Cannabis for inflammatory bowel disease.

“The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds.

Studies have revealed that the endocannabinoid system is involved in almost all major immune events. Cannabinoids may, therefore, be beneficial in inflammatory disorders.In murine colitis, cannabinoids decrease histologic and microscopic inflammation.

In humans, cannabis has been used to treat a plethora of gastrointestinal problems, including anorexia, emesis, abdominal pain, diarrhea, and diabetic gastroparesis.

Despite anecdotal reports on medical cannabis in inflammatory bowel disease (IBD), there are few controlled studies. In an observational study in 30 patients with Crohn’s disease (CD), we found that medical cannabis was associated with improvement in disease activity and reduction in the use of other medications.

In a more recent placebo-controlled study in 21 chronic CD patients, we showed a decrease in the CD activity index >100 in 10 of 11 subjects on cannabis compared to 4 of 10 on placebo. Complete remission was achieved in 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity.

In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use”

http://www.ncbi.nlm.nih.gov/pubmed/24969296

Cannabinoids: well-suited candidates for the treatment of perinatal brain injury.

“Perinatal brain injury can be induced by a number of different damaging events occurring during or shortly after birth… the number of clinical interventions available for the treatment of the affected newborn babies is extremely limited. Hence, there is a dramatic need to develop new effective therapies aimed to prevent acute brain damage and enhance the endogenous mechanisms of long-term brain repair.

The endocannabinoid system is an endogenous neuromodulatory system involved in the control of multiple central and peripheral functions. An early responder to neuronal injury, the endocannabinoid system has been described as an endogenous neuroprotective system that once activated can prevent glutamate excitotoxicity, intracellular calcium accumulation, activation of cell death pathways, microglia activation, neurovascular reactivity and infiltration of circulating leukocytes across the blood-brain barrier.

The modulation of the endocannabinoid system has proven to be an effective neuroprotective strategy to prevent and reduce neonatal brain injury in different animal models and species.

Also, the beneficial role of the endocannabinoid system on the control of the endogenous repairing responses (neurogenesis and white matter restoration) to neonatal brain injury has been described in independent studies.”

http://www.ncbi.nlm.nih.gov/pubmed/24961520

Cannibinoids offer novel treatment for pain in sickle cell disease, study suggests

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“Researchers have discovered that cannibinoids offer a novel approach to ease the chronic and acute pain caused by sickle cell disease.

“This paper provides proof that we can use other classifications of drugs to treat pain in patients with sickle cell disease,” Gupta said.

“Cannibinoids offer great promise in the treatment of chronic and acute pain, and they’re effective in much lower amounts than opioids — the only currently approved treatment for this disease.”

http://www.sciencedaily.com/releases/2010/07/100722121225.htm

Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: modulation by cannabinoids… Our observations in these mice suggest that both systemically administered and locally applied cannabinoids may be beneficial in treating pain in SCD.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913454/

Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: modulation by cannabinoids

Table 1

“Sickle cell disease (SCD) causes severe pain. We examined pain-related behaviors, correlative neurochemical changes, and analgesic effects of morphine and cannabinoids in transgenic mice expressing human sickle hemoglobin (HbS).

Importantly, cannabinoids attenuate pain in mice expressing HbS.

Cannabinoids offer a novel approach to treat chronic pain and hyperalgesia.

Inhaled or systemically injected cannabinoids are effective in treating pain in HIV/AIDS and multiple sclerosis and breakthrough pain in cancer.

Activation of peripheral cannabinoid receptors attenuates hyperalgesia in inflammation and cancer. Selective pharmacologic activation of peripheral cannabinoid receptors to attenuate pain is particularly appealing because it might avoid side effects associated with activation of cannabinoid receptors in the central nervous system.

Because pain in SCD may have both inflammatory and neuropathic components, we hypothesized that cannabinoids may provide pain relief in SCD…

Our observations in these mice suggest that both systemically administered and locally applied cannabinoids may be beneficial in treating pain in SCD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913454/

Marijuana’s potential for treating autoimmune disorders

“A new study provides evidence that THC (tetrahydrocannabinol), a principal ingredient in marijuana, may be beneficial in treating those with autoimmune disorders.

The study is the first to explore how tiny, yet powerful molecules called microRNAs are influenced by THC. The ability to alter microRNA expression could hold the key to successful treatments for a whole host of autoimmune diseases, including arthritis and multiple sclerosis.”

http://www.sciencedaily.com/releases/2013/11/131125121712.htm

Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression.

Fig. 1

“Cannabinoids are a group of compounds found in the marijuana plant (Cannabis sativaL.). Marijuana has been used both for recreational and medicinal purposes for several centuries.

Cannabinoids have been shown to be effective in the treatment of nausea and vomiting associated with cancer chemotherapy, anorexia and cachexia seen in HIV/AIDS patients, as well as neuropathic pain, and spasticity in multiple sclerosis.

More recently, the anti-inflammatory properties of cannabinoids are drawing significant attention. In the last 15 years, studies with marijuana cannabinoids led to the discovery of cannabinoid receptors (CB1 and CB2) and their endogenous ligands, which make up what is known as the endocannabinoid system.

Cannabinoids are a group of compounds present in Cannabis plant (Cannabis sativa L.). They mediate their physiological and behavioral effects by activating specific cannabinoid receptors. With the recent discovery of the cannabinoid receptors (CB1 and CB2) and the endocannabinoid system, research in this field has expanded exponentially.

Cannabinoids have been shown to act as potent immunosuppressive and anti-inflammatory agents and have been shown to mediate beneficial effects in a wide range of immune-mediated diseases such as multiple sclerosis, diabetes, septic shock, rheumatoid arthritis, and allergic asthma.

Cannabinoid receptor 1 (CB1) is mainly expressed on the cells of the central nervous system as well as in the periphery. In contrast, cannabinoid receptor 2 (CB2) is predominantly expressed on immune cells. The precise mechanisms through which cannabinoids mediate immunosuppression is only now beginning to be understood…

In this review, we will focus on apoptotic mechanisms of immunosuppression mediated by cannabinoids on different immune cell populations and discuss how activation of CB2 provides a novel therapeutic modality against inflammatory and autoimmune diseases as well as malignancies of the immune system, without exerting the untoward psychotropic effects…

…cannabinoids do induce apoptosis in immune cells, alleviating inflammatory responses and protecting the host from acute and chronic inflammation.

The cumulative effect of cannabinoids on all cell populations of the immune system can be beneficial, when there is a need for immune suppression.

For example, in patients with autoimmune diseases such as multiple sclerosis, arthritis and lupus, or in those with septic shock, where the disease is caused by activated immune cells, targeting the immune cells via CB2 agonists may trigger apoptosis and act as anti-inflammatory therapy.

CB2 select agonists are not psychoactive and because CB2 is expressed primarily in immune cells, use of CB2 agonists could provide a novel therapeutic modality against autoimmune and inflammatory diseases.

In addition to the use of exogenous cannabinoids, in vivo manipulation of endocannabinoids may also offer novel treatment opportunities against cancer and autoimmune diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005548/

Direct suppression of autoreactive lymphocytes in the central nervous system via the CB2 receptor.

The cannabinoid system is evolutionally conserved and is present in invertebrates and vertebrates. One of the best-studied cannabinoids is Δ9-tetrahydrocannabinol (THC), the predominant active component of Cannabis sativa or marijuana.

The marijuana plant has been exploited by humans since their early history and was used for centuries in Asian medicine to reduce the severity of pain, inflammation and asthma. However, only recently have the mechanisms of the medicinal properties of THC begun to be understood. This understanding is largely due to the identification and cloning of two cannabinoid receptors.

The cannabinoid system is now recognized as a regulator of both the nervous and immune systems.

Although marijuana has been used for centuries for the treatment of a variety of disorders, its therapeutic mechanisms are only now being understood.

The best-studied plant cannabinoid, delta9-tetrahydrocannabinol (THC), produced by Cannabis sativa and found in marijuana, has shown evidence of being immunosuppressive in both in vivo and in vitro.

These studies are theoretically in agreement with the suggestions of others that cannabinoid receptor agonists would be beneficial for the treatment of MS in humans.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219523/

Protective role of cannabinoid receptor type 2 in a mouse model of diabetic nephropathy.

“The cannabinoid receptor type 2 (CB2) has protective effects in chronic degenerative diseases. Our aim was to assess the potential relevance of the CB2 receptor in both human and experimental diabetic nephropathy (DN)…

The CB2 receptor is expressed by podocytes, and in experimental diabetes, CB2 beneficialactivation ameliorates both albuminuria and podocyte protein loss, suggesting a protective effect of signaling through CB2 in DN.

In conclusion, our findings may have important implications for DN. The beneficial effect… makes CB2 agonism an attractive new strategy for the treatment of DN. CB2 activation may also positively affect other diabetes-related complications as CB2 agonists may, under certain conditions, delay progression of atherosclerotic lesions and ameliorate diabetes-induced neuropathic pain…

Our study may thus pave the way for future clinical trials on CB2 agonists in humans.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161308/

Cannabinoids alter endothelial function in the Zucker rat model of type 2 diabetes.

“Circulating levels of anandamide are increased in diabetes, and cannabidiol ameliorates a number of pathologies associated with diabetes. The aim of the present study was to examine how exposure to anandamide or cannabidiol might affect endothelial dysfunction associated with Zucker Diabetic Fatty rats…

These studies suggest that increased circulating endocannabinoids may alter vascular function both positively and negatively in type 2 diabetes, and that part of the beneficial effect of cannabidiol in diabetes may be due to improved endothelium-dependent vasorelaxation.”

http://www.ncbi.nlm.nih.gov/pubmed/24120371

Activation of cannabinoid CB2 receptor ameliorates atherosclerosis associated with suppression of adhesion molecules.

“Adhesion molecules have been implicated in the development and progression of atherosclerosis. Cannabinoids have been reported to modulate the migration and adhesion molecules expression of various cell types.

Here we examined the effects of WIN55212-2, a cannabinoid receptor 1 (CB1-R)/cannabinoid receptor 2 (CB2-R) agonist on the development of atherosclerotic lesions…

WIN55212-2 seems to have direct anti-atherosclerotic effects in an animal model of atherosclerosis… these beneficial effects of WIN55212-2 may be mediated through the CB2 receptor.”

http://www.ncbi.nlm.nih.gov/pubmed/20075743