Tag Archives: medicinal

Evaluation of Δ(9)-tetrahydrocannabinol metabolites and oxidative stress in type 2 diabetic rats.

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“Cannabis has been known to be the oldest psychoactive plant for years. It is classified in the Cannabis genus, which is part of the Cannabacea family.

Cannabis sativa L. is the most common species. Δ9-tetrahydrocannabinol (THC) is the main psychoactive constituent identified in Cannabis sativa L.

THC is the most notable cannabinoid among all phytocannabinoids.

THC is exposed to degradation and converted into its active and inactive metabolites that are conjugated with glucuronic acid, and excreted in urine. THC is converted to active metabolite, 11-hydroxy-Δ9-THC (11-OH-THC), and then converted to an inactive metabolite, 11-nor-9-carboxy- Δ9-THC (THC – COOH).

ElSohly and Slade mention that C. sativa and its products have been used as medicinal agents.

Cannabinoids show a variety of therapeutic effects against chronic pain and muscle spasms, nausea and anorexia caused by HIV treatment, vomiting and nausea caused by cancer chemotherapy as well as anorexia associated with weight loss caused by immune deficiency syndrome.

Many studies report that THC provides protection against neuronal injury in a cell culture model of Parkinson disease and experimental models of Huntington disease, exhibits anti-oxidative action and mitigates the severity of the autoimmune response in an experimental model of diabetes.

The development and progression of diabetes mellitus and its complications arise out of increased oxidative damage. Kassab and Piwowar report that the best-known pathways of diabetic complications include oxidative stress.

The aims of the study presented in this paper were: (a) to explain the effects of THC on oxidative stress in T2DM treated with THC and (b) to determine the level of THC metabolites in the urine of diabetic and control rats induced by THC injection.

The object of the study is to examine the effects of Δ(9)-tetrahydrocannabinol (THC) against oxidative stress in the blood and excretion of THC metabolites in urine of type 2 diabetic rats.

These findings highlight that THC treatment may attenuate slightly the oxidative stress in diabetic rats.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818362/

Cannabimimetic Drugs: Recent Patents in Central Nervous System Disorders.

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“Agents acting via cannabinoid receptors have been widely developed; starting from the chemical structure of phytocannabinoids isolated from cannabis sativa plant, specific and selective compounds of these receptors have been produced ranging from partial to full agonists and /or antagonists endowed with different potency.

The enhanced interest on developing such classes of drugs is due to the beneficial properties widely reported by both anecdotal reports and scientific studies describing the potential medicinal use of cannabinoids and their derivatives in numerous pathological conditions in both in vitro and in vivo models.

The use of these drugs has been found to be of benefit in a wide number of neurological and neuropsychiatric disorders, and in many other diseases ranging from cancer, atherosclerosis, stroke, hypertension, inflammatory related disorders, and autoimmune diseases, just to mention some.

In particular, being the cannabinoid CB1 receptor a central receptor expressed by neurons of the central nervous system, the attention for the treatment of neurological diseases has been mainly focused on compounds acting via this receptor, however some of these compounds has been showed to act by alternative pathways in some cases unrelated to CB1 receptors.

Nonetheless, endocannabinoids are potent regulators of the synaptic function in the central nervous system and their levels are modulated in neurological diseases.

In this study, we focused on endocannabinoid mechanism of action in neuronal signaling and on cannabimimetic drug potential application in neurological disorders.

Finally, novel patents on cannabis-based drugs with applicability in central nervous system disorders are highlighted, to suggest future potential therapeutic utility of derivatives of this ancient plant.”

http://www.ncbi.nlm.nih.gov/pubmed/27334611

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease.

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“Using eight hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, the majority of whom were experiencing pain despite traditional treatment.

After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta-9-tetrahydrocannabinol on three separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was utilized to attempt to reduce the placebo effect.

Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model demonstrated a significant analgesic response for vaporized cannabis.

When subjective and psychoactive side effects (e.g., good drug effect, feeling high, etc.) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all p<0.0004). Psychoactive and subjective effects were dose dependent.

Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. As the two active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord.

PERSPECTIVE:

A cross-over, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months in order to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/27286745

Medicinal cannabis: Principal cannabinoids concentration and their stability evaluated by a high performance liquid chromatography coupled to diode array and quadrupole time of flight mass spectrometry method.

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“In the last few years, there has been a boost in the use of cannabis-based extracts for medicinal purposes, although their preparation procedure has not been standardized but rather decided by the individual pharmacists.

The present work describes the development of a simple and rapid high performance liquid chromatography method with UV detection (HPLC-UV) for the qualitative and quantitative determination of the principalcannabinoids (CBD-A, CBD, CBN, THC and THC-A) that could be applied to all cannabis-based medicinal extracts (CMEs) and easily performed by a pharmacist.

In order to evaluate the identity and purity of the analytes, a high-resolution mass spectrometry (HPLC-ESI-QTOF) analysis was also carried out. Full method validation has been performed in terms of specificity, selectivity, linearity, recovery, dilution integrity and thermal stability. Moreover, the influence of the solvent (ethyl alcohol and olive oil) was evaluated on cannabinoids degradation rate.

An alternative extraction method has then been proposed in order to preserve cannabis monoterpene component in final CMEs.”

http://www.ncbi.nlm.nih.gov/pubmed/27268223

RNA-seq analysis of delta -9-tetrahydrocannabinol-treated T cells reveals altered gene expression profiles that regulate immune response and cell proliferation.

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“Marijuana has drawn significant public attention and concern both for its medicinal and recreational use. Δ9-tetrahydrocannabinol (THC), which is the main bioactive component in marijuana, has also been shown to possess potent anti-inflammatory properties by virtue of its ability to activate cannabinoid receptor-2 (CB-2) expressed on immune cells.

In this study, we used RNA-seq to quantify the transcriptomes and transcript variants that are differentially regulated by THC in super antigen-activated lymph node cells and CD4+ T cells. We found that the expressions of many transcripts were altered by THC in both total lymph node cells and CD4+ T cells. Furthermore, the abundance of many miRNA precursors and long non-coding RNAs was dramatically altered in THC treated mice. For example, the expression of miR-17/92 cluster and miR-374b/421 cluster was down regulated by THC. On the other hand miR-146a which has been shown to induce apoptosis was up regulated by THC. Long non-coding RNAs that are expressed from the opposite strand of CD27 and Appbp2 were induced by THC.

In addition, THC treatment also caused alternative promoter usage and splicing. The functions of those altered transcripts were mainly related to immune response and cell proliferation.”

http://www.ncbi.nlm.nih.gov/pubmed/27268054

β-Caryophyllene attenuates palmitate-induced lipid accumulation through AMPK signaling by activating CB2 receptor in human HepG2 hepatocytes.

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“Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide, characterized by excessive hepatic lipid accumulation without significant ethanol consumption.

We have performed a screening for medicinal foods that inhibit hepatocytic lipid accumulation through activation of AMP-activated protein kinase (AMPK), which is a critical regulator of the hepatic lipid metabolism.

CONCLUSION:

Our results suggest that β-caryophyllene has the potential efficacy in preventing and ameliorating NAFLD and its associated metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/27234712

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

Can Cannabinoids Modulate Fibrotic Progression in Systemic Sclerosis?

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“Since ancient times, plants have been used for therapeutic purposes.

Cannabis sativa has been widely used as a medicinal herb by Ayurveda and traditional Chinese medicine for centuries.

According to our in vitro and in vivo experimental models, cannabinoids are able to modulate fibrosis.

The exact mechanism underlying this effect requires further investigation, but it seems to go beyond their anti-inflammatory and immunomodulatory properties.

Based on the above observations, we aimed to investigate the role of cannabinoids in systemic sclerosis (SSc), an autoimmune disease characterized by diffuse fibrosis.

Since preclinical data on cannabinoids show their capability to modulate fibrosis, inflammation and vasodilatation, these molecules could be ideal drugs for targeting SSc.”

http://www.ima.org.il/FilesUpload/IMAJ/0/193/96907.pdf

MicroRNA let-7d is a target of cannabinoid CB1 receptor and controls cannabinoid signaling.

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“Cannabinoid CB1 receptor, the molecular target of endocannabinoids and cannabis active components, is one of the most abundant metabotropic receptors in the brain. Cannabis is widely used for both recreational and medicinal purposes.

Despite the ever-growing fundamental roles of microRNAs in the brain, the possible molecular connections between the CB1 receptor and microRNAs are surprisingly unknown. Here, by using reporter gene constructs that express interaction sequences for microRNAs in human SH-SY5Y neuroblastoma cells, we show that CB1 receptor activation enhances the expression of several microRNAs, including let-7d.

Taken together, these findings provide the first evidence for a bidirectional link between the CB1 receptor and a microRNA, namely let-7d, and thus unveil a new player in the complex process of cannabinoid action.”

http://www.ncbi.nlm.nih.gov/pubmed/27179908

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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“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