Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease (Cannabis-SCD) -ClinicalTrials.gov Identifier: NCT01771731

“Cannabinoid-Based Therapy and Approaches to Quantify Pain in Sickle Cell Disease.

Our primary objective is to assess whether inhaling vaporized cannabis ameliorates chronic pain in patients with sickle cell disease (SCD). As these patients will all be on chronic opioid analgesics, the investigators will also assess the possible synergistic affect between inhaled cannabis and opioids.

The investigators will also assess the clinical safety of the concomitant use of cannabinoids and these opioids in patients with SCD by monitoring the short-term side effects associated with combined therapy.

Finally, the investigators will evaluate the short-term effects of inhaled cannabis on markers of inflammation and disease progression in patients with SCD.

Hypotheses are as follows:

  1. Inhaled cannabis will significantly reduce chronic pain in patients with SCD.
  2. Inhaled cannabis will significantly alter the short-term side effects experienced by patients who take opioids for SCD.
  3. Inhaled cannabis will significantly alter markers of inflammation and disease progression in patients with SCD compared to placebo.
Subjects will complete a 5-day pain diary prior to admission to the Clinical Research Center (CRC) to establish a baseline of pain. They will then be assigned to inhale either vaporized cannabis of mixed THC/CBD content (4.7% THC/5.1% CBD) or placebo cannabis (0% THC/0% CBD). Participants and personnel will be blinded as to assignment. Pain will be evaluated during the 5-day inpatient exposure. Participants will be asked to participate in two such 5-day sessions separated by at least a 2-week washout so that each will be exposed to the two experimental conditions.
Detailed Description:

This is a proof-of-principle investigation of the safety and potential effectiveness of inhaled vaporized cannabis when added to a stable analgesic regimen in sickle cell disease (SCD) patients with chronic pain. The study will be comprised of two 5-day intervention periods in the inpatient setting (the Clinical Research Center at SFGH), with completion of a 5-day daily pain diary prior to admission to establish an outpatient baseline. Participants will be randomly assigned, in double-blind fashion, to treatment with (A) vaporized cannabis with an approximately 1:1 ration of delta-9-tetrahydrocannabinol:cannabidiol or (B) vaporized placebo. Those who receive treatment A during the first admission will receive treatment B in the second, and those who receive treatment B during the first admission will receive treatment A in the second. The two admissions will be spaced at least 14 days apart.

On Day 1 of each admission, subjects will provide blood samples for baseline markers of inflammation and SCD disease progression. They will undergo assessments of pain, mood, and quality of life. At 12 pm on Day 1, they will inhale vaporized study agent (equivalent to 1 cannabis/placebo cigarette) using the Volcano® vaporizer; on Days 2-4 they will inhale study agent at 8 am, 2 pm, and 8 pm, and they will inhale their final dose on Day 5 at 8 am. Subjects will continue their pre-study analgesic regimen while in the study. If additional analgesia is required, supplemental therapy will be administered and the dose recorded. Pain measurements by visual analogue scale will be obtained every 2 hours while subjects are awake. On Day 5 a second set of blood samples for inflammation markers and disease progression will be obtained, and subjects will again complete pain, mood, and quality of life assessments.”

http://www.clinicaltrials.gov/ct2/show/study/NCT01771731#contacts

THC Can Manage Sickle Cell Disease

“Cannabinoids, the active ingredients in pot offer a new way to treat chronic and acute pain from sickle cell disease, ScienceDaily reports.

Currently the only treatment for the blood disease is opiods.

“Pain in SCD is described to be more intense than labor pain. The pain starts early in a patient’s life, often during infancy, and increases in severity with age.

[Cannibinoids are] effective in much lower amounts than opioids — the only currently approved treatment for this disease.”

http://www.eastbayexpress.com/LegalizationNation/archives/2010/07/23/daily-roundup-thc-can-manage-sickle-cell-disease-oakland-tweaks-medical-cannabis-taxes

Sickle Cell Pain May be Managed with Cannabis

“Can Medical Cannabis Help to Cure SCD?”

Sickle Cell Disease Pain May Be Managed 2

“Sickle cell disease (SCD) is a hereditary condition caused by a mutation in the haemoglobin gene, which leads to symptoms of anaemia, extreme pain, and organ damage if unmanaged.”

Sickle Cell Disease Pain May Be Managed 1

“Individuals suffering from SCD are far more likely to use cannabis than the general population, potentially for its analgesic properties.

In 2010, researchers at the University of Minnesota found that the synthetic THC analogue CP 55,940 was as effective as morphine sulphate in treating SCD-related severe pain in transgenic mice expressing human sickle haemoglobin, and that it was effective at smaller doses than the opioid.

In 2011, a further paper submitted by the same researchers to Blood (the Journal of the American Association of Hematology) indicated that CP 55,940 ameliorated severe pain associated with the hypoxia/reoxygenation cycle. CP 55,940 is a full agonist of both CB receptors, and is thought to act as an antagonist at the GPR55 receptor.

As well as this, cannabis has been repeatedly shown to act as a vasodilator, which could in itself assist in easing the blockages caused by build-up of sickle cells…

SCD is a painful and debilitating disease, and the overall inefficacy of opioid treatments and resultant poor quality of life for many sufferers is an indication that our approach to it is far from perfect.

If cannabis is a good candidate to replace opioids, it should be implemented forthwith to prevent ongoing suffering for existing patients.”

http://sensiseeds.com/en/blog/sickle-cell-pain-may-managed-cannabis/

Medical Marijuana Could Help Treat Sickle Cell Disease

sickle cell marijuana

“People who suffer from sickle cell disease have to deal with a lot of pain.

Patients with sickle cell disease have crescent shaped blood cells, compared to disc shaped blood cells in people who don’t suffer from sickle cell disease. These cells block blood flow, which causes pain, fatigue, and organ damage. I’ve heard people that suffer from sickle cell disease describe the pain as being like nails poking their entire body.

Doctors usually prescribe opiate based pain killers like morphine for sickle cell disease. Opiate prescriptions have a lot of side effects including respiratory issues, damage to organs, and addiction to name a few. Compare that to medical marijuana, which has far less harmful side effects, especially if consumed in food or vapor form. Patients should have the option to choose medical marijuana if they want to. From Minnesota Daily:

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.

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.

Right now researchers in California are teaming up with researchers at the University of Minnesota to find out how medical marijuana can help those suffering from sickle cell disease. Right now, sickle cell patients can get safe access to medical marijuana if they are in California. However, patients in Minnesota will have to wait until the condition is added to the list of approvable conditions in Minnesota, which could take awhile.”

http://www.theweedblog.com/medical-marijuana-could-help-treat-sickle-cell-disease/

Cannabis use in sickle cell disease: a questionnaire study.

“Cannabinoids are increasingly being considered for the management of various painful conditions, and could be considered as an option for treating acute pain in sickle cell disease (SCD).

The objective of this study was to determine the extent of use of cannabis in the community for pain and other symptom relief, and its side effects during self-administration in patients with SCD…

The main reasons for use were to reduce pain in 52%, and to induce relaxation or relieve anxiety and depression in 39%. Symptoms related to sedation and mood effects were reported in 77% of patients. The majority of patients (58%) expressed their willingness to participate in studies of cannabis as a medicine.

We conclude that research in the use of cannabinoids for pain relief in SCD would be both important and acceptable to adult patients.”

http://www.ncbi.nlm.nih.gov/pubmed/16173972

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

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/

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

The endocannabinoid system and its therapeutic exploitation.

Image result for Nat Rev Drug Discov.

“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.”  http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

Image result for West Indian Med J

“Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the ‘holy grail’ of endocannabinoid research.”

http://www.ncbi.nlm.nih.gov/pubmed/23155985