordered
respiration in rats and bulldogs. Because cannabinoid
receptor agonists are known to inhibit the excitatory
effects of serotonin on nodose ganglion cells,
we examined the effects of endogenous (oleamide)
and exogenous (delta9-tetrahydrocannabinol;
delta9THC) cannabimimetic agents on sleep-related
apnea.
DESIGN: Sleep architecture,
respiratory pattern, and apnea expression in
rats were assessed by polysomnography. A repeated
measures, within-subjects, fully nested crossover
design was used in which each animal was recorded
on exactly 12 occasions.
PARTICIPANTS: Eleven adult
male Sprague-Dawley rats were instrumented for
chronic polysomnography.
INTERVENTIONS: Animals were
recorded following intraperitoneal injection
of various doses of delta9THC, oleamide, and
serotonin, alone and in combination.
MEASUREMENTS AND RESULTS:
Our data show that delta9THC and oleamide each
stabilized respiration during all sleep stages.
With delta9THC, apnea index decreased by 42%
(F=2.63; p=0.04) and 58% (F=2.68; p=0.04) in
NREM and REM sleep, respectively. Oleamide produced
equivalent apnea suppression. This observation
suggests an important role for endocannabinoids
in maintaining autonomic stability during sleep.
Oleamide and delta9THC blocked serotonin-induced
exacerbation of sleep apnea (p<0.05 for each),
suggesting that inhibitory coupling between
cannabinoids and serotonin receptors in the
peripheral nervous system may act on apnea expression.
CONCLUSIONS: This study demonstrates
potent suppression of sleep-related apnea by
both exogenous and endogenous cannabinoids.
These findings are of relevance to the pathogenesis
and pharmacological treatment of sleep-related
breathing disorders.
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Freemon
FR. The effect of chronically administered
delta-9-tetrahydrocannabinol upon the polygraphically
monitored sleep of normal volunteers Drug
Alcohol Depend. 1982 Dec;10(4):345-53. |
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This study describes the effect of two weeks
of delta-9-tetrahydrocannabinol (THC) administration
upon normal sleep. The two subjects, two brothers
in their 20s, slept in the laboratory for 27
consecutive nights and then, after four nights
at home, for four additional nights. One subject,
after an adaption night, received placebo for
four baseline nights, 30 mg of THC for the next
14 nights, and placebo during four withdrawal
nights. The other subject received placebo during
this entire period. One year later the subjects
alternated these conditions. The subjects had
difficulty falling and staying asleep during
the first two nights of placebo after 14 consecutive
drug nights. This mild drug withdrawal insomnia
was not accompanied by the increase of REM sleep
which frequently accompanies withdrawal of other
drugs. Starting after about a week of THC administration,
and continuing for a week after drug discontinuance,
there was a marked decrease in the type of sleep
associated with slow waves in the electroencephalogram,
nonREM sleep stages 3 and 4. The fact that prolonged,
but not acute use, suppresses slow wave sleep
indicates that this commonly used drug produces
a poorly understood change in brain physiology.
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Feinberg
I, Jones R, Walker JM, Cavness C, March.
Effects of high dosage delta-9-tetrahydrocannabinol
on sleep patterns in man. J. Clin Pharmacol
Ther. 1975 Apr;17(4):458-66. |
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Electroencephalographic readings and eye movement
were recorded in experienced marihuana users
under placebo and tetrahydrocannabinol (THC).
Four subjects were studied for 3 baseline nights,
3 nights under initial dosage of 70 mg/day,
the last 3 nights of a 2-wk period of 210 mg/day,
and the first 3 nights of withdrawal. Three
other subjects were studied only during the
latter 2 conditions. Administration of THC significantly
reduced eye movement activity during sleep with
rapid eye movements (REM) and, to a lesser extent,
the duration of REM itself. Withdrawal led to
increases above baseline in both measures but
the "rebound" effect was greater for
eye movement. Stage 4 sleep tended to increase
on drug, but this effect was not statistically
significant. On withdrawal, stage 4 sleep decreased
significantly; this change was marked only on
the first withdrawal night. The functional or
biological significance of these changes is
unclear. Nevertheless, these are the most marked
effects of THC on brain electrical activity
demonstrated thus far. Since its pattern of
effects on sleep appears unique to THC, this
drug may prove to be a valuable tool in the
elucidation of the pharmacology of sleep. Possible
relations between effects on sleep pattern and
on behavior are discussed.
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