“Cannabis sativa L. is an ancient medicinal plant wherefrom over 120 cannabinoids are extracted. In the past two decades, there has been increasing interest in the therapeutic potential of cannabis-based treatments for neurological disorders such as epilepsy, and there is now evidence for the medical use of cannabis and its effectiveness for a wide range of diseases. Cannabinoid treatments for pain and spasticity in patients with multiple sclerosis (Nabiximols) have been approved in several countries. Cannabidiol (CBD), in contrast to tetra-hydro-cannabidiol (THC), is not a controlled substance in the European Union, and over the years there has been increasing use of CBD-enriched extracts and pure CBD for seizure disorders, particularly in children. No analytical controls are mandatory for CBD-based products and a pronounced variability in CBD concentrations in commercialized CBD oil preparations has been identified. Randomized controlled trials of plant-derived CBD for treatment of Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) have provided evidence of anti-seizure effects, and in June 2018, CBD was approved by the Food and Drug Administration as an add-on antiepileptic drug for patients two years of age and older with LGS or DS. Medical cannabis, with various ratios of CBD and THC and in different galenic preparations, is licensed in many European countries for several indications, and in July 2019, the European Medicines Agency also granted marketing authorisation for CBD in association with clobazam, for the treatment of seizures associated with LGS or DS. The purpose of this article is to review the availability of cannabis-based products and cannabinoid-based medicines, together with current regulations regarding indications in Europe (as of July 2019). The lack of approval by the central agencies, as well as social and political influences, have led to significant variation in usage between countries.”
“The aim of this review article is to summarize current knowledge about the role of cannabinoids and cannabinoid receptors in tumor disease modulation and to evaluate comprehensively the use of cannabinoids in cancer patients.
According to the PRISMA protocol, we have included data from a total of 105 articles.
Cannabinoids affect cancer progression by three mechanisms. The most important mechanism is the stimulation of autophagy and affecting the signaling pathways leading to apoptosis. The most important mechanism of this process is the accumulation of ceramide. Cannabinoids also stimulate apoptosis by mechanisms independent of autophagy. Other mechanisms by which cannabinoids affect tumor growth are inhibition of tumor angiogenesis, invasiveness, metastasis, and the modulation of the anti-tumor immune response.
In addition to the symptomatic therapy of cancer patients, the antitumor effects of cannabinoids (whether in monotherapy or in combination with other cancer therapies) have promising potential in the treatment of cancer patients. More clinical trials are needed to demonstrate the antitumor effect of cannabinoids.”
“To determine if cannabis may be used as an alternative or adjunct treatment for intermittent and chronic prescription opioid users.
Design: Retrospective cohort study.
Setting: A single-center cannabis medical practice site in California.
Patients: A total of 180 patients who had a chief complaint of low back pain were identified (International Classification of Diseases, 10th Revision, code M54.5). Sixty-one patients who used prescription opioids were analyzed.
Interventions: Cannabis recommendations were provided to patients as a way to mitigate their low back pain.
Outcome Measures: Number of patients who stopped opioids and change in morphine equivalents.
Results: There were no between-group differences based on demographic, experiential, or attitudinal variables. We found that 50.8% were able to stop all opioid usage, which took a median of 6.4 years (IQR=1.75–11 years) after excluding two patients who transitioned off opioids by utilizing opioid agonists. For those 29 patients (47.5%) who did not stop opioids, 9 (31%) were able to reduce opioid use, 3 (10%) held the same baseline, and 17 (59%) increased their usage. Forty-eight percent of patients subjectively felt like cannabis helped them mitigate their opioid intake but this sentiment did not predict who actually stopped opioid usage. There were no variables that predicted who stopped opioids, except that those who used higher doses of cannabis were more likely to stop, which suggests that some patients might be able to stop opioids by using cannabis, particularly those who are dosed at higher levels.
Conclusions: In this long-term observational study, cannabis use worked as an alternative to prescription opioids in just over half of patients with low back pain and as an adjunct to diminish use in some chronic opioid users.”
“There is growing recognition of the potential utility of medical cannabis as a harm reduction intervention.
Although used for this indication in other countries, there is an absence of UK clinical guidelines that supports such an approach. We administered a short survey to gain a better understanding of the potential role of medical cannabis by 39 people who were currently using illicit cannabis and accessing a specialist substance misuse treatment service.
It was identified that 36 (92.3%) respondents found that cannabis positively impacted upon their physical and/or mental wellbeing and 56.4% reported that they used less of other substances which are known to be more harmful as a result.
Therefore, while we acknowledge the small sample size, given the notable potential positive impact that medical cannabis could have as a harm reduction intervention, we propose that the use should be trialled within a specialist drug treatment setting.”
“Contact hypersensitivity (CHS) is an established animal model for allergic contact dermatitis. Dendritic cells (DCs) play an important role in the sensitization phase of CHS by initiating T cell responses to topically applied haptens. The cannabinoid receptors 1 (CB1) and 2 (CB2) modulate DC functions and inflammatory skin responses, but their influence on the capacity of haptenized DCs to induce CHS is still unknown. We found lower CHS responses to 2,4-dinitro-1-fluorobenzene (DNFB) in wild type (WT) mice after adoptive transfer of haptenized Cnr2-/- and Cnr1-/-/Cnr2-/- bone marrow (BM) DCs as compared to transfer of WT DCs. In contrast, induction of CHS was not affected in WT recipients after transfer of Cnr1-/- DCs. In vitro stimulated Cnr2-/- DCs showed lower CCR7 and CXCR4 expression when compared to WT cells, while in vitro migration towards the chemokine ligands was not affected by CB2. Upregulation of MHC class II and co-stimulatory molecules was also reduced in Cnr2-/- DCs. This study demonstrates that CB2 modulates the maturation phenotype of DCs but not their chemotactic capacities in vitro. These findings and the fact that CHS responses mediated by Cnr2-/- DCs are reduced suggest that CB2 is a promising target for the treatment of inflammatory skin conditions.”
“Several natural compounds have demonstrated potential for the treatment of central nervous system disorders such as ischemic cerebrovascular disease, glioblastoma, neuropathic pain, neurodegenerative diseases, multiple sclerosis and migraine.
This is due to their well-known antioxidant, anti-inflammatory, neuroprotective, anti-tumor, anti-ischemic and analgesic properties. Nevertheless, many of these molecules have poor aqueous solubility, low bioavailability and extensive gastrointestinal and/or hepatic first-pass metabolism, leading to a quick elimination as well as low serum and tissue concentrations.
Thus, the intranasal route emerged as a viable alternative to oral or parenteral administration, by enabling a direct transport into the brain through the olfactory and trigeminal nerves. With this approach, the blood-brain barrier is circumvented and peripheral exposure is reduced, thereby minimizing possible adverse effects.
Herein, brain-targeting strategies for the nose-to-brain delivery of natural compounds, including flavonoids, cannabinoids, essential oils and terpenes, will be reviewed and discussed. Brain and plasma pharmacokinetics of these molecules will be analyzed and related to their physicochemical characteristics and formulation properties.
Natural compounds constitute relevant alternatives for the treatment of brain diseases but often require loading into nanocarrier systems to reach the central nervous system in sufficient concentrations. Future challenges lie in a deeper characterization of their therapeutic mechanisms and in the development of effective, safe and brain-targeted delivery systems for their intranasal administration.”
“Neurofibromatosis type 1 (NF1) is a common genetic disorder. Pain is a major symptom of this disease which can be secondary to the development of plexiform and subcutaneous neurofibromas, musculoskeletal symptoms (such as scoliosis and pseudoarthrosis), and headaches. Visible neurofibromas add significant psychosocial distress for NF1 patients. Along with the chronic pain, psychosocial distress contributes to associated mood disorders, such as depression and anxiety.
Cannabis has been the focus of many studies for treating multiple conditions, including epilepsy, multiple sclerosis, Parkinsonism disease, and many chronic pain conditions. Cannabidiol (CBD) is the major non-psychotropic component of cannabis. CBD has shown anti-inflammatory and analgesic properties, as well as having mood stabilizer and anxiolytic effects.
In this report, we present the use of cannabidiol (CBD) for the management of chronic pain and concomitant mood disorder in an NF1 patient.”
“Confident relationships between diabetes and liver damage have previously been established.
This study was designed to evaluate hepaticinflammation, apoptosis, and endocannabinoid system alterations in diabetes with or without tropisetron treatment.
These findings strongly support the idea that diabetes-induced liver abnormality is mediated by inflammatory reactions, apoptosis, and endocannabinoid system, and that these effects can be alleviated by using tropisetron as an antioxidant and anti-inflammatory agent.”
“Endometriosis is a chronic painful disease highly prevalent in women that is defined by growth of endometrial tissue outside the uterine cavity and lacks adequate treatment.
Medical use of cannabis derivatives is a current hot topic and it is unknown whether phytocannabinoids may modify endometriosis symptoms and development.
Here we evaluate the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) in a mouse model of surgically-induced endometriosis.
In this model, female mice develop mechanical hypersensitivity in the caudal abdomen, mild anxiety-like behavior and substantial memory deficits associated with the presence of extrauterine endometrial cysts.
Interestingly, daily treatments with THC (2 mg/kg) alleviate mechanical hypersensitivity and pain unpleasantness, modify uterine innervation and restore cognitive function without altering the anxiogenic phenotype. Strikingly, THC also inhibits the development of endometrial cysts.
These data highlight the interest of scheduled clinical trials designed to investigate possible benefits of THC for women with endometriosis.”
“CBD was shown to have anti-seizure activity based on in vitro and in vivo models.
However, several reports of small series or case reports of the use of cannabis extracts in epilepsy yielded contradictory results and the efficacy of cannabis use in patients with epilepsy have also been inconclusive.
In 2013, the first Phase 1 trial for a purified form of CBD (Epidiolex/Epidyolex; >99% CBD), developed by GW Pharma, showed some efficacy signals and subsequently, a comprehensive program on the efficacy and tolerability of this compound for the treatment of drug-resistant epilepsies was initiated.
Results of these trials led to the FDA and EMA approval respectively in 2018 and 2019 for the treatment of seizures associated with two rare epilepsies: Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients two years of age and older.
Thus, CBD became the first FDA-approved purified drug substance derived from cannabis and also the first FDA-approved drug for the treatment of seizures in DS.
We detail the clinical studies using purified CBD (Epidiolex/Epidyolex), including the first open interventional exploratory study and Randomized Control Ttrials for DS and LGS.”