***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Cannabidiol is a component of marijuana that does not activate cannabinoid receptors , but moderately inhibits the degradation of the endocannabinoid an and amide . We previously reported that an elevation of an and amide levels in cerebrospinal fluid inversely correlated to psychotic symptoms . Furthermore , enhanced an and amide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition . In our translational approach , we performed a double-blind , r and omized clinical trial of cannabidiol vs amisulpride , a potent antipsychotic , in acute schizophrenia to evaluate the clinical relevance of our initial findings . Either treatment was safe and led to significant clinical improvement , but cannabidiol displayed a markedly superior side-effect profile . Moreover , cannabidiol treatment was accompanied by a significant increase in serum an and amide levels , which was significantly associated with clinical improvement . The results suggest that inhibition of an and amide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia Fifteen volunteers received cannabidiol ( CBD ) ( 320 μg/kg ) or placebo ( both orally , T0 ) , and 60 min later they consumed an ethanolic beverage ( 0.54 g/kg ) or placebo . The effects were measured at T1 ( 100 min after CBD ingestion ) , T2 ( 160 min ) and T3 ( 220 min ) using cognitive , perceptual and motor function tests . Factorial analysis indicated that test procedures could be adequately expressed by three rotated factors : A reaction speed factor ( I ) , a st and ing steadiness factor ( II ) and a psychomotor coordination/cognitive factor ( III ) . Ethanol produced a significant decrement in factor III . There was no demonstrable effect of CBD , either alone or in combination with ethanol . Neither CBD nor ethanol produced any significant effect on pulse rate . Prior administration of CBD did not significantly affect the blood ethanol levels . Whilst the subjects were able to identify correctly when they were given ethanol , they did not report any subjective effects of CBD Purpose The purpose of this study was to assess the effect on intraocular pressure ( IOP ) and the safety and tolerability of oromucosal administration of a low dose of delta-9-tetrahydrocannabinol ( Δ-9-THC ) and cannabidiol ( CBD ) . Patients and Methods A r and omized , double-masked , placebo-controlled , 4 way crossover study was conducted at a single center , using cannabis-based medicinal extract of Δ-9-THC and CBD .  Six patients with ocular hypertension or early primary open angle glaucoma received a single sublingual dose at 8 AM of 5 mg Δ-9-THC , 20 mg CBD , 40 mg CBD , or placebo . Main outcome measure was IOP . Secondary outcomes included visual acuity , vital signs , and psychotropic effects . Results Two hours after sublingual administration of 5 mg Δ-9-THC , the IOP was significantly lower than after placebo ( 23.5 mm Hg vs. 27.3 mm Hg , P=0.026 ) . The IOP returned to baseline level after the 4-hour IOP measurement . CBD administration did not reduce the IOP at any time . However , the higher dose of CBD ( 40 mg ) produced a transient elevation of IOP at 4 hours after administration , from 23.2 to 25.9 mm Hg ( P=0.028 ) . Vital signs and visual acuity were not significantly changed . One patient experienced a transient and mild paniclike reaction after Δ-9-THC administration . Conclusions A single 5 mg sublingual dose of Δ-9-THC reduced the IOP temporarily and was well tolerated by most patients . Sublingual administration of 20 mg CBD  did not reduce IOP , whereas 40 mg CBD produced a transient increase IOP rise The object of the experiment was to verify whether cannabidiol ( CBD ) reduces the anxiety provoked by delta 9-THC in normal volunteers , and whether this effect occurs by a general block of the action of delta 9-THC or by a specific anxiolytic effect . Appropriate measurements and scales were utilized and the eight volunteers received , the following treatments in a double-blind procedure : 0.5 mg/kg delta 9-THC , 1 mg/kg CBD , a mixture containing 0.5 mg/kg delta 9-THC and 1 mg/kg CBD and placebo and diazepam ( 10 mg ) as controls . Each volunteer received the treatments in a different sequence . It was verified that CBD blocks the anxiety provoked by delta 9-THC , however this effect also extended to marihuana-like effects and to other subjective alterations induced by delta 9-THC . This antagonism does not appear to be caused by a general block of delta 9-THC effects , since no change was detected in the pulse-rate measurements . Several further effects were observed typical of CBD and of an opposite nature to those of delta 9-THC . These results suggest that the effects of CBD , as opposed to those of delta 9-THC , might be involved in the antagonism of effects between the two cannabinoids 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 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more 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 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 Besides the psychoactive Delta(9)-tetrahydrocannabinol ( THC ) , hashish and marijuana as well as cannabis-based medicine extracts contain varying amounts of cannabidiol ( CBD ) and of the degradation product cannabinol ( CBN ) . The additional determination of these compounds is interesting from forensic and medical points of view because it can be used for further proof of cannabis exposure and because CBD is known to modify the effects of THC . Therefore , a method for the simultaneous quantitative determination of THC , its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol ( 11-OH-THC ) and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol ( THC-COOH ) , CBD and CBN from plasma was developed . The method was based on automatic solid-phase extraction with C(18 ) ec columns , derivatization with N , O-bistrimethylsilyltrifluoroacetamide ( BSTFA ) , and gas chromatography-electron impact ionization-mass spectrometry ( GC-EI-MS ) with deuterated st and ards . The limits of detection were between 0.15 and 0.29 ng/mL for THC , 11-OH-THC , THC-COOH , and CBD and 1.1 ng/mL for CBN . The method was applied in a prospect i ve pharmacokinetic study after single oral administration of 10 mg THC alone or together with 5.4 mg CBD in cannabis extract . The maximum plasma concentrations after cannabis extract administration ranged between 1.2 and 10.3 ng/mL ( mean 4.05 ng/mL ) for THC , 1.8 and 12.3 ng/mL ( mean 4.9 ng/mL ) for 11-OH-THC , 19 and 71 ng/mL ( mean 35 ng/mL 
    Output:
    
Similarly , chronic dosing with CBD had no effect on HR .
From the limited data available , we conclude that acute and chronic administration of CBD had no effect on BP or HR under control conditions , but reduces BP and HR in stressful conditions , and increases cerebral blood flow ( CBF ) in mouse models of stroke .