Cannabinoid system as a potential target for drug development in the treatment of cardiovascular disease.

“Although cannabinoids have been recreationally employed for thousands of years, it was not until the discovery of their specific receptors, in the early nineties, that the molecular basis of cannabinoid activity have began to be understood.

Growing research in this field has demonstrated not only that the action of cannabinoids in mammals is mainly receptor-mediated, but also that endogenous cannabinoids, such as anandamide, are produced, metabolized, and taken up across the cell membrane through a facilitated uptake process.

The exogenous administration of cannabinoids, as well as the manipulation of their endogenous levels have been related to a variety of effects, such as analgesia, (temporary) impairment of cognition and learning, appetite enhancement and peripheral vasodilation.

Hence, the endocannabinoid system, including the CB1 and CB2 receptors, the metabolizing enzyme fatty acid amide hydrolase and the anandamide transporter, is a potential target for the development of novel therapeutic drugs in the treatment of various conditions, such as pain, feeding disorders and vascular disease among others.

Although most of the research in the field of cannabinoids has been focused on their effects in the central nervous system, a growing line of evidence indicates that cannabinoids can also play a major role in the control of physiopathological functions in the cardiovascular system.

In this context, endocannabinoids have been proposed as novel possible hypotensive agents, and have been involved in the hypotension observed in septic shock, acute myocardial infarction and cirrhosis. In addition, a protective role for endocannabinoids has been described in ischemia.”

The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain.

European Neuropsychopharmacology Home

“The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressedcannabinoid receptor 2 (CB₂).

…the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.

Cannabis preparations, which have been used since thousands of years for the treatment of pain have recently come again into the focus as potential therapeutics for inflammatory and neuropathic pain conditions. Currently, cannabis extracts and synthetic preparations of the psychoactive cannabis compound Δ9-tetrahydrocannabinol (THC) have been approved in many countries for clinical pain management at doses and formulations that show on only minor central side effects…

A natural selective agonist for CB2 receptors is the plant volatile BCP, which represents a dietary phytocannabinoid. BCP is found in large amounts in the essential oils of many common spices and food plants… Several health effects have been attributed to BCP or medicinal plants containing BCP, including anti-inflammatory, local anesthetic, anti-carcinogenic, anti-fibrotic and anxiolytic-like activity.

In the present study, we investigated the analgesic effects of BCP in formalin-induced inflammation model and in a model of neuropathic pain, which involves the partial ligation of the sciatic nerve… BCP is the first natural CB2 receptor agonist, which could orally reduce inflammatory responses in different animal models of pain.

Thus, it is likely that BCP belongs to a group of common plant natural products with major potential impact on human health.

The oral intake of this dietary cannabinoid with vegetable food could be advantageous in the daily routine clinical practice over synthetic cannabinoid agonists.”

Therapeutic potential of cannabis in pain medicine†


“Cannabis has been of medicinal and social significance for millennia.

It is obtained from Cannabis sativa and the plant’s name reflects its ancient use—cannabis may represent a compound of Sanskrit and Hebrew words meaning ‘fragrant cane’, while sativa is Latin for cultivated.

Cannabis is also known as hemp.

Marijuana describes the dried cannabis flowers and leaves which are smoked, while hashish refers to blocks of cannabis resin which can be eaten.

Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic significance.

Cannabinoids (CBs) are chemical compounds derived from cannabis.

This review discusses the basic science and clinical aspects of CB pharmacology with a focus on pain medicine.

Advances in cannabis research have ensured a future for these analgesic molecules which have been used since antiquity.”

Activation of Cannabinoid CB2 receptors Reduces Hyperalgesia in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis.

“Clinical trials investigating the analgesic efficacy of cannabinoids in multiple sclerosis have yielded mixed results, possibly due to psychotropic side effects mediated by cannabinoid CB1 receptors. We hypothesized that a CB2-specific agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis…

Our results suggest that JWH-133 acts at CB2 receptors, most likely within the dorsal horn of the spinal cord, to suppress the hypersensitivity associated with experimental autoimmune encephalomyelitis.

These are the first pre-clinical studies to directly promote CB2 as a promising target for the treatment of central pain in an animal model of multiple sclerosis.”

Re-branding cannabis: the next generation of chronic pain medicine?

“The field of pain medicine is at a crossroads given the epidemic of addiction and overdose deaths from prescription opioids. Cannabis and its active ingredients, cannabinoids, are a much safer therapeutic option.

Despite being slowed by legal restrictions and stigma, research continues to show that when used appropriately, cannabis is safe and effective for many forms of chronic pain and other conditions, and has no overdose levels.

Current literature indicates many chronic pain patients could be treated with cannabis alone or with lower doses of opioids.

To make progress, cannabis needs to be re-branded as a legitimate medicine and rescheduled to a more pharmacologically justifiable class of compounds.

This paper discusses the data supporting re-branding and rescheduling of cannabis.”

Cannabinoids in the treatment of pain

“Cannabinoids and the endo-cannabinoid system play an important role in the sensation of pain. As conventional analgesics are often associated with serious side-effects, cannabinoids and agonists of their receptors offer a useful alternative or coanalgesic in the treatment of pain. The aim of this work is to summarize the role of cannabinoids and their receptors in nociception and pain treatment.”

Cannabinoids seem to be effective against neuropathic pain, inflammatory pain, post-operative pain and cancer pain. Their use as analgesics or coanalgesics may offer a useful alterative option for pain management in clinical practice.”

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

ScienceDaily: Your source for the latest research news

“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.”

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.”

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.”

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.””

“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.”

Antinociceptive activity of Delta9-tetrahydrocannabinol non-ionic microemulsions.

“Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent of Cannabis sativa L., has been widely studied for its potential pharmaceutical application in the treatment of various diseases and disturbs.

The aim of this work was to develop a stable aqueous Delta(9)-THC formulation acceptable for different ways of administration, and to evaluate the therapeutic properties of the new Delta(9)-THC based preparation for pain treatment.

Significant antinociceptive activity has been detected by both intraperitoneal and intragastric administration of the new Delta(9)-THC pharmaceutical preparation.”