“Objective: To evaluate effectiveness, tolerability and safety of an oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as add-on treatment in patients with severe chronic pain (SCP).
Conclusion: THC:CBD oromucosal spray proved to be an effective and well-tolerated add-on treatment for patients with elsewhere refractory chronic pain – especially of neuropathic origin.”
“Complimentary alternative medicine use is common in women with gynecologic cancers. Cannabinoid receptors are potential therapeutic targets in ovarian cancer. Communication with patients is critical regarding use of alternative therapies.” https://www.ncbi.nlm.nih.gov/pubmed/31193514
In this case report, we present the case of a female patient who demonstrated disease response after declining standard therapy and taking a combination of Laetrile and CBD oil. Previous clinical trials in humans have demonstrated no therapeutic effect in cancer patients taking Laetrile. However, basic science studies have identified cannabinoid receptors in ovarian cancer as potential therapeutic targets for cannabinoid use in treating malignancy.
In this case report, we highlight a dramatic response to combination Laetrile and CBD oil in a patient with widely metastatic Low grade serous ovarian cancer (LGSOC).
Laetrile is a semi-synthetic version of amygdaline, a chemical compound found in plants and fruit seeds. Both Laetrile and amygdaline contain cyanide within a common structural component. Theoretically, Laetrile has anti-cancer effects when cyanide is released via enzymatic degradation. However, a Cochrane review published in 2015 found no randomized or quasi randomized control trials supporting the use of Laetrile in cancer patients. Further, they argued that due to the risk of cyanide poisoning, Laetrile use should be discouraged in patients seeking the compound for alternative cancer therapy. Concerns for toxicity in combination with inability to demonstrate clinical efficacy led to an effective ban on the substance by the FDA in the 1980s. Nevertheless, the substance remains available for purchase in variable formulations commercially.
Cannabidiol (CBD) is a compound naturally derived from the cannabis plant.
The anti-cancer effects of CBD have been evaluated predominantly in the laboratory setting. Interestingly, ovarian cancer cell lines express GPR55, a target that is inhibited indirectly by CBD and that plays a role in prostate and ovarian cancer cell proliferation. Mouse model studies have also demonstrated cannabinoids inhibit tumor cell growth and induce apoptosis in gliomas, lymphomas, prostate, breast, lung, skin, and pancreatic cancer cells.”
https://www.sciencedirect.com/science/article/pii/S2352578919300517?via%3Dihub
“Neuropathic pain is caused by a lesion or dysfunction in the nervous system, and it may arise from illness, be drug-induced or caused by toxin exposure. Since the discovery of two G-protein-coupled cannabinoid receptors (CB1 and CB2) nearly three decades ago, there has been a rapid expansion in our understanding of cannabinoid pharmacology. This is currently one of the most active fields of neuropharmacology, and interest has emerged in developing cannabinoids and other small molecule modulators of CB1 and CB2 as therapeutics for neuropathic pain. This short review article provides an overview of the chemotypes currently under investigation for the development of novel neuropathic pain treatments targeting CB1 receptors.”
“Since 10 March 2017, physicians have been allowed to prescribe cannabis to patients with serious illnesses and in the absence of alternative therapies. Patients can obtain it as dried flowers or extracts in standardised pharmaceutical quality by prescription (narcotic prescription, except for cannabidiol) in pharmacies. When prescribing, physicians have to take a few things into account. The first step is to decide which therapeutic effects are to be achieved and which is the most suitable cannabis product. Cannabis for medical use must meet the requirements for pharmaceutical quality. An identity check must be carried out in the pharmacy on the basis of the monographs of the German Pharmacopoeia (DAB) or the German Pharmaceutical Codex/New Prescription Form (DAC/NRF). For the production of prescription drugs, e.g. capsules, drops or inhalates, there are also corresponding monographs for the preparation of prescription drugs. These standardised, quality-assured prescription formulas should be given preference in the case of a medical prescription. When prescribing an oral or inhalative form of application, it should be noted that the onset and duration of action are very different. Also, due to the complex pharmacology of cannabinoids, interindividual genetic differences in the metabolisation of ∆9-tetrahydrocannabinol (THC), the individual structure and function of the cannabinoid receptors, as well as differences in receptor density and distribution, the dosage and frequency of application must be individually determined. Last but not least, the dosage also depends on the type of disease and individual susceptibility to side effects. When prescribed for the first time, a creeping dosage with a very low initial dose is recommended.”
https://www.ncbi.nlm.nih.gov/pubmed/31187182
https://link.springer.com/article/10.1007%2Fs00103-019-02970-6
“Dravet syndrome is an infantile epileptic encephalopathy primarily caused by loss-of-function variants of the gene SCN1A Standard treatment regimens have very limited efficacy to combat the life-threatening seizures in Dravet syndrome or the behavioral-cognitive comorbidities of the disease. Recently there has been encouraging progress in developing new treatments for this disorder.
One of the clinical advances is cannabidiol (CBD), a compound naturally found in cannabis and shown to further reduce convulsive seizures in patients when used together with existing drug regimens. Like many other natural products, the exact therapeutic mechanism of CBD remains undefined.
Previously we have established a human cellular model of Dravet syndrome by differentiating patient-derived induced pluripotent stem cells (iPSCs) into telencephalic inhibitory and excitatory neurons. Here we have applied this model to investigate the antiepileptic mechanism(s) of CBD at the cellular level.
We first determined the effect of escalating the concentrations of CBD on neuronal excitability, using primary culture of rat cortical neurons. We found modulatory effects on excitability at submicromolar concentrations and toxic effects at high concentrations (15 µM). We then tested CBD at 50 nM, a concentration that corresponds to the estimated human clinical exposure, in telencephalic neurons derived from a patient iPSC line and control cell line H9. This 50 nM of CBD increased the excitability of inhibitory neurons but decreased the excitability of excitatory neurons, without changing the amplitude of sodium currents in either cell type.
Our findings suggest a cell type-dependent mechanism for the therapeutic action of CBD in Dravet syndrome that is independent of sodium channel activity.”
https://www.ncbi.nlm.nih.gov/pubmed/31186344
http://symposium.cshlp.org/content/early/2019/06/11/sqb.2018.83.038174
“Nabilone may be an effective treatment for agitation.”
https://www.ncbi.nlm.nih.gov/pubmed/31182351
https://www.sciencedirect.com/science/article/pii/S1064748119303550?via%3Dihub
“Nabilone (marketed as Cesamet) is a synthetic form of delta-9-tetrahydrocannabinol (Δ⁹-THC), the primary psychoactive component of cannabis (marijuana). Although structurally distinct from THC, nabilone mimics THC’s structure and pharmacological activity through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, however it is considered to be twice as active as Δ⁹-THC. Nabilone is approved by the FDA for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.” https://www.drugbank.ca/drugs/DB00486
“A pharmaceutical grade formulation of cannabidiol (CBD) has been approved for the treatment of Dravet syndrome and Lennox-Gastaut syndrome; however, this formulation is not yet available to patients outside the USA. In addition, CBD is thought to have broad anti-seizure properties that may be beneficial for other types of intractable epilepsy.
The aim of this study was to evaluate the efficacy, safety and tolerability of artisanal medical CBD oil in patients with developmental and epileptic encephalopathy (DEE) at the tertiary epilepsy center of Bambino Gesù Children’s Hospital in Rome, Italy.
Twenty-nine patients were enrolled in this study (41.4% male). The mean duration of exposure to artisanal CBD was 11.2 months [range 6-25 months; standard deviation (SD) ± 4.4 months]. Mean age at study enrollment was 9.3 years (range 1.9-16.3 years; SD ± 4.7 years). Eleven out of 29 patients (37.9%) had a ≥ 50% improvement in seizure frequency; one patient became seizure free. None of the patients reported worsening seizure frequency; however, 18 patients (62.1%) experienced no beneficial effect regarding seizure frequency. Adverse effects were reported in seven patients (24.14%), most commonly somnolence, decreased appetite and diarrhea. Adverse events were mild and transient, and no dose modification of CBD or other AEDs was required.
These data suggest that CBD may have beneficial effects in patients with DEE and an acceptable safety profile. Placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in patients with DEE.”
“Several studies have verified the important role of cannabinoid and cannabinoid receptor agonists in tumor progression. However, little is known about the precise role of CB2 expression level in the progression of non-small-cell lung cancer (NSCLC).
The expression of CB2 in NSCLC tissues and corresponding paracancerous tissues was examined using immunohistochemical staining assay.
Our data suggested that targeting CB2 may inhibit the growth and survival of NSCLC cells, which the Akt/mTOR/P70S6K pathway may be involved in. These results confer the pro-oncogenic role of CB2 in the progression of NSCLC, thus improving our understanding of CB2 in tumor progression.”
https://www.ncbi.nlm.nih.gov/pubmed/31176172
https://www.sciencedirect.com/science/article/pii/S0753332219321341?via%3Dihub
“Interest in cannabis and its related cannabinoids THC and CBD for use as anti-convulsant therapy has been progressively increasing. While the destigmatization of cannabis and cannabis related research have progressed in the last few decades, there are still many questions that remain answered. This review seeks to summarize the progress made in cannabis research in the past four decades and to identify possible directions for future research that are critical for the development of cannabinoid-based therapy in epilepsy.”
https://www.ncbi.nlm.nih.gov/pubmed/31176695
https://www.sciencedirect.com/science/article/pii/S0163725819301093?via%3Dihub
“Age-related cognitive decline has been associated with proinflammatory cytokines, yet the precise relationship between cognitive decline and cytokine load remains to be elucidated. β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist with established anti-inflammatory effects that is known to improve memory and increase lifespan. It is of interest to explore the potential of BCP to reduce age-related cognitive decline and proinflammatory cytokine load. In this study, we assessed changes in circulating cytokines across the lifespan, memory performance in young and aged mice, and the effects of BCP on memory function and cytokine load. The plasma levels of 12 cytokines were assessed in male Swiss-Webster mice at 3, 12, and 18 months of age using multiplexed flow cytometry. Working memory was compared in 3 and 12 month-old mice using spontaneous alternations. A dose-response function (100-300 mg/kg, subchronic administration) for BCP-induced memory restoration was determined in 3 and 12 month-old mice. Finally, the effects on cytokine levels of the peak memory enhancing dose of BCP was assessed in 18 month-old mice. Circulating levels of several cytokines significantly increased with age. Multilinear regression analysis showed that IL-23 levels were most strongly associated with age. Aged mice showed deficits in working memory and higher levels of IL-23, both of which were reversed by BCP treatment. BCP appears to reverse age-associated impairments in memory and modulates cytokine production. IL-23 may play a significant role in the aging process, and future research should determine whether it has utility as a biomarker for novel anti-aging therapeutics.”
https://www.ncbi.nlm.nih.gov/pubmed/31173795
https://www.sciencedirect.com/science/article/pii/S0166432819304516?via%3Dihub
“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
“Beta-caryophyllene is a dietary cannabinoid.” https://www.ncbi.nlm.nih.gov/pubmed/18574142
