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cbd and colon cancer research

Cbd and colon cancer research

So far, few studies have investigated the effects of CBD as an angiogenesis modulator. Solinas et al. discovered strong anti-angiogenic effects of CBD, both in vitro, reducing growth, migration, and invasion of HUVEC cells, and in vivo, using the Matrigel sponge assay in mice. Multiple mechanisms in modulating angiogenic factors relatingto impaired angiogenesis were observed [138].

Cannabinoids are terpenophenolics comprising a diphenol and a monoterpene moiety. The synthesis of the former part occurs via the polyketide pathway by the stepwise condensation of three malonyl-Coenzyme A molecules with hexanoyl-Coenzyme A, in order to yield olivetolic acid [18]. The monoterpene unit, geranyl-diphosphate, results from the head-to-tail condensation of geranyl-diphosphate and dimethylallyldiphosphate through the non-mevalonate pathway. Subsequently, olivetolic acid undergoes prenylation by geranyl-diphosphate ( Figure 1 ). The product of this synthesis, cannabigerolic acid, is the key metabolic intermediary of cannabinoid biosynthesis [19]. It represents the substrate of three enzymes: tetrahydrocannabinolic acid synthase convertingcannabigerolic acid to Δ9-THCA [16], cannabidiolic acid synthase yielding cannabidiolicacid [20], and cannabinochromenic acid synthase producing cannabinochromenic acid [21]. Recent research could identify in planta both the acidic forms of the cannabinoids [22] as well as the decarboxylated forms (THC, CBD, cannabichromene, cannabigerol, cannabinol)—albeit in much lower amounts [23]. Non-enzymatic decarboxylation of these compounds is promoted by heating (during smoking or baking), sunlight, and storage. It is believed that the high number of diverse cannabinoids identified so far from Cannabis occur due to non-enzymatic modifications [24]. Studies performed on laser-microdissected capitate-stalked trichomes could suggest that cannabinoids are also present in the multicellular stipes of capitate-stalked hairs in addition to the secretory portion of the trichomes [23]. The exact contribution of the stalk cells to the biosynthesis of cannabinoids and the source of these compounds in the stems remains to be elucidated.

Caution should be taken when CBD is administered in patients with hepatic impairment (risk of accumulation) or when taken with other drugs, because inducers/inhibitors of CYP3A4 or CYP2C19 can decrease/increase its plasmatic concentration [27,69]. Moreover, it acts as a CYP1A1 inducer and as an inhibitor of P-glycoprotein-mediated drug transport, which can affect the plasmatic concentration of co-administered drugs [27,69] ( Table 2 ).

In 2018, a clinical trial with 119 cancer patients was conducted over a four-year framed period. Patients were given CBD oil three days on and three days off, with an average dose of 10 mg twice a day (max 30 mg for increased tumor mass). In this study, patients with different types of cancer (e.g., breast, prostate, and esophageal) were included. From 119 cancer patients, the most stunning case was a 5-year-old male patient with anaplastic ependymoma, a very rare brain tumor. The patient had all the standard treatments (surgery, chemotherapy, radiotherapy). He started the treatment with CBD oil in February 2016, and in December 2016 the relevant scans showed that tumor volume had decreased by approximately 60%. The other patients from this study have reported that the side effects completely disappeared, and although the duration of treatment was six months, many continued the treatment [148]. Stella et al. reported a case in which two patients were diagnosed with high-grade gliomas. In addition to chemotherapy and a drug regimen, CBD oil (ranging from 300 to 450 mg/day) was also involved. Both patients had admissible clinical and imaging responses as well as positive responses to treatment at periodic assessments [149]. Another case study presents an 81-year-old woman who was diagnosed with ovarian cancer in March 2017. The patient declined all interventions due to the treatment toxicity. She started with alternative therapy CBD oil (1 drop sublingually/day) and Laetrile tablets, which contain purified amygdalin (500 mg 4 times/day). After two months, CT imaging showed a dramatic decrease in the size of the tumor [150]. In a recent comprehensive review, Dumitru et al. also observed that the phase II clinical trials results indicate an increased life span for patients treated with CBD. Currently CBD is in a 180-day clinical trial-randomized double-blind, placebo-controlled parallel multi-center study including 160 patients for the evaluation of the effect of the cannabinoid combined with standard treatment for patients that suffer from multiple myeloma, glioblastoma multiform, and GI malignancies (clinical trial: <"type":"clinical-trial","attrs":<"text":"NCT03607643","term_id":"NCT03607643">> NCT03607643) [151].

Table 3

The main physiological function of the endogenous cannabinoid system consists of inhibiting the release of other neurotransmitters (acetylcholine, dopamine, histamine, serotonin, glutamate, GABA, etc.) in the nervous system, usually by stimulating CB1receptors [30]. Cannabidiol presents a complex mechanism of action consisting of: weak blocking of CB1 receptors; an inverse agonist of CB2 receptors;stimulation of vanilloid receptors type 1 (TRPV1—transient receptor potential vanilloid 1) and type 2 (TRPV2—transient receptor potential vanilloid 2); increasing the concentration of anandamide (by blocking its hydrolysis), a fatty acid neurotransmitter (its effects being mediated through CB1 receptors in CNS and CB2 receptors in the periphery); stimulation of endogenous adenosine signalling (by binding to equilibrative nucleoside transporter-1); inhibition ofG-protein coupled receptor 55 (GPR55); and the stimulation of the 5-HT1a (serotonin receptor 1A) receptor, PPARγ (nuclear peroxisome proliferation activated receptor γ) and glycine receptor subtypes [26,31] ( Table 1 ).

There are few data regarding its safety profile in children (limited pharmacokinetic information) [44]. Due to limited studies, and the ability of CBD to cross the placenta and to arrive in breast milk, it is not recommended for use in pregnancy and lactation [27,67,68].

Characteristics of cannabidiol’s (CBD) pharmacokinetic profile.

Cristina Adriana Dehelean

In vitro-in vivoanticancer mechanism of CBD in different types of cancerand the related effects on proliferation/apoptosis/gene expression/oxidative stress/tumor growth [76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119].

4 Department of Pharmacology and Clinical Pharmacy, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania

Cbd and colon cancer research

Cannabidiol (CBD) is in the news and on the internet, but what is it, and how can it help you?

CBD for General Use

First, determine what symptom or problem you are experiencing. For example, CBD + CBN would be more effective for sleep-related problems. CBD + CBN + CBG might be more effective for inflammation-based problems. Even though you can take CBD and CBG by themselves, it is more effective to take cannabinoids in pairs or groups because when you combine cannabinoids, you create something known as the “entourage effect,” which allows each cannabinoid to be boosted by the other or a counterpart. By working backward, you can find the right combination for you.

Can CBD help me?

Victor Melgar, Chief Operations Officer of NALA Health tells us that NALA was started with the simple idea that CBD could pave the way for all natural healing and remedies through the power of cannabis. However, CBD is only part of the equation. In fact there are over 100 active and inactive cannabinoids found in the cannabis plant.