“Cannabis sativa active compounds are extensively studied for their therapeutic effects, beyond the well-known psychotropic activity. C. Sativa is used to treat different medical indications, such as multiple sclerosis, spasticity, epilepsy, ulcerative colitis and pain. Simultaneously, basic research is discovering new constituents of cannabis-derived compounds and their receptors capable of neuroprotection and neuronal activity modulation. The function of the various phytochemicals in different therapeutic processes is not fully understood, but their significant role is starting to emerge and be appreciated. In this review, we will consider the structure-activity relationship (SAR) of cannabinoid compounds able to bind to cannabinoid receptors and act as therapeutic agents in neuronal diseases, e.g., Parkinson’s disease.” https://www.ncbi.nlm.nih.gov/pubmed/29941830 http://www.mdpi.com/1420-3049/23/7/1526]]>
Tag Archives: therapeutic
Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1–CB2 Heteroreceptor Complexes
“Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L. that is attracting pharmacological interest because it is non-psychotropic and is abundant in some industrial hemp varieties. The aim of this work was to investigate in parallel the binding properties of CBG to cannabinoid CB1 (CB1R) and CB2 (CB2R) receptors and the effects of the compound on agonist activation of those receptors and of CB1–CB2 heteroreceptor complexes. The results indicate that CBG is indeed effective as regulator of endocannabinoid signaling. In conclusion, the results presented in this study reveal that the non-psychotropic phytocannabinoid, CBG, may exert beneficial actions with therapeutic potential via cannabinoid receptors.” https://www.frontiersin.org/articles/10.3389/fphar.2018.00632/full
“International Multi-Centre Collaboration Reveals that Cannabigerol Acts Directly on Cannabinoid Receptors CB1 and CB2” https://www.prnewswire.com/news-releases/international-multi-centre-collaboration-reveals-that-cannabigerol-acts-directly-on-cannabinoid-receptors-cb1-and-cb2-300671024.html
]]>“Illogical” cannabis regulation blocks research into therapeutic uses, say doctors
“Doctors should be able to prescribe cannabis legally and research its therapeutic use more easily, 20 prominent UK clinicians and academics have said.
In a letter to The Times on 20 June, they “strongly urge the government” to recategorise cannabis from schedule 1 to schedule 2 under the UK Misuse of Drugs Regulations 2001.
Schedule 1 is for illicit substances deemed to have no clinical application and which doctors cannot prescribe; schedule 2 drugs, including, for example, diamorphine (heroin), are subject to requirements relating to prescriptions.
Last week, Savid Javid, the home secretary, said that a panel would be set up to review the evidence for medical cannabis that could see the drug rescheduled.”
https://www.bmj.com/content/361/bmj.k2780.full]]>Appraising the "entourage effect": antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer.
“Breast cancer is the second leading cause of death among women. Although early diagnosis and development of new treatments have improved their prognosis, many patients present innate or acquired resistance to current therapies. New therapeutic approaches are therefore warranted for the management of this disease.
Extensive preclinical research has demonstrated that cannabinoids, the active ingredients of Cannabis sativa, trigger antitumor responses in different models of cancer. Most of these studies have been conducted with pure compounds, mainly Δ9-tetrahydrocannabinol (THC).
The cannabis plant, however, produces hundreds of other compounds with their own therapeutic potential and the capability to induce synergic responses when combined, the so-called “entourage effect”.
Here, we compared the antitumor efficacy of pure THC with that of a botanical drug preparation (BDP). The BDP was more potent than pure THC in producing antitumor responses in cell culture and animal models of ER+/PR+, HER2+ and triple-negative breast cancer. This increased potency was not due to the presence of the 5 most abundant terpenes in the preparation.
While pure THC acted by activating cannabinoid CB2 receptors and generating reactive oxygen species, the BDP modulated different targets and mechanisms of action. The combination of cannabinoids with estrogen receptor- or HER2-targeted therapies (tamoxifen and lapatinib, respectively) or with cisplatin, produced additive antiproliferative responses in cell cultures. Combinations of these treatments in vivo showed no interactions, either positive or negative.
Together, our results suggest that standardized cannabis drug preparations, rather than pure cannabinoids, could be considered as part of the therapeutic armamentarium to manage breast cancer.”
The Role of Cannabinoids in the Setting of Cirrhosis.
“Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis and specifically tailored to the different manifestations of hepatic decompensation. Antifibrogenic therapies are within an active area of investigation. The endocannabinoid system has been shown to play a role in liver disease, and cirrhosis specifically, with intriguing possible therapeutic benefits. The endocannabinoid system comprises cannabinoid receptors 1 (CB1) and cannabinoid receptor 2 (CB2) and their ligands, endocannabinoids and exocannabinoids. CB1 activation enhances fibrogenesis, whereas CB2 activation counteracts progression to fibrosis. Conversely, deletion of CB1 is associated with an improvement of hepatic fibrosis and steatosis, and deletion of CB2 results in increased collagen deposition, steatosis, and enhanced inflammation. CB1 antagonism has also demonstrated vascular effects in patients with cirrhosis, causing an increase in arterial pressure and vascular resistance as well as a decrease in mesenteric blood flow and portal pressure, thereby preventing ascites. In mice with hepatic encephalopathy, CB1 blockade and activation of CB2 demonstrated improved neurologic score and cognitive function. Endocannabinoids, themselves also have mechanistic roles in cirrhosis. Arachidonoyl ethanolamide (AEA) exhibits antifibrogenic properties by inhibition of HSC proliferation and induction of necrotic death. AEA induces mesenteric vasodilation and hypotension via CB1 induction. 2-arachidonoyl glycerol (2-AG) is a fibrogenic mediator independent of CB receptors, but in higher doses induces apoptosis of HSCs, which may actually show antifibrotic properties. 2-AG has also demonstrated growth-inhibitory and cytotoxic effects. The exocannabinoid, THC, suppresses proliferation of hepatic myofibroblasts and stellate cells and induces apoptosis, which may reveal antifibrotic and hepatoprotective mechanisms. Thus, several components of the endocannabinoid system have therapeutic potential in cirrhosis.” https://www.ncbi.nlm.nih.gov/pubmed/29890719 http://www.mdpi.com/2305-6320/5/2/52]]>
Betacaryophyllene – A phytocannabinoid as potential therapeutic modality for human sepsis?
“Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units.
The endogenous cannabinoid system (ECS) plays an important role in inflammation.
Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis.
Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R.
We propose BCP administration as novel treatment to reduce hyper-inflammation in human sepsis.”
“Cannabidiol (CBD) is a compound of 
“The endocannabinoid system (ECS) is composed of cannabinoid receptors, their endogenous ligands, and the enzymes involved in endocannabinoid turnover.
Modulating the activity of the ECS may influence a variety of physiological and pathophysiological processes.
A growing body of evidence indicates that activation of cannabinoid receptors by endogenous, plant-derived, or synthetic cannabinoids may exert beneficial effects on gastrointestinal inflammation and visceral pain.
The present ex vivo study aimed to investigate immunohistochemically the distribution of cannabinoid receptors CB1, CB2, G protein-coupled receptor 55 (GPR55), and peroxisome proliferation activation receptor alpha (PPARα) in the canine gastrointestinal tract.
Cannabinoid receptors showed a wide distribution in the gastrointestinal tract of the dog.
Since cannabinoid receptors have a protective role in inflammatory bowel disease, the present research provides an anatomical basis supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders and visceral hypersensitivity in canine acute or chronic enteropathies.”
“Currently available antidepressants have a substantial time lag to induce therapeutic response and a relatively low efficacy. The development of drugs that addresses these limitations is critical to improving public health.
Cannabidiol (CBD), a non-psychotomimetic component of