Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications.

“Cannabinoids form a singular family of plant-derived compounds (phytocannabinoids), endogenous signaling lipids (endocannabinoids), and synthetic derivatives with multiple biological effects and therapeutic applications in the central and peripheral nervous systems.

One of these properties is the regulation of neuronal homeostasis and survival, which is the result of the combination of a myriad of effects addressed to preserve, rescue, repair, and/or replace neurons, and also glial cells against multiple insults that may potentially damage these cells.

These effects are facilitated by the location of specific targets for the action of these compounds (e.g., cannabinoid type 1 and 2 receptors, endocannabinoid inactivating enzymes, and nonendocannabinoid targets) in key cellular substrates (e.g., neurons, glial cells, and neural progenitor cells).

This potential is promising for acute and chronic neurodegenerative pathological conditions. In this review, we will collect all experimental evidence, mainly obtained at the preclinical level, supporting that different cannabinoid compounds may be neuroprotective in adult and neonatal ischemia, brain trauma, Alzheimer’s disease, Parkinson’s disease, Huntington’s chorea, and amyotrophic lateral sclerosis.

This increasing experimental evidence demands a prompt clinical validation of cannabinoid-based medicines for the treatment of all these disorders, which, at present, lack efficacious treatments for delaying/arresting disease progression…”

http://www.ncbi.nlm.nih.gov/pubmed/26260390

HU-446 and HU-465, derivatives of the non-psychoactive cannabinoid cannabidiol, decrease the activation of encephalitogenic T cells.

“Cannabidiol (CBD), the non-psychoactive cannabinoid, has been previously shown by us to decrease peripheral inflammation and neuroinflammation in mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS).

Here we have studied the anti-inflammatory effects of newly synthesized derivatives of natural (-)-CBD ((-)-8,9-dihydro-7-hydroxy-CBD; HU-446) and of synthetic (+)-CBD ((+)-8,9-dihydro-7-hydroxy-CBD; HU-465)…

These results suggest that HU-446 and HU-465 have anti-inflammatory potential in inflammatory and autoimmune diseases. ”

http://www.ncbi.nlm.nih.gov/pubmed/26259697

Life Threatening Idiopathic Recurrent Angioedema Responding to Cannabis.

“We present a case of a 27-year-old man with recurrent episodes of angioedema since he was 19, who responded well to treatment with medical grade cannabis.

Initially, he responded to steroids and antihistamines, but several attempts to withdraw treatment resulted in recurrence. In the last few months before prescribing cannabis, the frequency and severity of the attacks worsened and included several presyncope events, associated with scrotal and neck swelling. No predisposing factors were identified, and extensive workup was negative.

The patient reported that he was periodically using cannabis socially and that during these periods he was free of attacks.

Recent data suggest that cannabis derivatives are involved in the control of mast cell activation. Consequently, we decided to try a course of inhaled cannabis as modulators of immune cell functions.

The use of inhaled cannabis resulted in a complete response, and he has been free of symptoms for 2 years.

An attempt to withhold the inhaled cannabis led to a recurrent attack within a week, and resuming cannabis maintained the remission, suggesting a cause and effect relationship.”

http://www.ncbi.nlm.nih.gov/pubmed/26257969

“Angioedema is swelling (edema) under the skin. It can happen in different parts of your body, and it’s usually caused by an allergic reation. When you have hereditary angioedema (HAE), a rare genetic condition causes the swelling, not allergies. You are born with this condition and will always have it. Treatment can help you live with it, though. Over the years, there have been big improvements in therapies, and researchers are still looking for more and better treatment options.” http://www.webmd.com/skin-problems-and-treatments/hereditary-angioedema

Cannabis, Cannabinoids, and Cerebral Metabolism: Potential Applications in Stroke and Disorders of the Central Nervous System.

“No compound has generated more attention in both the scientific and recently in the political arena as much as cannabinoids.

These diverse groups of compounds referred collectively as cannabinoids have both been vilified due to its dramatic and potentially harmful psychotropic effects and glorified due to its equally dramatic and potential application in a number of acute and chronic neurological conditions.

Previously illegal to possess, cannabis, the plant where natural form of cannabinoids are derived, is now accepted in a growing number of states for medicinal purpose, and some even for recreational use, increasing opportunities for more scientific experimentation.

The purpose of this review is to summarize the growing body of literature on cannabinoids and to present an overview of our current state of knowledge of the human endocannabinoid system in the hope of defining the future of cannabinoids and its potential applications in disorders of the central nervous system, focusing on stroke.”

http://www.ncbi.nlm.nih.gov/pubmed/26238742

Therapeutic potential of cannabis-related drugs.

“In this review, I will consider the dual nature of Cannabis and cannabinoids.

The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the ‘abuse’ of Cannabis outside the clinic.

The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma.

As with every other medicinal drug of course, the ‘trick’ will be to maximise the benefit and minimise the cost.

After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/26216862

An Overview of Products and Bias in Research.

“Cannabis is a genus of annual flowering plant.

Cannabis is often divided into 3 species-Cannabis sativa, Cannabis indica, and Cannabis ruderalis-but there is significant disagreement about this, and some consider them subspecies of the same parent species.

Cannabis sativa can grow to 5-18 feet or more, and often has a few branches.

Cannabis indica typically grows 2-4 feet tall and is compactly branched.

Cannabis ruderalis contains very low levels of Δ-9-tetrahyocannabinol so is rarely grown by itself. Cannabis ruderalis flowers as a result of age, not light conditions, which is called autoflowering. It is principally used in hybrids, to enable the hybrid to have the autoflowering property.

There are > 700 strains of cannabis, often with colorful names.

Some are strains of 1 of the 3 subspecies. Many are crossbred hybrids.

The strains can be named in a variety of ways: smell or lineage are common ways of naming. There are only a few rules about how the strains are named, and most strains’ names do not follow the rules.

There are 4 basic preparations of marijuana: bhang, hasish, oil (or hash oil), and leaves and/or buds.

In medical marijuana trials, subjective outcomes are frequently used but blind breaking can introduce significant bias. Blind breaking occurs when patients figure out if they are in the control or the treatment group. When this occurs, there is significant overestimation of treatment effect.”

http://www.ncbi.nlm.nih.gov/pubmed/26202343

Cannabinoids for the Treatment of Movement Disorders.

“Use of cannabinoids as medications has a long history.

Unfortunately, the prohibition of cannabis and its classification in 1970 as a schedule 1 drug has been a major obstacle in studying these agents in a systematic, controlled manner.

The number of class 1 studies (randomized, double-blind, placebo-controlled) in patients with movement disorders is limited. Hence, it is not possible to make recommendations on the use of these cannabinoids as primary treatments for any of the movement disorders at this time.

Fortunately, there is an expanding body of research in animal models of age-dependent and disease-related changes in the endocannabinoid system that is providing new targets for drug development.

Moreover, there is growing evidence of a “cannabinoid entourage effect” in which a combination of cannabinoids derived from the plant are more effective than any single cannabinoid for a number of conditions.

Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective.

As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will expand.”

http://www.ncbi.nlm.nih.gov/pubmed/26206230

Effect of Non-psychotropic Plant-derived Cannabinoids on Bladder Contractility: Focus on Cannabigerol.

“There are anecdotal reports that some Cannabis preparations may be useful for bladder dysfunctions.

Here, we investigated the effect of a number of non- psychotropic phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV), Δ9-tetrahydrocannabivarin (THCV) and cannabichromene (CBC) on mouse bladder contractility in vitro.

CBG, THCV, CBD and CBDV, but not CBC, at concentration ranging from 10(-8) M to 10(-4) M, decreased (with similar potency), the contractions induced by acetylcholine without significantly modifying the contractions induced by electrical stimulation.

The rank order of efficacy was CBG=THCV>CBD>CBDV.

In depth studies on CBG showed that the effect of this phytocannabinoid on acetylcholine-induced contractions was not affected by CB1 or CB2 receptor antagonists.

Additionally, CBG also reduced acetylcholine-induced contractions in the human bladder.”

http://www.ncbi.nlm.nih.gov/pubmed/26197538

Use and effects of cannabinoids in military veterans with posttraumatic stress disorder.

“Published evidence regarding the use of cannabis and cannabis derivatives by military veterans with posttraumatic stress disorder (PTSD) is reviewed.

SUMMARY:

When inhaled or delivered orally or transdermally, cannabinoids (the psychoactive components of unrefined marijuana and various derivative products) activate endogenous cannabinoid receptors, modulating neurotransmitter release and producing a wide range of central nervous system effects, including increased pleasure and alteration of memory processes. Those effects provide a pharmacologic rationale for the use of cannabinoids to manage the three core PTSD symptom clusters: reexperiencing, avoidance and numbing, and hyperarousal.

Cross-sectional studies have found a direct correlation between more severe PTSD symptomatology and increased motivation to use cannabis for coping purposes, especially among patients with difficulties in emotional regulation or stress tolerance. Data from 4 small studies suggested that cannabinoid use was associated with global improvements in PTSD symptoms or amelioration of specific PTSD symptoms such as insomnia and nightmares.

CONCLUSION:

While further research into cannabinoid treatment effects on PTSD symptoms is required, the evaluated evidence indicates that substantial numbers of military veterans with PTSD use cannabis or derivative products to control PTSD symptoms, with some patients reporting benefits in terms of reduced anxiety and insomnia and improved coping ability.”

http://www.ncbi.nlm.nih.gov/pubmed/26195653