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.

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“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.

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“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

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.

Philosophical Transactions of the Royal Society B: Biological Sciences: 367 (1607)

“Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released ‘endocannabinoids’ or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ(9)-tetrahydrocannabinol (Δ(9)-THC)) and Sativex (Δ(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB(2) receptors, and/or (v) adjunctive ‘multi-targeting’.”  https://www.ncbi.nlm.nih.gov/pubmed/23108552

“Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities”  http://rstb.royalsocietypublishing.org/content/367/1607/3353.long

Therapeutic aspects of cannabis and cannabinoids

The British Journal of Psychiatry

“HISTORY OF THERAPEUTIC USE

The first formal report of cannabis as a medicine appeared in China nearly 5000 years ago when it was recommended for malaria, constipation, rheumatic pains and childbirth and, mixed with wine, as a surgical analgesic. There are subsequent records of its use throughout Asia, the Middle East, Southern Africa and South America. Accounts by Pliny, Dioscorides and Galen remained influential in European medicine for 16 centuries.”

“It was not until the 19th century that cannabis became a mainstream medicine in Britain. W. B. O’Shaughnessy, an Irish scientist and physician, observed its use in India as an analgesic, anticonvulsant, anti-spasmodic, anti-emetic and hypnotic. After toxicity experiments on goats and dogs, he gave it to patients and was impressed with its muscle-relaxant, anticonvulsant and analgesic properties, and recorded its use-fulness as an anti-emetic.”

“After these observations were published in 1842, medicinal use of cannabis expanded rapidly. It soon became available ‘over the counter’ in pharmacies and by 1854 it had found its way into the United States Dispensatory. The American market became flooded with dozens of cannabis-containing home remedies.”

“Cannabis was outlawed in 1928 by ratification of the 1925 Geneva Convention on the manufacture, sale and movement of dangerous drugs. Prescription remained possible until final prohibition under the 1971 Misuse of Drugs Act, against the advice of the Advisory Committee on Drug Dependence.”

“In the USA, medical use was effectively ruled out by the Marijuana Tax Act 1937. This ruling has been under almost constant legal challenge and many special dispensations were made between 1976 and 1992 for individuals to receive ‘compassionate reefers’. Although this loophole has been closed, a 1996 California state law permits cultivation or consumption of cannabis for medical purposes, if a doctor provides a written endorsement. Similar arrangements apply in Italy and Canberra, Australia.”

“Results and Conclusions Cannabis and some cannabinoids are effective anti-emetics and analgesics and reduce intra-ocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.”

http://bjp.rcpsych.org/content/178/2/107.long

Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb.

“Delta(9)-tetrahydrocannabinol binds cannabinoid (CB(1) and CB(2)) receptors, which are activated by endogenous compounds (endocannabinoids) and are involved in a wide range of physiopathological processes (e.g. modulation of neurotransmitter release, regulation of pain perception, and of cardiovascular, gastrointestinal and liver functions).

The well-known psychotropic effects of Delta(9)-tetrahydrocannabinol, which are mediated by activation of brain CB(1) receptors, have greatly limited its clinical use. However, the plant Cannabis contains many cannabinoids with weak or no psychoactivity that, therapeutically, might be more promising than Delta(9)-tetrahydrocannabinol.

Here, we provide an overview of the recent pharmacological advances, novel mechanisms of action, and potential therapeutic applications of such non-psychotropic plant-derived cannabinoids. Special emphasis is given to cannabidiol,

the possible applications of which have recently emerged in inflammation, diabetes, cancer, affective and neurodegenerative diseases, and to Delta(9)-tetrahydrocannabivarin, a novel CB(1) antagonist which exerts potentially useful actions in the treatment of epilepsy and obesity.”

http://www.ncbi.nlm.nih.gov/pubmed/19729208

The therapeutic potential of novel cannabinoid receptors.

Cover image

“Cannabinoids produce a plethora of biological effects, including the modulation of neuronal activity through the activation of CB(1) receptors and of immune responses through the activation of CB(2) receptors. The selective targeting of either of these two receptor subtypes has clear therapeutic value. Recent evidence indicates that some of the cannabinomimetic effects previously thought to be produced through CB(1) and/or CB(2) receptors, be they on neuronal activity, on the vasculature tone or immune responses, still persist despite the pharmacological blockade or genetic ablation of CB(1) and/or CB(2) receptors. This suggests that additional cannabinoid and cannabinoid-like receptors exist. Here we will review this evidence in the context of their therapeutic value and discuss their true belonging to the endocannabinoid signaling system.”  http://www.ncbi.nlm.nih.gov/pubmed/19248809

“The therapeutic potential of novel cannabinoid receptors”  http://www.sciencedirect.com/science/article/pii/S0163725809000266

Cannabis Science Extracts Kill Cancer Cells In Cancer Patients Being Treated Through Its Licensed Distributor Rockbrook

“Cannabis Science, Inc. a pioneering U.S. biotech company developing pharmaceutical cannabis (marijuana derivative) products, is pleased to announce that numerous patients are reporting that Cannabis Science extract treatments are killing cancer cells.

Unlike most conventional cancer treatments, cannabis has an outstanding safety profile, and patients in states with medical marijuana laws are able to make an informed decision to legally try various cannabis preparations to determine what is most effective for their particular condition.

Some of these scientifically informed patients have chosen to self-administer Cannabis Science extracts supplied by Rockbrook to treat their own cancers. Cannabis Science is delighted that patients are reporting dramatic improvements in their conditions, including basal cell carcinoma, non-small cell lung cancer accompanied by COPD (chronic obstructive pulmonary disease), ovarian cancer, and glioma.”

More: http://www.reuters.com/article/2011/02/22/idUS223662+22-Feb-2011+BW20110222