Tag Archives: therapeutic

[Cannabis – therapy for the future?]

Posted on by

“Despite all the progress achieved in the treatment of chronic gastrointestinal diseases, in some patients the treatment does not reach long-term optimum effectiveness. Therefore a number of patients have turned to complementary and alternative medicine (CAM).

Of the different types of CAM patients with GIT diseases tend to prefer in particular homeopathy, acupuncture and not least phytotherapy, where therapeutic use of cannabis may also be included.

The pathophysiological basis of therapeutic effect of curative cannabis has not been fully clarified so far.

Many scientists in many fields of medicine and pharmacology have been engaged in the study of effects of cannabinoids on the body since the beginning of the 20th century with the interest significantly increasing in the 1980s.

The discovery of CB receptors (1988) and endogenous molecules which activate these receptors (1992) led to the discovery of the endocannabinoid system.

Pharmacological modulation of the endogenous cannabinoid system offers new therapeutic possibilities of treatment of many illnesses and symptoms including the GIT disorders, including of nausea, vomiting, cachexia, IBS, Crohns disease and some other disorders.

Cannabinoids are attractive due to their therapeutic potential – they affect a lot of symptoms with minimum side effects.

Experience of patients with GIT disorders show that the use of cannabis is effective and helps in cases where the standard therapy fails.”

http://www.ncbi.nlm.nih.gov/pubmed/26375695

Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety.

Posted on by

“Anxiety disorders are among the most prevalent psychiatric diseases with high personal costs and a remarkable socio-economic burden. However, current treatment of anxiety is far from satisfactory.

Novel pharmacological targets have emerged in the recent years, and attention has focused on the endocannabinoid (eCB) system, given the increasing evidence that supports its central role in emotion, coping with stress and anxiety.

In the management of anxiety disorders, drug development strategies have left apart the direct activation of type-1 cannabinoid receptors to indirectly enhance eCB signalling through the inhibition of eCB deactivation, that is, the inhibition of the fatty acid amide hydrolase (FAAH) enzyme.

In the present study, we provide evidence for the anxiolytic-like properties of a novel, potent and selective reversible inhibitor of FAAH, ST4070, orally administered to rodents.

Altogether, ST4070 offers a promising anxiolytic-like profile in preclinical studies, although further studies are warranted to clearly demonstrate its efficacy in the clinic management of anxiety disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26360704

Endocannabinoid regulation of amyloid-induced neuroinflammation.

Posted on by

“The modulation of endocannabinoid (EC) levels and the activation of cannabinoid receptors are seen as promising therapeutic strategies in a variety of diseases, including Alzheimer’s disease (AD).

These data reinforce the notion of a role for the EC system in neuroinflammation and open new perspectives on the relevance of modulating EC levels in the inflammed brain.”

http://www.ncbi.nlm.nih.gov/pubmed/26362942

Tetrahydrocannabivarin (THCv) reduces Default Mode Network and increases Executive Control Network Resting State Functional Connectivity in Healthy Volunteers.

Posted on by

“The cannabinoid CB1 Neutral Antagonist Tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity but without the depressogenic side-effects of inverse antagonists such as Rimonabant.

Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the Default Mode network and increases connectivity in the Cognitive Control network and Dorsal Visual Stream network.

This effect profile suggests possible therapeutic activity of THCv for obesity where functional connectivity has been found to be altered in these regions.”

http://www.ncbi.nlm.nih.gov/pubmed/26362774

Cannabinoid Ligands and Alcohol Addiction: A Promising Therapeutic Tool or a Humbug?

Posted on by

“The vast therapeutic potential of cannabinoids of both synthetic and plant-derived origins currently makes these compounds the focus of a growing interest. Although cannabinoids are still illicit drugs, their possible clinical usefulness, including treatment of acute or neuropathic pain, have been suggested by several studies.

In addition, some observations indicate that cannabinoid receptor antagonists may be useful for the treatment of alcohol dependence and addiction, which is a major health concern worldwide.

While the synergism between alcohol and cannabinoid agonists (in various forms) creates undesirable side effects when the two are consumed together, the administration of CB1 antagonists leads to a significant reduction in alcohol consumption.

Furthermore, cannabinoid antagonists also mitigate alcohol withdrawal symptoms.

Herein, we present an overview of studies focusing on the effects of cannabinoid ligands (agonists and antagonists) during acute or chronic consumption of ethanol.”

http://www.ncbi.nlm.nih.gov/pubmed/26353844

Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis.

Posted on by

“Chronic inflammation in rheumatoid arthritis (RA) is accompanied by activation of the sympathetic nervous system, which can support the immune system to perpetuate inflammation. Several animal models of arthritis already demonstrated a profound influence of adrenergic signaling on the course of RA.

Peripheral norepinephrine release from sympathetic terminals is controlled by cannabinoid receptor type 1 (CB1), which is activated by two major endocannabinoids (ECs), arachidonylethanolamine (anandamide) and 2-arachidonylglycerol.

These ECs also modulate function of transient receptor potential channels (TRPs) located on sensory nerve fibers, which are abundant in arthritic synovial tissue. TRPs not only induce the sensation of pain but also support inflammation via secretion of pro-inflammatory neuropeptides.

In addition, many cell types in synovial tissue express CB1 and TRPs.

In this review, we focus on CB1 and transient receptor potential vanilloid 1 (TRPV1)-mediated effects on RA since most anti-inflammatory mechanisms induced by cannabinoids are attributed to cannabinoid receptor type 2 (CB2) activation.

We demonstrate how CB1 agonism or antagonism can modulate arthritic disease.

The concept of functional antagonism with continuous CB1 activation is discussed.

Since fatty acid amide hydrolase (FAAH) is a major EC-degrading enzyme, the therapeutic possibility of FAAH inhibition is studied.

Finally, the therapeutic potential of ECs is examined since they interact with cannabinoid receptors and TRPs but do not produce central side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26343051

Cannabidiol as a Potential Treatment for Anxiety Disorders.

Posted on by

“Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders.

The purpose of the current review is to determine CBD’s potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies.

We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing.

Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations.

Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.”

http://www.ncbi.nlm.nih.gov/pubmed/26341731

Cannabinoids in the Treatment of Neurological Disorders

Posted on by

“The force of the recent explosion of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology.

Paradoxically, for 10 millennia this plant has been an integral part of human cultivation, where it was used for its fibers long before its pharmacological properties.

With regard to the latter, cannabis was well known to healers from China and India thousands of years ago; Greek and Roman doctors during classic times; Arab doctors during the Middle Ages; Victorian and Continental physicians in the nineteenth century; American doctors during the early twentieth century; and English doctors until 1971 when a variety of nonevidence-based remedies were removed from the British Pharmaceutical Codex.

The clinical data on cannabis therapeutics are meager and the vast majority are formed by surveys or small studies that are underpowered and/or suffer from multiple methodological flaws, often by virtue of limited research funding for nonaddiction-focused studies. Thus, we know relatively little about the clinical efficacy of cannabinoids for the various neurological disorders for which historical nonscientific and medical literature have advocated its use.

The relative scarcity of proven cannabis-based therapies is not due to data that show that cannabinoids are ineffective or unsafe, but rather reflects a poverty of medical interest and a failure by pharmaceutical companies arising from regulatory restrictions compounded by limits for patent rights on plant cannabinoid-containing preparations that have been used medicinally for millennia, as is the case for most natural products.

We are pleased to have gathered many of the world’s experts together on the basic biology of cannabinoids, as well as their potential role in treating neurologic and psychiatric disorders…

We hope that this issue of Neurotherapeutics will serve to mark the bounds of verifiable scientific knowledge of cannabinoids in the treatment of neuropsychiatric and neurological disorders. At the same time, our contributors have also helped identify areas for future research, as well as the strategies needed to move our base of knowledge forward.

We hope that this volume will help to accelerate the pace of the appropriately focused and productive research and double-blind placebo-controlled randomized trials to the point at which the care of patients is informed by valid data and not just anecdote.”

http://link.springer.com/article/10.1007/s13311-015-0388-0/fulltext.html

G protein-coupled receptor 18: A potential role for endocannabinoid signalling in metabolic dysfunction.

Posted on by

“Endocannabinoids are products of dietary fatty acids that are modulated by an alteration in food intake levels.

Overweight and obese individuals have substantially higher circulating levels of the arachidonic acid-derived endocannabinoids, anandamide and 2-arachidonoyl glycerol, and show an altered pattern of cannabinoid receptor expression.

These cannabinoid receptors are part of a large family of G protein-coupled receptors (GPCRs).

GPCRs are major therapeutic targets for various diseases within the cardiovascular, neurological, gastrointestinal and endocrine systems, as well as metabolic disorders such as obesity and type 2 diabetes mellitus.

Obesity is considered a state of chronic low grade inflammation elicited by an immunological response.

Interestingly, the newly deorphanised G protein-coupled receptor GPR18, which is considered to be a putative cannabinoid receptor, is proposed to have an immunological function.

In this review, the current scientific knowledge on GPR18 is explored including its localisation, signalling pathways and pharmacology.

Importantly, the involvement of nutritional factors and potential dietary regulation of GPR18 and its (patho)physiological roles are described.

Further research on this receptor and its regulation will enable a better understanding of the complex mechanisms of GPR18 and its potential as a novel therapeutic target for treating metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26337420

The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells.

Posted on by

“One of the most exciting areas of current research in the cannabinoid field is the study of the potential application of these compounds as antitumoral drugs. Here, we describe the signaling pathway that mediates cannabinoid-induced apoptosis of tumor cells. By using a wide array of experimental approaches, we identify the stress-regulated protein p8 (also designated as candidate of metastasis 1) as an essential mediator of cannabinoid antitumoral action and show that p8 upregulation is dependent on de novo-synthesized ceramide. We also observe that p8 mediates its apoptotic effect via upregulation of the endoplasmic reticulum stress-related genes ATF-4, CHOP, and TRB3. Activation of this pathway may constitute a potential therapeutic strategy for inhibiting tumor growth.”

http://www.ncbi.nlm.nih.gov/pubmed/16616335

“Marijuana has been used in medicine for many centuries, and nowadays there is a renaissance in the study of the therapeutic effects of cannabinoids. One of the most active areas of research in the cannabinoid field is the study of the potential antitumoral application of these drugs. Our results unravel the mechanism of cannabinoid antitumoral action by demonstrating the proapoptotic role of the stress protein p8 via its downstream targets ATF-4, CHOP, and TRB3.

The identification of this pathway may contribute to the design of therapeutic strategies for inhibiting tumor growth. In particular, our findings can help to improve the efficiency and selectivity of potential antitumoral therapies with cannabinoids.

Our results also support that cannabinoid treatment does not activate this pathway in nontransformed cells, in line with the belief that cannabinoid proapoptotic action is selective for tumor versus nontumor cells, and that cannabinoids act in a synergic fashion with ER stress inducers as well as with other antitumoral agents.

The identification of the p8-regulated pathway described here may contribute to the design of therapeutic strategies for inhibiting tumor growth. In particular, our findings can help to improve the efficiency and selectivity of a potential cannabinoid-based antitumoral therapy.”

http://www.sciencedirect.com/science/article/pii/S1535610806000857