Cannabis and Cannabinoids
Dilip Ghosh, Pulok K. Mukherjee in Natural Medicines, 2019
In 2010 nabiximols was first approved in the United Kingdom for the treatment of spasticity associated with multiple sclerosis (Tanasescu et al. 2011). In a pooled analysis of three trials investigating nabiximols or nabilone, Whiting et al. (2015) found that the cannabinoids decreased the patient self-reported spasticity score and improvement of a global impression of change score also favoured nabiximols over placebo. In the previous year, Koppel et al. (2014) also concluded that nabiximols and oral THC were ‘probably effective’ and oral cannabis extract was ‘established as effective’ in reducing patient reported spasticity scores. Considering these two favourable systematic reviews, the NASEM report concluded that there is substantial evidence that oral cannabinoids are effective for improving patient reported multiple sclerosis spasticity symptoms.
The clinical use of cannabinoid therapies in oncology patients
Betty Wedman-St. Louis in Cannabis, 2018
Cannabinoid therapies for cancer pain have been studied in a few randomized trials, but the evidence has been less than convincing. Studies published earlier than 2000 (reviewed by Campbell et al., 2001 [24]) demonstrated mild benefits, with patients reporting dose-limiting adverse effects. Comparators such as codeine and secobarbital were employed, but these presently are not commonly used in patients with severe cancer pain, so extrapolation of these results is difficult. More recently, cannabis extracts (nabiximols) have been used in two placebo-controlled trials [28,29]. Patients with moderate-to-severe cancer pain were given nabiximols (THC and CBD in combination), THC alone, or placebo in addition to opioids and other adjuvant pain medications. Those receiving the THC/CBD combination demonstrated modest benefits with a minimum of dose-related adverse effects. A second trial using similar methodology but graded dosing demonstrated better pain control and improvement in sleep with the two lower-dosed patient groups (1–4 sprays and 6–10 sprays per day, respectively). Significant adverse events were again seen in the highest dosing group (>10 sprays per day) [29]. Interestingly, a recent report of those study patients continuing long-term nabiximols therapy demonstrated continued benefit without escalation of their cannabinoids or opioids [30]. These results support the use of cannabinoids as adjuvant agents for those with cancer pain proving to be resistant to opioids.
Oral Medication
Valerie L. Stevenson, Louise Jarrett in Spasticity Management, 2016
Cannabis has been used recreationally for many hundreds of years, and there is evidence of its medicinal use in Europe dating back to the thirteenth century.75 More recently, it has been advocated for pain relief and spasticity by individuals who have experienced spinal cord injuries, and has particularly gained favour within the MS population. Cannabis in its natural form is classified as a class B drug in the UK (briefly between 2004 and 2009 it was downgraded to class C); its possession and supply remain illegal. The main active ingredient of the cannabis plant (Cannabis sativa) is delta-9-tetrahydrocannabinol (THC), which is available as a synthetic pharmaceutical product (Dronabinol, Marinol®). As THC is only one of over 60 cannabinoids, it is of course possible that its action is influenced by the presence of other cannabinoids. For this reason, studies and drug development have focused not only on the effectiveness of THC, but also on that of whole-plant extracts (available as THC:CBD oromucosal spray; nabiximols, Sativex: GW Pharma Ltd, UK). Nabiximols (THC:CBD) is an extract of Cannabis sativa L; it contains THC and CBD at a fixed ratio, delivered as an oromucosal spray, each 100 µL of which delivers 2.7 mg of THC and 2.5 mg of CBD.
Cannabis as a potential compound against various malignancies, legal aspects, advancement by exploiting nanotechnology and clinical trials
Published in Journal of Drug Targeting, 2022
Nazeer Hasan, Mohammad Imran, Afsana Sheikh, Suma Saad, Gaurav Chaudhary, Gaurav Kumar Jain, Prashant Kesharwani, Farhan J. Ahmad
Additionally, this study also demonstrated that THC showed a superior analgesic effect than codeine at the higher dose. However, its sedative effects may restrict the application of THC. A placebo-controlled, randomised, and double-blind study of nabiximols, an oromucosal spray combined with CBD and THC (1:1). This study was conducted on 360 patients against opioid-refractory pain and advanced cancer [88]. Patients received either the dose of nabiximols or placebo at high dose (11–16 sprays/day), medium dose (6–10 sprays/day), and low dose (1–4 sprays/day). The outcome of this study revealed that the medium and low doses of nabiximols exhibited better analgesic effects as compared to placebo after 5 weeks of treatment, while nabiximols at higher doses did not show any significant effects. The reason is subjects were not able to tolerate such a higher dose. Hence, nabiximol in required and optimised doses could be efficacious for advanced cancer and offer high-end therapeutic results in refractory pain associated with poorly ill patients. Another study was conducted by Johnson et al. [89] on 177 subjects with advanced cancer and uncontrolled cancer pain despite long-term opioid therapy. The study was conducted in various parts; placebo (59 patients), THC: CBD extract (60 patients), and THC extract (58 patients). The investigation exhibited that the pain was significantly reduced by THC: CBD, in which ∼30% reduction in pain was reported compared to the placebo group. Hence, many studies have already shown promising outcomes in cancer pain with the use of CBD.
A systematic review of European regional and national guidelines: a focus on the recommended use of nabiximols in the management of spasticity in multiple sclerosis
Published in Expert Review of Neurotherapeutics, 2022
Francisco Javier Carod-Artal, Peyman Adjamian, Carlos Vila Silván, Makarand Bagul, Claudio Gasperini
This analysis focussed on European guidelines, to reflect the more widespread regulatory approval of nabiximols in this region. Nabiximols is approved in several non-European countries including Israel, Colombia, Brazil, Chile, Peru, Canada, Australia, and New Zealand. To the best of our knowledge, these countries have not yet published any national guidelines covering the clinical use of nabiximols. One published guideline document from the USA recommended that ‘clinicians might offer Sativex oromucosal cannabinoid spray (nabiximols), where available, to reduce symptoms of spasticity, pain, or urinary frequency’ with a recommendation level of B (the second highest level) [36]. This is despite nabiximols not yet being approved in the USA [36]. Comparison of the similarities and differences between European guidelines and those published in other global regions is outside the scope of this review but may form the basis for future investigation.
Safety and tolerability of nabiximols oromucosal spray: a review of more than 15 years” accumulated evidence from clinical trials
Published in Expert Review of Neurotherapeutics, 2021
José María Prieto González, Carlos Vila Silván
Nabiximols (Sativex®, GW Pharma, Cambridge, UK) is an oromucosal spray containing a balanced ratio of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) as well as other cannabinoid and non-cannabinoid components [1]. The medicine is approved in several world regions as add-on therapy for symptomatic relief of moderate to severe spasticity due to multiple sclerosis (MS) in adults who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy [2]. Nabiximols was approved in the European Union (EU) based on pivotal randomized controlled trials (RCTs) demonstrating superior symptomatic improvement of moderate to severe MS spasticity versus placebo [3–5]. In the years before and decade since first approval of nabiximols in 2010, numerous other studies were or have been conducted in persons with MS spasticity or other conditions such as neuropathic pain and cancer pain.
Related Knowledge Centers
- Cancer Pain
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- Spasticity
- Cannabinoid
- Botanical Drug
- Multiple Sclerosis