Medical marijuana could treat pain caused by sickle cell disease

“A group of University of Minnesota researchers is testing to see if medical marijuana can help treat chronic pain caused by sickle cell disease, but state and federal laws are putting a hitch in their study.

As researchers continue with the study’s next step — conducting human trials — they’re heading to California, as Minnesota doesn’t easily allow testing cannabis on people. The state’s recently passed medical marijuana law doesn’t include sickle cell disease as a qualifying medical condition, but the University’s current research could play a role in how that law changes in the future.

“We find that cannabinoids have good outcomes in treating pain [in mice with sickle cell disease],” said chief researcher and associate professor of medicine Kalpna Gupta.

Gupta said the researchers are now ready to expand their study to patients. And in doing so, they will move to California, where medical marijuana became legal nearly two decades ago. Minnesota’s stricter version of that law will take effect next summer.

Right now, the Minnesota Department of Health is working to appoint members to a task force that will oversee medical cannabis therapeutic research in the coming months. The department is also fine-tuning the rules that outline patient access and qualifications.

Qualifying health conditions to receive medical cannabis in the Minnesota law include cancer, glaucoma, HIV/AIDS and seizures. Patients also qualify for the drug if they have chronic pain caused by cancer or a terminal illness.

Department of Health spokesman Mike Schommer said symptoms of sickle cell disease could potentially be added to the list of medical conditions in the future.

The main symptoms of sickle cell disease are fatigue and pain, and according to the state’s law, the commissioner of health may eventually add intractable pain to the list of qualifying medical conditions, making patients of sickle cell disease included.

Sickle cell patients have crescent-shaped blood cells instead of healthy, disc-shaped ones. Sickle cells block blood flow and cause pain and organ damage, according to the National Heart, Lung and Blood Institute.

Former University student Brianna Wilson has sickle cell anemia that gives her bone and muscle pain.

“Some people describe it as nails poking you, but for me, it’s pressure in my veins and upper body,” she said.

Physicians usually prescribe opiates, like morphine, to treat the pain, but researchers and patients agree that there are better ways to treat the disease. Wilson said the drugs are addictive and usually don’t offer good results.

School of Dentistry professor and pain expert Donald Simone, who is also working on the research project, said opiates sometimes have “problematic” side effects, such as respiratory depression. And Gupta said patients sometimes receive incorrect dosages of the drugs because their exact amount of pain is unknown.

Developing a means to measure the severe pain could be useful for doctors while making prescriptions, said biomedical engineering professor Bin He, another researcher who is involved in the project.

Medical marijuana is promising for sickle cell patients because it has a pain-relieving effect without as many severe side effects as morphine, Simone said.

The National Institutes of Health awarded the researchers $9.5 million in January to pursue studies on mice and patients. With that money, the research is expanding to California to test the effects of vaporized cannabis on 35 sickle cell disease patients beginning in July.

So far, the researchers’ study has found that mice with sickle cell disease are more sensitive to pain, especially when experiencing pressure, heat or cold, Simone said. By examining how neurons in the peripheral nerves and the spinal cord become overactive, the researchers are able to identify new ways to reduce pain, he said.

University of California-San Francisco professor Donald Abrams, who will lead the clinical trials in partnership with the Minnesota researchers, said there were many “hoops to jump through” in going forward with the study, like gaining approval from numerous government agencies.

Currently, 22 states and the District of Columbia allow medical marijuana programs, all varying in levels of strictness.

Minnesota’s law is among the nation’s strictest, and it prohibits patients from smoking or growing their own marijuana plants. The law mandates that two manufacturers operate four distribution centers each and that medical marijuana identification cards be available beginning July 2015 through a state-monitored registry.

“I can see [medical marijuana] helping,” Wilson said. “It’s chronic pain, so it should help, especially if it’s relaxing the muscles and things like that.””

http://www.mndaily.com/news/campus/2014/06/10/medical-marijuana-could-treat-pain-caused-sickle-cell-disease

“Medical Marijuana Policies Complicate Research Treating Chronic Sickle Cell Pain. A study by University of Minnesota researchers that was testing the effects of medical marijuana in treating chronic pain experienced by sickle cell patients has been forced out of the state due to a combination of restrictive state and federal policies stalling the project.”  http://www.huffingtonpost.com/2014/06/11/minnesota-medical-marijuana_n_5485383.html

Marijuana Helps Relieve MS Pain

“Researchers from the University of California, San Diego School of Medicine have found that smoking marijuana can help relieve pain, and muscle tightness “spasticity” in individuals with multiple sclerosis (MS). The study is published in the Canadian Medical Association Journal (CMAJ).”

http://www.medicalnewstoday.com/articles/245430.php

“Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394820/

Cannabinoid Modulation of Neuroinflammatory Disorders

Table 1.

Cannabis sativa is a herb belonging to the Cannabaceae family, characterized by palmate leaves and numerous fibers. Its first record as a medicine dates back to 5000 years ago and it was found in China, where cannabis was used for a myriad of purposes and diseases, including malaria, neuropathic pain, nausea, sexual dysfunction and constipation.

The use of cannabis spread from Central Asia and deeply influenced Indian folk medicine. However, sedative and psychotropic effects of cannabis turned it into a recreational drug. This fact resulted in discrimination against the consumption of the cannabis plant and its derivatives, which delayed the scientific findings in this field…

In recent years, a growing interest has been dedicated to the study of the endocannabinoid system. The isolation of Cannabis sativa main psychotropic compound, Δ(9)-tetrahydrocannabinol (THC), has led to the discovery of an atypical neurotransmission system that modulates the release of other neurotransmitters and participates in many biological processes, including the cascade of inflammatory responses.

In this context, cannabinoids have been studied for their possible therapeutic properties in neuroinflammatory diseases. In this review, historic and biochemical aspects of cannabinoids are discussed, as well as their function as modulators of inflammatory processes and therapeutic perspectives for neurodegenerative disorders, particularly, multiple sclerosis.

Cannabinoid compounds may be extracted from the plant (phytocannabinoids) or be artificially obtained (synthetic cannabinoids)…

To date, it is still impossible to prove or rule out all benefits of cannabis described empirically by ancient herbal practitioners. For now, science aims to understand how cannabinoid compounds are associated with neuroinflammation and how cannabis-based medicine can help millions of patients worldwide.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386505/

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/

Multiple sclerosis may disrupt endocannabinoid brain protection mechanism

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“Since the discovery of the endocannabinoids [eCB; anandamide and 2-arachidonoylglycerol (2-AG), various pathological conditions were shown to increase the eCB tone and to inhibit molecular mechanisms that are involved in the production, release, and diffusion of harmful mediators such as proinflammatory cytokines or excess glutamate.

In this issue of PNAS, Witting et al.  demonstrate that, unexpectedly and contrary to the effects of other brain diseases, cell damage induced by experimental autoimmune encephalomyelitis (EAE), an immune-mediated disease widely used as a laboratory model of multiple sclerosis (MS), does not lead to enhancement of eCB levels, although the cannabinoid receptors remain functional.

Nearly two decades ago, Lyman et al.  reported that Δ9-THC, the psychoactive component of marijuana, suppresses the symptoms of EAE. A few years later, Wirguin et al. reported the same effect by Δ8-THC, a more stable and less psychotropic analogue of Δ9-THC.

Thus, THC was shown to inhibit both clinical and histological signs of EAE even before the endocannabinoids were described.

THC was also shown to control spasticity and tremor in chronic relapsing EAE, a further autoimmune model of MS , and to inhibit glutamate release via activation of the CB1-cannabinoid receptor in EAE. Moreover, mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration after immune attack in EAE.

Thus, the brain loses some of its endogenous neuroprotective capacity, but it may still respond to exogenous treatment with 2-AG or other CB1 agonists. Assuming that the biochemical changes taking place in the EAE model of MS are similar to those in MS itself, these results represent a biochemical-based support to the positive outcome noted with cannabinoid therapy in MS.

These data suggest that the high level of IFN-γ in the CNS, noted in mice with EAE, disrupts eCB-mediated neuroprotection, while maintaining functional cannabinoid receptors, thus providing additional support for the use of cannabinoid-based medicine to treat MS.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458835/

Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection

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“Focal cerebral ischemia and traumatic brain injury induce an escalating amount of cell death because of harmful mediators diffusing from the original lesion site.

Evidence suggests that healthy cells surrounding these lesions attempt to protect themselves by producing endocannabinoids (eCBs) and activating cannabinoid receptors, the molecular target for marijuana-derived compounds.

Indeed, activation of cannabinoid receptors reduces the production and diffusion of harmful mediators.

Here, we provide evidence that an exception to this pattern is found in experimental autoimmuneencephalomyelitis (EAE), a mouse model of multiple sclerosis…

Our data suggest that the high level of CNS IFN-gamma associated with EAE disrupts eCB-mediated neuroprotection while maintaining functional cannabinoid receptors, thus providing additional support for the use of cannabinoid-based medicine to treat multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458883/

CBD-Rich Marijuana Fights Colon Cancer, New Study Finds

“In 2008, over one million individuals were diagnosed with colon cancer, also known as colorectal cancer or bowel cancer and it caused over 600,000 deaths globally. The results of a study published in the journal Phytomedicine in October 2013 suggest that a botanical extract made from high-CBD (cannabidiol) cannabis can selectively target colon cancer cells, while leaving healthy cells unharmed.

Researchers were able to reduce tumor growth and pre-cancerous lesions in mice with colon cancer using the pot molecule CBD as part of a “botanical drug substance”. The authors believe that CBD’s benefits as demonstrated by the results of the study could have clinical relevance for the use of cannabis-based medicines in cancer patients.

Current colon cancer treatments are not only very toxic but also fail to prevent the progression of the disease in some patients. Disease incidence and mortality have not reduced using screening strategies for colon cancer.

Researchers have made progress in investigating cannabis as a treatment for breast and brain cancers considering its antiproliferative CB1 and CB2-mediated effects in colorectal cancer cells and action in experimental models of colon cancer. The study was partially funded through grants from GW Pharmaceuticals and lead by researchers from Italy and the UK.”

http://blog.sfgate.com/smellthetruth/2014/01/06/cbd-rich-marijuana-fights-colon-cancer-new-study-finds/

“Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol” http://www.ncbi.nlm.nih.gov/pubmed/24373545

http://www.thctotalhealthcare.com/category/colon-cancer/

Cannabis Proves Effective In Treating Crohn’s Disease According To New Study

cannibis crohn's disease drug

“A new clinical study published in the journal Pharmacology and by the National Institute of Health has found that cannabis is effective in treating Crohn’s disease, which is a form of inflammatory bowel disease (IBD)…

The study, entitled: “Cannabis Finds Its Way into Treatment of Crohn’s Disease”  is co-authored by Rudolf Schicho, PhD and M. Storr, both of the Institute of Experimental and Clinical Pharmacology, Medical University of Graz in Graz, Austria.

In the study abstract, Schicho and Storr note that In ancient medicine, cannabis was widely used to treat and cure bowel disturbances and inflammation, and a recent clinical study now shows that the medicinal herb Cannabis sativa lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases.”

http://bionews-tx.com/news/2014/01/29/cannabis-proves-effective-treating-crohns-disease-according-new-study/

 http://www.thctotalhealthcare.com/category/crohns-disease/

Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine.

“Cannabis sativa L. has been utilized for treatment of pain and sleep disorders since ancient times.

This review examines modern studies on effects of Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on sleep. It goes on to report new information on the effects on sleep in the context of medical treatment of neuropathic pain and symptoms of multiple sclerosis, employing standardized oromucosal cannabis-based medicines containing primarily THC, CBD, or a 1 : 1 combination of the two (Sativex).

Sleep-laboratory results indicate a mild activating effect of CBD, and slight residual sedation with THC-predominant extracts. Experience to date with Sativex in numerous Phase I-III studies in 2000 subjects with 1000 patient years of exposure demonstrate marked improvement in subjective sleep parameters in patients with a wide variety of pain conditions including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis, with an acceptable adverse event profile.

No tolerance to the benefit of Sativex on pain or sleep, nor need for dosage increases have been noted in safety extension studies of up to four years, wherein 40-50% of subjects attained good or very good sleep quality, a key source of disability in chronic pain syndromes that may contribute to patients’ quality of life.”

http://www.ncbi.nlm.nih.gov/pubmed/17712817

Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

“For centuries Cannabis sativa and cannabis extracts have been used in natural medicine.

Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis.

In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma.

Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications.

The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.”

http://www.ncbi.nlm.nih.gov/pubmed/19832688