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

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“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

The enigma of cannabis use in spinal cord injury.

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“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.”

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

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“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

[Cannabinoids in pain medicine]

Der Schmerz

“The endocannabinoid system (ECS) controls a large number of vital functions.

Suboptimal tone of the ECS in certain regions of the nervous system may be associated with disorders that are also associated with pain.

Pain and inflammation processes can be modulated by the exogenous supply of cannabinoids.

Low-to-moderate pain-relieving effects and in individual cases large pain-relieving effects were observed in randomized, controlled studies of various types of chronic pain. People with chronic neuropathic pain and stress symptoms seem to particularly benefit.

The therapeutic range of cannabinoids is small; often small doses are sufficient for clinically significant effects. The “Cannabis-als-Medizin-Gesetz” (cannabis as medicine law) allows the prescription of cannabis preparations under certain conditions.

Available data indicate good long-term efficacy and tolerability. However, there is little systematic long-term experience from clinical studies.”

https://www.ncbi.nlm.nih.gov/pubmed/29881935

https://link.springer.com/article/10.1007%2Fs00482-018-0299-1

Endocannabinoids in Body Weight Control.

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“Maintenance of body weight is fundamental to maintain one’s health and to promote longevity. Nevertheless, it appears that the global obesity epidemic is still constantly increasing.

Endocannabinoids (eCBs) are lipid messengers that are involved in overall body weight control by interfering with manifold central and peripheral regulatory circuits that orchestrate energy homeostasis.

Initially, blocking of eCB signaling by first generation cannabinoid type 1 receptor (CB1) inverse agonists such as rimonabant revealed body weight-reducing effects in laboratory animals and men. Unfortunately, rimonabant also induced severe psychiatric side effects.

At this point, it became clear that future cannabinoid research has to decipher more precisely the underlying central and peripheral mechanisms behind eCB-driven control of feeding behavior and whole body energy metabolism.

Here, we will summarize the most recent advances in understanding how central eCBs interfere with circuits in the brain that control food intake and energy expenditure. Next, we will focus on how peripheral eCBs affect food digestion, nutrient transformation and energy expenditure by interfering with signaling cascades in the gastrointestinal tract, liver, pancreas, fat depots and endocrine glands.

To finally outline the safe future potential of cannabinoids as medicines, our overall goal is to address the molecular, cellular and pharmacological logic behind central and peripheral eCB-mediated body weight control, and to figure out how these precise mechanistic insights are currently transferred into the development of next generation cannabinoid medicines displaying clearly improved safety profiles, such as significantly reduced side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/29849009

http://www.mdpi.com/1424-8247/11/2/55

Cannabis for the Management of Cancer Symptoms: THC Version 2.0?

Cannabis and Cannabinoid Research cover image

“The landscape of medical cannabis is rapidly expanding. Cannabis preparations have been used in medicine for millennia, and now there is a strong renaissance in the study of their therapeutic properties.

The vast majority of controlled clinical trials that support the medical use of what is commonly known as “cannabis” or “marijuana” have actually been conducted with purified cannabinoids or a single extract of Cannabis sativa that contains an equimolecular proportion of Δ9-THC and CBD.

Based on these studies, THC/dronabinol (Marinol) and its synthetic analogue nabilone (Cesamet), as well as nabiximols (Sativex), are already approved by several regulatory agencies, including FDA, Health Canada, and EMA, as antiemetic, anticachexic, analgesic, or antispastic medicines.

This study provides a precious piece of information on the use of medical cannabis for the management of cancer symptoms.”

https://www.liebertpub.com/doi/10.1089/can.2018.0009

Endocannabinoid system and anticancer properties of cannabinoids

Folia Biologica et Oecologica

“Cannabinoids impact human body by binding to cannabinoids receptors (CB1 and CB2).

The two main phytocannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

THC interacts with CB1 receptors occurring in central nervous system and is responsible for psychoactive properties of marijuana. CBD has low affinity to CB1 receptor, has no psychoactive characteristics and its medical applications can be wider.

CB receptors are part of a complex machinery involved in regulation of many physiological processes – endocannabinoid system.

Cannabinoids have found some applications in palliative medicine, but there are many reports concerning their anticancer affects.

Agonists of CB1 receptors stimulate accumulation of ceramides in cancer cells, stress of endoplasmic reticulum (ER stress) and, in turn, apoptosis. Effects of cannabinoids showing low affinity to CB receptors is mediated probably by induction of reactive oxygen species production.

Knowledge of antitumor activity of cannabinoids is still based only on preclinical studies and there is a necessity to conduct more experiments to assess the real potential of these compounds.”

https://content.sciendo.com/view/journals/fobio/12/1/article-p11.xml

Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol

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“Cannabidiol (CBD), a major constituent of Cannabis, has been shown to be a powerful anti-inflammatory and anti-anxiety drug, without exerting a psychotropic effect. However, when given either intraperitoneally or orally as a purified product, a bell-shaped dose-response was observed, which limits its clinical use.
In the present study, we have studied in mice the anti-inflammatory and anti-nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients.
In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between the anti-inflammatory and anti-nociceptive responses and the dose, with increasing responses upon increasing doses, which makes this plant medicine ideal for clinical uses.
The clone 202 extract reduced zymosan-induced paw swelling and pain in mice, and prevented TNFα production in vivo. It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD.
We therefore propose that Cannabis clone 202 (Avidekel) extract is superior over CBD for the treatment of inflammatory conditions.”  https://www.scirp.org/journal/PaperInformation.aspx?paperID=53912
“In conclusion, we recommend standardized plant extract of the Cannabis clone 202 for treatment of various inflammatory conditions.” https://file.scirp.org/Html/5-2500582_53912.htm

The influence of THC:CBD oromucosal spray on driving ability in patients with multiple sclerosis-related spasticity.

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“Driving ability is a key function for the majority of patients with multiple sclerosis (MS) to help maintain daily interactions. Both physical and cognitive disability, as well as treatments, may affect the ability to drive. Spasticity is a common symptom associated with MS, and it may affect driving performance either directly or via the medications used to treat it.

In this article, we review the evidence relating the antispasticity medicine, Δ9-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®), and its potential impact on driving performance.

The results from THC:CBD oromucosal spray driving studies and real-world registries did not show any evidence of an increase in motor vehicle accidents associated with THC:CBD oromucosal spray. The majority of patients reported an improvement in driving ability after starting THC:CBD oromucosal spray, and it was speculated that this may be related to reduced spasticity and/or better cognitive function.

THC:CBD oromucosal spray was shown not to impair driving performance.”

https://www.ncbi.nlm.nih.gov/pubmed/29761015

https://onlinelibrary.wiley.com/doi/abs/10.1002/brb3.962

Enhanced endocannabinoid tone as a potential target of pharmacotherapy.

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“The endocannabinoid system is up-regulated in numerous pathophysiological states such as inflammatory, neurodegenerative, gastrointestinal, metabolic and cardiovascular diseases, pain, and cancer. It has been suggested that this phenomenon primarily serves an autoprotective role in inhibiting disease progression and/or diminishing signs and symptoms.

Accordingly, enhancement of endogenous endocannabinoid tone by inhibition of endocannabinoid degradation represents a promising therapeutic approach for the treatment of many diseases. Importantly, this allows for the avoidance of unwanted psychotropic side effects that accompany exogenously administered cannabinoids.

The effects of endocannabinoid metabolic pathway modulation are complex, as endocannabinoids can exert their actions directly or via numerous metabolites. The two main strategies for blocking endocannabinoid degradation are inhibition of endocannabinoid-degrading enzymes and inhibition of endocannabinoid cellular uptake.

To date, the most investigated compounds are inhibitors of fatty acid amide hydrolase (FAAH), an enzyme that degrades the endocannabinoid anandamide. However, application of FAAH inhibitors (and consequently other endocannabinoid degradation inhibitors) in medicine became questionable due to a lack of therapeutic efficacy in clinical trials and serious adverse effects evoked by one specific compound.

In this paper, we discuss multiple pathways of endocannabinoid metabolism, changes in endocannabinoid levels across numerous human diseases and corresponding experimental models, pharmacological strategies for enhancing endocannabinoid tone and potential therapeutic applications including multi-target drugs with additional targets outside of the endocannabinoid system (cyclooxygenase-2, cholinesterase, TRPV1, and PGF-EA receptors), and currently used medicines or medicinal herbs that additionally enhance endocannabinoid levels.

Ultimately, further clinical and preclinical studies are warranted to develop medicines for enhancing endocannabinoid tone.”

https://www.ncbi.nlm.nih.gov/pubmed/29729263

https://www.sciencedirect.com/science/article/pii/S0024320518302352