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

Abstract

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.

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…Furthermore, in patients with advanced cancer, the ⌬ 9 -THC:CBD extract, unlike ⌬ 9 -THC extract only, produced significantly stronger relief of pain than placebo (404). Sativex was well tolerated, and there was no loss of effect with longterm use (405). A randomized, placebo-controlled study shows that low dose (1-4 sprays/day) and medium dose (6 -10 sprays/day) of Sativex is more efficacious than high dose (11-16 sprays/day) against pain (690).…”

Phytotherapeutical implications in pain perception - focusing on schizophrenia

“…Already famous for its analgesic proprieties, even recent studies demonstrating that its psychoinactive component, cannabidiol (CBD) has possible positive effects on neuropathic pain [68] also shows potential in treating psychotic symptomatology, CBD looking to carry a pharmacological profile comparable to that of an atypical antipsychotic [69]. From the compounds belonging to C. Sativa, cannabinoids are the most representative ones and possess proven efficacy in the treatment of neuropathic pain [70], but their area of pain treatment is larger including cancer pain [71], rheumatoid arthritis [72], improves spasticity in MS patients [73] and also might be an answer to neuropathic orofacial pain [70]. Evidence suggests the possibility that cannabidiol the non-psychoactive component of C. Sativa, also plays a role of relief in inflammatory pain, reversing thermal and mechanical hyperalgesia induced in inflammatory pain animal models [68].…”

“…At the same time, a tolerance/dependence statistic has not been assessed for Cesamet® (Nabilone, Meda Pharmaceuticals, Somerset, New Jersey, USA) and regarding Marinol® (Dronabinol, Abbvie Inc., North Chicago, ILN, USA), new evidence suggests the presence of a psychoactive effect resembling the one met in cannabis use if utilized in the treatment of chronic non-cancer pain patients [81]. On the other hand, Sativex® (GW Pharmaceuticals, Salisbury, UK) composed by plant-derived cannabinoids THC and cannabidiol provided analgesic reaction to cancer pain [71] and to neuropathic pain encountered in MS [82], even ameliorating longterm spasticity in MS patients [73]. Considering the analgesic effect that Sativex® (GW Pharmaceuticals, Salisbury, UK) manifests over cancer pain and knowing that in the case of schizophrenia there is encountered a high rate of cancer occurrence [83,84,85], it can be speculated that the cannabinoidic compound might also ameliorate or cure pain in the context of schizophrenia.…”

“…Because current results are in need of confirmation we are eager to engage in this controversial research. We present below several plants relevant for pain and/or schizophrenia in the Antihypertensive [51],hypoglycaemic [52], wound healing [53], anti-HIV [54], antidepressant [55], antihelmitic, aphrodisiac [56], treatment of diarrhea, urinary disorders and skin disorders [57] Cannabis sativa (Cannabaceae) cannabidiol (CBD) -neuropathic pain [68,70], inflammatory pain [68], cancer pain [71]; cannabingerol (CBG) -intestinal inflammation pain [76,77]; cannabinoids -cancer pain [71], rheumatoid arthritis pain [72], neuropathic orofacial pain [70]; THC(∆ 9 -tetrahydrocannabidiol) -cancer pain [71] CBDPharmacological profile similar to atypical antipsychotic [69], antipsychotic effect (86) hallucinogen proprieties [67]; ∆ 9 -tetrahydrocannabidiol (THC) -potential schizophrenia outcomes [87]; cannabinoidsimproves spasticity in MS patients [73]; CBDtreatment of intestinal inflammation [76,77] diuretic, anti-emetic, antiepileptic, anti-inflammatory, painkilling and antipyretic properties [97] Corydalis yanhuso (Papaveraceae) Antinociceptive effect in pain animal models, inflammatory pain relief amendment of neuropathic pain [93] anxiolytic properties [98]; primary dysmenorrhea [99]; improve the efficacy of chemotherapy [100]; extract -attenuated cardiac hypertrophy [101]; treatment of various pains [98], insomnia, reducing inflammation and several compounds present antidepressant, antimicrobial and anti-inflammatory activities [95], sedative, and hypnotic properties …”

An Overview of Products and Bias in Research

“…It has been used in studies of the treatment of multiple sclerosis (MS)-related spasticity, neuropathic pain, and bladder complaints. It has also been used in studies considering its role in the treatment of neuropathic and cancer pain [17][18][19]. Nabiximols are indicated in the UK for the treatment of moderate-to-severe spasticity related to MS, which has not responded adequately to other antispasticity medication.…”