Self-management strategies amongst Australian women with endometriosis: a national online survey.

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“Endometriosis has a significant negative impact on the lives of women, and current medical treatments often do not give sufficient pain relief or have intolerable side effects for many women. The majority of women with primary dysmenorrhea use self-management strategies (including self-care techniques or lifestyle choices) to help manage period related symptoms, but little is known about self-management in women with endometriosis.

The aim of this survey was to determine the prevalence of use, safety, and self-rated effectiveness of common forms of self-management.

Cannabis, heat, hemp/CBD oil, and dietary changes were the most highly rated in terms of self-reported effectiveness in pain reduction. Physical interventions such as yoga/Pilates, stretching, and exercise were rated as being less effective.

Self-management was very commonly used by women with endometriosis and form an important part of self-management.

Women using cannabis reported the highest self-rated effectiveness.”

https://www.ncbi.nlm.nih.gov/pubmed/30646891

https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-019-2431-x

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∆9-Tetrahydrocannabinol, a major marijuana component, enhances the anesthetic effect of pentobarbital through the CB1 receptor.

 “∆9 Tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), major psychoactive constituents of marijuana, induce potentiation of pentobarbital-induced sleep in mice.

We have elucidated the mechanism of enhancement of the anesthetic effect of pentobarbital by cannabinoids.

These results suggest that binding of ∆9-THC to the CB1 receptor is involved in the synergism with pentobarbital, and that potentiating effect of CBD with pentobarbital may differ from that of ∆9-THC. We successfully demonstrated that ∆9-THC enhanced the anesthetic effect of pentobarbital through the CB1 receptor.”

https://www.ncbi.nlm.nih.gov/pubmed/30636988

“The pharmacological results indicate the effect of ∆9-THC co-administered with pentobarbital was a synergistic, but not additive, action in mice. Further evidence suggests the CB1 receptor plays an important role as a trigger in potentiating pentobarbital-induced sleep by ∆9-THC.”

https://link.springer.com/article/10.1007%2Fs11419-018-0457-2

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Preclinical safety and efficacy of cannabidivarin for early life seizures.

Neuropharmacology

“A significant proportion of neonatal and childhood seizures are poorly controlled by existing anti-seizure drugs (ASDs), likely due to prominent differences in ionic homeostasis and network connectivity between the immature and mature brain. In addition to the poor efficacy of current ASDs, many induce apoptosis, impair synaptic development, and produce behavioral deficits when given during early postnatal development.

There is growing interest in new targets, such as cannabidiol (CBD) and its propyl analog cannabidivarin (CBDV) for early life indications. While CBD was recently approved for treatment of refractory childhood epilepsies, little is known about the efficacy or safety of CBDV.

Here, we addressed this gap through a systematic evaluation of CBDV against multiple seizure models in postnatal day (P) 10 and 20 animals. We also evaluated the impact of CBDV on acute neurotoxicity in immature rats.

CBDV (50-200 mg/kg) displayed an age and model-specific profile of anticonvulsant action.

Finally, CBDV treatment generally avoided induction of neuronal degeneration in immature rats.

Together, the efficacy and safety profile of CBDV suggest it may have therapeutic value for early life seizures.”

https://www.ncbi.nlm.nih.gov/pubmed/30633929

https://www.sciencedirect.com/science/article/pii/S0028390818306786?via%3Dihub

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Latitudinal Adaptation and Genetic Insights Into the Origins of Cannabis sativa L.

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“Cannabis is one of the most important industrial crops distributed worldwide. However, the phylogeographic structure and domestication knowledge of this crop remains poorly understood.

In this study, sequence variations of five chloroplast DNA (cpDNA) regions were investigated to address these questions. For the 645 individuals from 52 Cannabis accessions sampled (25 wild populations and 27 domesticated populations or cultivars), three haplogroups (Haplogroup H, M, L) were identified and these lineages exhibited distinct high-middle-low latitudinal gradients distribution pattern.

This pattern can most likely be explained as a consequence of climatic heterogeneity and geographical isolation. Therefore, we examined the correlations between genetic distances and geographical distances, and tested whether the climatic factors are correlated with the cpDNA haplogroup frequencies of populations. The “isolation-by-distance” models were detected for the phylogeographic structure, and the day-length was found to be the most important factor (among 20 BioClim factors) that influenced the population structures.

Considering the distinctive phylogeographic structures and no reproductive isolation among members of these lineages, we recommend that Cannabis be recognized as a monotypic genus typified by Cannabis sativa L., containing three subspecies: subsp. sativa, subsp. Indica, and subsp. ruderalis. Within each haplogroup which possesses a relatively independent distribution region, the wild and domesticated populations shared the most common haplotypes, indicating that there are multiregional origins for the domesticated crop.

Contrast to the prevalent Central-Asia-Origin hypothesis of C. saltiva, molecular evidence reveals for the first time that the low latitude haplogroup (Haplogroup L) is the earliest divergent lineage, implying that Cannabis is probably originated in low latitude region.”

https://www.ncbi.nlm.nih.gov/pubmed/30627133

https://www.frontiersin.org/articles/10.3389/fpls.2018.01876/full

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Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer.

 Related image“In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain.

The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety.

Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB1 and CB2.

CBD is present in both medicinal and fibre-type C. sativa plants, but, unlike Δ9-THC, it is completely nonpsychoactive. Fibre-type C. sativa (hemp) differs from medicinal C. sativa, since it contains only few levels of Δ9-THC and high levels of CBD and related nonpsychoactive compounds.

In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials.

CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and Δ9-THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models.

These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity.

In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of Δ9-THC deprived hemp.”

https://www.ncbi.nlm.nih.gov/pubmed/30627539

https://www.hindawi.com/journals/bmri/2018/1691428/

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Epidiolex (Cannabidiol): A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes.

 SAGE Journals

“OBJECTIVE: To review the efficacy, safety, pharmacology and pharmacokinetics of pure, plant-derived cannabidiol (CBD; Epidiolex) in the treatment of Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS).

DATA SYNTHESIS: Pure, plant-based CBD is a pharmaceutical grade extract that exhibits clinically significant antiseizure properties, with a hypothesized multimodal mechanism of action. In the GWPCARE trial series, CBD displayed superior efficacy in reducing key seizure frequencies (convulsive seizures in DS; drop seizures in LGS) by 17% to 23% compared with placebo as adjunctive therapy to standard antiepileptic drugs in patients 2 years of age and older. Common adverse effects were somnolence, diarrhea, and elevated hepatic transaminases. Noteworthy drug-drug interactions included clobazam, valproates, and significant inducers/inhibitors of CYP2C19 and 3A4 enzymes.

Relevance to Patient Care and Clinical Practice: A discussion regarding CBD dosing, administration, adverse effects, monitoring parameters, and interactions is provided to guide clinicians. CBD offers patients with DS and LGS a new treatment option for refractory seizures.

CONCLUSION:

This is the first cannabis-derived medication with approval from the US Food and Drug Administration. This CBD formulation significantly reduces seizures as an adjunct to standard antiepileptic therapies in patients ≥2 years old with DS and LGS and is well tolerated.”

https://www.ncbi.nlm.nih.gov/pubmed/30616356

https://journals.sagepub.com/doi/abs/10.1177/1060028018822124?journalCode=aopd

“Why marijuana is headed for the mainstream. The credibility of cannabis as a source of a legitimate pharmaceutical ingredient in prescription medications took a major step forward in 2018 when the FDA approved Epidiolex (cannabidiol) for two types of severe seizures. Epidiolex was a stellar candidate for approval. It reduced convulsive seizures by about 40% and has a good safety profile.”  https://www.ncbi.nlm.nih.gov/pubmed/30620324

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The effects of cannabinoids on the endocrine system.

“Cannabinoids are the derivatives of the cannabis plant, the most potent bioactive component of which is tetrahydrocannabinol (THC). The most commonly used drugs containing cannabinoids are marijuana, hashish, and hashish oil.

These compounds exert their effects via interaction with the cannabinoid receptors CB1 and CB2. Type 1 receptors (CB1) are localised mostly in the central nervous system and in the adipose tissue and many visceral organs, including most endocrine organs. Type 2 cannabinoid receptors (CB2) are positioned in the peripheral nervous system (peripheral nerve endings) and on the surface of the immune system cells.

Recently, more and more attention has been paid to the role that endogenous ligands play for these receptors, as well as to the role of the receptors themselves. So far, endogenous cannabinoids have been confirmed to participate in the regulation of food intake and energy homeostasis of the body, and have a significant impact on the endocrine system, including the activity of the pituitary gland, adrenal cortex, thyroid gland, pancreas, and gonads.

Interrelations between the endocannabinoid system and the activity of the endocrine system may be a therapeutic target for a number of drugs that have been proved effective in the treatment of infertility, obesity, diabetes, and even prevention of diseases associated with the cardiovascular system.”

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Gender and the Politics of Marijuana

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“The objectives of this study were to understand why, even though women are more liberal than men on a broad range of issues, when it comes to the increasingly prominent issue of marijuana legalization, the direction of the gender gap is reversed, with women more conservative than men.

We find that women’s role as mothers cannot explain this gap, and that mothers are in fact no different from those without children in terms of their support for marijuana policy, as well as their reported use of marijuana. The greater religiosity of women does play a prominent role in the gender gap on marijuana policy, but does not account for the full difference of opinion between women and men. Our findings suggest that men’s greater propensity relative to women to use marijuana is a major driver behind the gender gap.

Conclusions

Not only are attitudes on marijuana legalization likely to continue to liberalize, but as marijuana legalization and marijuana use become normalized, rather than viewed as immoral and dangerous behavior, the existing gender gap should shrink.”

https://onlinelibrary.wiley.com/doi/abs/10.1111/ssqu.12558

“Drug use, religion explain ‘reverse gender gap’ on marijuana”  https://www.sciencedaily.com/releases/2018/11/181126134251.htm?fbclid=IwAR072Y-SGz0PElUfNtQCTe56kzRC5ZBDoBMmlW2oTagAOy-IOcT_8UxVCEI

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Cannabidiol.

Chemical structure

“Cannabidiol has not been studied in nursing women taking the pharmaceutical product.

Cannabidiol has been detected in the breastmilk of some mothers who used cannabis products recreationally.

If cannabidiol is required by the mother, it is not a reason to discontinue breastfeeding.

However, since no information is available on the use of cannabidiol during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.”

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The Misclassification of Medical Marijuana.

Journal of the American Academy of Psychiatry and the Law

“Marijuana has a complicated legal, social, and economic history in the United States, as well as an uncertain future. Marijuana has been consistently tied to racial minority groups since its arrival in the United States in the 1900s, and former Attorney General Jeff Sessions further propagated that notion. AG Sessions even recently wrote a memo that directly contradicted Obama-era policy, demonstrating that the current legal status of marijuana in both state and federal government is currently up for debate. While several states have legalized marijuana for medical or even recreational purposes, federal law still categorizes cannabis as a drug with no currently accepted medical use and a high potential for abuse. The comparison between marijuana, opioids, and ketamine in this article demonstrates that marijuana has been unnecessarily withheld and stigmatized by the federal government. Also reviewed is the impact of stringent marijuana-based legal policies upon the racial makeup of prison populations. The implications of current policy upon potential and future research are also discussed, with the determination that current policy has stymied research and prevented a more accurate determination of the risks and benefits of medical marijuana.”

https://www.ncbi.nlm.nih.gov/pubmed/30593477

“Cannabis was initially marked as Schedule I for reasons related to race and class. The federal government has restricted access to marijuana on the basis of its unknown risks and lack of proven benefits despite the fact that synthetic cannabinoids have been demonstrated to elicit FDA-approved benefits. This article demonstrates that marijuana should be removed from the Schedule I listing, as would be consistent with the labeling of ketamine and opioids, and reclassified as a Schedule III or Schedule II drug. Given the beneficial medical use, possible side effects, and potential for abuse and addiction of each drug, medical cannabis has been unfairly kept from the public through its unnecessary classification as a Schedule I drug.”

http://jaapl.org/content/46/4/472.long

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