***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: 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 R and omized controlled trials ( RCTs ) in palliative cancer care often experience method ological problems . In this paper we discuss issues of major concern , including recruitment , patient attrition and compliance , arising from an RCT that compared comprehensive palliative care to conventional care .  The main criteria for trial entry were incurable malignant disease and a survival expectancy of between 2 and 9 months . Patients '  health-related quality of life ( HRQL ) , self-assessed by multi-item question naires , was a defined endpoint . The planned number of patients was successfully recruited , although the patients were referred late in the course of their disease so that follow-up tended to be short . Compliance in completing HRQL question naires was good up to 1 month before the patient 's death ; but in the final weeks it was found to drop substantially . Based on our experience , recommendations are given for those planning similar research . Procedures for improving patient recruitment are suggested , stressing the need for local data management , repeated information to referral sources , extensive screening for potentially eligible patients and simple referral routines . Precise inclusion criteria , including prognostic factors other than physicians ' estimates of life expectancy , should be used to ensure a sufficient follow-up period . For HRQL assessment , multi-item question naires can achieve excellent compliance up to 1 month before patients ' death , but in order to evaluate the very final weeks of life we recommend the use of simpler methods Rationale No studies to date have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol in HIV+ marijuana smokers . Objectives The aim of this study was to compare dronabinol ( 0 , 10 , 20 , 30 mg p.o . ) and marijuana [ 0.0 , 1.8 , 2.8 , 3.9 % Δ9-tetrahydrocannabinol ( THC ) ] in two sample s of HIV+ marijuana smokers : those with ( n=15 ) and those without ( n=15 ) a clinical ly significant loss of muscle mass ( < 90 % body cell mass/height ) , which is one component of AIDS wasting . Methods Mood , physical symptoms , self-selected food intake , cardiovascular data , and cognitive task performance were measured before and repeatedly after dronabinol and marijuana administration in eight 7-h sessions . Marijuana and dronabinol were administered in r and omized order using a within-subject , staggered , double-dummy design . Results As compared to placebo , ( 1 ) marijuana ( 1.8 , 2.8 , 3.9 % THC ) and the lower dronabinol doses ( 10 , 20 mg ) were well tolerated ( e.g. , few physical symptoms , significant increases in ratings of “ good drug effect ” ) in both groups of participants ; the highest dose of dronabinol ( 30 mg ) was poorly tolerated in a subset of participants ; ( 2 ) marijuana and dronabinol significantly increased caloric intake in the low bioelectrical impedance analysis ( BIA ) group but not in the normal BIA group ; and ( 3 ) drug effects on cognitive performance were minor . Conclusions These data suggest that for experienced marijuana smokers with clinical ly significant muscle mass loss , both dronabinol ( at acute doses at least four to eight times the current recommendation ) and marijuana produce substantial and comparable increases in food intake without producing adverse effects BACKGROUND A pilot study ( NCT00316563 ) to determine if delta-9-tetrahydrocannabinol ( THC ) can improve taste and smell ( chemosensory ) perception as well as appetite , caloric intake , and quality of life ( QOL ) for cancer patients with chemosensory alterations . PATIENTS AND METHODS Adult advanced cancer patients , with poor appetite and chemosensory alterations , were recruited from two sites and r and omized in a double-blinded manner to receive either THC ( 2.5 mg , Marinol ( ® ) ; Solvay Pharma Inc. , n = 24 ) or placebo oral capsules ( n = 22 ) twice daily for 18 days . Twenty-one patients completed the trial . At baseline and posttreatment , patients completed a panel of patient-reported outcomes : Taste and Smell Survey , 3-day food record , appetite and macronutrient preference assessment s , QOL question naire , and an interview . RESULTS THC and placebo groups were comparable at baseline . Compared with placebo , THC-treated patients reported improved ( P = 0.026 ) and enhanced ( P < 0.001 ) chemosensory perception and food ' tasted better ' ( P = 0.04 ) . Premeal appetite ( P = 0.05 ) and proportion of calories consumed as protein increased compared with placebo ( P = 0.008 ) . THC-treated patients reported increased quality of sleep ( P = 0.025 ) and relaxation ( P = 0.045 ) . QOL scores and total caloric intake were improved in both THC and placebo groups . CONCLUSIONS THC may be useful in the palliation of chemosensory alterations and to improve food enjoyment for cancer patients A placebo-controlled crossover design , with each treatment period lasting 6 weeks , was used to investigate effects of dronabinol in 15 patients with a diagnosis of probable Alzhemer 's disease who were refusing food . Eleven patients completed both study periods ; one patient who died of a heart attack 2 weeks before the end of the study was also included in the analysis . The study was terminated in 3 patients : one developed a gr and mal seizure and 2 developed serious intercurrent infections . Body weight of study subjects increased more during the dronabinol treatment than during the placebo periods . Dronabinol treatment decreased severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first . Adverse reactions observed more commonly during the dronabinol treatment than during placebo periods included euphoria , somnolence and tiredness , but did not require discontinuation of therapy . These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer 's disease The administration of single oral doses of delta‐9‐tetrahydrocannabinol ( THC ) to patients with cancer pain demonstrated a mild analgesic effect . At a dose of 20 mg , however , THC induced side effects that would prohibit its therapeutic use including somnolence , dizziness , ataxia , and blurred vision . Alarming adverse reactions were also observed at this dose . THC , 10 mg , was well tolerated and , despite its sedative effect , may have analgesic potential Rationale Dronabinol ( Δ9tetrahydrocannabinol ) is approved for HIV-related anorexia , yet , little is known about its effects in HIV-positive marijuana smokers . HIV-negative marijuana smokers require higher than recommended dronabinol doses to experience expected effects . Objectives Employing a within-subjects , double-blind , placebo-controlled design , we assessed the effects of repeated high-dose dronabinol in HIV-positive marijuana smokers taking antiretroviral medication . Methods Participants ( N = 7 ) , who smoked marijuana 4.2 ± 2.3 days/week , resided in a residential laboratory for two 16-day stays , receiving  dronabinol  ( 10 mg QID ) in one stay and placebo in the other . Efficacy was assessed with objective ly verified food intake and body weight . Tolerability was measured with sleep , subjective , and cognitive assessment s. For analyses , each inpatient stay was divided into two phases , days 1–8 and 9–16 ; we compared dronabinol ’s effects with placebo in each 8-day phase to investigate tolerance . Results Despite sustained increases in self-reported food cravings  , dronabinol only increased caloric intake in the initial 8 days of dosing . Similarly , sleep quality was improved only in the first 8 days of dosing  .  Dronabinol ’s mood-enhancing effects were sustained across the 16-day inpatient stay . Dronabinol was well tolerated , causing few negative subjective or cognitive effects . Conclusions In HIV-positive marijuana smokers , high dronabinol doses safely and effectively increased caloric intake . However , repeated high-dose dronabinol appeared to result in selective tolerance to these effects . These findings indicate that HIV-positive individuals who smoke marijuana may require higher dronabinol doses than are recommended by the FDA . Future research to establish optimal dosing regimens , and reduce the development of tolerance , is required & NA ;  Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies UNLABELLED Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge . Nabiximols ( Nabiximols is the U.S. Adopted Name [ USAN ] for Sativex [ GW Pharma Ltd , Wiltshire , U.K. ] , which does not yet have an INN ) , a novel cannabinoid formulation , is undergoing investigation as add-on therapy for this population . In a r and omized , double-blind , placebo-controlled , grade d-dose study , patients with advanced cancer and opioid-refractory pain received placebo or nabiximols at a low dose ( 1 - 4 sprays/day ) , medium dose ( 6 - 10 sprays/day ) , or high dose ( 11 - 16 sprays/day ) 
    Output:
    
In one moderate quality study of 469 cancer patients with cancer-associated anorexia , megestrol was superior to cannabinoids in improving appetite , producing > 10 % weight gain and tolerability .
In another study comparing megestrol to dronabinol in HIV patients , megestrol treatment led to higher weight gain without any differences in tolerability and safety .
We found no convincing , unbiased , high quality evidence suggesting that cannabinoids are of value for anorexia or cachexia in cancer or HIV patients