Clinical experiences with cannabinoids in spasticity management in multiple sclerosis.

“Spasticity is a common symptom among patients with multiple sclerosis (MS). This study aims to assess the effectiveness and safety of the combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in clinical practice for the treatment of spasticity in MS…

Retrospective observational study with patients treated with inhaled THC/CBD…

 THC/CBD was effective in 80% of patients…

CONCLUSIONS:

THC/CBD appears to be a good alternative to standard treatment as it improves refractory spasticity in MS and has an acceptable toxicity profile.”

http://www.ncbi.nlm.nih.gov/pubmed/24035293

Treatment of spasticity in multiple sclerosis: new perspectives regarding the use of cannabinoids.

“Spasticity remains a prevalent symptom in multiple sclerosis, with a significant associated disability and quality of life impairment… Cannabinoids provide a new way for therapy.

A delta-9-tetrahydrocannabinol plus cannabidiol (1:1) association, administered through an oromucosal route, has been approved in several countries including Spain; it causes a specific effect on CB(1) and CB(2) receptors, with traditional psychotropic cannabis actions being minimized.

Randomized, placebo-controlled trials, as well as longer-term open-label extensions, have shown a clear-cut efficacy to reduce spasticity and their associated symptoms in those patients refractory to other therapies, with a good tolerability/safety profile.

No tolerance, abuse or addictive issues have been found…”

http://www.ncbi.nlm.nih.gov/pubmed/23011861

Cannabidiol-Induced Apoptosis in Human Leukemia Cells: A Novel Role of Cannabidiol in the Regulation of p22phox and Nox4 Expression

“Marijuana has been suggested as a potent therapeutic agent alleviating such complications as intraocular pressure in glaucoma and cachexia, nausea, and pain in AIDS and cancer patients. A number of recent studies now suggest the possible use of these compounds for the treatment of cannabinoid receptor-expressing tumors…

In the current study, we examined the effects of the nonpsychoactive cannabinoid, cannabidiol, on the induction of apoptosis in leukemia cells. Exposure of leukemia cells to cannabidiol led to cannabinoid receptor 2 (CB2)-mediated reduction in cell viability and induction in apoptosis. Furthermore, cannabidiol treatment led to a significant decrease in tumor burden and an increase in apoptotic tumors in vivo…

Together, the results from this study reveal that cannabidiol, acting through CB2 and regulation of Nox4 and p22phox expression, may be a novel and highly selective treatment for leukemia…

In summary, the current study demonstrates that CBD-induced apoptosis may constitute a novel approach to treat malignancies of the immune system…”

Full text: http://molpharm.aspetjournals.org/content/70/3/897.long

Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells

“Plant-derived cannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the main psychoactive and nonpsychoactive components of cannabis, respectively, possess myriad pharmacological properties…

Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects…

Together, these results support existence of yet-to-be identified sites of interaction, i.e., receptors and/or ion channels associated with Ca2+ influx of natural cannabinoids such as CBD and THC, the identification of which has the potential to provide for novel strategies and agents of therapeutic interest.”

Full text: http://www.jleukbio.org/content/81/6/1512.long

Gamma-irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL-60 myeloblastic leukemia cells.

“Two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabidiol-dimethylheptyl (CBD-DMH), induced apoptosis in a human acute myeloid leukemia (AML) HL-60 cell line…

  Caspase-3 activation was observed after the cannabinoid treatment, and may represent a mechanism for the apoptosis.

Our data suggest a possible new approach to treatment of AML.”

http://www.ncbi.nlm.nih.gov/pubmed/14692532

Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Protective effect of cannabidiol against cadmium hepatotoxicity in rats.

“The protective effect of cannabidiol, the non-psychoactive component of Cannabis sativa, against liver toxicity induced by a single dose of cadmium chloride was investigated in rats…

 It was concluded that cannabidiol may represent a potential option to protect the liver tissue from the detrimental effects of cadmium toxicity.”

http://www.ncbi.nlm.nih.gov/pubmed/23993482

Neuroprotection and reduction of glial reaction by cannabidiol treatment after sciatic nerve transection in neonatal rats.

“The clinical use of neurotrophic factors is difficult due to side effects and elevated costs, but other molecules might be effective and more easily obtained. Among them, some are derived from Cannabis sativa.

Cannabidiol (CBD) is the major non-psychotropic component found on the surface of such plant leaves.

The present study aimed to investigate the neuroprotective potential of CBD…

The present results show that CBD possesses neuroprotective characteristics that may, in turn, be promising for future clinical use.”

http://www.ncbi.nlm.nih.gov/pubmed/23981015

Cannabis with high cannabidiol content is associated with fewer psychotic experiences.

“An increasing number of authors identify cannabidiol, another component of the cannabis plant, as an antipsychotic agent. The objective of the current study is to investigate the role of cannabidiol content in the association between cannabis use and psychiatric symptoms in a large non-clinical population of cannabis users…

CONCLUSION:

Although the observed effects are subtle, using high cannabidiol content cannabis was associated with significantly lower degrees of psychotic symptoms providing further support for the antipsychotic potential of cannabidiol.”

http://www.ncbi.nlm.nih.gov/pubmed/21592732

Cannabis, a complex plant: different compounds and different effects on individuals.

“Cannabis is a complex plant, with major compounds such as delta-9-tetrahydrocannabinol and cannabidiol, which have opposing effects. The discovery of its compounds has led to the further discovery of an important neurotransmitter system called the endocannabinoid system.

This system is widely distributed in the brain and in the body, and is considered to be responsible for numerous significant functions.

There has been a recent and consistent worldwide increase in cannabis potency, with increasing associated health concerns. A number of epidemiological research projects have shown links between dose-related cannabis use and an increased risk of development of an enduring psychotic illness. However, it is also known that not everyone who uses cannabis is affected adversely in the same way.

What makes someone more susceptible to its negative effects is not yet known, however there are some emerging vulnerability factors, ranging from certain genes to personality characteristics.

 In this article we first provide an overview of the biochemical basis of cannabis research by examining the different effects of the two main compounds of the plant and the endocannabinoid system, and then go on to review available information on the possible factors explaining variation of its effects upon different individuals.”

http://www.ncbi.nlm.nih.gov/pubmed/23983983