Category Archives: THC (Delta-9-Tetrahydrocannabinol)
Targeting Cannabinoid Receptors in Brain Tumors

“Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances — the endocannabinoids — that activate specific cell surface receptors.
Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways, mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor cells and the inhibition of tumor angiogenesis.
Of interest, cannabinoids seem to be selective antitumoral compounds as they kill glioma cells but not their nontransformed astroglial counterparts.
On the basis of these preclinical findings, a pilot clinical study of Δ9-tetrahydrocannabinol (Δ9-THC) in patients with recurrent glioblastoma multiforme has been recently run. The fair safety profile of Δ9-THC, together with its possible growth-inhibiting action on tumor cells, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”
http://link.springer.com/chapter/10.1007%2F978-0-387-74349-3_17
Study: Cannabinoids Limit Neuroblastoma Cell Proliferation

“The administration of the cannabinoids THC and CBD limit cancer activity in neuroblastoma cells in culture and in animals, according to preclinical data published in the journal Current Oncology.
Neuroblastoma is an aggressive form of childhood cancer that often goes inadequately addressed by conventional treatment.
Investigators reported that both types of cannabinoids reduced neuroblastoma cell viability, but that CBD demonstrated superior anti-cancer ability. The study is the first to document the anti-cancer properties of CBD in this particular cancerous cell line.
They concluded, “Our findings about the activity of CBD in nbl (neuroblastoma) support and extend previous findings about the anti-tumor activities of CBD in other tumors and suggest that cannabis extracts enriched in CBD and not in THC could be suitable for the development of novel non-psychotropic therapeutic strategies in nbl.” http://enewspf.com/2016/04/21/study-cannabinoids-limit-neuroblastoma-cell-proliferation/
“In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791143/?report=reader
Synthetic Cannabinoids versus Natural Marijuana: A Comparison of Expectations

“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.
“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.”
New review sheds light on cannabinoids anticancer mechanisms

“The palliative effects of cannabinoids on cancer-related symptoms are well established.
In fact, many drugs comprised of delta-9-tetrahydrocannabinol (THC) or its synthetic analogues are currently approved in Canada for use in the management of chemotherapy-induced nausea and vomiting, pain relief, and appetite stimulation.
While this may provide adequate treatment to the symptoms endured by cancer patients, what if cannabis can all together treat and cure cancer?
Latest discoveries on cannabinoids and their anticancer properties focus on their molecular mechanisms of action and have been discussed in a recently published review article in Current Oncology, a peer-reviewed journal (Velasco, Sanchez, & Guzman, 2016).
It is important to begin by understanding that our body possesses an endogenous cannabinoid system.”
https://news.liftcannabis.ca/2016/04/21/new-review-sheds-light-cannabinoids-anticancer-mechanisms/
“Anticancer mechanisms of cannabinoids” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/
A Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray.
“Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray has proved efficacious in the treatment of spasticity in multiple sclerosis and chronic pain.
A thorough QT/QTc study was performed to investigate the effects of THC/CBD spray on electrocardiogram (ECG) parameters in compliance with regulatory requirements, evaluating the effect of a recommended daily dose (8 sprays/day) and supratherapeutic doses (24 or 36 sprays/day) of THC/CBD spray on the QT/QTc interval in 258 healthy volunteers.
The safety, tolerability, and pharmacokinetic profile of THC/CBD spray were also evaluated. Therapeutic and supratherapeutic doses of THC/CBD spray had no effect on cardiac repolarization with primary and secondary endpoints of QTcI and QTcF/QTcB, respectively, showing similar results. There was no indication of any effect on heart rate, atrioventricular conduction, or cardiac depolarization and no new clinically relevant morphological changes were observed.
Overall, 19 subjects (25.0%) in the supratherapeutic (24/36 daily sprays of THC/CBD spray) dose group and one (1.6%) in the moxifloxacin group withdrew early due to intolerable AEs. Four psychiatric serious adverse events (AEs) in the highest dose group resulted in a reduction in the surpatherapeutic dose to 24 sprays/day.
In conclusion, THC/CBD spray does not significantly affect ECG parameters. Additionally, THC/CBD spray is well tolerated at therapeutic doses with an AE profile similar to previous clinical studies.”
Cannabimovone, a Cannabinoid with a Rearranged Terpenoid Skeleton from Hemp
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“An investigation of the polar fractions from a nonpsychotropic variety of hemp (Cannabis sativa L.) afforded cannabimovone, a polar cannabinoid with a rearranged 2(34) abeo-terpenoid skeleton, biogenetically originating from the intramolecular aldolization of a 2′,3′-seco-menthanyl precursor.
The structure of cannabimovone was elucidated by spectroscopic analysis, whereas attempts to mimic its biogenetic derivation from cannabidiol gave only anhydrocannabimovone, the intramolecular oxy-Michael adduct of the crotonized version of the elusive natural products.
Biological evaluation of cannabimovone against metabotropic (CB1, CB2) and ionotropic (TRPs) cannabinoid receptors showed a significant activity only for ionotropic receptors, especially TRPV1, whereas anhydrocannabimovone exhibited strong activity at both ionotropic and metabotropic cannabinoid receptors.
Overall, the biological profile of anhydrocannabimovone was somewhat similar to that of THC, suggesting a remarkable tolerance to constitutional and configurational changes.”
http://onlinelibrary.wiley.com/doi/10.1002/ejoc.200901464/abstract
ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

“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.”
Industrial hemp decreases intestinal motility stronger than indian hemp in mice.
“Indian hemp has shown beneficial effects in various gastrointestinal conditions but it is not widely accepted due to high content of tetrahydrocannabinol resulting in unwanted psychotropic effects.
Since industrial hemp rich in cannabidiol lacks psychotropic effects the aim of research was to study the effects of industrial hemp on intestinal motility.
Although not completely without psychotropic activity cannabidiol could be a potential replacement for tetrahydrocannabinol.
Since industrial hemp infuse rich in cannabidiol reduces intestinal motility in healthy mice cannabidiol should be further evaluated for the treatment of intestinal hypermotility.”