The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
Holland, Rohan M - One of the best experts on this subject based on the ideXlab platform.
-
Nabiximols as an agonist replacement therapy during cannabis withdrawal : a randomized clinical trial
'American Medical Association (AMA)', 2014Co-Authors: Allsop, David J, Copeland Jan, Booth Jessica, Mcgregor, Iain S, Lintzeris Nicholas, Dunlop, Adrian J, Montebello Mark, Sadler Craig, Rivas, Gonzalo R, Holland, Rohan MAbstract:IMPORTANCE: There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract Nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. OBJECTIVE: To evaluate the safety and efficacy of Nabiximols in treating cannabis withdrawal. DESIGN, SETTING, AND PARTICIPANTS: A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. INTERVENTIONS: A 6-day regimen of Nabiximols (maximum daily dose, 86.4 mg of Δ9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. MAIN OUTCOMES AND MEASURES: Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. RESULTS: Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F₈,₃₇₇.₉₇ = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between Nabiximols and placebo treatment (χ²₁ = 0.79; P = .67), and those receiving Nabiximols did not report greater intoxication (F₁,₆ = 0.22; P = .97). The number (F₁,₅₀ = 0.3; P = .59) and severity (F₁,₅₀ = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of Nabiximols over placebo for self-reported cannabis use (F₁,₄₈ = 0.29; P = .75), cannabis-related problems (F₁,₄₉ = 2.33; P = .14), or cannabis dependence (F₁,₅₀ < 0.01; P = .89). CONCLUSIONS AND RELEVANCE: In a treatment-seeking cohort, Nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as Nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of Nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations.11 page(s
-
Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial
American Medical Association, 2014Co-Authors: Allsop, David J, Copeland Jan, Booth Jessica, Mcgregor, Iain S, Lintzeris Nicholas, Dunlop, Adrian J, Montebello Mark, Sadler Craig, Rivas, Gonzalo R, Holland, Rohan MAbstract:Importance: There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract Nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. Objective: To evaluate the safety and efficacy of Nabiximols in treating cannabis withdrawal. Design, Settings and Participants: A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. Interventions: A 6-day regimen of Nabiximols (maximum daily dose, 86.4 mg of [DELTA]9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. Main Outcomes and Measures: Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. Results: Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F8,377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between Nabiximols and placebo treatment ([chi]21 = 0.79; P = .67), and those receiving Nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of Nabiximols over placebo for self-reported cannabis use (F1,48 = 0.29; P = .75), cannabis-related problems (F1,49 = 2.33; P = .14), or cannabis dependence (F1,50 < 0.01; P = .89). Conclusions and Relevance: In a treatment-seeking cohort, Nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as Nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of Nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations. Trial Registration: anzctr.org.au Identifier: ACTRN1261100039890
G Comi - One of the best experts on this subject based on the ideXlab platform.
-
A randomized, doubleblind, placebo-controlled, parallel-group, enriched-design study of Nabiximols* (Sativex [R], as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol 2011;18:1122–31
2020Co-Authors: A Novotna, Jan Mares, S Ratcliffe, I Novakova, Marta Vachova, O Zapletalova, Claudio Gasperini, C Pozzilli, Luca Ausili Cefaro, G ComiAbstract:Background: Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design. Methods: A 19-week follow-up, multicentre, double-blind, randomized, placebocontrolled, parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy. Subjects were treated with Nabiximols, as add-on therapy, in a single-blind manner for 4 weeks, after which those achieving an improvement in spasticity of ‡20% progressed to a 12-week randomized, placebocontrolled phase. Results: Of the 572 subjects enrolled, 272 achieved a ‡20% improvement after 4 weeks of single-blind treatment, and 241 were randomized. The primary end-point was the difference between treatments in the mean spasticity Numeric Rating Scale (NRS) in the randomized, controlled phase of the study. Intention-to-treat (ITT) analysis showed a highly significant difference in favour of Nabiximols (P = 0.0002). Secondary end-points of responder analysis, Spasm Frequency Score, Sleep Disturbance NRS Patient, Carer and Clinician Global Impression of Change were all significant in favour of Nabiximols. Conclusions: The enriched study design provides a method of determining the efficacy and safety of Nabiximols in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it. Hence, the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment
-
Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis
'Wiley', 2018Co-Authors: M. Sorosina, G Comi, F. Clarelli, L. Ferre, A.m. Osiceanu, N.t. Unal, E. Mascia, V. Martinelli, F. Benigni, F. EspositoAbstract:Background and purpose: Nabiximols (Sativex \uae ) is a cannabinoid-based compound used for the treatment of moderate to severe spasticity in multiple sclerosis (MS). The aim of the study was to investigate the effect of the administration of Nabiximols on blood transcriptome profile of patients with MS and to interpret it in the context of pathways and networks. Methods: Whole-genome expression profiling was performed in whole blood of 33 subjects with MS at baseline and after 4 weeks of drug treatment. Patients were classified as responders (n = 19) and non-responders (n = 14). Pathway and network analyses on genes modulated by the drug were performed, followed by in vitro stimulation of peripheral blood mononuclear cells with pro-inflammatory agents to support the immunomodulatory properties of the drug. Results: Individual effect size was modest; however, we observed a downregulation of several immune-related pathways after 4 weeks of treatment, which was more pronounced when restricting analyses to responders. Interesting hub molecules functionally related to the immune system emerged from network analysis, including NFKB1, FYN, MAP14 and TP53. The immunomodulatory properties of the drug were confirmed through in vitro assays in peripheral blood mononuclear cells collected from patients with MS. Conclusions: Our findings support the immunomodulatory activity of cannabinoids in patients with MS. Further studies in more specific cell types are needed to refine these results
-
a randomized double blind placebo controlled parallel group enriched design study of Nabiximols sativex as add on therapy in subjects with refractory spasticity caused by multiple sclerosis
European Journal of Neurology, 2011Co-Authors: A Novotna, Jan Mares, S Ratcliffe, I Novakova, Marta Vachova, O Zapletalova, Claudio Gasperini, C Pozzilli, Luca Ausili Cefaro, G ComiAbstract:Background: Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design. Methods: A 19-week follow-up, multicentre, double-blind, randomized, placebo-controlled, parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy. Subjects were treated with Nabiximols, as add-on therapy, in a single-blind manner for 4 weeks, after which those achieving an improvement in spasticity of ≥20% progressed to a 12-week randomized, placebo-controlled phase. Results: Of the 572 subjects enrolled, 272 achieved a ≥20% improvement after 4 weeks of single-blind treatment, and 241 were randomized. The primary end-point was the difference between treatments in the mean spasticity Numeric Rating Scale (NRS) in the randomized, controlled phase of the study. Intention-to-treat (ITT) analysis showed a highly significant difference in favour of Nabiximols (P = 0.0002). Secondary end-points of responder analysis, Spasm Frequency Score, Sleep Disturbance NRS Patient, Carer and Clinician Global Impression of Change were all significant in favour of Nabiximols. Conclusions: The enriched study design provides a method of determining the efficacy and safety of Nabiximols in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it. Hence, the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment.
-
A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of Nabiximols* (Sativex ®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis
'Wiley', 2011Co-Authors: A Novotna, Jan Mares, S Ratcliffe, I Novakova, Marta Vachova, O Zapletalova, Claudio Gasperini, C Pozzilli, Luca Ausili Cefaro, G ComiAbstract:Background: Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design. Methods: A 19-week follow-up, multicentre, double-blind, randomized, placebo-controlled, parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy. Subjects were treated with Nabiximols, as add-on therapy, in a single-blind manner for 4 weeks, after which those achieving an improvement in spasticity of >= 20% progressed to a 12-week randomized, placebo-controlled phase. Results: Of the 572 subjects enrolled, 272 achieved a >= 20% improvement after 4 weeks of single-blind treatment, and 241 were randomized. The primary end-point was the difference between treatments in the mean spasticity Numeric Rating Scale (NRS) in the randomized, controlled phase of the study. Intention-to-treat (ITT) analysis showed a highly significant difference in favour of Nabiximols (P = 0.0002). Secondary end-points of responder analysis, Spasm Frequency Score, Sleep Disturbance NRS Patient, Carer and Clinician Global Impression of Change were all significant in favour of Nabiximols. Conclusions: The enriched study design provides a method of determining the efficacy and safety of Nabiximols in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it. Hence, the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment
Allsop, David J - One of the best experts on this subject based on the ideXlab platform.
-
Nabiximols as an agonist replacement therapy during cannabis withdrawal : a randomized clinical trial
'American Medical Association (AMA)', 2014Co-Authors: Allsop, David J, Copeland Jan, Booth Jessica, Mcgregor, Iain S, Lintzeris Nicholas, Dunlop, Adrian J, Montebello Mark, Sadler Craig, Rivas, Gonzalo R, Holland, Rohan MAbstract:IMPORTANCE: There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract Nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. OBJECTIVE: To evaluate the safety and efficacy of Nabiximols in treating cannabis withdrawal. DESIGN, SETTING, AND PARTICIPANTS: A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. INTERVENTIONS: A 6-day regimen of Nabiximols (maximum daily dose, 86.4 mg of Δ9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. MAIN OUTCOMES AND MEASURES: Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. RESULTS: Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F₈,₃₇₇.₉₇ = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between Nabiximols and placebo treatment (χ²₁ = 0.79; P = .67), and those receiving Nabiximols did not report greater intoxication (F₁,₆ = 0.22; P = .97). The number (F₁,₅₀ = 0.3; P = .59) and severity (F₁,₅₀ = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of Nabiximols over placebo for self-reported cannabis use (F₁,₄₈ = 0.29; P = .75), cannabis-related problems (F₁,₄₉ = 2.33; P = .14), or cannabis dependence (F₁,₅₀ < 0.01; P = .89). CONCLUSIONS AND RELEVANCE: In a treatment-seeking cohort, Nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as Nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of Nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations.11 page(s
-
Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial
American Medical Association, 2014Co-Authors: Allsop, David J, Copeland Jan, Booth Jessica, Mcgregor, Iain S, Lintzeris Nicholas, Dunlop, Adrian J, Montebello Mark, Sadler Craig, Rivas, Gonzalo R, Holland, Rohan MAbstract:Importance: There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract Nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. Objective: To evaluate the safety and efficacy of Nabiximols in treating cannabis withdrawal. Design, Settings and Participants: A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. Interventions: A 6-day regimen of Nabiximols (maximum daily dose, 86.4 mg of [DELTA]9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. Main Outcomes and Measures: Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. Results: Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F8,377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between Nabiximols and placebo treatment ([chi]21 = 0.79; P = .67), and those receiving Nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of Nabiximols over placebo for self-reported cannabis use (F1,48 = 0.29; P = .75), cannabis-related problems (F1,49 = 2.33; P = .14), or cannabis dependence (F1,50 < 0.01; P = .89). Conclusions and Relevance: In a treatment-seeking cohort, Nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as Nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of Nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations. Trial Registration: anzctr.org.au Identifier: ACTRN1261100039890
Marilyn A Huestis - One of the best experts on this subject based on the ideXlab platform.
-
Nabiximols combined with motivational enhancement cognitive behavioral therapy for the treatment of cannabis dependence a pilot randomized clinical trial
PLOS ONE, 2018Co-Authors: Jose M Trigo, Alexandra Soliman, Lena C Quilty, Benedikt Fischer, Jurgen Rehm, Peter Selby, Allan J Barnes, Marilyn A HuestisAbstract:Background The current lack of pharmacological treatments for cannabis use disorder (CUD) warrants novel approaches and further investigation of promising pharmacotherapy. We previously showed that Nabiximols (27 mg/ml Δ9-tetrahydrocannabinol (THC)/ 25 mg/ml cannabidiol (CBD), Sativex®) can decrease cannabis withdrawal symptoms. Here, we assessed in a pilot study the tolerability and safety of self-titrated Nabiximols vs. placebo among 40 treatment-seeking cannabis-dependent participants. Methods Subjects participated in a double blind randomized clinical trial, with as-needed Nabiximols up to 113.4 mg THC/105 mg CBD or placebo daily for 12 weeks, concurrently with Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). Primary outcome measures were tolerability and abstinence, secondary outcome measures were days and amount of cannabis use, withdrawal, and craving scores. Participants received up to CDN$ 855 in compensation for their time. Results Medication was well tolerated and no serious adverse events (SAEs) were observed. Rates of adverse events did not differ between treatment arms (F1,39 = 0.205, NS). There was no significant change in abstinence rates at trial end. Participants were not able to differentiate between subjective effects associated with Nabiximols or placebo treatments (F1,40 = 0.585, NS). Cannabis use was reduced in the Nabiximols (70.5%) and placebo groups (42.6%). Nabiximols reduced cannabis craving but no significant differences between the Nabiximols and placebo groups were observed on withdrawal scores. Conclusions Nabiximols in combination with MET/CBT was well tolerated and allowed for reduction of cannabis use. Future clinical trials should explore the potential of high doses of Nabiximols for cannabis dependence.
-
Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: A pilot randomized clinical trial
2018Co-Authors: Jose M Trigo, Alexandra Soliman, Lena C Quilty, Benedikt Fischer, Jurgen Rehm, Peter Selby, Allan J Barnes, Marilyn A Huestis, Tony P. George, David L. StreinerAbstract:BackgroundThe current lack of pharmacological treatments for cannabis use disorder (CUD) warrants novel approaches and further investigation of promising pharmacotherapy. We previously showed that Nabiximols (27 mg/ml Δ9-tetrahydrocannabinol (THC)/ 25 mg/ml cannabidiol (CBD), Sativex®) can decrease cannabis withdrawal symptoms. Here, we assessed in a pilot study the tolerability and safety of self-titrated Nabiximols vs. placebo among 40 treatment-seeking cannabis-dependent participants.MethodsSubjects participated in a double blind randomized clinical trial, with as-needed Nabiximols up to 113.4 mg THC/105 mg CBD or placebo daily for 12 weeks, concurrently with Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). Primary outcome measures were tolerability and abstinence, secondary outcome measures were days and amount of cannabis use, withdrawal, and craving scores. Participants received up to CDN$ 855 in compensation for their time.ResultsMedication was well tolerated and no serious adverse events (SAEs) were observed. Rates of adverse events did not differ between treatment arms (F1,39 = 0.205, NS). There was no significant change in abstinence rates at trial end. Participants were not able to differentiate between subjective effects associated with Nabiximols or placebo treatments (F1,40 = 0.585, NS). Cannabis use was reduced in the Nabiximols (70.5%) and placebo groups (42.6%). Nabiximols reduced cannabis craving but no significant differences between the Nabiximols and placebo groups were observed on withdrawal scores.ConclusionsNabiximols in combination with MET/CBT was well tolerated and allowed for reduction of cannabis use. Future clinical trials should explore the potential of high doses of Nabiximols for cannabis dependence.
-
Cannabis craving and withdrawal.
2018Co-Authors: Jose M Trigo, Alexandra Soliman, Lena C Quilty, Benedikt Fischer, Jurgen Rehm, Peter Selby, Allan J Barnes, Marilyn A Huestis, Tony P. George, David L. StreinerAbstract:Circles (white placebo, black Nabiximols) represent mean (+SEM). In a) cannabis withdrawal from the Cannabis Withdrawal Checklist (CWC). In b) craving for cannabis from the Marijuana Craving Questionnaire (MCQ). Generalized Linear Mixed Model (GLMM) analyses followed by one-way ANOVA, * (p < .05) vs Nabiximols group.
-
Study medication rates/effects in cannabis use.
2018Co-Authors: Jose M Trigo, Alexandra Soliman, Lena C Quilty, Benedikt Fischer, Jurgen Rehm, Peter Selby, Allan J Barnes, Marilyn A Huestis, Tony P. George, David L. StreinerAbstract:Circles (white placebo, black Nabiximols) represent mean (+SEM). In a) self-titrated medication (sprays/day) as reported in the smoking diary. In b) total average cannabis intake (g) per week as reported in the timeline followback (TLFB) (week 0) and smoking diary (weeks 1–12). In c) mean percentage of days using cannabis (Nabiximols n = 20–13, placebo n = 20–14).
-
Cannabinoids of interest in urine were quantified using two-dimensional gas chromatography-mass spectrometry (2D-GCMS).
2018Co-Authors: Jose M Trigo, Alexandra Soliman, Lena C Quilty, Benedikt Fischer, Jurgen Rehm, Peter Selby, Allan J Barnes, Marilyn A Huestis, Tony P. George, David L. StreinerAbstract:Table represents creatinine-normalized mean urine Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD) and cannabinol (CBN) concentrations for Nabiximols and placebo groups.
Marie Fallon - One of the best experts on this subject based on the ideXlab platform.
-
an open label extension study to investigate the long term safety and tolerability of thc cbd oromucosal spray and oromucosal thc spray in patients with terminal cancer related pain refractory to strong opioid analgesics
Journal of Pain and Symptom Management, 2013Co-Authors: Jeremy R Johnson, Dominique Lossignol, Mary Burnellnugent, Marie FallonAbstract:Abstract Context Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, Nabiximols; Sativex ® ) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. Objectives This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. Methods In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray ( n =39) or THC spray ( n =4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. Results The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. Conclusion This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.
-
Nabiximols for opioid treated cancer patients with poorly controlled chronic pain a randomized placebo controlled graded dose trial
The Journal of Pain, 2012Co-Authors: Russell K Portenoy, Stephen Wright, Elena Doina Ganaemotan, Silvia Allende, Ronald Yanagihara, Lauren Shaiova, Sharon M Weinstein, Robert D Mcquade, Marie FallonAbstract:Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge. Nabiximols (Nabiximols is the US Adopted Name (USAN) for Sativex (GW Pharma Ltd, Wiltshire, UK), which does not yet have an INN), a novel cannabinoid formulation, is undergoing investigation as add-on therapy for this population. In a randomized, double-blind, placebo-controlled, graded-dose study, patients with advanced cancer and opioid-refractory pain received placebo or nabix- imols 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 questionnaires measured quality of life and mood. A total of 360 patients were randomized; 263 com- pleted. 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 anal- ysis 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 questionnaires 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 na- biximols 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 randomized, double-blind, placebo-controlled, graded-dose study demonstrated efficacy and safety at low and medium doses. a 2012 by the American Pain Society
