human
***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: Objective : To test whether cannabinoids reduce urge incontinence episodes without affecting voiding in patients with multiple sclerosis . This was part of the multicentre trial of the Cannabinoids in Multiple Sclerosis ( CAMS ) study . Subjects and methods : The CAMS study r and omised 630 patients to receive oral administration of cannabis extract , Δ9-tetrahydrocannabinol ( THC ) or matched placebo . For this sub study subjects completed incontinence diaries . Results : All three groups showed a significant reduction , p<0.01 , in adjusted episode rate ( i.e. correcting for baseline imbalance ) from baseline to the end of treatment : cannabis extract , 38 % ; THC , 33 % ; and placebo , 18 % . Both active treatments showed significant effects over placebo ( cannabis extract , p=0.005 ; THC , p=0.039 ) . Conclusion : The findings are suggestive of a clinical effect of cannabis on incontinence episodes in patients with MS . This is in contrast to the negative finding of the CAMS study , where no difference was seen in the primary outcome of spasticity Summary A prospect i ve r and omized double-blind trial comparing the butyrophenone analogue domperidone ( D ) and the synthetic cannabinoid nabilone ( N ) in the treatment of cytotoxic-induced emesis was conducted in 38 patients receiving highly emetogenic chemotherapy regimens ( 70 % containing cisplatin ) . Patients received 20 mg D or 1 mg N the night before chemotherapy and 8-hourly on each chemotherapy day for two consecutive cycles of treatment . Three of 19 patients r and omized to N completed only one cycle because of disease progression ( 2 ) or subjectively adverse effects ( 1 ) . Four of 19 patients completed only one cycle of D because of lack of efficacy ( 3 ) or chemotherapy toxicity ( 1 ) . In all , 32 cycles of N and 33 cycles of D were evaluable for efficacy . The mean number of vomiting episodes in cycle 1 was 4.76 for N and 12.95 for D ( P<0.02 ) . The corresponding values for cycle 2 were 4.27 and 7.69 ( P>0.10 ) , and for cycles 1 and 2 combined , 4.53 for N and 10.81 for D ( P<0.01 ) . Nausea and food intake scores did not differ significantly , although there was a trend towards less nausea and an increased food intake with N. Subjectively adverse effects were more frequent with N and included drowsiness , dizziness , dry mouth , and postural hypotension . N is superior to D for the control of cytotoxic-induced emesis A preliminary trial of oral delta-9-tetrahydrocannabinol ( THC ) demonstrated an analgesic effect of the drug in patients experiencing cancer pain .  Placebo and 5 , 10 , 15 , and 20 mg THC were administered double blind to ten patients .  Pain relief significantly superior to placebo was demonstrated at high dose levels ( 15 and 20 mg ) . At these levels , substantial sedation and mental clouding were reported UNLABELLED We assessed the efficacy of dronabinol ( Marinol capsules ; Solvay Pharmaceuticals , Brussels , Belgium ) , a synthetic Delta(9)-THC ( tetrahydrocannabinol ) , in 30 patients taking opioids for chronic pain to determine its potential analgesic effects as an adjuvant treatment . Phase I of this 2-phase study was a r and omized , single-dose , double-blinded , placebo-controlled , crossover trial in which subjects were r and omly administered either 10 mg or 20 mg of dronabinol or identical placebo capsules over the course of three , 8-hour visits . Baseline self-report measures , hourly ratings of pain intensity , pain relief , pain bothersomeness , treatment satisfaction , mood , side effects , and blood serum levels were obtained . Phase II was an extended open-label titrated trial of dronabinol as add-on medication to patients on stable doses of opioids . Results of the Phase I study showed that patients who received dronabinol experienced decreased pain intensity and increased satisfaction compared with placebo . No differences in benefit were found between the 20 mg and 10 mg doses . In the Phase II trial , titrated dronabinol contributed to significant relief of pain , reduced pain bothersomeness , and increased satisfaction compared with baseline . The incidence of side effects was dose-related . Overall , the use of dronabinol was found to result in additional analgesia among patients taking opioids for chronic noncancer pain . PERSPECTIVE This study examines the effect of adding a cannabinoid to the regimen of patients with chronic pain who report significant pain despite taking stable doses of opioids . The results of our preliminary study suggest that dronabinol , a synthetic THC , may have an additive effect on pain relief Abstract Objective To evaluate the effect of the oral synthetic δ-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis . Design R and omised double blind placebo controlled crossovertrial . Setting Outpatient clinic , University Hospital of Aarhus , Denmark . Participants 24 patients aged between 23 and 55 years with multiple sclerosis and central pain . Intervention Orally administered dronabinol at a maximum doseof 10 mg daily or corresponding placebo for three weeks ( 15 - 21days ) , separated by a three week washout period . Main outcome measure Median spontaneous pain intensity ( numericalrating scale ) in the last week of treatment . Results Median spontaneous pain intensity was significantlylower during dronabinol treatment than during placebo treatment(4.0 ( 25th to 75th centiles 2.3 to 6.0 ) v 5.0 ( 4.0 to 6.4),P = 0.02 ) , and median pain relief score ( numerical rating scale)was higher ( 3.0 ( 0 to 6.7 ) v > 0 ( 0 to 2.3 ) , P = 0.035 ) . Thenumber needed to treat for 50 % pain relief was 3.5 ( 95 % confidenceinterval 1.9 to 24.8 ) . On the SF-36 quality of life scale , thetwo items bodily pain and mental health indicated benefits fromactive treatment compared with placebo . The number of patients with adverse events was higher during active treatment , especiallyin the first week of treatment . The functional ability of themultiple sclerosis patients did not change . Conclusions Dronabinol has a modest but clinical ly relevantanalgesic effect on central pain in patients with multiple sclerosis . Adverse events , including dizziness , were more frequent withdronabinol than with placebo during the first week of treatment This study compared the efficacy of a tetrahydrocannabinol : cannabidiol ( THC : CBD ) extract , a nonopioid analgesic endocannabinoid system modulator , and a THC extract , with placebo , in relieving pain in patients with advanced cancer . In total , 177 patients with cancer pain , who experienced inadequate analgesia despite chronic opioid dosing , entered a two-week , multicenter , double-blind , r and omized , placebo-controlled , parallel-group trial . Patients were r and omized to THC : CBD extract ( n = 60 ) , THC extract ( n = 58 ) , or placebo ( n = 59 ) . The primary analysis of change from baseline in mean pain Numerical Rating Scale ( NRS ) score was statistically significantly in favor of THC : CBD compared with placebo ( improvement of -1.37 vs. -0.69 ) , whereas the THC group showed a nonsignificant change ( -1.01 vs. -0.69 ) . Twice as many patients taking THC : CBD showed a reduction of more than 30 % from baseline pain NRS score when compared with placebo ( 23 [ 43 % ] vs. 12 [ 21 % ] ) . The associated odds ratio was statistically significant , whereas the number of THC group responders was similar to placebo ( 12 [ 23 % ] vs. 12 [ 21 % ] ) and did not reach statistical significance . There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups . No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment . However , the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Question naire showed a worsening in nausea and vomiting with THC : CBD compared with placebo ( P = 0.02 ) , whereas THC had no difference ( P = 1.0 ) . Most drug-related adverse events were mild/moderate in severity . This study shows that THC : CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids A prospect i ve r and omised double blind crossover trial was conducted comparing the new synthetic cannabinoid nabilone with oral domperidone in a group of children receiving repeated identical courses of emetogenic chemotherapy for a variety of malignant diseases . Eighteen of 23 consecutive eligible children , aged 10 months to 17 years , completed the trial . When taking nabilone they experienced significantly fewer vomiting episodes and less nausea , and two thirds expressed a preference for the drug . The most common side effects of treatment with nabilone were somnolence and dizziness , with one patient being disturbed by hallucinations . The results indicate that nabilone is an effective antiemetic for children having chemotherapy , even for young children . It seems to be superior in this respect to domperidone , and although it has a higher incidence of side effects , these are mostly acceptable to patients . It can be recommended as an alternative to conventional antiemetic treatment throughout childhood The objective was to determine whether a cannabis-based medicinal extract ( CBME ) benefits a range of symptoms due to multiple sclerosis ( MS ) . A parallel group , double-blind , r and omized , placebo-controlled study was undertaken in three centres , recruiting 160 out patients with MS experiencing significant problems from at least one of the following : spasticity , spasms , bladder problems , tremor or pain . The interventions were oromucosal sprays of matched placebo , or whole plant CBME containing equal amounts of delta-9- tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) at a dose of 2.5- 120 mg of each daily , in divided doses . The primary outcome measure was a Visual Analogue Scale ( VAS ) score for each patient ’s most troublesome symptom . Additional measures included VAS scores of other symptoms , and measures of disability , cognition , mood , sleep and fatigue . Following CBME the primary symptom score reduced from mean ( SE ) 74.36 ( 11.1 ) to 48.89 ( 22.0 ) following CBME and from 74.31 ( 12.5 ) to 54.79 ( 26.3 ) following placebo [ ns ] . Spasticity VAS scores were significantly reduced by CBME ( Sativex ) in comparison with placebo ( P- 0.001 ) . There were no significant adverse effects on cognition or mood and intoxication was generally mild Objective : To test the effectiveness and long term safety of cannabinoids in multiple sclerosis ( MS ) , in a follow up to the main Cannabinoids in Multiple Sclerosis ( CAMS ) study . Methods : In total , 630 patients with stable MS with muscle spasticity from 33 UK centres were r and omised to receive oral Δ9-tetrahydrocannabinol ( Δ9-THC ) , cannabis extract , or placebo in the main 15 week CAMS study . The primary outcome was change in the Ashworth spasticity scale . Secondary outcomes were the Rivermead Mobility Index , timed 10 metre walk , UK Neurological Disability Score , postal Barthel Index , General Health Question naire-30 , and a series of nine category rating scales . Following the main study , patients were invited to continue medication , double blinded , for up to12 months in the follow up study reported here . Results : Intention to treat analysis of data from the 80 % of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months ( Δ9-THC mean reduction 1·82 ( n = 154 , 95 % confidence interval ( CI ) 0.53 to 3.12 ) , cannabis extract 0.10 ( n = 172 , 95 % CI −0.99 to 1.19 ) , placebo −0.23 ( n = 176 , 95 % CI −1.41 to 0.94 ) ; p = 0.04 unadjusted for ambulatory status and centre , p = 0.01 adjusted ) . There was suggestive evidence for treatment effects of Δ9-THC on some aspects of disability . There were no major safety concerns . Overall , patients felt that these drugs were helpful in treating their disease . Conclusions : These data provide limited evidence for a longer term treatment effect of cannabinoids . A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS 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 . 
    Output:
    
agent
Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials .
There was an increased risk of short-term AEs with cannabinoids , including serious AEs .
Common AEs included dizziness , dry mouth , nausea , fatigue , somnolence , euphoria , vomiting , disorientation , drowsiness , confusion , loss of balance , and hallucination .
CONCLUSIONS AND RELEVANCE There was moderate- quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity .
There was low- quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy , weight gain in HIV infection , sleep disorders , and Tourette syndrome .
Cannabinoids were associated with an increased risk of short-term AEs
***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: Objective : To test whether cannabinoids reduce urge incontinence episodes without affecting voiding in patients with multiple sclerosis . This was part of the multicentre trial of the Cannabinoids in Multiple Sclerosis ( CAMS ) study . Subjects and methods : The CAMS study r and omised 630 patients to receive oral administration of cannabis extract , Δ9-tetrahydrocannabinol ( THC ) or matched placebo . For this sub study subjects completed incontinence diaries . Results : All three groups showed a significant reduction , p<0.01 , in adjusted episode rate ( i.e. correcting for baseline imbalance ) from baseline to the end of treatment : cannabis extract , 38 % ; THC , 33 % ; and placebo , 18 % . Both active treatments showed significant effects over placebo ( cannabis extract , p=0.005 ; THC , p=0.039 ) . Conclusion : The findings are suggestive of a clinical effect of cannabis on incontinence episodes in patients with MS . This is in contrast to the negative finding of the CAMS study , where no difference was seen in the primary outcome of spasticity Summary A prospect i ve r and omized double-blind trial comparing the butyrophenone analogue domperidone ( D ) and the synthetic cannabinoid nabilone ( N ) in the treatment of cytotoxic-induced emesis was conducted in 38 patients receiving highly emetogenic chemotherapy regimens ( 70 % containing cisplatin ) . Patients received 20 mg D or 1 mg N the night before chemotherapy and 8-hourly on each chemotherapy day for two consecutive cycles of treatment . Three of 19 patients r and omized to N completed only one cycle because of disease progression ( 2 ) or subjectively adverse effects ( 1 ) . Four of 19 patients completed only one cycle of D because of lack of efficacy ( 3 ) or chemotherapy toxicity ( 1 ) . In all , 32 cycles of N and 33 cycles of D were evaluable for efficacy . The mean number of vomiting episodes in cycle 1 was 4.76 for N and 12.95 for D ( P<0.02 ) . The corresponding values for cycle 2 were 4.27 and 7.69 ( P>0.10 ) , and for cycles 1 and 2 combined , 4.53 for N and 10.81 for D ( P<0.01 ) . Nausea and food intake scores did not differ significantly , although there was a trend towards less nausea and an increased food intake with N. Subjectively adverse effects were more frequent with N and included drowsiness , dizziness , dry mouth , and postural hypotension . N is superior to D for the control of cytotoxic-induced emesis A preliminary trial of oral delta-9-tetrahydrocannabinol ( THC ) demonstrated an analgesic effect of the drug in patients experiencing cancer pain .  Placebo and 5 , 10 , 15 , and 20 mg THC were administered double blind to ten patients .  Pain relief significantly superior to placebo was demonstrated at high dose levels ( 15 and 20 mg ) . At these levels , substantial sedation and mental clouding were reported UNLABELLED We assessed the efficacy of dronabinol ( Marinol capsules ; Solvay Pharmaceuticals , Brussels , Belgium ) , a synthetic Delta(9)-THC ( tetrahydrocannabinol ) , in 30 patients taking opioids for chronic pain to determine its potential analgesic effects as an adjuvant treatment . Phase I of this 2-phase study was a r and omized , single-dose , double-blinded , placebo-controlled , crossover trial in which subjects were r and omly administered either 10 mg or 20 mg of dronabinol or identical placebo capsules over the course of three , 8-hour visits . Baseline self-report measures , hourly ratings of pain intensity , pain relief , pain bothersomeness , treatment satisfaction , mood , side effects , and blood serum levels were obtained . Phase II was an extended open-label titrated trial of dronabinol as add-on medication to patients on stable doses of opioids . Results of the Phase I study showed that patients who received dronabinol experienced decreased pain intensity and increased satisfaction compared with placebo . No differences in benefit were found between the 20 mg and 10 mg doses . In the Phase II trial , titrated dronabinol contributed to significant relief of pain , reduced pain bothersomeness , and increased satisfaction compared with baseline . The incidence of side effects was dose-related . Overall , the use of dronabinol was found to result in additional analgesia among patients taking opioids for chronic noncancer pain . PERSPECTIVE This study examines the effect of adding a cannabinoid to the regimen of patients with chronic pain who report significant pain despite taking stable doses of opioids . The results of our preliminary study suggest that dronabinol , a synthetic THC , may have an additive effect on pain relief Abstract Objective To evaluate the effect of the oral synthetic δ-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis . Design R and omised double blind placebo controlled crossovertrial . Setting Outpatient clinic , University Hospital of Aarhus , Denmark . Participants 24 patients aged between 23 and 55 years with multiple sclerosis and central pain . Intervention Orally administered dronabinol at a maximum doseof 10 mg daily or corresponding placebo for three weeks ( 15 - 21days ) , separated by a three week washout period . Main outcome measure Median spontaneous pain intensity ( numericalrating scale ) in the last week of treatment . Results Median spontaneous pain intensity was significantlylower during dronabinol treatment than during placebo treatment(4.0 ( 25th to 75th centiles 2.3 to 6.0 ) v 5.0 ( 4.0 to 6.4),P = 0.02 ) , and median pain relief score ( numerical rating scale)was higher ( 3.0 ( 0 to 6.7 ) v > 0 ( 0 to 2.3 ) , P = 0.035 ) . Thenumber needed to treat for 50 % pain relief was 3.5 ( 95 % confidenceinterval 1.9 to 24.8 ) . On the SF-36 quality of life scale , thetwo items bodily pain and mental health indicated benefits fromactive treatment compared with placebo . The number of patients with adverse events was higher during active treatment , especiallyin the first week of treatment . The functional ability of themultiple sclerosis patients did not change . Conclusions Dronabinol has a modest but clinical ly relevantanalgesic effect on central pain in patients with multiple sclerosis . Adverse events , including dizziness , were more frequent withdronabinol than with placebo during the first week of treatment This study compared the efficacy of a tetrahydrocannabinol : cannabidiol ( THC : CBD ) extract , a nonopioid analgesic endocannabinoid system modulator , and a THC extract , with placebo , in relieving pain in patients with advanced cancer . In total , 177 patients with cancer pain , who experienced inadequate analgesia despite chronic opioid dosing , entered a two-week , multicenter , double-blind , r and omized , placebo-controlled , parallel-group trial . Patients were r and omized to THC : CBD extract ( n = 60 ) , THC extract ( n = 58 ) , or placebo ( n = 59 ) . The primary analysis of change from baseline in mean pain Numerical Rating Scale ( NRS ) score was statistically significantly in favor of THC : CBD compared with placebo ( improvement of -1.37 vs. -0.69 ) , whereas the THC group showed a nonsignificant change ( -1.01 vs. -0.69 ) . Twice as many patients taking THC : CBD showed a reduction of more than 30 % from baseline pain NRS score when compared with placebo ( 23 [ 43 % ] vs. 12 [ 21 % ] ) . The associated odds ratio was statistically significant , whereas the number of THC group responders was similar to placebo ( 12 [ 23 % ] vs. 12 [ 21 % ] ) and did not reach statistical significance . There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups . No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment . However , the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Question naire showed a worsening in nausea and vomiting with THC : CBD compared with placebo ( P = 0.02 ) , whereas THC had no difference ( P = 1.0 ) . Most drug-related adverse events were mild/moderate in severity . This study shows that THC : CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids A prospect i ve r and omised double blind crossover trial was conducted comparing the new synthetic cannabinoid nabilone with oral domperidone in a group of children receiving repeated identical courses of emetogenic chemotherapy for a variety of malignant diseases . Eighteen of 23 consecutive eligible children , aged 10 months to 17 years , completed the trial . When taking nabilone they experienced significantly fewer vomiting episodes and less nausea , and two thirds expressed a preference for the drug . The most common side effects of treatment with nabilone were somnolence and dizziness , with one patient being disturbed by hallucinations . The results indicate that nabilone is an effective antiemetic for children having chemotherapy , even for young children . It seems to be superior in this respect to domperidone , and although it has a higher incidence of side effects , these are mostly acceptable to patients . It can be recommended as an alternative to conventional antiemetic treatment throughout childhood The objective was to determine whether a cannabis-based medicinal extract ( CBME ) benefits a range of symptoms due to multiple sclerosis ( MS ) . A parallel group , double-blind , r and omized , placebo-controlled study was undertaken in three centres , recruiting 160 out patients with MS experiencing significant problems from at least one of the following : spasticity , spasms , bladder problems , tremor or pain . The interventions were oromucosal sprays of matched placebo , or whole plant CBME containing equal amounts of delta-9- tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) at a dose of 2.5- 120 mg of each daily , in divided doses . The primary outcome measure was a Visual Analogue Scale ( VAS ) score for each patient ’s most troublesome symptom . Additional measures included VAS scores of other symptoms , and measures of disability , cognition , mood , sleep and fatigue . Following CBME the primary symptom score reduced from mean ( SE ) 74.36 ( 11.1 ) to 48.89 ( 22.0 ) following CBME and from 74.31 ( 12.5 ) to 54.79 ( 26.3 ) following placebo [ ns ] . Spasticity VAS scores were significantly reduced by CBME ( Sativex ) in comparison with placebo ( P- 0.001 ) . There were no significant adverse effects on cognition or mood and intoxication was generally mild Objective : To test the effectiveness and long term safety of cannabinoids in multiple sclerosis ( MS ) , in a follow up to the main Cannabinoids in Multiple Sclerosis ( CAMS ) study . Methods : In total , 630 patients with stable MS with muscle spasticity from 33 UK centres were r and omised to receive oral Δ9-tetrahydrocannabinol ( Δ9-THC ) , cannabis extract , or placebo in the main 15 week CAMS study . The primary outcome was change in the Ashworth spasticity scale . Secondary outcomes were the Rivermead Mobility Index , timed 10 metre walk , UK Neurological Disability Score , postal Barthel Index , General Health Question naire-30 , and a series of nine category rating scales . Following the main study , patients were invited to continue medication , double blinded , for up to12 months in the follow up study reported here . Results : Intention to treat analysis of data from the 80 % of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months ( Δ9-THC mean reduction 1·82 ( n = 154 , 95 % confidence interval ( CI ) 0.53 to 3.12 ) , cannabis extract 0.10 ( n = 172 , 95 % CI −0.99 to 1.19 ) , placebo −0.23 ( n = 176 , 95 % CI −1.41 to 0.94 ) ; p = 0.04 unadjusted for ambulatory status and centre , p = 0.01 adjusted ) . There was suggestive evidence for treatment effects of Δ9-THC on some aspects of disability . There were no major safety concerns . Overall , patients felt that these drugs were helpful in treating their disease . Conclusions : These data provide limited evidence for a longer term treatment effect of cannabinoids . A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS 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 . 
    Output:
    