Use of cannabinoids in cancer patients: A Society of Gynecologic Oncology (SGO) clinical practice statement.

Gynecologic Oncology“Tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) affect the human endocannabinoid system.

Cannabinoids reduce chemotherapy induced nausea or vomiting (CINV) and neuropathic pain.

Each state has its own regulations for medical and recreational cannabis use.

Effects of cannabinoids on chemotherapy, immunotherapy, and tumor growth remain under investigation.

Providers should focus indications, alternatives, risks and benefits of medical cannabis use to make appropriate referrals.”

https://www.ncbi.nlm.nih.gov/pubmed/31932107

https://www.gynecologiconcology-online.net/article/S0090-8258(19)31805-0/fulltext

Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain.

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“Endometriosis is a chronic painful disease highly prevalent in women that is defined by growth of endometrial tissue outside the uterine cavity and lacks adequate treatment.

Medical use of cannabis derivatives is a current hot topic and it is unknown whether phytocannabinoids may modify endometriosis symptoms and development.

Here we evaluate the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) in a mouse model of surgically-induced endometriosis.

In this model, female mice develop mechanical hypersensitivity in the caudal abdomen, mild anxiety-like behavior and substantial memory deficits associated with the presence of extrauterine endometrial cysts.

Interestingly, daily treatments with THC (2 mg/kg) alleviate mechanical hypersensitivity and pain unpleasantness, modify uterine innervation and restore cognitive function without altering the anxiogenic phenotype. Strikingly, THC also inhibits the development of endometrial cysts.

These data highlight the interest of scheduled clinical trials designed to investigate possible benefits of THC for women with endometriosis.”

https://www.ncbi.nlm.nih.gov/pubmed/31931958

https://elifesciences.org/articles/50356

The role of cannabinoids in epilepsy treatment: a critical review of efficacy results from clinical trials.

Image result for Epileptic Disorders journal “CBD was shown to have anti-seizure activity based on in vitro and in vivo models.

However, several reports of small series or case reports of the use of cannabis extracts in epilepsy yielded contradictory results and the efficacy of cannabis use in patients with epilepsy have also been inconclusive.

In 2013, the first Phase 1 trial for a purified form of CBD (Epidiolex/Epidyolex; >99% CBD), developed by GW Pharma, showed some efficacy signals and subsequently, a comprehensive program on the efficacy and tolerability of this compound for the treatment of drug-resistant epilepsies was initiated.

Results of these trials led to the FDA and EMA approval respectively in 2018 and 2019 for the treatment of seizures associated with two rare epilepsies: Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients two years of age and older.

Thus, CBD became the first FDA-approved purified drug substance derived from cannabis and also the first FDA-approved drug for the treatment of seizures in DS.

We detail the clinical studies using purified CBD (Epidiolex/Epidyolex), including the first open interventional exploratory study and Randomized Control Ttrials for DS and LGS.”

https://www.ncbi.nlm.nih.gov/pubmed/31916540

https://www.jle.com/fr/revues/epd/e-docs/the_role_of_cannabinoids_in_epilepsy_treatment_a_critical_review_of_efficacy_results_from_clinical_trials_316030/article.phtml

The proposed mechanism of action of CBD in epilepsy.

Image result for Epileptic Disorders journal“Highly purified cannabidiol (CBD) (approved as Epidiolex® in the United States) has demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut or Dravet syndrome in four randomized controlled trials.

While the mechanism of action of CBD underlying the reduction of seizures in humans is unknown, CBD possesses affinity for multiple targets, across a range of target classes, resulting in functional modulation of neuronal excitability, relevant to the pathophysiology of many disease types, including epilepsy.

Here we present the pharmacological data supporting the role of three such targets, namely Transient receptor potential vanilloid-1 (TRPV1), the orphan G protein-coupled receptor-55 (GPR55) and the equilibrative nucleoside transporter 1 (ENT-1).”

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy.

Image result for frontiers in neurology“Controlled and open label trials have demonstrated efficacy of cannabidiol for certain epileptic encephalopathies.

However, plant derived cannabidiol products have been used almost exclusively. Efficacy of synthetically derived cannabidiol has not been studied before.

The objective of this study was to evaluate tolerability and efficacy of synthetic cannabidiol in patients with pharmacoresistant epilepsy.

Efficacy and tolerance in our study of synthetic CBD treatment in pharmacoresistant epilepsy is similar to open label studies using plant derived CBD.

Regarding economic and ecological aspects, synthetic cannabidiol might be a reasonable alternative to plant derived cannabidiol.”

https://www.ncbi.nlm.nih.gov/pubmed/31920934

“Over the last decade, the therapeutic use of cannabidiol (CBD) in intractable epilepsies has increased considerably. Its anticonvulsant properties have been shown in several animal models for acute and chronic epilepsy.

Recent randomized, controlled trials have demonstrated that CBD is superior to placebo in seizure reduction in children with Dravet syndrome and patients with Lennox-Gastaut syndrome. In addition, open label studies indicate that cannabidiol has anticonvulsive properties in a broader range of epilepsy syndromes and etiologies.

In summary, the results of this study provide class III evidence of efficacy and safety of synthetic cannabidiol in children and adults with pharmacoresistant epilepsy. Additional studies investigating efficacy and tolerance of synthetic CBD in larger cohorts are needed.”

https://www.frontiersin.org/articles/10.3389/fneur.2019.01313/full

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam.

Epilepsy Research“To evaluate the efficacy of open-label, highly purified cannabidiol (CBD, Epidiolex®) in treating refractory epilepsy relative to the concomitant use of clobazam (CLB) as well as the clinical implications of changes in CLB and norclobazam (nCLB) levels.”

“With or without concomitant CLB, CBD may be effective in reducing seizure frequency.”   https://www.sciencedirect.com/science/article/abs/pii/S0920121119303778?via%3Dihub

“With or without concomitant CLB, CBD can be effective in reducing seizure frequency. “

https://www.ncbi.nlm.nih.gov/pubmed/31923763

Cannabidiol-induced panicolytic-like effects and fear-induced antinociception impairment: the role of the CB1 receptor in the ventromedial hypothalamus.

Image result for Springer Link“The behavioural effects elicited by chemical constituents of Cannabis sativa, such as cannabidiol (CBD), on the ventromedial hypothalamus (VMH) are not well understood. There is evidence that VMH neurons play a relevant role in the modulation of unconditioned fear-related defensive behavioural reactions displayed by laboratory animals.

OBJECTIVES:

This study was designed to explore the specific pattern of distribution of the CB1 receptors in the VMH and to investigate the role played by this cannabinoid receptor in the effect of CBD on the control of defensive behaviours and unconditioned fear-induced antinociception.

METHODS:

A panic attack-like state was triggered in Wistar rats by intra-VMH microinjections of N-methyl-D-aspartate (NMDA). One of three different doses of CBD was microinjected into the VMH prior to local administration of NMDA. In addition, the most effective dose of CBD was used after pre-treatment with the CB1 receptor selective antagonist AM251, followed by NMDA microinjections in the VMH.

RESULTS:

The morphological procedures demonstrated distribution of labelled CB1 receptors on neuronal perikarya situated in dorsomedial, central and ventrolateral divisions of the VMH. The neuropharmacological approaches showed that both panic attack-like behaviours and unconditioned fear-induced antinociception decreased after intra-hypothalamic microinjections of CBD at the highest dose (100 nmol). These effects, however, were blocked by the administration of the CB1 receptor antagonist AM251 (100 pmol) in the VMH.

CONCLUSION:

These findings suggest that CBD causes panicolytic-like effects and reduces unconditioned fear-induced antinociception when administered in the VMH, and these effects are mediated by the CB1 receptor-endocannabinoid signalling mechanism in VMH.”

https://www.ncbi.nlm.nih.gov/pubmed/31919563

https://link.springer.com/article/10.1007%2Fs00213-019-05435-5

“panicolytic: That reduces the flight reflex in animals when faced with danger. Any drug that has this effect.” https://en.wiktionary.org/wiki/panicolytic

Effects of short-term cannabidiol treatment on response to social stress in subjects at clinical high risk of developing psychosis.

 “Stress is a risk factor for psychosis and treatments which mitigate its harmful effects are needed.

Cannabidiol (CBD) has antipsychotic and anxiolytic effects.

OBJECTIVES:

We investigated whether CBD would normalise the neuroendocrine and anxiety responses to stress in clinical high risk for psychosis (CHR) patients.

RESULTS:

One-way analysis of variance (ANOVA) revealed a significant effect of group (HC, CHR-P, CHR-CBD (p = .005) on cortisol reactivity as well as a significant (p = .003) linear decrease. The change in cortisol associated with experimental stress exposure was greatest in HC controls and least in CHR-P patients, with CHR-CBD patients exhibiting an intermediate response. Planned contrasts revealed that the cortisol reactivity was significantly different in HC compared with CHR-P (p = .003), and in HC compared with CHR-CBD (p = .014), but was not different between CHR-P and CHR-CBD (p = .70). Across the participant groups (CHR-P, CHR-CBD and HC), changes in anxiety and experience of public speaking stress (all p’s < .02) were greatest in the CHR-P and least in the HC, with CHR-CBD participants demonstrating an intermediate level of change.

CONCLUSIONS:

Our findings show that it is worthwhile to design further well powered studies which investigate whether CBD may be used to affect cortisol response in clinical high risk for psychosis patients and any effect this may have on symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/31915861

“Antipsychotic effects of CBD have been linked to its effects on levels of the endogenous cannabinoid anandamide (AEA) potentially by inhibiting its catalytic enzyme fatty acid amide hydrolase (FAAH). Recent preclinical work has also suggested that CBD may block the anxiogenic effects of chronic stress that was associated with a concomitant decrease in the expression of FAAH following CBD treatment. To the best of our knowledge, this is the first study to have investigated the effects of short-term treatment with CBD on experimentally induced stress in the context of psychosis risk. Notwithstanding its limitations, the present study provides a strong rationale for future studies to investigate whether CBD may have potential to mitigate the harmful effects of stress in the course of daily life by attenuating the altered neuroendocrine and psychological responses to acute stress in CHR participants.”

https://link.springer.com/article/10.1007%2Fs00213-019-05442-6

Effects of acute cannabidiol administration on anxiety and tremors induced by a Simulated Public Speaking Test in patients with Parkinson’s disease.

Image result for journal of psychopharmacology“Cannabidiol (CBD) is one of the main components of Cannabis sativa and has anxiolytic properties, but no study has been conducted to evaluate the effects of CBD on anxiety signs and symptoms in patients with Parkinson’s disease (PD).

This study aimed to evaluate the impacts of acute CBD administration at a dose of 300 mg on anxiety measures and tremors induced by a Simulated Public Speaking Test (SPST) in individuals with PD.

METHODS:

A randomised, double-blinded, placebo-controlled, crossover clinical trial was conducted. A total of 24 individuals with PD were included and underwent two experimental sessions within a 15-day interval. After taking CBD or a placebo, participants underwent the SPST. During the test, the following data were collected: heart rate, systemic blood pressure and tremor frequency and amplitude. In addition, the Visual Analog Mood Scales (VAMS) and Self-Statements during Public Speaking Scale were applied. Statistical analysis was performed by repeated-measures analysis of variance (ANOVA) while considering the drug, SPST phase and interactions between these variables.

RESULTS:

There were statistically significant differences in the VAMS anxiety factor for the drug; CBD attenuated the anxiety experimentally induced by the SPST. Repeated-measures ANOVA showed significant differences in the drug for the variable related to tremor amplitude as recorded by the accelerometer.

CONCLUSION:

Acute CBD administration at a dose of 300 mg decreased anxiety in patients with PD, and there was also decreased tremor amplitude in an anxiogenic situation.”

https://www.ncbi.nlm.nih.gov/pubmed/31909680

https://journals.sagepub.com/doi/abs/10.1177/0269881119895536?journalCode=jopa

Cannabinoids and Opioids in the Treatment of Inflammatory Bowel Diseases.

Image result for clinical and translational gastroenterology“In traditional medicine, Cannabis sativa has been prescribed for a variety of diseases. Today, the plant is largely known for its recreational purpose, but it may find a way back to what it was originally known for: a herbal remedy. Most of the plant’s ingredients, such as Δ-tetrahydrocannabinol, cannabidiol, cannabigerol, and others, have demonstrated beneficial effects in preclinical models of intestinal inflammation. Endogenous cannabinoids (endocannabinoids) have shown a regulatory role in inflammation and mucosal permeability of the gastrointestinal tract where they likely interact with the gut microbiome. Anecdotal reports suggest that in humans, Cannabis exerts antinociceptive, anti-inflammatory, and antidiarrheal properties. Despite these reports, strong evidence on beneficial effects of Cannabis in human gastrointestinal diseases is lacking. Clinical trials with Cannabis in patients suffering from inflammatory bowel disease (IBD) have shown improvement in quality of life but failed to provide evidence for a reduction of inflammation markers. Within the endogenous opioid system, mu opioid receptors may be involved in anti-inflammation of the gut. Opioids are frequently used to treat abdominal pain in IBD; however, heavy opioid use in IBD is associated with opioid dependency and higher mortality. This review highlights latest advances in the potential treatment of IBD using Cannabis/cannabinoids or opioids.”

https://www.ncbi.nlm.nih.gov/pubmed/31899693

https://journals.lww.com/ctg/Abstract/latest/Cannabinoids_and_Opioids_in_the_Treatment_of.99898.aspx