Effect of Δ-9-Tetrahydrocannabinol and Cannabidiol on Nocturnal Sleep and Early-Morning Behavior in Young Adults The effect of opioids on sleep architecture. Cannabidiol in Humans—The Quest for Therapeutic Targets Psychomotor performance in relation to acute oral administration of Δ9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia A double-blind trial of delta 9-tetrahydrocannabinol in primary anorexia nervosa. The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. Effects of Oral L-Carnitine Administration in Narcolepsy Patients: A Randomized, Double-Blind, Cross-Over and Placebo-Controlled Trial Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis.
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 Δ-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 assessment s 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 STUDY OBJECTIVES The effect of opioid medications on sleep architecture has been demonstrated in patients with comorbid pain or opioid addiction . This study examined whether commonly used opioid medications have an adverse effect on sleep architecture in healthy adults . METHODS Forty-two healthy subjects were examined with  polysomnography  after a bedtime dose of placebo , sustained-release morphine sulfate ( 15 mg ) , or methadone ( 5 mg ) on each of 3 different nights in a double-blind multiple crossover study in a sleep laboratory in the General Clinical Research Center at an academic medical center . RESULTS Both opioid drugs significantly reduced deep sleep and increased stage 2 sleep ( both p < .01 ) ; neither had an effect on sleep efficiency , wake after sleep onset , or total sleep time . CONCLUSIONS Single doses of oral opioid medications can significantly affect sleep architecture in healthy adults , and observed reductions in slow-wave sleep following opioid administration may have important implication s for the pathogenesis of opioid-use related fatigue Cannabidiol ( CBD ) , a major phytocannabinoid constituent of cannabis , is attracting growing attention in medicine for its anxiolytic , antipsychotic , antiemetic and anti-inflammatory properties . However , up to this point , a comprehensive literature review of the effects of CBD in humans is lacking . The aim of the present systematic review is to examine the r and omized and crossover studies that administered CBD  to healthy controls and to clinical patients . A systematic search was performed in the electronic data bases PubMed and EMBASE using the key word “ cannabidiol ” . Both monotherapy and combination studies ( e.g. , CBD + ∆9-THC ) were included . A total of 34 studies were identified : 16 of these were experimental studies , conducted in healthy subjects , and 18 were conducted in clinical population s , including multiple sclerosis ( six studies ) , schizophrenia and bipolar mania ( four studies ) , social anxiety disorder ( two studies ) , neuropathic and cancer pain ( two studies ) , cancer anorexia ( one study ) , Huntington ’s disease ( one study ) , insomnia ( one study ) , and epilepsy ( one study ) . Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC . Moreover , some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and /or intensify ∆9-THC-induced effects , whereas others suggest that it may inhibit ∆9-THC-induced effects . Finally , preliminary clinical trials suggest that high-dose oral CBD ( 150–600 mg/d ) may exert a therapeutic effect for social anxiety disorder , insomnia and epilepsy , but also that it may cause mental sedation . Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users . The high levels of central cannabinoid ( CB1 ) receptors in the basal ganglia , the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity . Based on the close relationship between cannabis use , the endogenous cannabinoid system and motor disturbances found in schizophrenia , we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients . This prospect i ve , double-blind , placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-h and ed volunteers ( age 27.9 ± 2.9 years , 12 male ) by comparing Δ9-tetrahydrocannabinol ( Δ9-THC ) and st and ardized cannabis extract containing Δ9-THC and cannabidiol .  Psychomotor performance was assessed by using a finger tapping test series . Cannabis extract , but not Δ9-THC , revealed a significant reduction of right-h and tapping frequencies that was also found in schizophrenia . As to the pure Δ9-THC condition , left-h and tapping frequencies were correlated with the plasma concentrations of the Δ9-THC metabolite 11-OH-THC . These effects are thought to be related to cannabinoid actions on CB1 receptors in the basal ganglia , the cerebral cortex and the cerebellum . Our data further demonstrate that acute CB1 receptor activation under the cannabis extract condition may also affect intermanual coordination ( IMC ) as an index of interhemispheric transfer . AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve . This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum INTRODUCTION Cannabis and agonists of the brain cannabinoid receptor ( CB1R ) produce acute  memory impairments in humans . However , the extent to which cannabinoids impair the component processes of encoding and retrieval has not been established in humans . The objective of this analysis was to determine whether the administration of Δ9-Tetrahydrocannabinol ( THC ) , the principal psychoactive constituent of cannabis , impairs encoding and /or retrieval of verbal information . MATERIAL S AND METHODS Healthy subjects were recruited from the community . Subjects were administered the Rey-Auditory Verbal Learning Test ( RAVLT ) either before administration of THC ( experiment # 1 ) ( n=38 ) or while under the influence of THC ( experiment # 2 ) ( n=57 ) . Immediate and delayed recall on the RAVLT was compared . Subjects received intravenous THC , in a placebo-controlled , double-blind , r and omized manner at doses known to produce behavioral and subjective effects consistent with cannabis intoxication . RESULTS Total immediate recall , short delayed recall , and long delayed recall were reduced in a statistically significant manner only when the RAVLT was administered to subjects while they were under the influence of THC ( experiment # 2 ) and not when the RAVLT was administered prior . CONCLUSIONS THC acutely interferes with encoding of verbal memory without interfering with retrieval . These data suggest that learning information prior to the use of cannabis or cannabinoids is not likely to disrupt recall of that information . Future studies will be necessary to determine whether THC impairs encoding of non-verbal information , to what extent THC impairs memory consolidation , and the role of other cannabinoids in the memory-impairing effects of cannabis . CLINICAL TRIAL INFORMATION Cannabinoids , Neural Synchrony , and Information Processing ( THC-Gamma ) http:// clinical trials.gov/ct2/show/ study /NCT00708994 NCT00708994 Pharmacogenetics of Cannabinoid Response http:// clinical trials.gov/ct2/show/NCT00678730 NCT00678730 In phase 1 of the study , 3 mg/kg daily of cannabidiol ( CBD ) was given for 30 days to 8 health human volunteers . Another 8 volunteers received the same number of identical capsules containing glucose as placebo in a double-blind setting . Neurological and physical examinations , blood and urine analysis , ECG and EEG were performed at weekly intervals . In phase 2 of the study , 15 patients suffering from secondary generalized epilepsy with temporal focus were r and omly divided into two groups . Each patient received , in a double-blind procedure , 200 - 300 mg daily of CBD or placebo . The drugs were administered for along as 4 1/2 months . Clinical and laboratory examinations , EEG and ECG were performed at 15- or 30-day intervals . Throughout the experiment the patients continued to take the antiepileptic drugs prescribed before the experiment , although these drugs no longer controlled the signs of the disease . All patients and volunteers tolerated CBD  very well and no signs of toxicity or serious side effects were detected on examination . 4 of the 8 CBD subjects remained almost free of convulsive crises throughout the experiment and 3 other patients demonstrated partial improvement in their clinical condition .  CBD was ineffective in 1 patient . The clinical condition of 7 placebo patients remained unchanged whereas the condition of 1 patient clearly improved . The potential use of CBD as an antiepileptic drug and its possible potentiating effect on other antiepileptic drugs are discussed CONTEXT Cannabis use can both increase and reduce anxiety in humans . The neurophysiological substrates of these effects are unknown . OBJECTIVE To investigate the effects of 2 main psychoactive constituents of Cannabis sativa ( Delta9-tetrahydrocannabinol [ Delta9-THC ] and cannabidiol [ CBD ] ) on regional brain function during emotional processing . DESIGN Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety . Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC , 600 mg of CBD , or a placebo in a double-blind , r and omized , placebo-controlled design . PARTICIPANTS Fifteen healthy , English-native , right-h and ed men who had used cannabis 15 times or less in their life . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygenation level-dependent response ) , electrodermal activity ( skin conductance response [ SCR ] ) , and objective and subjective ratings of anxiety . RESULTS Delta9-Tetrahydrocannabinol increased anxiety , as well as levels of intoxication , sedation , and psychotic symptoms , whereas there was a trend for a reduction in anxiety following administration of CBD . The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD . Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces , and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations . Delta9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas . CONCLUSIONS Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural , electrodermal , and symptomatic response to fearful faces . The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety , whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions Animal and human studies have suggested that cannabidiol ( CBD ) may possess anxiolytic properties , but how these effects are mediated central ly is unknown . The aim of the present study was to investigate this using functional neuroimaging . Regional cerebral blood flow ( rCBF ) was measured at rest using 99mTc-ECD SPECT in 10 healthy male volunteers , r and omly divided into two groups of five subjects . Each subject was studied on two occasions , 1 week apart . In the first session , subjects were given an oral dose of CBD ( 400 mg ) or placebo , in a double-blind procedure . SPECT images were acquired 90 min after drug ingestion . The Visual Analogue Mood Scale was applied to assess subjective states . In the second session , the same procedure was performed using the drug that had not been administered in the previous session . Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping ( SPM ) . CBD significantly decreased subjective anxiety and increased mental sedation , while placebo did not induce significant changes . Assessment of brain regions where anxiolytic effects of CBD were predicted a priori revealed two voxel clusters of significantly decreased ECD uptake in the CBD relative to the placebo condition ( p<0.001 , uncorrected for multiple comparisons ) . These included a medial temporal cluster encompassing the left amygdala – hippocampal complex , extending into the hypothalamus , and a second cluster in the left posterior cingulate gyrus . There was also a cluster of greater activity with CBD than placebo in the left parahippocampal gyrus ( p<0.001 ) . These results suggest that CBD has anxiolytic properties , and that these effects are mediated by an action on limbic and paralimbic brain areas Rationale Nighttime agitation occurs frequently in patients with dementia and represents the number one burden on caregivers today . Current treatment options are few and limited due to substantial side effects . Objectives The aim of the study was to measure the effect of the cannabinoid dronabinol on nocturnal motor activity . Methods In an open-label pilot study , six consecutive patients in the late stages of dementia and suffering from circadian and behavioral disturbances — five patients with Alzheimer ’s disease and one patient with vascular dementia — were treated with 2.5 mg dronabinol daily for 2 weeks . Motor activity was measured objective ly using actigraphy . Results Compared to baseline , dronabinol led to a reduction in nocturnal motor activity ( P=0.028 ) . These findings were corroborated by improvements in Neuropsychiatric Inventory total score ( P=0.027 ) as well as in subscores for agitation , aberrant motor , and nighttime behaviors ( P<0.05 ) . No side effects were observed . Conclusions The study suggests that dronabinol was able to reduce nocturnal motor activity and agitation in severely demented patients . Thus , it appears that dronabinol may be a safe new treatment option for behavioral and circadian disturbances in dementia Δ9-Tetrahydrocannabinol ( Δ9-THC ) , the most prominent psychoactive cannabinoid in Cannabis sativa L. ( marijuana ) , has been reported to have properties of appetite stimulation , promotion of weight gain , and antiemetic efficacy in selected patient population s. In this 4-week , double-blind , crossover study , 11 female patients with primary anorexia nervosa ( PAN ) were evaluated on Δ9-THC and on an active placebo , diazepam . All patients participated in a st and ardized behavior modification treatment program . The following data were obtained : ( 1 ) daily weight , ( 2 ) daily caloric intake , and ( 3 ) weekly psychiatric assessment s. The two groups were comparable on all measures at baseline except for two items on the behavioral rating scales . The only significant differences found between the changes over time on Δ9-THC versus diazepam were more pathology on Δ9-THC for somatization , interpersonal sensitivity , and sleep disturbance . Three patients experienced severe dysphoric reactions consisting of paranoid ideation and feelings of loss of control during Δ9-THC administration . One week after the study ended , each subject was given the highest dose level of Δ8-THC achieved in the study , and periodic blood sample s were obtained coincident with self-rated “ subjective high ” assessment s and pulse measurements . Quantitative analyses of these sample s indicated peak times of 1 to 5 hours postdose for Δ9- THC and for its primary active metabolite , 11-hydroxy-THC , which generally coincided with peak times for “ subjective high ” and pulse rate . The results of this clinical investigation suggest that Δ9-THC is not efficacious , in short-term administration , in the treatment of primary anorexia nervosa and is associated with significant psychic disturbance in some PAN patients BACKGROUND Interactions between glutamatergic and endocannabinoid systems may contribute to schizophrenia , dissociative states , and other psychiatric conditions . Cannabidiol ( CBD ) , a cannabinoid-1/2 ( CB1/2 ) receptor weak partial agonist or antagonist , may play a role in the treatment of schizophrenia . OBJECTIVE This study tested the hypothesis that CBD would attenuate the behavioral effects of the NMDA receptor antagonist , ketamine , in healthy human subjects . METHODS Ten male healthy volunteers were evaluated twice in a r and omized order . In both sessions they received ketamine ( bolus of 0.26 mg/kg/1 min followed by IV infusion of 0.25mg/kg over 30 min ) preceded by either CBD ( 600 mg ) or placebo . Psychopathology was assessed using the Brief Psychiatric Rating Scale ( BPRS ) and the CADSS ( Clinician Administered Dissociative States Scale ) at regular intervals from 30 min before to 90 min after ketamine administration . RESULTS CBD significantly augmented the activating effects of ketamine , as measured by the activation subscales of the BPRS . However , CBD also showed a non-significant trend to reduce ketamine-induced depersonalization , as measured by the CADSS . CONCLUSION These data describe a complex pattern of psychopharmacologic interactions between CBD and ketamine at the doses of each agent studied in this experiment Cannabis sativa , the most widely used illicit drug , has profound effects on levels of anxiety in animals and humans . Although recent studies have helped provide a better underst and ing of the neurofunctional correlates of these effects , indicating the involvement of the amygdala and cingulate cortex , their reciprocal influence is still mostly unknown . In this study dynamic causal modelling ( DCM ) and Bayesian model selection ( BMS ) were used to explore the effects of pure compounds of C. sativa [ 600 mg of cannabidiol ( CBD ) and 10 mg Delta 9-tetrahydrocannabinol ( Delta 9-THC ) ] on prefrontal-subcortical effective connectivity in 15 healthy subjects who underwent a double-blind r and omized , placebo-controlled fMRI paradigm while viewing faces which elicited different levels of anxiety . In the placebo condition , BMS identified a model with driving inputs entering via the anterior cingulate and forward intrinsic connectivity between the amygdala and the anterior cingulate as the best fit . CBD but not Delta 9-THC disrupted forward connectivity between these regions during the neural response to fearful faces . This is the first study to show that the disruption of prefrontal-subocritical connectivity by CBD may represent neurophysiological correlates of its anxiolytic properties Background : Central pain in multiple sclerosis ( MS ) is common and often refractory to treatment . Methods : We conducted a single-center , 5-week ( 1-week run-in , 4-week treatment ) , r and omized , double-blind , placebo-controlled , parallel-group trial in 66 patients with MS and central pain states ( 59 dysesthetic , seven painful spasms ) of a whole-plant cannabis-based medicine ( CBM ) , containing delta-9-tetrahydrocannabinol : cannabidiol ( THC : CBD ) delivered via an oromucosal spray , as adjunctive analgesic treatment . Each spray delivered 2.7 mg of THC and 2.5 of CBD , and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours . Results : Sixty-four patients ( 97 % ) completed the trial , 34 received CBM . In week 4 , the mean number of daily sprays taken of CBM ( n = 32 ) was 9.6 ( range 2 to 25 , SD = 6.0 ) and of placebo ( n = 31 ) was 19.1 ( range 1 to 47 , SD = 12.9 ) . Pain and sleep disturbance were recorded daily on an 11-point numerical rating scale . CBM was superior to placebo in reducing the mean intensity of pain ( CBM mean change −2.7 , 95 % CI : −3.4 to −2.0 , placebo –1.4 95 % CI : −2.0 to −0.8 , comparison between groups , p = 0.005 ) and sleep disturbance ( CBM mean change –2.5 , 95 % CI : −3.4 to −1.7 , placebo –0.8 , 95 % CI : −1.5 to −0.1 , comparison between groups , p = 0.003 ) . CBM was generally well tolerated , although more patients on CBM than placebo  reported dizziness , dry mouth , and somnolence . Cognitive side effects were limited to long-term memory storage . Conclusions : Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated This study investigated the contribution of different cannabinoids to the subjective , behavioral and neurophysiological effects of smoked marijuana . Healthy marijuana users ( 12 men , 11 women ) participated in four sessions . They were r and omly assigned to a low or a high Δ9-tetrahydrocannabinol group ( THC ; 1.8 % versus 3.6 % ) . In the four sessions under blinded conditions subjects smoked marijuana cigarettes containing placebo ( no active cannabinoids ) , or cigarettes containing THC with low or high levels of cannabichromene ( CBC ; 0.1 % versus 0.5 % ) and low or high levels of cannabidiol ( CBD ; 0.2 % versus 1.0 % ) . Dependent measures included subjective reports , measures of cognitive task performance and neurophysiological measures [ electroencephalographic ( EEG ) and event-related potential ( ERP ) ] . Compared to placebo , active THC cigarettes produced expected effects on mood , behavior and brain activity . A decrease in performance , reduction in EEG power and attenuation of ERP components reflecting attentional processes were observed during tests of working memory and episodic memory . Most of these effects were not dose-dependent . Varying the concentrations of CBC and CBD did not change subjects ' responses on any of the outcome measures . These findings are consistent with previous studies indicating that THC and its metabolites are the primary active constituents of marijuana . They also suggest that neurophysiological EEG and ERP measures are useful biomarkers of the effects of THC CONTEXT 1',1'dimethylheptyl-Delta8-tetrahydrocannabinol-11-oic acid ( CT-3 ) , a potent analog of THC-11-oic acid , produces marked antiallodynic and analgesic effects in animals without evoking the typical effects described in models of cannabinoids . Therefore , CT-3 may be an effective analgesic for poorly controlled resistant neuropathic pain . OBJECTIVE To examine the analgesic efficacy and safety of CT-3 in chronic neuropathic pain in humans . DESIGN AND SETTING R and omized , placebo-controlled , double-blind crossover trial conducted in Germany from May-September 2002 . PARTICIPANTS Twenty-one patients ( 8 women and 13 men ) aged 29 to 65 years ( mean , 51 years ) who had a clinical presentation and examination consistent with chronic neuropathic pain ( for at least 6 months ) with hyperalgesia ( n = 21 ) and allodynia ( n = 7 ) . INTERVENTIONS Patients were r and omized to two 7-day treatment orders in a crossover design . Two daily doses of CT-3 ( four 10-mg capsules per day ) or identical placebo capsules were given during the first 4 days and 8 capsules per day were given in 2 daily doses in the following 3 days . After a washout and baseline period of 1 week each , patients crossed over to the second 7-day treatment period . MAIN OUTCOME MEASURES Visual analog scale ( VAS ) and verbal rating scale scores for pain ; vital sign , hematologic and blood chemistry , and electrocardiogram measurements ; scores on the Trail-Making Test and the Addiction Research Center Inventory-Marijuana scale ; and adverse effects . RESULTS The mean differences over time for the VAS values in the CT-3-placebo sequence measured 3 hours after intake of study drug differed significantly from those in the placebo-CT-3 sequence ( mean [ SD ] , -11.54 [ 14.16 ] vs 9.86 [ 21.43 ] ; P = .02 ) . Eight hours after intake of the drug , the pain scale differences between groups were less marked . No dose response was observed . Adverse effects , mainly transient dry mouth and tiredness , were reported significantly more often during CT-3 treatment ( mean [ SD ] difference , -0.67 [ 0.50 ] for CT-3-placebo sequence vs 0.10 [ 0.74 ] for placebo-CT-3 sequence ; P = .02 ) . There were no significant differences with respect to vital signs , blood tests , electrocardiogram , Trail-Making Test , and Addiction Research Center Inventory-Marijuana scale . No carryover or period effects were observed except on the Trail-Making Test . CONCLUSIONS In this preliminary study , CT-3 was effective in reducing  chronic neuropathic pain  compared with placebo . No major adverse effects were observed Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness , cataplexy , and rapid eye movement ( REM ) sleep abnormalities . A genome-wide association study ( GWAS ) identified a novel narcolepsy-related single nucleotide polymorphism ( SNP ) , which is located adjacent to the carnitine palmitoyltransferase 1B ( CPT1B ) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids . The mRNA expression levels of CPT1B were associated with this SNP . In addition , we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients . To assess the efficacy of oral l-carnitine for the treatment of narcolepsy , we performed a clinical trial administering l-carnitine ( 510 mg/day ) to patients with the disease . The study design was a r and omized , double-blind , cross-over and placebo-controlled trial . Thirty narcolepsy patients were enrolled in our study . Two patients were withdrawn and 28 patients were included in the statistical analysis ( 15 males and 13 females , all with HLA-DQB1 * 06:02 ) . l-carnitine treatment significantly improved the total time for dozing off during the daytime , calculated from the sleep logs , compared with that of placebo-treated periods . l-carnitine efficiently increased serum acylcarnitine levels , and reduced serum triglycerides concentration . Differences in the Japanese version of the Epworth Sleepiness Scale ( ESS ) and the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) vitality and mental health subscales did not reach statistical significance between l-carnitine and placebo . This study suggests that oral l-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients . Trial Registration University hospital Medical Information Network ( UMIN ) CONTEXT Cannabis sativa use can impair verbal learning , provoke acute psychosis , and increase the risk of schizophrenia . It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms . OBJECTIVES To investigate the effects of 2 main psychoactive constituents of C. sativa , Delta9-tetrahydrocannabinol ( Delta9-THC ) and cannabidiol , on regional brain function during verbal paired associate learning . DESIGN Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task . Each imaging session was preceded by the ingestion of Delta9-THC ( 10 mg ) , cannabidiol ( 600 mg ) , or placebo in a double-blind , r and omized , placebo-controlled , repeated- measures , within-subject design . SETTING University research center . PARTICIPANTS Fifteen healthy , native English-speaking , right-h and ed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygen level-dependent response ) , performance in a verbal learning task , and objective and subjective ratings of psychotic symptoms , anxiety , intoxication , and sedation . RESULTS Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety , intoxication , and sedation , whereas no significant effect was noted on these parameters following administration of cannabidiol .  Performance in the verbal learning task was not significantly modulated by either drug . Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident . Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs , which was directly correlated with concurrently induced psychotic symptoms . In contrast , administration of cannabidiol had no such effect . CONCLUSION The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms , respectively
Findings were mixed and showed various effects of cannabinoid administration on several aspects of sleep .
This paper review s the literature regarding the effects of cannabinoid administration on  sleep in humans .