Therapeutic potential of cannabis in pain medicine†

BJA

“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.”

http://bja.oxfordjournals.org/content/101/1/59.long

http://www.thctotalhealthcare.com/category/pain-2/

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Cannabidiol, a Major Non-Psychotrophic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts.

“Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort.

Here we report that the major non-psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid-femoral fractures.

Using Fourier Transform Infrared Spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus.

Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes.”

http://www.ncbi.nlm.nih.gov/pubmed/25801536

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Cannabidiol arrests onset of autoimmune diabetes in NOD mice.

Figure 2

“Cannabidiol (CBD) is a potent anti-inflammatory agent. It is effective in supressing IFN-γ and TNF-α production and progression of autoimmune Th1-mediated rheumatoid arthritis by inhibition of T cell proliferation. This observation led us to investigate the possible effects of CBD on additional autoimmune diseases.

We have previously reported that cannabidiol (CBD) lowers the incidence of diabetes in young non-obese diabetes-prone (NOD) female mice.

In the present study we show that administration of CBD to 11-14 week old female NOD mice… ameliorates the manifestations of the disease…

CBD was extracted from Cannabis resin (hashish)…

Our data strengthen our previous assumption that CBD, known to be safe in man, can possibly be used as a therapeutic agent for treatment of type 1 diabetes.

CBD is not psychoactive and has anti-inflammatory and anti autoimmune properties.

Based on the above presented results, on the previously documented anti-inflammatory effects of CBD and on its clinical safety, it seems reasonable to consider the use of CBD for controlling type 1 diabetes at an early stage of the disease.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270485/

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Texas A&M Pharmacy Researcher Fights Cancer, Pain With New Cannabinoid Receptor Drug

DrDaiLu

“Dr. Lu has been working to find new types of chemotherapeutic drugs that both kill pancreatic cancer and suppress the cancer pain at the same time by targeting a special G-protein coupled receptor that belongs to the biological system responsible for the effects of Tetrahydrocannabinol (THC), a compound derived from some varieties of cannabis (hemp) or made synthetically, that is the primary psychoactive agent in marijuana and hashish.

 Dr. Lu says pancreatic cancer cells have more type 2 cannabinoid receptors than do healthy cells.

 Consequently, drug molecules that selectively activate this receptor can induce cancer cell death without affecting normal pancreatic cells, noting that when given to mice with pancreatic tumors, the molecule prevented tumor growth and suppressed the spread of cancer to healthy organs.

 Meanwhile, this class of compounds also generates painkillers comparable to morphine’s pain killing effect…”

More: http://www.bionews-tx.com/news/2013/08/20/texas-am-pharmacy-researcher-fights-cancer-pain-with-new-cannabinoid-receptor-drug/

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The Use of Marijuana or Synthetic Cannabinoids for the Treatment of Headache – MedScape

“Pharmacological preparations of cannabinoid compounds have a variety of therapeutic uses in medicine, including different pain syndromes, but have not been previously reported as beneficial for cluster headache.We present a patient with cluster headache who was refractory to multiple acute and preventive medications but successfully aborted his attacks with recreational marijuana use; subsequent use of dronabinol provided equally effective pain relief. The beneficial effect may be related to the high concentration of cannabinoid receptors in the hypothalamus, which has been implicated as a site of dysfunction in neuroimaging studies of patients with cluster headache.

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 1970s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation, an increasing number of patients practice a self-prescription with cannabis products for relieving a variety of symptoms.

  The majority of patients used natural cannabis products such as marihuana, hashish, and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription…

 …this survey demonstrates a successful use of cannabis products for the treatment of a multitude of various illnesses and symptoms. This use was usually accompanied only by slight and in general acceptable side effects…”

http://www.medscape.com/viewarticle/738529

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Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.

115-11-cover

“Cannabis (marijuana, hashish, or cannabinoids) has been used for medical and recreational purposes for many centuries and is likely the only medicine or illicit drug that has constantly evoked tremendous interest or controversy within both the public domain and medical research. Cannabinoids appear to be able to modulate pain, nausea, vomiting, epilepsy, ischemic stroke, cerebral trauma, multiple sclerosis, tumors, and other disorders in humans and/or animals.

Cannabis acts on 2 types of cannabinoid receptors, the CB1 and CB2 receptors, which are distributed mainly in the brain and immune system, respectively. In the brain, CB1 receptors are also targeted by endogenous cannabinoids (i.e., endocannabinoids) such as anandamide (AEA), 2-arachidonylglycerol, and arachidonylethanolamide…

…since adult hippocampal neurogenesis is suppressed following chronic administration of opiates, alcohol, nicotine, and cocaine, the present study suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic administration…

Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.”  

https://www.jci.org/articles/view/25509

“University Of Saskatchewan Research Suggests Marijuana Analogue Stimulates Brain Cell Growth”  http://www.sciencedaily.com/releases/2005/10/051016083817.htm

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Fatty acid amide hydrolase: a potential target for next generation therapeutics.

Abstract

“Endocannabinoids are amides, esters and ethers of long chain polyunsaturated fatty acids, which act as new lipid mediators. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of Delta(9)-tetrahydrocannabinol, the active principle of Cannabis sativa preparations like hashish and marijuana. The activity of AEA at its receptors is limited by cellular uptake through a specific membrane transporter, followed by intracellular degradation by a fatty acid amide hydrolase (FAAH). Growing evidence demonstrates that FAAH is the critical regulator of the endogenous levels of AEA, suggesting that it may serve as an attractive therapeutic target for the treatment of human disorders. In particular, FAAH inhibitors may be next generation therapeutic drugs of potential value for the treatment of pathologies in the central nervous system and in the periphery. Here, the potential applications of these inhibitors for human disease will be reviewed, with an emphasis on the properties of hydro(pero)xy-anandamides. In fact, these oxygenated derivatives of AEA are the most powerful inhibitors of FAAH of natural origin as yet discovered. In addition, new insights into the promoter region of FAAH gene will be presented, and the therapeutic potential of mimetics of transcription factors of this gene in the management of human infertility will be discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/16472164

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Fatty acid amide hydrolase: a gate-keeper of the endocannabinoid system.

Abstract

“The family of endocannabinoids contains several polyunsaturated fatty acid amides such as anandamide (AEA), but also esters such as 2-arachidonoylglycerol (2-AG). These compounds are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of Delta9-tetrahydrocannabinol (Delta9-THC), the active principle of Cannabis sativa preparations like hashish and marijuana. The activity of AEA at its receptors is limited by cellular uptake, through a putative membrane transporter, followed by intracellular degradation by fatty acid amide hydrolase (FAAH). Growing evidence demonstrates that FAAH is the critical regulator of the endogenous levels of AEA, suggesting that it may serve as an attractive therapeutic target for the treatment of human disorders. In particular, FAAH inhibitors may be next generation therapeutics of potential value for the treatment of pathologies of the central nervous system, and of peripheral tissues. Investigations into the structure and function of FAAH, its biological and therapeutic implications, as well as a description of different families of FAAH inhibitors, are the topic of this chapter.”

http://www.ncbi.nlm.nih.gov/pubmed/18751909

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Cannabinoids in medicine: A review of their therapeutic potential.

“In order to assess the current knowledge on the therapeutic potential of cannabinoids, a meta-analysis was performed through Medline and PubMed up to July 1, 2005. The key words used were cannabis, marijuana, marihuana, hashish, hashich, haschich, cannabinoids, tetrahydrocannabinol, THC, dronabinol, nabilone, levonantradol, randomised, randomized, double-blind, simple blind, placebo-controlled, and human. The research also included the reports and reviews published in English, French and Spanish.

For the final selection, only properly controlled clinical trials were retained, thus open-label studies were excluded. Seventy-two controlled studies evaluating the therapeutic effects of cannabinoids were identified. For each clinical trial, the country where the project was held, the number of patients assessed, the type of study and comparisons done, the products and the dosages used, their efficacy and their adverse effects are described.

 Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer and AIDS), analgesics, and in the treatment of multiple sclerosis, spinal cord injuries, Tourette’s syndrome, epilepsy and glaucoma.”

http://www.ncbi.nlm.nih.gov/pubmed/16540272

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Neurobiology and systems physiology of the endocannabinoid system.

Abstract

“Endocannabinoids are synthesised from lipid precursors, are released from postsynaptic neurons in an activity-dependent way, and act as retrograde signalling messengers on specific G (i)-protein-coupled cannabinoid (CB (1)) receptors on presynaptic terminals. Hence, endocannabinoids are in a strategic position to regulate transmitter release. CB (1)-receptors are abundant on GABAergic, glutamatergic and dopaminergic synapses and play an essential role in a variety of cognitive processes and in the control of behaviour. The endocannabinoid system is not only the target of the psychoactive components of the hemp plant (tetrahydrocannabinol from hashish and marijuana) but has also been exploited for drugs acting as agonists (e.g. dronabinol) or antagonists (e.g. rimonabant) of the CB (1)-receptor. The former drugs exert orexigenic effects and can be used for the mitigation of anorexia e.g. in cancer patients, but have also been used for the treatment of multiple sclerosis. The latter have been used to treat adipositas. The role of the endocannabinoid system in the development of drug dependence has been discussed controversially, but recent evidence suggests that chronic stimulation of the endocannabinoid system may facilitate drug dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/19434559

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