Cannabis Therapeutics and the Future of Neurology.

Image result for frontiers in integrative neuroscience

“Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes.

While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain.

This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE).

Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB1 and CB2 (tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), 5-HT1A (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics.

The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/30405366

https://www.frontiersin.org/articles/10.3389/fnint.2018.00051/full

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Combined THC and CBD to treat pain in epidermolysis bullosa: a report of three cases.

British Journal of Dermatology banner

“Epidermolysis bullosa (EB) is a genetic blistering disorder characterized by intense pain related to disease pathology and care-based interventions. Opioid-based therapies underpin pain-care in EB however are unable to provide adequate analgesia in a significant proportion of patients. Cannabinoid-based medicines (CBMs) have been increasingly studied for pain conditions of various etiologies and pose as a novel dimension for pain-care in EB. We present three cases of EB who were prescribed pharmaceutical-grade sublingually administered CBMs comprising tetrahydrocannabinol (THC) and cannabidiol (CBD). All three patients reported improved pain scores, reduced pruritus and reduction in overall analgesic drug intake. ”

https://www.ncbi.nlm.nih.gov/pubmed/30347109

https://onlinelibrary.wiley.com/doi/abs/10.1111/bjd.17341

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

Cannabis in palliative care: current challenges and practical recommendations.

 “Pain and symptom control challenges are common in palliative care, and the search for other therapeutic strategies is ongoing.

Unfortunately, patients and their caregivers are receiving little information or support from healthcare providers regarding the increasingly popular cannabinoid-based medicines (CBM).

Clinicians, meanwhile, feel understandably perplexed by the discrepancy between the available evidence and the rapid interest in which patients and their families have demonstrated for CBM.

There is an urgent need to address the many challenges that are delaying the appropriate integration of CBM into clinical practice, notwithstanding the obvious need for a solid general knowledge of pharmacology, mechanism of action and available clinical evidence supporting its use.

The authors will address these challenges and provide practical recommendations regarding patient assessment for the use of CBM. The authors will also make suggestions regarding patient expectations in order to define clear objectives, review the necessary precautions prior to initiating treatment, aid in selecting the appropriate strain and route of administration as well as establishing proper titration and monitoring protocols. The authors will also discuss the lesser known but potentially therapeutic psychoactive effects of cannabis.

As this class of therapeutic agents are likely to play a major role in palliative medicine in the near future, clinicians would benefit from familiarizing themselves with CBM and we can expect that patients and their caregivers will appreciate receiving support in their search for safe and effective therapeutic alternatives.”

https://www.ncbi.nlm.nih.gov/pubmed/30180728

http://apm.amegroups.com/article/view/20097

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabis and cannabinoid drug development: evaluating botanical versus single molecule approaches.

Publication Cover

“Accumulating evidence suggests that the endocannabinoid system is a promising target for the treatment of a variety of health conditions.

Two paths of cannabinoid drug development have emerged. One approach is focused on developing medications that are directly derived from the cannabis plant. The other utilizes a single molecule approach whereby individual phytocannabinoids or novel cannabinoids with therapeutic potential are identified and synthesized for pharmaceutical development.

This commentary discusses the unique challenges and merits of botanical vs single molecule cannabinoid drug development strategies, highlights how both can be impacted by legalization of cannabis via legislative processes, and also addresses regulatory and public health considerations that are important to consider as cannabinoid medicine advances as a discipline.”

https://www.ncbi.nlm.nih.gov/pubmed/30179534

https://www.tandfonline.com/doi/abs/10.1080/09540261.2018.1474730?journalCode=iirp20

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Should Cannabinoids Be Added to Multimodal Pain Regimens After Total Hip and Knee Arthroplasty?

Journal of Arthroplasty Home

“This study investigated the effects of dronabinol on pain, nausea, and length of stay following total joint arthroplasty (TJA).

CONCLUSION:

These findings suggest that further investigation into the role of cannabinoid medications for non-opioid pain control in the post-arthroplasty patient may hold merit.”

https://www.ncbi.nlm.nih.gov/pubmed/30170713

“In conclusion, our study suggests that cannabinoids may have a role in post-arthroplasty pain management and may reduce patient’s need for opioid-containing pain medications. Further randomized, prospective clinical trials are warranted to shed more light onto the possible beneficial effects of cannabinoid medications in the orthopedic surgery patient population.” https://www.arthroplastyjournal.org/article/S0883-5403(18)30670-3/fulltext

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Optimization Of A Preclinical Therapy Of Cannabinoids In Combination With Temozolomide Against Glioma.

 Biochemical Pharmacology “Glioblastoma multiforme (GBM) is the most frequent and aggressive form of brain cancer. These features are explained at least in part by the high resistance exhibited by these tumors to current anticancer therapies. Thus, the development of novel therapeutic approaches is urgently needed to improve the survival of the patients suffering this devastating disease.

Δ9-Tetrahydrocannabinol (THC, the major active ingredient of marijuana), and other cannabinoids have been shown to exert antitumoral actions in animal models of cancer, including glioma. The mechanism of these anticancer actions relies, at least in part, on the ability of these compounds to stimulate autophagy-mediated apoptosis in tumor cells.

Previous observations from our group demonstrated that local administration of THC (or of THC + CBD at a 1:1 ratio, a mixture that resembles the composition of the cannabinoid-based medicine Sativex®) in combination with Temozolomide, the benchmark agent for the treatment of GBM, synergistically reduces the growth of glioma xenografts.

With the aim of optimizing the possible clinical utilization of cannabinoids in anti-GBM therapies, in this work we explored the anticancer efficacy of the systemic administration of cannabinoids in combination with TMZ in preclinical models of glioma.

Our results show that oral administration of THC+CBD (Sativex-like extracts) in combination with TMZ produces a strong antitumoral effect in both subcutaneous and intracranial glioma cell-derived tumor xenografts. In contrast, combined administration of Sativex-like and BCNU (another alkylating agent used for the treatment of GBM which share structural similarities with the TMZ) did not show a stronger effect than individual treatments.

Altogether, our findings support the notion that the combined administration of TMZ and oral cannabinoids could be therapeutically exploited for the management of GBM.”

https://www.ncbi.nlm.nih.gov/pubmed/30125556

https://www.sciencedirect.com/science/article/abs/pii/S0006295218303496

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabis shenanigans: advocating for the restoration of an effective treatment of pain following spinal cord injury.

 Image result for spinal cord series and cases

“Cannabis is an effective treatment for pain following spinal cord injury that should be available to patients and researchers.

The major argument against the rescheduling of cannabis is that the published research is not convincing. This argument is disingenuous at best, given that the evidence has been presented and rejected at many points during the political dialog. Moreover, the original decision to criminalize cannabis did not utilize scientific or medical data.

There is tension between the needs of a society to protect the vulnerable by restricting the rights of others to live well and with less pain. It is clear that this 70-year war on cannabis has had little effect in controlling the supply of cannabis.

Prohibition can never succeed; “it is a tyranny from which every independent mind revolts.”

People living with chronic pain should not have to risk addiction, social stigma, restrictions on employment and even criminal prosecution in order to deal with their pain.

It is time to end the shenanigans and have an open, transparent discussion of the true benefits of this much-beleaguered medicine.”

https://www.ncbi.nlm.nih.gov/pubmed/30109133

https://www.nature.com/articles/s41394-018-0096-1

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

The enigma of cannabis use in spinal cord injury.

Image result for spinal cord series and cases

“Cannabis use in medicine continues to confound practitioners.

There is confusing interpretation of the efficacy and adverse event data, highlighting the complexity of this unique plant.

Cannabis may have a neuroprotective role in SCI.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

[A brief history of marijuana in the western world].

Image result for Rev Neurol.

“Marijuana is a substance with a long and controversial history.

At different times in its history, which goes back over 5,000 years, this plant has been used for different purposes, ranging from recreational and leisure to its use in the treatment of several diseases or to offer relief in processes that entail a certain type of malaise, and including its consideration as a means of relaxation and meditation.

Although it was supposed that the roots of marijuana lay in Central America, it is now known that this is but an urban legend with little credibility and that its origins can be found recorded in Chinese medical references dating back to the year 2737 BC.

Although this plant was not originally from Central America, it has aroused interest around the world, and above all in Mexico. It is in this country where the use of cannabis has gone from applications in textiles and medicine to its free sale, the bans on its use due to political and social pressures, its tolerance and, recently, its decriminalisation for recreational and medicinal use.

Unfortunately there are few references on the history of this plant in Mexico, and thus we have considered it interesting to present some data about the generalities of marijuana, a brief history in the world, the development of decriminalisation in North America, its medicinal uses and its course through Mexico to the present day.”

https://www.ncbi.nlm.nih.gov/pubmed/30039841

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous