Tag Archives: marijuana

Marihuana as Medicine

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“BETWEEN 1840 and 1900, European and American medical journals published more than 100 articles on the therapeutic use of the drug known then as Cannabis indica (or Indian hemp) and now as marihuana.

It was recommended as an appetite stimulant, muscle relaxant, analgesic, hypnotic, and anticonvulsant. As late as 1913 Sir William Osler recommended it as the most satisfactory remedy for migraine.

Today the 5000-year medical history of cannabis has been almost forgotten.

Its use declined in the early 20th century because the potency of preparations was variable, responses to oral ingestion were erratic, and alternatives became available—injectable opiates and, later, synthetic drugs such as aspirin and barbiturates.

In the United States, the final blow was struck by the Marihuana Tax Act of 1937. Designed to prevent nonmedical use, this law made cannabis so difficult to obtain for medical purposes that it was removed from the pharmacopeia.”

http://jama.jamanetwork.com/article.aspx?articleid=388943#Abstract

The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research.

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“The authors present case histories indicating that a number of patients find cannabis (marihuana) useful in the treatment of their bipolar disorder.

Some used it to treat mania, depression, or both. They stated that it was more effective than conventional drugs, or helped relieve the side effects of those drugs.

One woman found that cannabis curbed her manic rages; she and her husband have worked to make it legally available as a medicine. Others described the use of cannabis as a supplement to lithium (allowing reduced consumption) or for relief of lithium’s side effects.

Another case illustrates the fact that medical cannabis users are in danger of arrest, especially when children are encouraged to inform on parents by some drug prevention programs.

An analogy is drawn between the status of cannabis today and that of lithium in the early 1950s, when its effect on mania had been discovered but there were no controlled studies.

In the case of cannabis, the law has made such studies almost impossible, and the only available evidence is anecdotal. The potential for cannabis as a treatment for bipolar disorder unfortunately can not be fully explored in the present social circumstances.”

http://www.ncbi.nlm.nih.gov/pubmed/9692379

Synthetic Cannabinoids versus Natural Marijuana: A Comparison of Expectations

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ScienceDaily

“A new study evaluated the expected outcomes of both synthetic and natural marijuana.

An article entitled “Comparison of Outcome Expectancies for Synthetic Cannabinoids and Botanical Marijuana,” from The American Journal of Drug and Alcohol Abuse, studied the expected outcomes of both synthetic and natural marijuana.

186 adults who had previously used both synthetic and natural marijuana, as well as 181 who had previously used only botanical marijuana, were surveyed about their expected outcomes of using either type of cannabinoid.

The results showed that the expected negative effects were significantly higher for synthetic marijuana than for natural marijuana across both categories of use history.

Despite the more commonly expected negative effects of synthetic cannabinoids, the most cited reasons for using these compounds were wider availability, avoiding a positive drug test, curiosity, perceived legality, and cost.

Authors concluded, “Given growing public acceptance of recreational and medical marijuana, coupled with negative perceptions and increasing regulation of synthetic cannabinoid compounds, botanical marijuana is likely to remain more available and more popular than synthetic cannabinoids.”

https://www.sciencedaily.com/releases/2016/04/160427081800.htm

“Comparison of outcome expectancies for synthetic cannabinoids and botanical marijuana.” http://www.ncbi.nlm.nih.gov/pubmed/26910181

 

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Comparison of outcome expectancies for synthetic cannabinoids and botanical marijuana.

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“Although initially developed for medical purposes, synthetic cannabinoids have also been consumed for recreational purposes.

To evaluate whether agreement with positive and negative outcome expectancies differed for synthetic cannabinoids versus botanical marijuana, and assess reported reasons for using synthetic cannabinoids.

A significant interaction revealed that participants who had used both synthetic cannabinoids and botanical marijuana indicated lower agreement with positive expectancies for synthetic cannabinoids, and higher agreement with positive expectancies for botanical marijuana, than did those participants who used only botanical marijuana.

There was no interaction between type of drug and use history on agreement with negative expectancies, and participants agreed more strongly with negative outcome expectancies for synthetic cannabinoids than for botanical marijuana whether they had used one or both types of these drugs.

The most frequently provided reasons for using synthetic cannabinoids included availability, perceived legality, cost, curiosity, and social interaction.

Given growing public acceptance of recreational and medical marijuana, coupled with negative perceptions and increasing regulation of synthetic cannabinoid compounds, botanical marijuana is likely to remain more available and more popular than synthetic cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/26910181

Marijuana is medicine, Journal of the American Medical Association concludes

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“Marijuana is one hundred percent a form of medicine, researchers conclude in a bombshell series of reports released by the Journal of the American Medical Association. Cannabis has been used medicinally for thousands of years” http://blog.sfgate.com/smellthetruth/2015/06/23/marijuana-is-medicine-journal-of-the-american-medical-association-concludes/

http://blog.sfgate.com/smellthetruth/2015/06/23/marijuana-is-medicine-journal-of-the-american-medical-association-concludes/

“Cannabinoids for Medical Use. A Systematic Review and Meta-analysis.”  http://jama.jamanetwork.com/article.aspx?articleid=2338251

In Vitro Propagation of Cannabis sativa L. and Evaluation of Regenerated Plants for Genetic Fidelity and Cannabinoids Content for Quality Assurance.

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“Cannabis sativa L. (Marijuana; Cannabaceae), one of the oldest medicinal plants in the world, has been used throughout history for fiber, food, as well as for its psychoactive properties.

The dioecious and allogamous nature of C. sativa is the major constraint to maintain the consistency in chemical profile and overall efficacy if grown from seed. Therefore, the present optimized in vitro propagation protocol of the selected elite germplasm via direct organogenesis and quality assurance protocols using genetic and chemical profiling provide an ideal pathway for ensuring the efficacy of micropropagated Cannabis sativa germplasm.

A high frequency shoot organogenesis of C. sativa was obtained from nodal segments in 0.5 μM thidiazuron medium and 95 % in vitro rhizogenesis is obtained on half-strength MS medium supplemented with 500 mg/L activated charcoal and 2.5 μM indole-3-butyric acid. Inter Simple Sequence Repeats (ISSR) and Gas Chromatography-Flame Ionization Detection (GC-FID) are successfully used to monitor the genetic stability in micropropagated plants up to 30 passages in culture and hardened in soil for 8 months.”

http://www.ncbi.nlm.nih.gov/pubmed/27108324

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

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Image result for Curr Clin Pharmacol.

“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

Orexin-A represses satiety-inducing POMC neurons and contributes to obesity via stimulation of endocannabinoid signaling.

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“In the hypothalamic arcuate nucleus (ARC), proopiomelanocortin (POMC) neurons and the POMC-derived peptide α-melanocyte-stimulating hormone (α-MSH) promote satiety. POMC neurons receive orexin-A (OX-A)-expressing inputs and express both OX-A receptor type 1 (OX-1R) and cannabinoid receptor type 1 (CB1R) on the plasma membrane.

OX-A is crucial for the control of wakefulness and energy homeostasis and promotes, in OX-1R-expressing cells, the biosynthesis of the endogenous counterpart of marijuana’s psychotropic and appetite-inducing component Δ9-tetrahydrocannabinol, i.e., the endocannabinoid 2-arachidonoylglycerol (2-AG), which acts at CB1R.

We report that OX-A/OX-1R signaling at POMC neurons promotes 2-AG biosynthesis, hyperphagia, and weight gain by blunting α-MSH production via CB1R-induced and extracellular-signal-regulated kinase 1/2 activation- and STAT3 inhibition-mediated suppression ofPomcgene transcription. Because the systemic pharmacological blockade of OX-1R by SB334867 caused anorectic effects by reducing food intake and body weight, our results unravel a previously unsuspected role for OX-A in endocannabinoid-mediated promotion of appetite by combining OX-induced alertness with food seeking. Notably, increased OX-A trafficking was found in the fibers projecting to the ARC of obese mice (ob/oband high-fat diet fed) concurrently with elevation of OX-A release in the cerebrospinal fluid and blood of mice.

Furthermore, a negative correlation between OX-A and α-MSH serum levels was found in obese mice as well as in human obese subjects (body mass index > 40), in combination with elevation of alanine aminotransferase and γ-glutamyl transferase, two markers of fatty liver disease.

These alterations were counteracted by antagonism of OX-1R, thus providing the basis for a therapeutic treatment of these diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/27071101

No more pain upon Gq-protein-coupled receptor activation: role of endocannabinoids.

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“Marijuana has been used to relieve pain for centuries.

The analgesic mechanism of its constituents, the cannabinoids, was only revealed after the discovery of cannabinoid receptors (CB1 and CB2) two decades ago.”

http://www.ncbi.nlm.nih.gov/pubmed/24494686

Marijuana-derived Δ-9-tetrahydrocannabinol suppresses Th1/Th17 cell-mediated delayed-type hypersensitivity through microRNA regulation.

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“∆9-Tetrahydrocannabinol (THC) is one of the major bioactive cannabinoids derived from the Cannabis sativa plant and is known for its anti-inflammatory properties. Delayed-type hypersensitivity (DTH) is driven by proinflammatory T helper cells including the classic inflammatory Th1 lineage as well as the more recently discovered Th17 lineage. In the current study, we investigated whether THC can alter the induction of Th1/Th17 cells involved in mBSA-induced DTH response. THC treatment (20 mg/kg) of C57BL/6 mice with DTH caused decreased swelling and infiltration of immune cells at the site of antigen rechallenge. Additionally, THC treatment decreased lymphocyte activation as well as Th1/Th17 lineage commitment, including reduced lineage-specific transcription factors and cytokines. Interestingly, while DTH caused an overexpression of miR-21, which increases Th17 differentiation via SMAD7 inhibition, and downregulation of miR-29b, an IFN-γ inhibitor, THC treatment reversed this microRNA (miR) dysregulation. Furthermore, when we transfected primary cells from DTH mice with miR-21 inhibitor or miR-29b mimic, as seen with THC treatment, the expression of target gene message was directly impacted increasing SMAD7 and decreasing IFN-γ expression, respectively. In summary, the current study suggests that THC treatment during DTH response can simultaneously inhibit Th1/Th17 activation via regulation of microRNA (miRNA) expression.

KEY MESSAGES:

• THC treatment inhibits simultaneous Th1/Th17 driven inflammation. • THC treatment corrects DTH-mediated microRNA dysregulation. • THC treatment regulates proinflammatory cytokines and transcription factors.”

http://www.ncbi.nlm.nih.gov/pubmed/27038180