[Therapeutic potential of Cannabis sativa].

SciELO - Scientific Electronic Library Online

“Cannabis sativa (marihuana) is considered an illicit drug due to its psychoactive properties. Recently, the Chilean government opened to the use cannabis in the symptomatic treatment of some patients. The biological effects of cannabis render it useful for the complementary treatment of specific clinical situations such as chronic pain. We retrieved scientific information about the analgesic properties of cannabis, using it as a safe drug. The drug may block or inhibit the transmission of nervous impulses at different levels, an effect associated with pain control. Within this context and using adequate doses, forms and administration pathways, it can be used for chronic pain management, considering its effectiveness and low cost. It could also be considered as an alternative in patients receiving prolonged analgesic therapies with multiple adverse effects.”

Single and combined effects of delta9 -tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain.

British Journal of Pharmacology

“It has been suggested that the non-psychoactive phytocannabinoid cannabidiol (CBD) can impact the pharmacological effects of delta-9-tetrahydrocannabinol (THC). We tested the hypothesis that CBD and THC would significantly mitigate mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain, and that CBD+THC combinations would produce synergistic effects. We also tested the hypothesis that CBD would attenuate oxaliplatin- and vincristine- induced mechanical sensitivity.

KEY RESULTS:

Both CBD and THC alone attenuated mechanical allodynia in mice treated with paclitaxel. Very low ineffective doses of CBD and THC were synergistic when given in combination. CBD also attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity, while THC significantly attenuated vincristine- but not oxaliplatin-induced mechanical sensitivity. The low dose combination significantly attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity.

CONCLUSIONS AND IMPLICATIONS:

CBD may be potent and effective at preventing the development of CIPN, and its clinical utility may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of Cannabis-based pharmacotherapies.”

https://www.ncbi.nlm.nih.gov/pubmed/28548225

http://onlinelibrary.wiley.com/doi/10.1111/bph.13887/abstract

Modulation of CB1 cannabinoid receptor by allosteric ligands: Pharmacology and therapeutic opportunities.

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“Cannabinoid pharmacology has been intensely studied because of cannabis’ pervasive medicinal and non-medicinal uses as well as for the therapeutic potential of cannabinoid-based drugs for the treatment of pain, anxiety, substance abuse, obesity, cancer and neurodegenerative disorders. The identification of allosteric modulators of the cannabinoid receptor 1 (CB1) has given a new direction to the development of cannabinoid-based therapeutics due to the many advantages offered by targeting allosteric site(s). Allosteric receptor modulators hold potential to develop subtype-specific and pathway-specific therapeutics. Here we briefly discuss the first-generation of allosteric modulators of CB1 receptor, their structure-activity relationships, signaling pathways and the allosteric binding site(s) on the CB1 receptor.”

https://www.ncbi.nlm.nih.gov/pubmed/28527758

http://www.sciencedirect.com/science/article/pii/S0028390817302307

Systematic review of the potential role of cannabinoids as antiproliferative agents for urological cancers.

“The palliative effects of cannabis sativa (marijuana), which include appetite stimulation, attenuation of nausea and emesis, and pain relief, are well known.

The active components of cannabis sativa (cannabinoids) and their derivatives have received growing interest due to their diverse pharmacological activities, such as cell growth inhibition and tumour regression.

The aim of this review is to look at the current evidence on the antiproliferative effects of cannabinoids in urological malignancies, including renal, prostate, bladder, and testicular cancers.

The search yielded a total of 93 studies from Medline and PubMed, of which 23 studies were included in the final analysis. To date, there are various in vitro studies elucidating the potential mechanism of action of cannabinoids for urological cancers, along with population-based studies specifically for testicular malignancies. To date, no clinical trials have been conducted for urological cancer patients.

These results demonstrate that the role of endocannabinoids for urological malignancies is an area of active research. Further research is required not only to evaluate the crosstalk between cancer signaling pathways and cannabinoids, but also large randomized clinical studies with urological patients need to be conducted before cannabinoids can be introduced as potential therapeutic options for urological neoplasms.”

https://www.ncbi.nlm.nih.gov/pubmed/28515817

http://www.cuaj.ca/index.php/journal/article/view/4371

Cannabis as medicine

Image result for the BMJ

“Evidence supports reform to allow the legitimate study, regulation, and prescription of therapeutic cannabinoids.hemp

From its first recorded uses in China through to the early 20th century, cannabis has had a place in the pharmacopoeia. Queen Victoria’s personal physician, Russel Reynolds, opined in the Lancet in 1890, “Indian hemp, when pure and administered carefully, is one of the most valuable medicines we possess.” This opinion was based on current best evidence: the careful and documented observation of its effects in medical conditions.

In a similar vein, calls have been made to reconsider the role of cannabis in today’s society. Two well informed British politicians recently told The BMJ, “We have heard striking testimonies from patients… that cannabis has ‘given them their life back.’” Added to this, the international position on cannabis as a potential medication has changed, with international agencies and many governments relaxing a prohibitionist stance.”

http://www.bmj.com/content/357/bmj.j2130

Neuroprotection in oxidative stress-related neurodegenerative diseases: role of endocannabinoid system modulation.

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“Redox imbalance may lead to overproduction of reactive oxygen and nitrogen species (ROS/RNS) and subsequent oxidative tissue damage which is a critical event in the course of neurodegenerative diseases. It is still not fully elucidated, however, whether oxidative stress is the primary trigger or a consequence in process of neurodegeneration.

Recent Advances: Increasing evidence suggests that oxidative stress is involved in the propagation of neuronal injury and consequent inflammatory response, which in concert promote development of pathological alterations characteristic of most common neurodegenerative diseases.

Critical Issue: Accumulating recent evidence also suggests that there is an important interplay between the lipid endocannabinoid system (ECS; comprising of the main cannabinoid 1 and 2 receptors (CB1 and CB2), endocannabinoids and their synthetic and metabolizing enzymes) and various key inflammatory and redox-dependent processes.

FUTURE DIRECTIONS:

Targeting the ECS in order to modulate redox state-dependent cell death, and to decrease consequent or preceding inflammatory response holds therapeutic potential in multitude of oxidative stress-related acute or chronic neurodegenerative disorders from stroke and traumatic brain injury to Alzheimer`s and Parkinson`s diseases, and multiple sclerosis, just to name a few, which will be discussed in this overview.”

Cannabidiol administration reduces sublesional cancellous bone loss in rats with severe spinal cord injury.

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“Patients with spinal cord injury (SCI) undergo severe loss of bone mineral below the level of lesion, and data on available treatment options after SCI is scarce.

The aim of this work was to investigate the therapeutic effect of cannabidiol (CBD), a non-psychoactive cannabis, on sublesional bone loss in a rat model of SCI.

In conclusion, CBD administration attenuated SCI-induced sublesional cancellous bone loss.”

https://www.ncbi.nlm.nih.gov/pubmed/28479140

http://www.sciencedirect.com/science/article/pii/S0014299917303230

Comparative in silico analyses of Cannabis sativa, Prunella vulgaris and Withania somnifera compounds elucidating the medicinal properties against rheumatoid arthritis

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“From last decade, there has been progressive improvement in computational drug designing. Several diseases are being cured from different plant extracts and products.

Rheumatoid arthritis (RA) is the most shared disease among auto-inflammatory diseases. Tumor necrosis factor (TNF)-α is associated with RA pathway and has adverse effects.

Extensive literature review showed that plant species under study (Cannabis sativa, Prunella vulgaris and Withania somnifera) possess anti-inflammatory, anti-arthritic and anti-rheumatic properties.

13 anti-inflammatory compounds were characterized and filtered out from medicinal plant species and analyzed for RA by targeting TNF-α through in silicoanalyses. By using ligand based pharmacophore generation approach and virtual screening against natural products libraries we retrieved twenty unique molecules that displayed utmost binding affinity, least binding energies and effective drug properties. The docking analyses revealed that Ala-22, Glu-23, Ser-65, Gln-67, Tyr-141, Leu-142, Asp-143, Phe-144 and Ala-145 were critical interacting residues for receptor-ligand interactions.

It is proposed that the RA patients should use reported compounds for the prescription of RA by targeting TNF-α. This report is opening new dimensions for designing innovative therapeutic targets to cure RA.”

https://www.ncbi.nlm.nih.gov/pubmed/28472734

http://www.sciencedirect.com/science/article/pii/S1093326317302735

Combined cannabinoid therapy via an oromucosal spray.

“Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects.”  https://www.ncbi.nlm.nih.gov/pubmed/16969427

“Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.”  https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=4&p_RefId=1021517

“Sativex(®) (nabiximols, USAN name) oromucosal spray contains the two main active constituents of Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 molecular ratio, and acts as an endocannabinoid system modulator.”  https://www.ncbi.nlm.nih.gov/pubmed/21449855

“Abuse potential and psychoactive effects of δ-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine. Evidence to date suggests that abuse or dependence on Sativex is likely to occur in only a very small proportion of recipients.” https://www.ncbi.nlm.nih.gov/pubmed/21542664

GPR55 and the regulation of glucose homeostasis.

Image result for Int J Biochem Cell Biol.

“Pathophysiological conditions such as obesity and type 2 diabetes (T2D) are reportedly associated to over-activation of the endocannabinoid system (ECS). Therefore, modulation of the ECS offers potential therapeutic benefits on those diseases. GPR55, the receptor for L-α-lysophosphatidylinositol (LPI) that has also affinity for various cannabinoid ligands, is distributed at the central and peripheral level and it is involved in several physiological processes. This review summarizes the localization and role of GPR55 in tissues that are crucial for the regulation of glucose metabolism, and provides an update on its contribution in obesity and insulin resistance. The therapeutic potential of targeting the GPR55 receptor is also discussed.”

https://www.ncbi.nlm.nih.gov/pubmed/28457969