Effect of adding medical cannabis to analgesic treatment in patients with low back pain related to fibromyalgia: an observational cross-over single centre study.

Image result for Clin Exp Rheumatol.

“Low back pain (LBP) occurs in many patients with fibromyalgia (FM). The current study aimed to assess the possible pain and function amelioration associated with medical cannabis therapy (MCT) in this setting.

METHODS:

31 patients were involved in an observational cross-over study. The patients were screened, treated with 3 months of standardised analgesic therapy (SAT): 5 mg of oxycodone hydrochloride equivalent to 4.5 mg oxycodone and 2.5 mg naloxone hydrochloride twice a day and duloxetine 30 mg once a day. Following 3 months of this therapy, the patients could opt for MCT and were treated for a minimum of 6 months. Patient reported outcomes (PRO’s) included: FIQR, VAS, ODI and SF-12 and lumbar range of motion (ROM) was recorded using the modified Schober test.

RESULTS:

While SAT led to minor improvement as compared with baseline status, the addition of MCT allowed a significantly higher improvement in all PRO’s at 3 months after initiation of MCT and the improvement was maintained at 6 months. ROM improved after 3 months of MCT and continued to improve at 6 months.

CONCLUSIONS:

This observational cross-over study demonstrates an advantage of MCT in FM patients with LBP as compared with SAT. Further randomised clinical trial studies should assess whether these results can be generalised to the FM population at large.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Light-activatable cannabinoid prodrug for combined and target-specific photodynamic and cannabinoid therapy.

“Cannabinoids are emerging as promising antitumor drugs. However, complete tumor eradication solely by cannabinoid therapy remains challenging. In this study, we developed a far-red light activatable cannabinoid prodrug, which allows for tumor-specific and combinatory cannabinoid and photodynamic therapy. This prodrug consists of a phthalocyanine photosensitizer (PS), reactive oxygen species (ROS)-sensitive linker, and cannabinoid. It targets the type-2 cannabinoid receptor (CB2R) overexpressed in various types of cancers. Upon the 690-nm light irradiation, the PS produces cytotoxic ROS, which simultaneously cleaves the ROS-sensitive linker and subsequently releases the cannabinoid drug. We found that this unique multifunctional prodrug design offered dramatically improved therapeutic efficacy, and therefore provided a new strategy for targeted, controlled, and effective antitumor cannabinoid therapy.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabinoids in depressive disorders.

 Life Sciences “Cannabis sativa is one of the most popular recreational and medicinal plants. Benefits from use of cannabinoid agents in epilepsy, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and others have been suggested. It seems that the endocannabinoid system is also involved in the pathogenesis and treatment of depression, though its role in this mental disease has not been fully understood yet. Both the pro- and antidepressant activity have been reported after cannabis consumption and a number of pre-clinical studies have demonstrated that both agonist and antagonist of the endocannabinoid receptors act similarly to antidepressants. Responses to the cannabinoid agents are relatively fast, and most probably, the noradrenergic, serotoninergic, glutamatergic neurotransmission, neuroprotective activity, as well as modulation of the hypothalamic-pituitary-adrenal axis are implicated in the observed effects. Based on the published data, the endocannabinoid system evidently gives novel ideas and options in the field of antidepressant treatment, however further studies are needed to determine which group of patients could benefit from this type of therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/30290188

https://www.sciencedirect.com/science/article/pii/S0024320518306040?via%3Dihub

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Genetic and pharmacological regulation of the endocannabinoid CB1 receptor in Duchenne muscular dystrophy.

 Nature Communications

“The endocannabinoid system refers to a widespread signaling system and its alteration is implicated in a growing number of human diseases.

However, the potential role of endocannabinoids in skeletal muscle disorders remains unknown. Here we report the role of the endocannabinoid CB1 receptors in Duchenne’s muscular dystrophy.

In murine and human models, CB1 transcripts show the highest degree of expression at disease onset, and then decline overtime. Similar changes are observed for PAX7, a key regulator of muscle stem cells. Bioinformatics and biochemical analysis reveal that PAX7 binds and upregulates the CB1 gene in dystrophic more than in healthy muscles.

Rimonabant, an antagonist of CB1, promotes human satellite cell differentiation in vitro, increases the number of regenerated myofibers, and prevents locomotor impairment in dystrophic mice.

In conclusion, our study uncovers a PAX7-CB1 cross talk potentially exacerbating DMD and highlights the role of CB1 receptors as target for potential therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/30262909

“We propose that the endocannabinoid system participates in the development of degenerative muscle disease, through effects on muscle differentiation, regeneration, and repair processes, and suggest that CB1 receptor may represent a potential target for the adjuvant therapy of muscle dystrophies.”

https://www.nature.com/articles/s41467-018-06267-1

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Bortezomib And Endocannabinoid/Endovanilloid System: A Synergism In Osteosarcoma.

Pharmacological Research

“Osteosarcoma is the most common primary malignant tumor of bone in children and adolescents.

Bortezomib (BTZ) is an approved anticancer drug, classified as a selective reversible inhibitor of the ubiquitin-dependent proteasome system, that leads to cancer cell cycle arrest and apoptosis reducing the invasion ability of Osteosarcoma cells in vitro. It also regulates the RANK/RANKL/OPG system, involved in the pathogenesis of bone tumors and in cell migration.

A side effect of BTZ is to induce painful sensory peripheral neuropathy which lead to cessation of therapy or dose reduction.

Recently BTZ has been evaluated in combination with Cannabinoids targeting CB1 receptor, demonstrating a promising synergic effect.

The Endocannabinoid/Endovanilloid (EC/EV) system includes two G protein-coupled receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel and their endogenous ligands and enzymes.

CB1 and CB2 are expressed mainly in Central Nervous System and Immune Peripheral cells respectively. TRPV1 is also expressed in primary sensory neurons and is involved in pain modulation.

EC/EV system induces apoptosis, reduces invasion and cell proliferation in Osteosarcoma cell lines and is involved in bone metabolism.

We analyzed the effects of BTZ, alone and in combination with selective agonists at CB2 (JWH-133) and TRPV1 (RTX) receptors, in the Osteosarcoma cell line (HOS) on Apoptosis, Cell Cycle progression, migration and bone balance. We observed that the stimulation of CB2 and TRPV1 receptors increase the efficacy of BTZ in inducing apoptosis and reducing invasion, cell cycle progression and by modulating bone balance.

These data suggest the possibility to use BTZ, in combination with EC/EV agonists, in Osteosarcoma therapy reducing its dose and its side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/30267762

https://www.sciencedirect.com/science/article/abs/pii/S1043661818310387

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome.

 Annals of Clinical and Translational Neurology banner

“Both Δ9 Tetrahydrocannabidiol (THC) and cannabidiol (CBD) components of cannabis, have been shown to have anticonvulsant effects.

Cannabis oils are used to treat seizures in drug-resistant epilepsy (DRE). Recent trials provide data on dosing, side effects, and efficacy of CBD, yet there is a paucity of information on THC in epilepsy.

Primary objective was to establish dosing and tolerability of TIL-TC150 – a cannabis plant extract produced by Tilray®, containing 100 mg/mL CBD and 2 mg/mL THC- in children with Dravet syndrome. Secondary objectives were to assess impact of therapy on seizures, electroencephalogram (EEG) and quality of life.

RESULTS:

Nineteen participants completed the 20-week intervention. Mean dose achieved was 13.3 mg/kg/day of CBD (range 7-16 mg/kg/day) and 0.27 mg/kg/day of THC (range 0.14-0.32 mg/kg/day). Adverse events, common during titration included somnolence, anorexia, and diarrhea. Abnormalities of liver transaminases and platelets were observed with concomitant valproic acid therapy. There was a statistically significant improvement in quality of life, reduction in EEG spike activity, and median motor seizure reduction of 70.6%, with 50% responder rate of 63%.

CONCLUSIONS:

TIL-TC150 was safe and well tolerated in our subjects. TIL-TC150 treatment resulted in a reduction in seizure counts, spike index on EEG, and improved quality of life measures. This study provides safety and dosing information for THC-containing cannabinoid preparations.”

https://www.ncbi.nlm.nih.gov/pubmed/30250864

https://onlinelibrary.wiley.com/doi/abs/10.1002/acn3.621

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Combined CB2 Receptor Agonist and Photodynamic Therapy Synergistically Inhibit Tumor Growth in Triple Negative Breast Cancer.

Photodiagnosis and Photodynamic Therapy

“Triple negative breast cancer (TNBC) is the deadliest form of breast cancer because compared with other types of breast cancer, it is more aggressive, diagnosed at later stage and more likely to develop recurrence.

Many patients do not experience adequate tumor control after current clinical treatments involving surgical removal, chemotherapy and/or radiotherapy, leading to disease progression and significantly decreased quality of life.

Here we report a new combinatory therapy strategy involving cannabinoid-based medicine and photodynamic therapy (PDT) for the treatment of TNBC.

This combinatory therapy targets two proteins upregulated in TNBC: the cannabinoid CB2 receptor (CB2R, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the combined CB2R agonist and TSPO-PDT treatment resulted in synergistic inhibition in TNBC cell and tumor growth.

This combinatory therapy approach provides new opportunities to treat TNBC with high efficacy. In addition, this study provides new evidence on the therapeutic potential of CB2R agonists for cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/30240926

https://www.sciencedirect.com/science/article/pii/S1572100018301571?via%3Dihub

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: a study protocol for a pilot and definitive randomised double-blind placebo-controlled trial (CannabisCINV).

BMJ Journals

“Chemotherapy-induced nausea and vomiting (CINV) remains an important issue for patients receiving chemotherapy despite guideline-consistent antiemetic therapy. Trials using delta-9-tetrahydrocannabinol-rich (THC) products demonstrate limited antiemetic effect, significant adverse events and flawed study design. Trials using cannabidiol-rich (CBD) products demonstrate improved efficacy and psychological adverse event profile. No definitive trials have been conducted to support the use of cannabinoids for this indication, nor has the potential economic impact of incorporating such regimens into the Australian healthcare system been established. CannabisCINV aims to assess the efficacy, safety and cost-effectiveness of adding TN-TC11M, an oral THC/CBD extract to guideline-consistent antiemetics in the secondary prevention of CINV.

METHODS AND ANALYSIS:

The current multicentre, 1:1 randomised cross-over, placebo-controlled pilot study will recruit 80 adult patients with any malignancy, experiencing CINV during moderate to highly emetogenic chemotherapy despite guideline-consistent antiemetics. Patients receive oral TN-TC11M (THC 2.5mg/CBD 2.5 mg) capsules or placebo capsules three times a day on day -1 to day 5 of cycle A of chemotherapy, followed by the alternative drug regimen during cycle B of chemotherapy and the preferred drug regimen during cycle C. The primary endpoint is the proportion of subjects attaining a complete response to CINV. Secondary and tertiary endpoints include regimen tolerability, impact on quality of life and health system resource use. The primary assessment tool is patient diaries, which are filled from day -1 to day 5. A subsequent randomised placebo-controlled parallel phase III trial will recruit a further 250 patients.

ETHICS AND DISSEMINATION:

The protocol was approved by ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences.”

https://www.ncbi.nlm.nih.gov/pubmed/30209152

https://bmjopen.bmj.com/content/8/9/e020745

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabidiol as a suggested candidate for treatment of autism spectrum disorder.

 Progress in Neuro-Psychopharmacology and Biological Psychiatry “Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication, restricted and repetitive patterns of behavior, interests, or activities and often intellectual disabilities.

No effective treatment for the core symptoms of ASD is currently available.

There is increasing interest in cannabinoids, especially cannabidiol (CBD), as monotherapy or add-on treatment for the core symptoms and co-morbidities of ASD.

In this review we summarize the available pre-clinical and clinical data regarding the safety and effectiveness of medical cannabis, including CBD, in young ASD patients.

Cannabidiol seems to be a candidate for the treatment of ASD.”

https://www.ncbi.nlm.nih.gov/pubmed/30171992

https://www.sciencedirect.com/science/article/pii/S0278584618304445?via%3Dihub

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Variability of Multiple Sclerosis Spasticity Symptoms in Response to THC:CBD Oromucosal Spray: Tracking Cases through Clinical Scales and Video Recordings.

Logo Case Reports in Neurology

“Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune demyelinating disease of the central nervous system. Patients exhibit heterogeneous patterns of disabling symptoms, including spasticity. In the majority of patients with MS spasticity, it and its associated symptoms contribute to disability, interfere with performance of everyday activities, and impair quality of life. Even under treatment with oral antispasticity drugs, about a third of patients continue to experience spasticity of moderate to severe intensity, underscoring the need for additional treatment options.

The efficacy of tetrahydrocannabinol: cannabidiol (THC:CBD) oromucosal spray as add-on therapy in patients with refractory MS spasticity has been demonstrated in clinical trials and observational studies.

To gain insight into patients’ response to treatment at the individual level, in-depth changes from baseline in various clinical scales and video-assessed parameters were evaluated in patients with resistant MS spasticity before and after 1 month of treatment with THC:CBD oromucosal spray. All 6 patients showed ≥20% improvement in the spasticity Numerical Rating Scale (i.e., were initial responders to treatment), but displayed individual variability in other spasticity-related parameters.

Improved Modified Ashworth Scale scores were observed in 5 cases, with a reduction of -2/-3 points in lower limb scores for 1 patient who also showed benefit in terms of a more stable gait but modest improvement in the timed 10-meter walk test (10MWT). Improvement in the 10MWT (or 25-foot walk test) was noted in 4 of the 6 cases. THC:CBD oromucosal spray also improved upper limb function as indicated by faster 9-Hole Peg Test results.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous