title: The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS) Prospective randomized double-blind trial of nabilone versus domperidone in the treatment of cytotoxic-induced emesis Analgesic effect of delta-9-tetrahydrocannabinol. Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. Nabilone: an alternative antiemetic for cancer chemotherapy. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis Influence of treatment of Tourette syndrome with delta9-tetrahydrocannabinol (delta9-THC) on neuropsychological performance. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study Cannabis in painful HIV-associated sensory neuropathy Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial Effect of Sublingual Application of Cannabinoids on Intraocular Pressure: A Pilot Study Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting* Smoked cannabis for chronic neuropathic pain: a randomized controlled trial MUltiple Sclerosis and Extract of Cannabis: results of the MUSEC trial The Effects of Nabilone on Sleep in Fibromyalgia: Results of a Randomized Controlled Trial Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial Double-blind multiple-dose crossover study of the antiemetic effect of intramuscular levonantradol compared to prochlorperazine. Psychoactive Drugs and Quality of Life Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias). Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy. The Subjective Psychoactive Effects of Oral Dronabinol Studied in a Randomized, Controlled Crossover Clinical Trial for Pain Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial Pain measurements and side effect profile of the novel cannabinoid ajulemic acid Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients Sativex successfully treats neuropathic pain characterised by allodynia: A randomised, double-blind, placebo-controlled clinical trial Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. Double-blind comparison of the antiemetic effects of nabilone and prochlorperazine on chemotherapy-induced emesis. Treatment of Tourette Syndrome with Delta-9-Tetrahydrocannabinol (Δ9-THC): No Influence on Neuropsychological Performance Crossover comparison of the antiemetic efficacy of nabilone and alizapride in patients with nonseminomatous testicular cancer receiving cisplatin therapy Cannabis and cancer chemotherapy. A comparison of oral delta‐9‐thc and prochlorperazine A cross‐over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis Nabilone: an effective antiemetic in patients receiving cancer chemotherapy. Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy. Efficacy of tetrahydrocannabinol in patients refractory to standard antiemetic therapy Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial. Nabilone for the treatment of pain in fibromyalgia. Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. A comparison with prochlorperazine and a placebo. Randomized crossover study of the antiemetic activity of levonantradol and metoclopramide in cancer patients receiving chemotherapy Antiemetic effect of tetrahydrocannabinol. Compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis. A double-blind, controlled trial of nabilone vs. prochlorperazine for refractory emesis induced by cancer chemotherapy. Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial. Effect of Dronabinol on Nutritional Status in HIV Infection A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. A multi-institutional Phase III study of nabilone vs. placebo in chemotherapy-induced nausea and vomiting. Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: a double-blind, crossover trial. [Randomized comparative trial of a new anti-emetic: nabilone, in cancer patients treated with cisplatin]. A randomised multicentre single blind comparison of a cannabinoid anti-emetic (levonantradol) with chlorpromazine in patients receiving their first cytotoxic chemotherapy. [Effect of the synthetic cannabinoid dronabinol on central pain in patients with multiple sclerosis--secondary publication]. Antiemetic effect of delta 9-tetrahydrocannabinol in chemotherapy-associated nausea and emesis as compared to placebo and compazine. Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting.
abstract: 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 . 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 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 Previous studies have suggested that marijuana ( cannabis sativa ) and delta-9-tetrahydrocannabinol ( delta9-THC ) , the major psychoactive ingredient of marijuana , are effective in the therapy of tics and associated behavioral disorders in Tourette Syndrome ( TS ) . Because there is also evidence that cannabis sativa may cause cognitive impairment in healthy users , we performed a r and omized double-blind placebo-controlled crossover trial for delta9-THC in 12 adult TS patients to investigate whether treatment of TS with a single dose of delta9-THC at 5.0 to 10.0 mg causes significant side effects on neuropsychological performance . Using a variety of neuropsychological tests , we found no significant differences after treatment with delta9-THC compared to placebo treatment in verbal and visual memory , reaction time , intelligence , sustained attention , divided attention , vigilance , or mood . Only when using the Symptom Checklist 90-R ( SCL-90-R ) did our data provide evidence for a deterioration of obsessive-compulsive behavior ( OCB ) and a trend towards an increase in phobic anxiety . However , these results should be interpreted with caution as SCL-90-R has known limitations on measuring OCB . We suggest that the increase in phobic anxiety is mainly due to the fact that a single-dose treatment rules out the possibility of administering the dosage slowly . In contrast to results obtained from healthy marijuana users , a single-dose treatment with delta9-THC in patients suffering from TS does not cause cognitive impairment . We therefore suggest that further investigations should concentrate on the effects of a longer-term therapy of TS with delta9-THC Objective : Cannabis may alleviate some symptoms associated with multiple sclerosis ( MS ) . This study investigated the effect of an orally administered st and ardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity . Methods : During their inpatient rehabilitation programme , 57 patients were enrolled in a prospect i ve , r and omized , double-blind , placebo-controlled crossover study of cannabis-extract capsules st and ardized to 2.5 mg tetrahydrocannabinol ( THC ) and 0.9 mg cannabidiol ( CBD ) each . Patients in group A started with a drug escalation phase from 15 to maximally 30 mg THC by 5 mg per day if well tolerated , being on active medication for 14 days before starting placebo . Patients in group B started with placebo for seven days , crossed to the active period ( 14 days ) and closed with a three-day placebo period ( active drug dose escalation and placebo sham escalation as in group A ) . Measures used included daily self-report of spasm frequency and symptoms , Ashworth Scale , Rivermead Mobility Index , 10-m timed walk , nine-hole peg test , paced auditory serial addition test ( PASAT ) , and the digit span test . Results : In the 50 patients included into the intention-to-treat analysis set , there were no statistically significant differences associated with active treatment compared to placebo , but trends in favour of active treatment were seen for spasm frequency , mobility and getting to sleep . In the 37 patients ( per- protocol set ) who received at least 90 % of their prescribed dose , improvements in spasm frequency ( P- 0.013 ) and mobility after excluding a patient who fell and stopped walking were seen ( P- 0.01 ) . Minor adverse events were slightly more frequent and severe during active treatment , and toxicity symptoms , which were generally mild , were more pronounced in the active phase . Conclusion : A st and ardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable side effects in MS patients with persistent spasticity not responding to other drugs Objective : To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model . Methods : Prospect i ve r and omized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy . Patients were r and omly assigned to smoke either cannabis ( 3.56 % tetrahydrocannabinol ) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days . Primary outcome measures included ratings of chronic pain and the percentage achieving > 30 % reduction in pain intensity . Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model . Results : Fifty patients completed the entire trial . Smoked cannabis reduced daily pain by 34 % ( median reduction ; IQR = −71 , −16 ) vs 17 % ( IQR = −29 , 8) with placebo ( p = 0.03 ) . Greater than 30 % reduction in pain was reported by 52 % in the cannabis group and by 24 % in the placebo group ( p = 0.04 ) . The first cannabis cigarette reduced chronic pain by a median of 72 % vs 15 % with placebo ( p < 0.001 ) . Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli ( p ≤ 0.05 ) but appeared to have little effect on the painfulness of noxious heat stimulation . No serious adverse events were reported . Conclusion : Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy . The findings are comparable to oral drugs used for chronic neuropathic pain Background : Spasticity is a common and poorly controlled symptom of multiple sclerosis . Our objective was to determine the short-term effect of smoked cannabis on this symptom . Methods : We conducted a placebo-controlled , crossover trial involving adult patients with multiple sclerosis and spasticity . We recruited participants from a regional clinic or by referral from specialists . We r and omly assigned participants to either the intervention ( smoked cannabis , once daily for three days ) or control ( identical placebo cigarettes , once daily for three days ) . Each participant was assessed daily before and after treatment . After a washout interval of 11 days , participants crossed over to the opposite group . Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale . Our secondary outcomes included patients ’ perception of pain ( as measured using a visual analogue scale ) , a timed walk and changes in cognitive function ( as measured by patient performance on the Paced Auditory Serial Addition Test ) , in addition to ratings of fatigue . Results : Thirty-seven participants were r and omized at the start of the study , 30 of whom completed the trial . Treatment with smoked cannabis result ed in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo ( p < 0.0001 ) . In addition , treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo ( p = 0.008 ) . Scores for the timed walk did not differ significantly between treatment and placebo ( p = 0.2 ) . Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo ( p = 0.003 ) . No serious adverse events occurred during the trial . Interpretation : Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity . Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact 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 ABSTRACT Objective : To compare the efficacy and tolerability of dronabinol , ondansetron , or the combination for delayed chemotherapy-induced nausea and vomiting ( CINV ) in a 5-day , double-blind , placebo-controlled study . Research design and methods : Patients receiving moderately to highly emetogenic chemotherapy received dexamethasone ( 20 mg PO ) , ondansetron ( 16 mg IV ) and either placebo or dronabinol ( 2.5 mg ) prechemotherapy on day 1 . Patients r and omized to active treatment ( dronabinol and /or ondansetron )  also received dronabinol ( 2.5 mg ) after chemotherapy on day 1 . On day 2 , fixed doses of placebo , dronabinol ( 10 mg ) , ondansetron ( 16 mg ) , or combination therapy were administered . On days 3–5 , patients received placebo , flexible doses of dronabinol ( 10–20 mg ) , ondansetron ( 8–16 mg ) , or dronabinol and ondansetron ( 10–20 mg dronabinol , 8–16 mg ondansetron ) . Main outcome measures : Total response ( TR = nausea intensity < 5 mm on visual analog scale , no vomiting/retching , no rescue antiemetic ) , nausea ( occurrence and intensity ) and vomiting/retching episodes . Results : Sixty-four patients were r and omized ; 61 analyzed for efficacy . TR was similar with dronabinol ( 54 % ) , ondansetron ( 58 % ) , and combination therapy ( 47 % ) versus placebo ( 20 % ) . Nausea absence was significantly greater in active treatment groups ( dronabinol , 71 % ; ondansetron , 64 % ; combination therapy , 53 % ) versus placebo ( 15 % ; p < 0.05 vs. placebo for all ) . Nausea intensity and vomiting/retching were lowest in patients treated with dronabinol . Active treatments were well tolerated . The low number of patients due to slow enrollment limits the interpretation of these data . Conclusions : Dronabinol or ondansetron was similarly effective for the treatment of CINV . Combination therapy with dronabinol and ondansetron was not more effective than either agent alone . Active treatments were well tolerated Background : Chronic neuropathic pain affects 1%–2 % of the adult population and is often refractory to st and ard pharmacologic treatment . Patients with chronic pain have reported using smoked cannabis to relieve pain , improve sleep and improve mood . Methods : Adults with post-traumatic or postsurgical neuropathic pain were r and omly assigned to receive cannabis at four potencies ( 0 % , 2.5 % , 6 % and 9.4 % tetrahydrocannabinol ) over four 14-day periods in a crossover trial . Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle , followed by a nine-day washout period . Daily average pain intensity was measured using an 11-point numeric rating scale . We recorded effects on mood , sleep and quality of life , as well as adverse events . Results : We recruited 23 participants ( mean age 45.4 [ st and ard deviation 12.3 ] years , 12 women [ 52 % ] ) , of whom 21 completed the trial . The average daily pain intensity , measured on the 11-point numeric rating scale , was lower on the prespecified primary contrast of 9.4 % v. 0 % tetrahydrocannabinol ( 5.4 v. 6.1 , respectively ; difference = 0.7 , 95 % confidence interval [ CI ] 0.02–1.4 ) . Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief . Participants receiving 9.4 % tetrahydrocannabinol reported improved ability to fall asleep ( easier , p = 0.001 ; faster , p < 0.001 ; more drowsy , p = 0.003 ) and improved quality of sleep ( less wakefulness , p = 0.01 ) relative to 0 % tetrahydrocannabinol . We found no differences in mood or quality of life . The most common drug-related adverse events during the period when participants received 9.4 % tetrahydrocannabinol were headache , dry eyes , burning sensation in areas of neuropathic pain , dizziness , numbness and cough . Conclusion : A single inhalation of 25 mg of 9.4 % tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain , improved sleep and was well tolerated . Further long-term safety and efficacy studies are indicated . ( International St and ard R and omised Controlled Trial Register no. IS RCT N68314063 Objective Multiple sclerosis ( MS ) is associated with chronic symptoms , including muscle stiffness , spasms , pain and insomnia . Here we report the results of the Multiple Sclerosis and Extract of Cannabis ( MUSEC ) study that aim ed to substantiate the patient based findings of previous studies . Patients and methods Patients with stable MS at 22 UK centres were r and omised to oral cannabis extract ( CE ) ( N=144 ) or  placebo ( N=135 ) , stratified by centre , walking ability and use of antispastic medication . This double blind , placebo controlled , phase III study had a screening period , a 2 week dose titration phase from 5 mg to a maximum of 25 mg of tetrahydrocannabinol daily and a 10 week maintenance phase . The primary outcome measure was a category rating scale ( CRS ) measuring patient reported change in muscle stiffness from baseline . Further CRSs assessed body pain , spasms and sleep quality . Three vali date d MS specific patient reported outcome measures assessed aspects of spasticity , physical and psychological impact , and walking ability . Results The rate of relief from muscle stiffness after 12 weeks was almost twice as high with CE than with placebo ( 29.4 % vs 15.7 % ; OR 2.26 ; 95 % CI 1.24 to 4.13 ; p=0.004 , one sided ) . Similar results were found after 4 weeks and 8 weeks , and also for all further CRSs . Results from the MS scales supported these findings . Conclusion The study met its primary objective to demonstrate the superiority of CE over placebo in the treatment of  muscle stiffness in MS . This was supported by results for secondary efficacy variables . Adverse events in participants treated with CE were consistent with the known side effects of cannabinoids . No new safety concerns were observed . Trial registration number NCT00552604 BACKGROUND : Sleep disorders affect many patients with chronic pain conditions . Cannabis has been reported by several patient population s to help sleep . We evaluated the safety and efficacy of nabilone , a synthetic cannabinoid , on sleep disturbance in fibromyalgia ( FM ) , a disease characterized by widespread chronic pain and insomnia . METHODS : We conducted a r and omized , double-blind , active-control , equivalency crossover trial to compare nabilone ( 0.5–1.0 mg before bedtime ) to amitriptyline ( 10–20 mg before bedtime ) in patients with FM with chronic insomnia . Subjects received each drug for 2 wk with a 2-wk washout period . The primary outcome was sleep quality , measured by the Insomnia Severity Index and the Leeds Sleep Evaluation Question naire . Secondary outcomes included pain , mood , quality of life , and adverse events ( AEs ) . RESULTS : Thirty-one subjects were enrolled and 29 completed the trial ( 26 women , mean age 49.5 yr ) . Although sleep was improved by both amitriptyline and nabilone , nabilone was superior to amitriptyline ( Insomnia Severity Index difference = 3.2 ; 95 % confidence interval = 1.2–5.3 ) . Nabilone was marginally better on the restfulness ( Leeds Sleep Evaluation Question naire difference = 0.5 [ 0.0–1.0 ] ) but not on wakefulness ( difference = 0.3 [ −0.2 to 0.8 ] ) . No effects on pain , mood , or quality of life were observed . AEs were mostly mild to moderate and were more frequent with nabilone . The most common AEs for nabilone were dizziness , nausea , and dry mouth . CONCLUSIONS : Nabilone is effective in improving sleep in patients with FM and is well tolerated . Low-dose nabilone given once daily at bedtime may be considered as an alternative to amitriptyline . Longer trials are needed to determine the duration of effect and to characterize long-term safety BACKGROUND Multiple sclerosis is associated with muscle stiffness , spasms , pain , and tremor . Much anecdotal evidence suggests that cannabinoids could help these symptoms . Our aim was to test the notion that cannabinoids have a beneficial effect on spasticity and other symptoms related to multiple sclerosis . METHODS We did a r and omised , placebo-controlled trial , to which we enrolled 667 patients with stable multiple sclerosis and muscle spasticity . 630 participants were treated at 33 UK centres with oral cannabis extract ( n=211 ) , Delta9-tetrahydrocannabinol ( Delta9-THC ; n=206 ) , or placebo ( n=213 ) . Trial duration was 15 weeks . Our primary outcome measure was change in overall spasticity scores , using the Ashworth scale . Analysis was by intention to treat . FINDINGS 611 of 630 patients were followed up for the primary endpoint . We noted no treatment effect of cannabinoids on the primary outcome ( p=0.40 ) . The estimated difference in mean reduction in total Ashworth score for participants taking cannabis extract compared with placebo was 0.32 ( 95 % CI -1.04 to 1.67 ) , and for those taking Delta9-THC versus placebo it was 0.94 ( -0.44 to 2.31 ) . There was evidence of a treatment effect on patient-reported spasticity and pain ( p=0.003 ) , with improvement in spasticity reported in 61 % ( n=121 , 95 % CI 54.6 - 68.2 ) , 60 % ( n=108 , 52.5 - 66.8 ) , and 46 % ( n=91 , 39.0 - 52.9 ) of participants on cannabis extract , Delta9-THC , and placebo , respectively . INTERPRETATION Treatment with cannabinoids did not have a beneficial effect on spasticity when assessed with the Ashworth scale . However , though there was a degree of unmasking among the patients in the active treatment groups , objective improvement in mobility and patients ' opinion of an improvement in pain suggest cannabinoids might be clinical ly useful & NA ; The objective was to investigate the effectiveness of cannabis‐based medicines for treatment of  chronic pain associated with brachial plexus root avulsion . This condition is an excellent human model of central neuropathic pain as it represents an unusually homogenous group in terms of anatomical location of injury , pain descriptions and patient demographics . Forty‐eight patients with at least one avulsed root and baseline pain score of four or more on an 11‐point ordinate scale participated in a r and omised , double‐blind , placebo‐controlled , three period crossover study . All patients had intractable symptoms regardless of current analgesic therapy . Patients entered a baseline period of 2 weeks , followed by three , 2‐week treatment periods during each of which they received one of three oromucosal spray preparations . These were placebo and two whole plant extracts of Cannabis sativa L. : GW‐1000‐02 ( Sativex ® ) , containing Δ9tetrahydrocannabinol (THC):cannabidiol ( CBD ) in an approximate 1:1 ratio and GW‐2000‐02 , containing primarily THC . The primary outcome measure was the mean pain severity score during the last 7 days of treatment . Secondary outcome measures included pain related quality of life assessment s. The primary outcome measure failed to fall by the two points defined in our hypothesis . However , both this measure and measures of sleep showed statistically significant improvements . The study medications were generally well tolerated with the majority of adverse events , including intoxication type reactions , being mild to moderate in severity and resolving spontaneously . Studies of longer duration in neuropathic pain are required to confirm a clinical ly relevant , improvement in the treatment of this condition Twenty cancer patients who received chemotherapy  were entered into a double-blind crossover design antiemetic study comparing 1 mg levonantradol , an investigational synthetic cannabinoid , to 10 mg prochlorperazine .  Sixteen patients completed the crossover . For each antiemetic course , four doses of each study medication were given intramuscularly 2 hours before chemotherapy and then 2 , 6 , and 10 hours after chemotherapy administration . There were no statistical differences in patients ' responses to levonantradol and prochlorperazine . The frequency of side effects was greater with levonantradol than with prochlorperazine . The most common side effect of levonantradol were somnolence , dry mouth , dizziness , tachycardia , postural hypotension , and blurred vision , while those for prochlorperazine were somnolence , dry mouth , and tachycardia This study was performed on a representative sample of the Danish population in order to investigate the connection to the use of psychoactive drugs and quality of life ( QOL ) by way of a question naire-based survey . The question naire was mailed in February 1993 to 2,460 persons aged between 18 and 88 , r and omly selected from the CPR ( Danish Central Register ) , and 7,222 persons from the Copenhagen Perinatal Birth Cohort 1959—61.A total of 1,501 persons between the ages 18 and 88 years and 4,626 persons between the ages 31 and 33 years returned the question naire ( response rates of 61.0 % and 64.1 % , respectively ) . Variables investigated in this study were ten different  psychotropic drugs and quality of life . Our study showed that over half the Danish population had used illegal psychotropic drugs . The most commonly used was cannabis ( marijuana ) though experience of this drug appeared not to co-vary with QOL to any significant extent . Cocaine , amphetamine , and psilocybin had been used by 1.2 to 3.3 % of the population and this varied with QOL to a clear albeit small extent . LSD has been used by 1.2 % of the population and the users had a QOL score 10 % lower than those who had never used psychotropic drugs . The group with the lowest quality of life was found to be persons who had used heroin , morphine , methadone , and a mixture of alcohol and tranquilizers ( 10—20 % below the group with the highest quality of life ) Nabilone , a synthetic cannabinoid , and Prochlorperazine were compared in a double-blind crossover study of 34 patients with lung cancer undergoing a 3-day schedule of chemotherapy with Cyclophosphamide , Adriamycin and Etoposide .  Symptom scores were significantly better for patients on nabilone for nausea , retching and vomiting ( P less than 0.05 ) . Fewer subjects vomited with nabilone ( P = 0.05 ) and the number of vomiting episodes was lower ( P less than 0.05 ) ; no patients on nabilone required additional parenteral anti-emetic . More patients preferred nabilone for anti-emetic control ( P less than 0.005 ) . Adverse effects common with nabilone were drowsiness ( 57 % ) , postural dizziness ( 35 % ) and lightheadedness ( 18 % ) . Euphoria was seen in 14 % and a " high " in 7 % . Erect systolic blood pressure was lower in nabilone patients on Day 1 ( P = 0.05 ) but postural hypotension was a major problem in only 7 % . Nabilone is an effective oral anti-emetic drug for moderately toxic chemotherapy , but the range and unpredictability of its side-effects warrant caution in its use In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVES To assess the efficacy of a cannabis-based medicine ( CBM ) in the treatment of  pain due to rheumatoid arthritis ( RA ) . METHODS We compared a CBM ( Sativex ) with placebo in a r and omized , double-blind , parallel group study in 58 patients over 5 weeks of treatment . The CBM was administered by oromucosal spray in the evening and assessment s were made the following morning . Efficacy outcomes assessed were pain on movement , pain at rest , morning stiffness and sleep quality measured by a numerical rating scale , the Short-Form McGill Pain Question naire ( SF-MPQ ) and the DAS28 measure of disease activity . RESULTS Seventy-five patients were screened and 58 met the eligibility criteria . Thirty-one were r and omized to the CBM and 27 to placebo .  Mean ( S.D. ) daily dose achieved in the final treatment week was 5.4 ( 0.84 ) actuations for the CBM and 5.3 ( 1.18 ) for placebo . In comparison with placebo , the CBM produced statistically significant improvements in pain on movement , pain at rest , quality of sleep , DAS28 and the SF-MPQ pain at present component . There was no effect on morning stiffness but baseline scores were low . The large majority of adverse effects were mild or moderate , and there were no adverse effect-related withdrawals or serious adverse effects in the active treatment group . CONCLUSIONS In the first ever controlled trial of a CBM in RA , a significant analgesic effect was observed and disease activity was significantly suppressed following Sativex treatment . Whilst the differences are small and variable across the population , they represent benefits of clinical relevance and show the need for more detailed investigation in this indication BACKGROUND Peripheral neuropathic pain ( PNP ) associated with allodynia poses a significant clinical challenge . The efficacy of Δ(9 ) -tetrahydrocannabinol/cannabidiol ( THC/CBD ) oromucosal spray , a novel cannabinoid formulation , was investigated in this 15-week r and omized , double-blind , placebo-controlled parallel group study . METHODS In total , 303 patients with PNP associated with allodynia were screened ; 128 were r and omized to THC/CBD spray and 118 to placebo , in addition to their current analgesic therapy . The co- primary efficacy endpoints were the 30 % responder rate in PNP 0 - 10 numerical rating scale ( NRS ) score and the mean change from baseline to the end of treatment in this score . Various key secondary measures of pain and functioning were also investigated . RESULTS At the 30 % responder level , there were statistically significant treatment differences in favour of THC/CBD spray in the full analysis ( intention-to-treat ) data set [ p = 0.034 ; 95 % confidence interval ( CI ) : 1.05 - 3.70 ] . There was also a reduction in mean PNP 0 - 10 NRS scores in both treatment groups that was numerically higher in the THC/CBD spray group , but which failed to reach statistical significance . Secondary measures of sleep quality 0 - 10 NRS score ( p = 0.0072 ) and Subject Global Impression of Change ( SGIC ) ( p = 0.023 ) also demonstrated statistically significant treatment differences in favour of THC/CBD spray treatment . CONCLUSIONS These findings demonstrate that , in a meaningful proportion of otherwise treatment-resistant patients , clinical ly important improvements in pain , sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray . THC/CBD spray was well tolerated and no new safety concerns were identified 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 UNLABELLED A r and omized , double-blinded , placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis . In a crossover design , each participant was exposed to 4 single dosing sessions of placebo or to low ( 1 % tetrahydrocannabinol [ THC ] ) , medium ( 4 % THC ) , or high ( 7 % THC ) doses of cannabis . Baseline spontaneous pain , evoked pain , and cognitive testing were performed . Subjects were then administered aerosolized cannabis or placebo and the pain intensity and subjective " highness " score was measured at 5 , 15 , 30 , 45 , and 60 minutes and then every 30 minutes for an additional 3 hours . Cognitive testing was performed at 5 and 30 minutes and then every 30 minutes for an additional 3 hours . The primary analysis compared differences in spontaneous pain over time between doses using linear mixed effects models . There was a significant difference in spontaneous pain scores between doses ( P < .001 ) . Specific significant comparisons were placebo versus low , medium , and high doses ( P = .031 , .04 , and < .001 , respectively ) and high versus low and medium doses ( both P < .001 ) . There was a significant effect of the high dose on foam brush and von Frey evoked pain ( both P < .001 ) . There was a significant negative effect ( impaired performance ) of the high dose on 2 of the 3 neuropsychological tests ( Paced Auditory Serial Addition Test , Trail Making Test Part B. PERSPECTIVE This small , short-term , placebo-controlled trial of inhaled cannabis demonstrated a dose-dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain . This adds preliminary evidence to support further research on the efficacy of the cannabinoids in neuropathic pain Background : Many cannabinoid medications are approved in North America or in phase III trials , such as dronabinol , nabilone , or nabiximols . Little is known about their subjective psychoactive effects when used for pain management . We hypothesized that when used for pain , dronabinol has psychoactive effects in a dose-response relationship , whose peak effects are comparable with smoking marijuana . Methods : This was a r and omized controlled trial of single dose placebo , 10 or 20 mg dronabinol in 30 chronic noncancer pain patients taking opioids and not using marijuana . Participants completed the Addiction Research Center Inventory ( ARCI ) hourly for 8 hours during 3 monitored sessions . Comparison sample was the ARCI ratings in participants with no pain ( N=20 ) , monitored every 30 minutes after smoking a 1.99 % THC ( low ) and a 3.51 % ( high strength ) marijuana cigarette . Results : The 10 and 20 mg dronabinol doses had significantly elevated scores over time on 4/5 subscales versus placebo ( P<0.05 ) . Average daily morphine use , total pain relief ( TOTPAR ) , age , sex , and baseline pain level were not significant covariates . ARCI peak effects at 2 hours were similar to peak effects of smoked marijuana at 30 minutes ( P=0.80 , 10 mg = low strength , 20 mg = high strength ) . Conclusions : In pain patients , oral dronabinol has similar psychoactive effects to smoking marijuana . This risk must be considered in any decision to prescribe cannabinoid medications for pain Despite management with opioids and other pain modifying therapies , neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals . Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception . We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV . This was a phase II , double-blind , placebo-controlled , crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy ( DSPN ) . Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes ; they continued on their pre study analgesic regimens throughout the trial . Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting . Treatments were placebo and active cannabis ranging in potency between 1 and 8 % Δ-9-tetrahydrocannabinol , four times daily for 5 consecutive days during each of 2 treatment weeks , separated by a 2-week washout . The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale ( DDS ) from a pretreatment baseline to the end of each treatment week . Secondary measures included assessment s of mood and daily functioning . Of 127 volunteers screened , 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments . Among the completers , pain relief was greater with cannabis than placebo ( median difference in DDS pain intensity change , 3.3 points , effect size=0.60 ; p=0.016 ) . The proportions of subjects achieving at least 30 % pain relief  with cannabis versus placebo were 0.46 ( 95%CI 0.28 , 0.65 ) and 0.18 ( 0.03 , 0.32 ) . Mood and daily functioning improved to a similar extent during both treatment periods . Although most side effects were mild and self-limited , two subjects experienced treatment-limiting toxicities . Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN Pre clinical findings on ajulemic acid ( AJA ) showed analgesic and anti-allodynic effects without psychoactive properties making it an appealing substance for the treatment of pain . A recently published r and omized double-blind crossover clinical trial described the pain-reducing effects and side effect profile of AJA on 21 patients with chronic neuropathic pain . In this report from this same sample the effects of AJA on the mechanical hypersensitivity , on pain , and on psychological and physical performance were further characterized . During a 5-week study period , patients were divided into two 7-day treatment groups receiving either AJA or placebo capsules first , respectively . All patients received 40 and 80 mg of AJA or placebo daily in each treatment period . Pain measurements included the determination of mechanical hypersensitivity using the von Frey hair method as well as the visual analog scale ( VAS ) , for which the number needed to treat ( NNT ) was calculated . The side effect profile of the compound was evaluated using psychotropic and physical measurements as well as obtaining reports on possible subjective side effects . The results showed no significant reduction in mechanical hypersensitivity ( p=0.052 ) , although a tendency towards pain reduction could be seen . The VAS score showed significant pain reduction ( p=0.021 ) and NNT values for 30 % pain relief were 2.14 for the first treatment group and 5.29 for the second treatment group . No significant findings were observed regarding psychotropic or physical measurements . Reported subjective side effects were mainly dry mouth , tiredness and dizziness and did not increase with dose elevation . Overall , these study findings indicate that AJA shows pain-reducing effects on patients with chronic neuropathic pain without clinical ly relevant psychotropic or physical side effects Objective To compare the analgesic efficacy and side effects of the synthetic cannabinoid nabilone with those of the weak opioid dihydrocodeine for chronic neuropathic pain . Design R and omised , double blind , crossover trial of 14 weeks ’ duration comparing dihydrocodeine and nabilone . Setting Outpatient units of three hospitals in the United Kingdom . Participants 96 patients with chronic neuropathic pain , aged 23 - 84 years . Main outcome measures The primary outcome was difference between nabilone and dihydrocodeine in pain , as measured by the mean visual analogue score computed over the last 2 weeks of each treatment period . Secondary outcomes were changes in mood , quality of life , sleep , and psychometric function . Side effects were measured by a question naire . Intervention Patients received a maximum daily dose of 240 mg dihydrocodeine or 2 mg nabilone at the end of each escalating treatment period of 6 weeks . Treatment periods were separated by a 2 week washout period . Results Mean baseline visual analogue score was 69.6 mm ( range 29.4 - 95.2 ) on a 0 - 100 mm scale . 73 patients were included in the available case analysis and 64 patients in the per protocol analysis . The mean score was 6.0 mm longer for nabilone than for dihydrocodeine ( 95 % confidence interval 1.4 to 10.5 ) in the available case analysis and 5.6 mm ( 10.3 to 0.8 ) in the per protocol analysis . Side effects were more frequent with nabilone . Conclusion Dihydrocodeine provided better pain relief than the synthetic cannabinoid nabilone and had slightly fewer side effects , although no major adverse events occurred for either drug . Trial registration Current Controlled Trials IS RCT N15330757 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 ) . Average pain , worst pain and sleep disruption were measured daily during 5 weeks of treatment ; other question naires measured quality of life and mood .  A total of 360 patients were r and omized ; 263 completed . There were no baseline differences across groups . The 30 % responder rate primary analysis was not significant for nabiximols versus placebo ( overall P = .59 ) . A secondary continuous responder analysis of average daily pain from baseline to end of study demonstrated that the proportion of patients reporting analgesia was greater for nabiximols than placebo overall ( P = .035 ) , and specifically in the low-dose ( P = .008 ) and medium-dose ( P = .039 ) groups . In the low-dose group , results were similar for mean average pain ( P = .006 ) , mean worst pain ( P = .011 ) , and mean sleep disruption ( P = .003 ) . Other question naires showed no significant group differences . Adverse events were dose-related and only the high-dose group compared unfavorably with placebo . This study supports the efficacy and safety of nabiximols at the 2 lower-dose levels and provides important dose information for future trials . PERSPECTIVE Nabiximols , a novel cannabinoid formulation , may be a useful add-on analgesic for patients with opioid-refractory cancer pain . A r and omized , double-blind , placebo-controlled , grade d-dose study demonstrated efficacy and safety at low and medium doses Generalized Social Anxiety Disorder ( SAD ) is one of the most common anxiety conditions with impairment in social life . Cannabidiol ( CBD ) , one major non-psychotomimetic compound of the cannabis sativa plant , has shown anxiolytic effects both in humans and in animals . This preliminary study aim ed to compare the effects of a simulation public speaking test ( SPST ) on healthy control ( HC ) patients and treatment-naïve SAD patients who received a single dose of CBD or placebo .  A total of 24 never-treated patients with SAD were allocated to receive either CBD ( 600 mg ; n=12 ) or placebo ( placebo ; n=12 ) in a double-blind r and omized design 1 h and a half before the test . The same number of HC ( n=12 ) performed the SPST without receiving any medication . Each volunteer participated in only one experimental session in a double-blind procedure . Subjective ratings on the Visual Analogue Mood Scale ( VAMS ) and Negative Self-Statement scale ( SSPS-N ) and physiological measures ( blood pressure , heart rate , and skin conductance ) were measured at six different time points during the SPST . The results were su bmi tted to a repeated- measures analysis of variance . Pretreatment with CBD significantly reduced anxiety , cognitive impairment and discomfort in their speech performance , and significantly decreased alert in their anticipatory speech . The placebo group presented higher anxiety , cognitive impairment , discomfort , and alert levels when compared with the control group as assessed with the VAMS . The SSPS-N scores evidence d significant increases during the testing of placebo group that was almost abolished in the CBD group . No significant differences were observed between CBD and HC in SSPS-N scores or in the cognitive impairment , discomfort , and alert factors of VAMS . The increase in anxiety induced by the SPST on subjects with SAD was reduced with the use of CBD , result ing in a similar response as the HC Abstract Cannabinoids are known to have analgesic properties . We evaluated the effect of oro‐mucosal sativex , ( THC : CBD ) , an endocannabinoid system modulator , on pain and allodynia , in 125 patients with neuropathic pain of peripheral origin in a five‐week , r and omised , double‐blind , placebo‐controlled , parallel design trial . Patients remained on their existing stable analgesia . A self‐titrating regimen was used to optimise drug administration . Sixty‐three patients were r and omised to receive sativex and 62 placebo .  The mean reduction in pain intensity scores ( primary outcome measure ) was greater in patients receiving sativex than placebo ( mean adjusted scores −1.48 points vs. −0.52 points on a 0–10 Numerical Rating Scale ( p = 0.004 ; 95 % CI : −1.59 , −0.32 ) . Improvements in Neuropathic Pain Scale composite score ( p = 0.007 ) , sleep NRS ( p = 0.001 ) , dynamic allodynia ( p = 0.042 ) , punctate allodynia ( p = 0.021 ) , Pain Disability Index ( p = 0.003 ) and Patient ’s Global Impression of Change ( p < 0.001 ) were similarly greater on sativex vs. placebo . Sedative and gastrointestinal side effects were reported more commonly by patients on active medication . Of all participants , 18 % on sativex and 3 % on placebo withdrew during the study . An open‐label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks 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 The antiemetic effect of oral nabilone , a synthetic cannabinoid , given at a dose of 2 mg every 12 hours was compared to oral slow-release capsules of prochlorperazine given at a dose of 10 mg every 12 hours by a double-blind crossover method in 37 patients receiving cancer chemotherapy .  Patients received one of the following as the primary emetic stimulus : high-dose cis-dichlorodiammineplatinum(II ) ( DDP ) , low-dose DDP , mechlorethamine , streptozotocin , actinomycin D , or DTIC . Although results varied according to strength of emetic stimulus received , both nabilone and prochlorperazine appeared to produce antiemetic effects . Eighteen of the 37 patients achieved a complete or partial elimination of symptoms : seven with nabilone alone , three with prochlorperazine alone , and eight with each drug . Nabilone appeared to be the more effective antiemetic for patients who received chemotherapy agents other than high dose DDP ; it was equivalent to prochlorperazine for those who did receive high-dose DDP . Side effects from prochlorperazine were limited to mild drowsiness occurring among 35 % of the patients . The side effects from nabilone were drowsiness and dizziness which occurred frequently and were dose-limiting in 25 % of patients Previous studies provide evidence that marijuana ( Cannabis sativa ) and delta-9-tetrahydrocannabinol ( Δ9-THC ) , the major psychoactive ingredient of marijuana , respectively , are effective in the treatment of tics and behavioral problems in Tourette syndrome ( TS ) . It , therefore , has been speculated that the central cannabinoid receptor system might be involved in TS pathology . However , in healthy marijuana users there is an ongoing debate as to whether the use of cannabis causes acute and /or long-term cognitive deficits . In this r and omized double-blind placebo-controlled study , we investigated the effect of a treatment with up to 10 mg Δ9-THC over a 6-week period on neuropsychological performance in 24 patients suffering from TS . During medication and immediately as well as 5–6 weeks after withdrawal of Δ9-THC treatment , no detrimental effect was seen on learning curve , interference , recall and recognition of word lists , immediate visual memory span , and divided attention . Measuring immediate verbal memory span , we even found a trend towards a significant improvement during and after treatment . Results from this study corroborate previous data suggesting that in patients suffering from TS , treatment with Δ9-THC  causes neither acute nor long-term cognitive deficits . Larger and longer- duration controlled studies are recommended to provide more information on the adverse effect profile of THC in patients suffering from TS Summary Twenty nonseminomatous testicular cancer patients not pretreated with emetogenic chemotherapy  were included in a crossover study of antiemetic therapy . Patients were r and omly assigned to receive either nabilone ( 2 × 2 mg/day ) or alizapride ( 3 × 150 mg/day ) prior to beginning lowdose cisplatin chemotherapy . Patients on nabilone had significantly fewer episodes of emesis than those on alizapride ( medians , 1.1 vs 2.9;p<0.01 ) . Nabilone was superior to alizapride in giving complete relief from nausea ( medians , 65 % vs 30%;p<0.01 ) , and was more effective in shortening the duration of nausea ( medians , 1.3 h vs 5.1 h;p<0.01 ) ; however , it caused more adverse effects . It is concluded that nabilone has greater antiemetic activity than alizapride in young patients receiving low-dose cisplatin chemotherapy . Nabilone dosage should be reduced to decrease the incidence and degree of adverse reactions while leaving the definite antiemetic activity unchanged Delta‐9‐tetrahydrocannabinol ( THC ) and prochlorperazine ( Compazine ) were found to be equally efficacious in reducing nausea and vomiting associated with cancer chemotherapy across a wide range of chemotherapeutic regimens and tumor types . Both drugs were administered orally one hour before chemotherapy , then every four hours for a total of four doses . Compazine was administered in a fixed dose of 10 mg ; THC was administered by body surface area ( BSA ) : BSA < 1.4 m2 = 7.5 mg ; BSA 1.4‐1.8 m2 = 10 mg ; and BSA > 1.8 m2 = 12.5 mg . Two hundred and fourteen subjects ( 75 % of whom had previously received Compazine with varying results ) were evaluated employing a double‐blind , crossover design . Additional parameters evaluated were study drug effects on appetite , food intake , mood , activity , relaxation , interaction , and concentration . There were significant drug effects with THC : less ability to concentrate ( P < 0.01 ) , less social interaction ( P < 0.05 ) , and less activity ( P < 0.05 ) . There were no significant differences between the two drugs in the level of food intake or appetite .  Patients of all ages did equally well on both drugs . Neither past marijuana use nor past Compazine use were related to study drug efficacy . Those patients who correctly identified their THC cycle did better on THC versus those who could not correctly identify which antiemetic they had received ( P < 0.05 ) . There were more drug‐related effects associated with THC , but these did not reduce the patients ' preference for the drug , and were associated with nausea reduction ( P < 0.05 ) AN ANTI-EMETIC DRUG , NABILONE , a synthetic cannabinoid , has been compared with prochlorperazine in 24 lung cancer patients receiving cancer chemotherapy . Each of the drugs studied was given orally every 12 hours , starting the night before chemotherapy , during one of two consecutive identical chemotherapy cycles in accordance with a double-blind crossover r and om order assignment . Single doses were 2 mg of nabilone , or 15 mg of prochlorperazine . The chemotherapeutic regimens given included the following drugs in various combinations : Cis-platinum , vincristine , cyelophosphamide , adriamycin , vinde-sine , and etoposide ( VP16 ) . Nabilone was significantly superior to prochlorperazine in the reduction of vomiting episodes . Side effects , mainly vertigo , were evident in nearly half of the patients after nabilone , and three patients were withdrawn from the study due to decreased coordination and hallucinations after nabilone .  Side effects from prochlorperazine were limited to mild drowsiness in one patient . Two-thirds of the patients preferred nabilone to prochlorperazine . We conclude that nabilone is a moderately effective anti-emetic drug , but that the unpredictability of its side effects call for careful patient information , especially with elderly out patients . We recommend that at least after the first dose of nabilone , the patient should be kept under close observation during 4 hours Abstract Central neuropathic pain ( CNP ) occurs in many multiple sclerosis ( MS ) patients . The provision of adequate pain relief to these patients can very difficult . Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol ( CBD ) oromucosal spray ( USAN name , nabiximols ; Sativex , GW Pharmaceuticals , Salisbury , Wiltshire , UK ) , to alleviate CNP . Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment , in a double-blind manner , for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain . This parallel-group phase of the study was then followed by an 18-week r and omized-withdrawal study ( 14-week open-label treatment period plus a double-blind 4-week r and omized-withdrawal phase ) to investigate time to treatment failure and show maintenance of efficacy . A total of 339 patients were r and omized to phase A ( 167 received THC/CBD spray and 172 received placebo )  . Of those who completed phase A , 58 entered the r and omized-withdrawal phase . The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met , with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo ( p = 0.234 ) . However , an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point ( p = 0.046 ) . During the r and omized-withdrawal phase , the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray , with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group ( p = 0.04 ) . The mean change from baseline in Pain Numerical Rating Scale ( NRS ) ( p = 0.028 ) and sleep quality NRS ( p = 0.015 ) scores , both secondary endpoints in phase B , were also statistically significant compared to placebo , with estimated treatment differences of −0.79 and 0.99 points , respectively , in favor of THC/CBD spray treatment . The results of the current investigation were equivocal , with conflicting findings in the two phases of the study . While there were a large proportion of responders to THC/CBD spray treatment during the phase A double-blind period , the primary endpoint was not met due to a similarly large number of placebo responders . In contrast , there was a marked effect in phase B of the study , with an increased time to treatment failure in the THC/CBD spray group compared to placebo . These findings suggest that further studies are required to explore the full potential of THC/CBD spray in these patients Eighty evaluable patients receiving chemotherapy were entered on a r and om prospect i ve double-blind study to evaluate the effectiveness of nabilone , a synthetic cannabinoid , compared to prochlorperazine . Most of these patients received cisplatin , a drug that universally produces severe nausea and vomiting , as part of a combination chemotherapy regimen . The patients served as their own controls , receiving either nabilone or prochlorperazine during two consecutive treatment courses with the identical chemotherapy . Side effects consisting of hypotension and lethargy were more pronounced with nabilone .  Toxicity , in general , did not preclude antiemetic treatment and in no way interfered with chemotherapy . Sixty patients ( 75 per cent ) reported nabilone to be more effective than prochlorperazine for relief of nausea and vomiting . Of these 60 patients , 46 required further chemotherapy and continued taking nabilone as the antiemetic of choice Two double-blind , crossover trials comparing the antiemetic effectiveness of nabilone , a new synthetic cannabinoid , with that of prochlorperazine were conducted in patients with severe nausea and vomiting associated with anticancer chemotherapy .  Of 113 patients evaluated , 90 ( 80 per cent ) responded to nabilone therapy  , whereas only 36 ( 32 per cent ) responded to prochlorperazine ( P less than 0.001 ) . Complete relief of symptoms was infrequent , occurring only in nine patients ( 8 per cent ) given nabilone . When both drugs were compared , both nausea ( P less than 0.01 ) and vomiting episodes ( P less than 0.001 ) were significantly lower in patients given nabilone . Moreover , patients clearly favored nabilone for continued use ( P less than 0.001 ) . Predominant side effects noted by patients were similar for both agents and included somnolence , dry mouth and dizziness but were about twice as frequent and more often severe in patients receiving nabilone . In addition , four patients ( 3 per cent ) taking nabilone had side effects ( hallucinations in three , hypotension in one ) that required medical attention . Euphoria associated with nabilone was infrequent ( 16 per cent ) and mild Summary Oral delta-9-tetrahydrocannabinol ( THC ) , 15 mg/m2 , was compared to prochlorperazine ( PCZ ) , 10 mg . for the control of cancer chemotherapy-related emesis .  Thirty-six patients whose vomiting was refractory to st and ard antiemetic therapy  were entered in this r and omized comparative cross-over study . THC decreased nausea and vomiting in 23 of 36 ( 64 % ) patients compared to 1 of 36 receiving PCZ . THC efficacy was not dependent on the class of antineoplastic-agent inducing the emetic symptoms , age of patients or type of sensorial change experienced . Using the 15 mg/m2 dose , all patients experienced transient sensorial changes , characterized as a pleasant “ high ” in 19 or a variable state of dysphoria in 17 cases . This study confirms the usefulness of THC in patients whose chemotherapy-induced nausea and vomiting is refractory to other st and ard antiemetics . While excellent antiemetic control was achieved at the dosage 15 mg/m2 , dysphoria was encountered at this dose level and we recommend that an initial dose of 5 mg/m2 which , if necessary , can be carefully increased to achieve maximum antiemetic benefit BACKGROUND Preliminary studies suggested that delta-9-tetrahydrocannabinol ( THC ) , the major psychoactive ingredient of Cannabis sativa L. , might be effective in the treatment of Tourette syndrome ( TS ) . This study was performed to investigate for the first time under controlled conditions , over a longer-term treatment period , whether THC is effective and safe in reducing tics in TS . METHOD In this r and omized , double-blind , placebo-controlled study , 24 patients with TS , according to DSM-III-R criteria , were treated over a 6-week period with up to 10 mg/day of THC . Tics were rated at 6 visits ( visit 1 , baseline ; visits 2 - 4 , during treatment period ; visits 5 - 6 , after withdrawal of medication ) using the Tourette Syndrome Clinical Global Impressions scale ( TS-CGI ) , the Shapiro Tourette-Syndrome Severity Scale ( STSSS ) , the Yale Global Tic Severity Scale ( YGTSS ) , the self-rated Tourette Syndrome Symptom List ( TSSL ) , and a videotape-based rating scale . RESULTS Seven patients dropped out of the study or had to be excluded , but only 1 due to side effects . Using the TS-CGI , STSSS , YGTSS , and video rating scale , we found a significant difference ( p < .05 ) or a trend toward a significant difference ( p < .10 ) between THC and placebo groups at visits 2 , 3 , and /or 4 . Using the TSSL at 10 treatment days ( between days 16 and 41 ) there was a significant difference ( p < .05 ) between both groups . ANOVA as well demonstrated a significant difference ( p = .037 ) . No serious adverse effects occurred . CONCLUSION Our results provide more evidence that THC is effective and safe in the treatment of tics . It , therefore , can be hypothesized that the central cannabinoid receptor system might play a role in TS pathology Delta-9-tetrahydrocannabinol ( THC ) is an effective antiemetic as compared with placebos in patients receiving chemotherapy for cancer . In this study we compared THC with prochlorperazine ( compazine ) in a r and omized , double-blind , crossover trial with patients who had failed to benefit from st and ard antiemetic therapy .  Regardless of the emetic activity of the chemotherapeutic agents , there were more complete responses to THC courses ( in 36 of 79 courses ) than to prochlorperazine ( in 16 of 78 courses ) . Of 25 patients who were treated with both drugs and who expressed a preference , 20 preferred THC ( P = 0.005 ) . Among patients under 20 years of age there was a higher proportion of complete responses to THC courses ( 15 of 20 ) than among older patients ( 21 of 59 courses ; P = 0.004 ) . Increased food intake occurred more frequently with THC ( P = 0.008 ) and was associated with the presence of a " high . " Of 36 THC courses result ing in complete antiemetic responses , 32 were associated with a high . We conclude that THC is an effective antiemetic in many patients who receive chemotherapy for cancer and for whom other antiemetics are ineffective . ( N Engl J Med 302:135 - -138 , 1980 ) Symptoms relating to spasticity are common in multiple sclerosis ( MS ) and can be difficult to treat . We have investigated the efficacy , safety and tolerability of a st and ardized oromucosal whole plant cannabis-based medicine ( CBM ) containing delta-9 tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) , upon spasticity in MS . A total of 189 subjects with definite MS and spasticity were r and omized to receive daily doses of active preparation ( n = 124 ) or placebo ( n = 65 ) in a double blind study over 6 weeks . The primary endpoint was the change in a daily subject-recorded Numerical Rating Scale of spasticity . Secondary endpoints included a measure of spasticity ( Ashworth Score ) and a subjective measure of spasm . The primary efficacy analysis on the intention to treat ( ITT ) population ( n = 184 ) showed the active preparation to be significantly superior ( P = 0.048 ) . Secondary efficacy measures were all in favour of active preparation but did not achieve statistical significance . The responder analysis favoured active preparation , 40 % of subjects achieved > 30 % benefit ( P = 0.014 ) . Eight withdrawals were attributed to adverse events ( AEs ) ; six were on active preparation and two on placebo . We conclude that this CBM may represent a useful new agent for treatment of the symptomatic relief of spasticity in MS Anecdotal reports in Tourette 's syndrome ( TS ) have suggested that marijuana ( cannabis sativa ) and delta-9-tetrahydrocannabinol ( Delta(9)-THC ) , the major psychoactive ingredient of marijuana , reduce tics and associated behavioral disorders . We performed a r and omized double-blind placebo-controlled crossover single-dose trial of Delta(9)-THC ( 5.0 , 7.5 or 10.0 mg ) in 12 adult TS patients . Tic severity was assessed using a self-rating scale ( Tourette 's syndrome Symptom List , TSSL ) and examiner ratings ( Shapiro Tourette 's syndrome Severity Scale , Yale Global Tic Severity Scale , Tourette 's syndrome Global Scale ) . Using the TSSL , patients also rated the severity of associated behavioral disorders . Clinical changes were correlated to maximum plasma levels of THC and its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol ( 11-OH-THC ) and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid ( THC-COOH ) . Using the TSSL , there was a significant improvement of tics ( p=0.015 ) and obsessive-compulsive behavior ( OCB ) ( p = 0.041 ) after treatment with Delta(9)-THC compared to placebo . Examiner ratings demonstrated a significant difference for the subscore " complex motor tics " ( p = 0.015 ) and a trend towards a significant improvement for the subscores " motor tics " ( p = 0.065 ) , " simple motor tics " ( p = 0.093 ) , and " vocal tics " ( p = 0.093 ) . No serious adverse reactions occurred . Five patients experienced mild , transient side effects . There was a significant correlation between tic improvement and maximum 11-OH-THC plasma concentration . Results obtained from this pilot study suggest that a single-dose treatment with Delta(9)-THC is effective and safe in treating tics and OCB in TS . It can be speculated that clinical effects may be caused by 11-OH-THC . A more long-term study is required to confirm these results UNLABELLED A r and omized , double-blind , placebo-controlled trial was conducted to determine the benefit of nabilone in pain management and quality of life improvement in 40 patients with fibromyalgia . After a baseline assessment , subjects were titrated up on nabilone , from 0.5 mg PO at bedtime to 1 mg BID over 4 weeks or received a corresponding placebo . At the 2- and 4-week visits , the primary outcome measure , visual analog scale ( VAS ) for pain , and the secondary outcome measures , number of tender points , the average tender point pain threshold , and the Fibromyalgia Impact Question naire ( FIQ ) , were evaluated . After a 4-week washout period , subjects returned for re assessment of the outcome measures . There were no significant differences in population demographics between groups at baseline . There were significant decreases in the VAS ( -2.04 , P < .02 ) , FIQ ( -12.07 , P < .02 ) , and anxiety ( -1.67 , P < .02 ) in the nabilone treated group at 4 weeks . There were no significant improvements in the placebo group . The treatment group experienced more side effects per person at 2 and 4 weeks ( 1.58 , P < .02 and 1.54 , P < .05 ) , respectively . Nabilone appears to be a beneficial , well-tolerated treatment option for fibromyalgia patients , with significant benefits in pain relief and functional improvement . PERSPECTIVE To our knowledge , this is the first r and omized , controlled trial to assess the benefit of nabilone , a synthetic cannabinoid , on pain reduction and quality of life improvement in patients with fibromyalgia . As nabilone improved symptoms and was well-tolerated , it may be a useful adjunct for pain management in fibromyalgia The antiemetic activity and side-effects of delta-9-tetrahydrocannabinol ( THC ) were evaluated in 116 patients ( median age 61 years ) receiving combined 5-fluorouracil and semustine ( methyl CCNU ) therapy for gastrointestinal carcinoma . In a double-blind study , patients were r and omized to receive THC , 15 mg orally three times a day , prochlorperazine , 10 mg orally three times a day , or placebo . The THC had superior antiemetic activity in comparison to placebo , but it showed no advantage over prochlorperazine . Central nervous system side-effects , however , were significantly more frequent and more severe with THC . With the dosage and schedule we used , and in our patient population of largely elderly adults , THC therapy result ed in an overall more unpleasant treatment experience than that noted with prochlorperazine or placebo . Although THC may have a role in preventing nausea and vomiting associated with cancer chemotherapy , this role must be more clearly defined before THC can be recommended for general use Summary In a r and omized crossover study 57 cancer patients receiving chemotherapy with high emetic potential were treated with low-dose levonantradol or st and ard-dose metoclopramide and crossed over to the other antiemetic drug in the next identical chemotherapy cycle . In the 45 patients evaluable for treatment response the antiemetic efficacy of levonantradol was significantly better : 62 % had less nausea and 58 % less vomiting , as against 11 % and 16 % , respectively , with metoclopramide .  Patient preference for antiemetic treatment was levonantradol in 49 % and metoclopramide in 22 % of cases . Levonantradol treatment was accompanied by a relatively high incidence of side-effects ( 71 % ) compared with metoclopramide ( 29 % ) . The antiemetic efficacy of each single drug was incomplete in most cases of this trial , and antiemetic combination therapy is recommended for further trials Fifty-five patients harboring a variety of neoplasms and previously found to have severe nausea or emesis from antitumor drugs were given antiemetic prophylaxis in a double-blind , r and omized , crossover fashion . Tetrahydrocannabinol ( THC ) , prochlorperazine , and placebo were compared . Nausea was absent in 40 of 55 patients receiving THC , eight of 55 patients receiving prochlorperazine , and five of 55 in the placebo group . The antiemetic effect of THC appeared to be more efficacious for  cyclophosphamide , fluorouracil , and doxorubicin hydrochloride  , and less so for  mechlorethamine hydrochloride  and the  nitrosureas . Tetrahydrocannabinol appears to offer significant control of nausea in most patients and exceeding by far that provided by prochlorperazine Summary Twenty-seven patients who were refractory to previously used common antiemetic treatment while on chemotherapy have been entered in a crossover , double-blind , r and omized study aim ed to compare efficacy and toxicity of 2 mg b.i.d . oral nabilone and 10 mg b.i.d . oral prochlorperazine .  Eighteen patients are presently evaluable for efficacy . Severity of nausea was less during the nabilone period of administration . The number of vomiting ejections and dry retching episodes was significantly less ( P P P cis -plantinum- ( 50 mg/m 2 ) and adriamycin-pluscyclophosphamide-induced vomiting BACKGROUND Neuropathic pain ( NPP ) is a chronic syndrome suffered by patients with multiple sclerosis ( MS ) , for which there is no cure . Underlying cellular mechanisms involved in its pathogenesis are multifaceted , presenting significant challenges in its management . METHODS A r and omized , double-blind , placebo-controlled study involving 15 relapsing-remitting MS patients with MS-induced NPP was conducted to evaluate nabilone combined with gabapentin ( GBP ) .  Eligible patients stabilized on GBP ( ≥1,800 mg/day ) with inadequate pain relief were recruited . Nabilone or placebo was titrated over 4 weeks ( 0.5 mg/week increase ) followed by 5-week maintenance of 1 mg oral nabilone ( placebo ) twice daily . Primary outcomes included two daily patient-reported measures using a 100-mm visual analog scale ( VAS ) , pain intensity ( VASpain ) , and impact of pain on daily activities ( VASimpact ) . Hierarchical regression modeling was conducted on each outcome to determine if within-person pain trajectory differed across study groups , during 63-day follow-up . RESULTS After adjustment for key patient-level covariates ( e.g. , age , sex , Exp and ed Disability Status Scale , duration of MS , baseline pain ) , a significant group × time(2 ) interaction term was reported for both the VASpain ( P < 0.01 ) and VASimpact score ( P < 0.01 ) , demonstrating the adjusted rate of decrease for both outcomes was statistically greater in nabilone vs placebo study group . No significant difference in attrition rates was noted between treatments . Nabilone was well tolerated , with dizziness/drowsiness most frequently reported . CONCLUSION Nabilone as an adjunctive to GBP is an effective , well-tolerated combination for MS-induced NPP . The results of this study identify a novel therapeutic combination for use in this population of patients predisposed to tolerability issues that may otherwise prevent effective pain management OBJECTIVE : To examine the effect of dronabinol ( delta-9-tetrahydrocannabinol ) on appetite and nutritional status in patients with symptomatic HIV infection and weight loss . DESIGN : Double-blind , r and omized , placebo-controlled , crossover trial with two five-week treatment periods separated by a two-week washout period . Patients received dronabinol 5 mg twice daily before meals or placebo . SETTING : A university-based HIV/AIDS clinic and a large infectious disease private practice largely devoted to care of patients with HIV . PARTICIPANTS : Twelve HIV-infected patients who had had at least a 2.25-kg weight loss participated in the study . Five patients completed the protocol , and seven withdrew ( two because of drug intolerance , two because of disease progression , two because of noncompliance , and one because of experimental antiretroviral therapy ) . MAIN OUTCOME MEASURES : Main outcome measures included caloric intake , weight , percent body fat , serum prealbumin , and symptom distress . RESULTS : During dronabinol treatment , subjects experienced increased percent body fat ( one percent , p=0.04 ) ; decreased symptom distress ( p=0.04 ) ; and trends toward weight gain ( 0.5 kg , p=0.13 ) , increased prealbumin ( 29.0 mg/L , p=0.11 ) , and improved appetite score ( p=0.14 ) . CONCLUSIONS : In a selected group of HIV-infected patients with weight loss , short-term treatment with dronabinol may result in improvement in nutritional status and symptom distress UNLABELLED The Food and Drug Administration ( FDA ) , Substance Abuse and Mental Health Services Administration ( SAMHSA ) , and the National Institute for Drug Abuse ( NIDA ) report that no sound scientific studies support the medicinal use of cannabis . Despite this lack of scientific validation , many patients routinely use " medical marijuana , " and in many cases this use is for pain related to nerve injury . We conducted a double-blinded , placebo-controlled , crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain . Thirty-eight patients with central and peripheral neuropathic pain underwent a st and ardized procedure for smoking either high-dose ( 7 % ) , low-dose ( 3.5 % ) , or placebo cannabis . In addition to the primary outcome of pain intensity , secondary outcome measures included evoked pain using heat-pain threshold , sensitivity to light touch , psychoactive side effects , and neuropsychological performance . A mixed linear model demonstrated an analgesic response to smoking cannabis . No effect on evoked pain was seen . Psychoactive effects were minimal and well-tolerated , with some acute cognitive effects , particularly with memory , at higher doses . PERSPECTIVE This study adds to a growing body of evidence that cannabis may be effective at ameliorating neuropathic pain , and may be an alternative for patients who do not respond to , or can not tolerate , other drugs . However , the use of marijuana as medicine may be limited by its method of administration ( smoking ) and modest acute cognitive effects , particularly at higher doses Abstract Background : Muscle spasticity is common in multiple sclerosis ( MS ) , occurring in more than 60 % of patients . Objective : To compare Sativex with placebo in relieving symptoms of spasticity due to MS . Methods : A 15-week , multicenter , double-blind , r and omized , placebo-controlled , parallel-group study in 337 subjects with MS spasticity not fully relieved with current anti-spasticity therapy . Results : The primary endpoint was a spasticity 0–10 numeric rating scale ( NRS ) . Intention-to-treat ( ITT ) analysis showed a non-significant improvement in NRS score , in favor of Sativex . The per protocol ( PP ) population ( 79 % of subjects ) change in NRS score and responder analyses ( ≥30 % improvement from baseline ) were both significantly superior for Sativex , compared with placebo : −1·3 versus −0·8 points ( change from baseline , p=0·035 ) ; and 36 % versus 24 % ( responders , p=0·040 ) . These were supported by the time to response ( ITT : p=0·068 ; PP : p=0·025 ) analyses , carer global impression of change assessment ( p=0·013 ) and timed 10-meter walk ( p=0·042 ) . Among the subjects who achieved a ≥30 % response in spasticity  with Sativex , 98 , 94 and 73 % reported improvements of 10 , 20 and 30 % , respectively , at least once during the first 4 weeks of treatment . Sativex was generally well tolerated , with most adverse events reported being mild-to-moderate in severity . Discussion and conclusions : The 0–10 NRS and responder PP analyses demonstrated that Sativex treatment result ed in a significant reduction in treatment-resistant spasticity , in subjects with advanced MS and severe spasticity . The response observed within the first 4 weeks of treatment appears to be a useful aid to prediction of responder/non-responder status The effects of dronabinol on appetite and weight were evaluated in 139 patients with AIDS-related anorexia and > or = 2.3 kg weight loss in a multi-institutional study . Patients were r and omized to receive 2.5 mg dronabinol twice daily or placebo . Patients rated appetite , mood , and nausea by using a 100-mm visual analogue scale 3 days weekly . Efficacy was evaluable in 88 patients . Dronabinol was associated with increased appetite above baseline ( 38 % vs 8 % for placebo , P = 0.015 ) , improvement in mood ( 10 % vs -2 % , P = 0.06 ) , and decreased nausea ( 20 % vs 7 % ; P = 0.05 ) . Weight was stable in dronabinol patients , while placebo recipients had a mean loss of 0.4 kg ( P = 0.14 ) . Of the dronabinol patients , 22 % gained > or = 2 kg , compared with 10.5 % of placebo recipients ( P = 0.11 ) . Side effects were mostly mild to moderate in severity ( euphoria , dizziness , thinking abnormalities ) ; there was no difference in discontinued therapy between dronabinol ( 8.3 % ) and placebo ( 4.5 % ) recipients . Dronabinol was found to be safe and effective for anorexia associated with weight loss in patients with AIDS CONTEXT Neuropathic pain caused by chemotherapy limits dosing and duration of potentially life-saving anti-cancer treatment and impairs quality of life . Chemotherapeutic neuropathy responds poorly to conventional treatments , and there is an urgent medical need for new treatments . Recent pre clinical studies demonstrate that cannabinoid agonists suppress established chemotherapy-evoked neuropathy . OBJECTIVES This was a pilot trial to begin to investigate a currently available cannabinoid agent , nabiximols ( oral mucosal spray containing cannabinoids ) , in the treatment of chemotherapy-induced neuropathic pain . METHODS A r and omized , placebo-controlled crossover pilot study was done in 16 patients with established chemotherapy-induced neuropathic pain . A 0 - 10 point numeric rating scale for pain intensity ( NRS-PI ) was used as the primary outcome measure . RESULTS When examining the whole group , there was no statistically significant difference between the treatment and the placebo groups on the NRS-PI . A responder analysis demonstrated that there were five participants who reported a two-point or greater reduction in pain that trended toward statistical significance and the number needed to treat was five . CONCLUSION Chemotherapy-induced neuropathic pain is particularly resistant to currently available treatments . This pilot trial found a number needed to treat of five and an average decrease of 2.6 on an 11-point NRS-PI in five " responders " ( as compared with a decrease of 0.6 with placebo ) and supports that it is worthwhile to study nabiximols in a full r and omized , placebo-controlled trial of chemotherapy-induced neuropathic pain Summary A prospect i ve , r and omized , double-blind , crossover study of nabilone versus placebo was undertaken in three university cancer centers to determine the antiemetic efficacy and toxicity of nabilone in patients experiencing nausea and vomiting due to cancer chemotherapy . Identical study drug ( 2 mg of nabilone or placebo ) was given the evening before and the morning of chemotherapy and for at least 24 h afterwards on a b.i.d . schedule . Careful assessment of nausea , vomiting and finally patient preference for study drug was carried out on each of two identical courses of combination chemotherapy . Fifty-four patients were entered . Of the 24 patients fully evaluable for efficacy , nabilone significantly reduced the mean number of vomiting episodes ( 7 vs. 19 , P P P = 0.001 ) . Side effects were common with nabilone but acceptable and in 49 patients who were evaluable for toxicity consisted primarily of dizziness ( 65 % ) , drowsiness ( 51 % ) , dry mouth ( 31 % ) , sleep disturbance ( 14 % ) , ataxia ( 8 % ) , nausea ( 8 % ) and euphoria ( 6 % ) . Nabilone is an effective antiemetic agent for chemotherapy-induced nausea and vomiting In a r and omized , double-blind , crossover trial , nabilone was compared to prochlorperazine for control of cancer chemotherapy-induced emesis in 30 children 3.5 to 17.8 years of age . All subjects received two consecutive identical cycles of chemotherapy with the trial antiemetics given in accordance to a body weight-based dosage schedule beginning eight to 12 hours before treatment . The overall rate of improvement of retching and emesis was 70 % during the nabilone and 30 % during the prochlorperazine treatment cycles ( P = .003 , chi 2 test ) . On completion of the trial , 66 % of the children stated that they preferred nabilone , 17 % preferred prochlorperazine , and 17 % had no preference ( P = .015 , chi 2 test ) . Major side effects ( dizziness , drowsiness , and mood alteration ) were more common ( 11 % v 3 % ) during the nabilone treatment cycles . CNS side effects appeared to be dose related and were most likely to occur when the nabilone dosage exceeded 60 micrograms/kg/d , but individual tolerance to nabilone varied considerably . Lower dosages of nabilone were associated with equivalent efficacy and no major side effects .  Nabilone appears to be a safe , effective , and well-tolerated antiemetic drug for children receiving cancer chemotherapy . Although major side effects may occur at higher dosages , nabilone is preferable to prochlorperazine because of improved efficacy A r and omized , double-blind controlled trial of nabilone versus chlorpromazine was performed in 20 patients with advanced gynaecological cancer who received chemotherapy including cis-platinum .  Each patient served as his own control . Nabilone was administered at a dose of 3 mg given orally three times a day , starting the day before cis-platinum and ending the day after . Chlorpromazine was administered at a dose of 12.5 mg given IM , 15 minutes before the start of cis-platinum . Nabilone , in comparison with chlorpromazine did not significantly reduce the number of vomiting . Ten patients preferred nabilone , 5 preferred chlorpromazine and 3 were undecided . Predominant side effects noted by patients were similar for both agents and included somnolence , dry mouth and orthostatic hypotension . No other intervention besides reassurance of the patient was necessary to treat these adverse reactions One hundred and eight patients selected to receive combinations of highly emetic cytotoxic chemotherapy for malignant disease were included in a study of anti-emetic therapy . The patients were r and omly allocated to receive levonantradol ( 0.5 , 0.75 or 1 mg ) or chlorpromazine ( 25 mg ) prior to receiving their first course of cytotoxic therapy . The appropriate anti-emetic was administered 2 hr prior to the start of chemotherapy , 2 hr after chemotherapy and subsequently at 4-hourly intervals for a further 8 hr . The extent of anorexia , nausea and vomiting along with other side-effects were assessed at regular intervals by physicians and nursing staff during the 24 hr following chemotherapy . In addition , a self- assessment question naire was completed by the patients . Levonantradol ( 0.5 mg ) was superior to chlorpromazine ( 25 mg ) as an anti-emetic . Both were reasonably well tolerated , although at this dose of levonantradol 22 % of patients experienced dysphoric reactions . At higher doses of levonantradol the proportion of patients experiencing these reactions rose to 50 % , but without a concomitant increase in antiemetic activity . Neither drug achieved satisfactory control of vomiting in patients receiving combinations containing cis-platinum . We conclude that levonantradol ( 0.5 mg ) is a more effective anti-emetic than chlorpromazine ( 25 mg ) in patients receiving cytotoxic chemotherapy . However , its use can not be recommended due to its high incidence of unacceptable central nervous system side-effects Cannabinoids reduce allodynia/hyperalgesia in animal pain models , but few clinical studies evaluated the analgesic action in humans . We aim ed to evaluate the effect of delta-9-tetrahydrocannabinol ( dronabinol ) on central pain in MS patients . Twenty-four MS patients participated in a double-blind placebo-controlled crossover trial . Dronabinol reduced the spontaneous pain intensity significantly compared with placebo ( 4.0 ( 2.3 - 6.0 ) vs. 5.0 ( 4.0 - 6.4 ) , median ( 25th-75th percentiles ) , p = 0.02 ) . Though dronabinol 's analgesic effect is modest , its use should be evaluated considering the general difficulty in treating central pain Fifty-five patients harboring a variety of neoplasms and previously found to have severe nausea or emesis from antitumor drugs were given antiemetic prophylaxis in a double-blind , r and omized crossover fashion . delta 9-Tetrahydrocannabinol ( THC ) , prochlorperazine , and placebo were compared . Nausea was absent in 40 of 55 patients receiving THC , in 8 of 55 patients receiving prochlorperazine , and in 5 of 55 in the placebo group . THC appeared to be more efficacious in controlling the emesis associated with cyclophosphamide , 5-fluorouracil , and doxorubicin and less so for nitrogen mustard and the nitrosourea . THC appears to offer significant control of nausea in most patients and exceeds by far that provided by prochlorperazine ( P less than 0.005 ) Dronabinol ( Marinol , Roxane Laboratories , Columbus , OH ) and prochlorperazine were tested alone and in combination in a r and omized , double-blind , parallel group , multicenter study . Patients were r and omized to receive either 1 ) dronabinol 10 mg every 6 hr plus placebo ; 2 ) placebo plus prochlorperazine 10 mg every 6 hr ; or 3 ) dronabinol and prochlorperazine , each 10 mg every 6 hr . Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy ; all was given orally . Only 29 % of patients in group 3 versus 47 % in group 1 and 60 % in group 2 experienced nausea after chemotherapy . In addition , the median duration per episode and severity of nausea were significantly less with combination therapy . Vomiting occurred after chemotherapy in 41 % , 55 % , and 35 % of patients in groups 1 , 2 , and 3 , respectively . The median duration per episode of vomiting was 1 min in group 3 versus two in group 1 and four in group 2 . Side effects , primarily CNS , were more common in group 1 than in group 2 ; addition of prochlorperazine to dronabinol appeared to decrease the frequency of dysphoric effects seen with the latter agent . The combination was significantly more effective than was either single agent in controlling chemotherapy-induced nausea and vomiting AIMS Despite progress in anti-emetic treatment , many patients still suffer from chemotherapy-induced nausea and vomiting ( CINV ) . This is a pilot , r and omized , double-blind , placebo-controlled phase II clinical trial design ed to evaluate the tolerability , preliminary efficacy , and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine ( CBM ) containing delta-9-tetrahydrocannabinol and cannabidiol , taken in conjunction with st and ard therapies in the control of CINV . METHODS Patients suffering from CINV despite prophylaxis with st and ard anti-emetic treatment were r and omized to CBM or placebo , during the 120 h  post-chemotherapy  period , added to st and ard anti-emetic treatment .  Tolerability was measured as the number of withdrawals from the study during the titration period because of adverse events ( AEs ) . The endpoint for the preliminary efficacy analysis was the proportion of patients showing complete or partial response . RESULTS Seven patients were r and omized to CBM and nine to placebo . Only one patient in the CBM arm was withdrawn due to AEs . A higher proportion of patients in the CBM group experienced a complete response during the overall observation period [ 5/7 ( 71.4 % ) with CMB vs. 2/9 ( 22.2 % ) with placebo , the difference being 49.2 % ( 95 % CI 1 % , 75 % ) ] , due to the delayed period . The incidence of AEs was higher in the CBM group ( 86 % vs. 67 % ) . No serious AEs were reported . The mean daily dose was 4.8 sprays in both groups . CONCLUSION Compared with placebo , CBM added to st and ard antiemetic therapy was well tolerated and provided better protection against delayed CINV . These results should be confirmed in a phase III clinical trial
target: 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
background: IMPORTANCE Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms , but their efficacy for specific indications is not clear .
  OBJECTIVE To conduct a systematic review of the benefits and adverse events ( AEs ) of cannabinoids .