“The most bioactive ingredient of cannabis (Cannabis sativa or indica) extracts, Δ9-tetrahydrocannabinol (THC), was identified in the 1960s as one of more than 110 phytocannabinoids. It activates receptors of chemically different endogenous ligands (endocannabinoids) that, unlike THC, are metabolized by several enzymes of the endocannabinoid system. Here, the complexity of the plant-derived and endogenous cannabinoids (eCBs) is discussed, to better appreciate the challenge of: (i) dissecting their mutual interactions; (ii) understanding their impact on human pathophysiology; and (iii) exploiting them for human disease. To this aim, missing pieces to the eCB puzzle must be urgently found, by solving the 3D structures of key components, and interrogating noncanonical modes of regulation and trafficking of these lipid signals.”
Tag Archives: cannabis
Untargeted characterization of extracts from Cannabis sativa L. cultivars by gas and liquid chromatography coupled to mass spectrometry in high resolution mode.
“Elucidation of Cannabis composition is required to evaluate the potential of this plant for pharmacological uses, but also for implementation in breeding programs with agronomical purposes. The aim of the present study was to develop a method for untargeted analysis of polar and non-polar Cannabis extracts.
For this purpose, extracts from 17 cultivars of Cannabis sativa L. were analyzed by gas chromatography-time-of-flight/mass spectrometry (GC-TOF/MS) and liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC-QTOF MS/MS) in high resolution mode.
One hundred sixty-nine compounds were identified in the extracts by searching MS and MS/MS information. Among identified families, there were mainly cannabinoids, terpenoids, lipids and flavonoids, but also some interesting compounds such as amino and organic acids, among others.
Relative contents of terpenoids and cannabinoids in the same cultivars grown in greenhouse and field were compared. Compositional differences in the profile of terpenoids and cannabinoids between both types of grown conditions were found.”
https://www.ncbi.nlm.nih.gov/pubmed/31816756
https://www.sciencedirect.com/science/article/abs/pii/S0039914019310173?via%3Dihub
Cannabidiol Improves Cognitive Impairment and Reverses Cortical Transcriptional Changes Induced by Ketamine, in Schizophrenia-Like Model in Rats.
“Cannabidiol (CBD), a non-psychotropic cannabinoid, demonstrates antipsychotic-like and procognitive activities in humans and in animal models of schizophrenia.
The mechanisms of these beneficial effects of CBD are unknown. Here, we examined behavioral effects of CBD in a pharmacological model of schizophrenia-like cognitive deficits induced by repeated ketamine (KET) administration. In parallel, we assessed transcriptional changes behind CBD activities in the prefrontal cortex (PFC), the main brain area linked to schizophrenia-like pathologies.
Male Sprague-Dawley rats were injected for 10 days with KET followed by 6 days of CBD. The cognitive performance was evaluated in the novel object recognition test followed by PFC dissections for next-generation sequencing (RNA-Seq) analysis and bioinformatics.
We observed that KET-induced learning deficits were rescued by CBD (7.5 mg/kg).
Similarly, CBD reversed transcriptional changes induced by KET. The majority of the genes affected by KET and KET-CBD were allocated to astroglial and microglial cells and associated with immune-like processes mediating synaptogenesis and neuronal plasticity. These genes include C1qc, C1qa, C1qb, C2, and C3 complement cascade elements, Irf8 factor and Gpr84, Gpr34, Cx3cr1, P2ry12, and P2ry6 receptors. The main pathway regulators predicted to be involved included TGFβ1 and IFNγ. In addition, CBD itself upregulated oxytocin mRNA in the PFC.
The present data suggest that KET induces cognitive deficits and transcriptional changes in the PFC and that both effects are sensitive to a reversal by CBD treatment.”
https://www.ncbi.nlm.nih.gov/pubmed/31823199
https://link.springer.com/article/10.1007%2Fs12035-019-01831-2
Cannabis Use in Children With Pantothenate Kinase-Associated Neurodegeneration.
“Pantothenate kinase-associated neurodegeneration is characterized by severe, progressive dystonia. This study aims to describe the reported usage of cannabis products among children with pantothenate kinase-associated neurodegeneration.
METHODS:
A cross-sectional, 37-item survey was distributed in April 2019 to the families of 44 children who participate in a clinical registry of individuals with pantothenate kinase-associated neurodegeneration.
RESULTS:
We received 18 responses (40.9% response rate). Children were a mean of 11.0 (SD 4.3) years old. The 15 respondents with dystonia or spasticity were on a median of 2 tone medications (range 0-9). Seven children had ever used cannabis (38.9%). The most common source of information about cannabis was other parents. Children who had ever used cannabis were on more tone medications, were more likely to have used opiates, were less likely to be able to roll, and less likely to sit comfortably, than children who had never used cannabis. Four children reported moderate or significant improvement in dystonia with cannabis. Other areas reported to be moderate or significantly improved were pain (n = 3), sleep (n = 4), anxiety (n = 3), and behavior (n = 2). Adverse effects included sadness (n = 1), agitation/behavior change (n = 1), and tiredness (n = 1).
CONCLUSION:
Cannabis use was commonly reported among children with pantothenate kinase-associated neurodegeneration whose parents responded to a survey, particularly when many other dystonia treatments had been tried. Physicians should be aware that parents may treat their child with severe, painful dystonia with cannabis. Placebo-controlled studies of products containing cannabidiol and 9-tetrahydrocannabinol are needed for pediatric tone disorders.”
https://www.ncbi.nlm.nih.gov/pubmed/31823681
https://journals.sagepub.com/doi/abs/10.1177/0883073819890516?journalCode=jcna
More evidence of cannabis efficacy in restless legs syndrome.
Recently, patients’ statement of a remarkable and total remission of RLS symptoms following cannabis use has been reported. Here, we confirm and extend these findings to more patients with RLS.
The antinociceptive effect of marijuana has been documented in many painful neurological conditions, and the potential benefit of cannabis use in patients with refractory RLS should therefore be questioned by robust clinical trials.”
https://www.ncbi.nlm.nih.gov/pubmed/31820197
https://link.springer.com/article/10.1007%2Fs11325-019-01978-1
Characteristics of Dispensary Patients that Limit Alcohol after Initiating Cannabis.
“Many patients have reported that they decrease their use of opioids after starting medical cannabis (MC) but less is known for alcohol.
The objective of this exploratory study was to identify any factors which differentiate alcohol abaters from those that do not modify their alcohol use after starting MC (non-abaters).
Comparisons were made to identify any demographic, dosing, or health history characteristics which differentiated alcohol abaters (N = 47) from non-abaters (N = 65). Respondents selected from among a list of 37 diseases/health conditions (e.g. diabetes, sleep disorders).
Abaters and non-abaters were indistinguishable in terms of sex, age, or prior drug history. A greater percentage of abaters (59.6%) than non-abaters (40.6%, p < .05) reported using MC two or more times per day. Abaters were more likely to be employed (68.1%) than non-abaters (51.1%, p < .05). Abaters also reported having significantly more health conditions and diseases (3.3 ± 2.0) than non-abaters (2.4 ± 1.4, p < .05).
This small study offers some insights into the profile of patients whose self-reported alcohol intake decreased following initiation of MC. Additional prospective or controlled research into the alcohol abatement phenomenon following MC may be warranted.”
https://www.ncbi.nlm.nih.gov/pubmed/31813342
https://www.tandfonline.com/doi/abs/10.1080/02791072.2019.1694199?journalCode=ujpd20
The effect of high maternal linoleic acid on endocannabinoid signalling in rodent hearts.
“The endocannabinoid system (ECS), modulated by metabolites of linoleic acid (LA), is important in regulating cardiovascular function.
In pregnancy, LA is vital for foetal development.
Data indicate that a high LA diet alters cell viability and CB2 expression, potentially influencing cardiac function during pregnancy and development of the offspring’s heart.”
https://www.ncbi.nlm.nih.gov/pubmed/31814560
“A number of previous studies have shown that polyunsaturated fatty acids (PUFAs) and phytosterols are critically important for human health. Hempseed is a rich source of plant oil, which contains more than 80% PUFAs. The fatty acids in hempseed oil include a variety of essential fatty acids, including linoleic acid ”
https://link.springer.com/article/10.1007%2Fs10059-011-0042-6
Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain.
“Chronic pain affects a significant percentage of the United States population, and available pain medications like opioids have drawbacks that make long-term use untenable.
Cannabinoids show promise in the management of pain, but long-term treatment of pain with cannabinoids has been challenging to implement in preclinical models. We developed a voluntary, gelatin oral self-administration paradigm that allowed male and female mice to consume ∆9-tetrahydrocannabinol, cannabidiol, or morphine ad libitum.
Mice stably consumed these gelatins over 3 weeks, with detectable serum levels. Using a real-time gelatin measurement system, we observed that mice consumed gelatin throughout the light and dark cycles, with animals consuming less THC-gelatin than the other gelatin groups.
Consumption of all three gelatins reduced measures of allodynia in a chronic, neuropathic sciatic nerve injury model, but tolerance to morphine developed after 1 week while THC or CBD reduced allodynia over three weeks. Hyperalgesia gradually developed after sciatic nerve injury, and by the last day of testing, THC significantly reduced hyperalgesia, with a trend effect of CBD, and no effect of morphine. Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by THC, CBD, and morphine.
This study demonstrates that mice voluntarily consume both cannabinoids and opioids via gelatin, and that cannabinoids provide long-term relief of chronic pain states. In addition, ultrasonic clicks may objectively represent mouse pain status and could be integrated into future pain models.”
Oral medicinal cannabinoids to relieve symptom burden in the palliative care of patients with advanced cancer: a double-blind, placebo controlled, randomised clinical trial of efficacy and safety of cannabidiol (CBD).
“Despite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids, but there is little high quality evidence to guide clinicians. This study aims to define the role of cannabidiol (CBD) in the management of symptom burden in patients with advanced cancer undergoing standard palliative care.
METHODS AND DESIGN:
This study is a multicentre, randomised, placebo controlled, two arm, parallel trial of escalating doses of oral CBD. It will compare efficacy and safety outcomes of a titrated dose of CBD (100 mg/mL formulation, dose range 50 mg to 600 mg per day) against placebo. There is a 2-week patient determined titration phase, using escalating doses of CBD or placebo to reach a dose that achieves symptom relief with tolerable side effects. This is then followed by a further 2-week assessment period on the stable dose determined in collaboration with clinicians.
DISCUSSION:
A major strength of this study is that it will target symptom burden as a whole, rather than just individual symptoms, in an attempt to describe the general improvement in wellbeing previously reported by some patients in open label, non controlled trials of medicinal cannabis. Randomisation with placebo is essential because of the well-documented over reporting of benefit in uncontrolled trials and high placebo response rates in cancer pain trials. This will be the first placebo controlled clinical trial to evaluate rigorously the efficacy, safety and acceptability of CBD for symptom relief in advanced cancer patients. This study will provide the medical community with evidence to present to patients wishing to access medicinal cannabis for their cancer related symptoms.”
https://www.ncbi.nlm.nih.gov/pubmed/31810437
https://bmcpalliatcare.biomedcentral.com/articles/10.1186/s12904-019-0494-6
CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based chemotherapy in breast cancer.
“Cannabidiol (CBD) has emerged as a potential agent for breast cancer management.
In this work, the potential use of cannabidiol in solution (CBDsol) and encapsulated in polymeric microparticles when combined with paclitaxel (PTX) and doxorubicin (DOX) in breast cancer treatment has been evaluated for the first time using MCF-7 and MDA-MB-231 cells. CBDsol, previously administered at suboptimal concentrations (cell death <10%), enhanced the PTX and DOX effect in both breast cancer cells.
The co-administration of CBDsol and PTX or DOX showed a synergistic effect. PLGA-502 was selected as the most suitable polymer to develop CBD-loaded microparticles. The developed formulation (CBD-Mps) was effective as monotherapy, showing extended antiproliferative activity for at least 10 days, and when combined with PTX or DOX.
In fact, the use of CBD-Mps allows the combination of both, pre and co-administration strategies, with a single administration, also showing a significant increase in PTX and DOX antiproliferative activity. Finally, the anticancer effect of both CBDsol and CBD-Mps as monotherapy or in combination with PTX was also confirmed in ovo, usingMDA-MB-231-derived tumours.
This data evidences the promising inclusion of CBD in conventional breast cancer chemotherapy and the use of CBD-Mps for the extended release of this cannabinoid, optimising the effect of the chemotherapeutic agents.”
https://www.ncbi.nlm.nih.gov/pubmed/31811927
https://www.sciencedirect.com/science/article/pii/S0378517319309615?via%3Dihub