Nightmares and the Cannabinoids.

“The cannabinoids, δ9 tetrahydrocannabinol and its analogue, nabilone, have been found to reliably attenuate the intensity and frequency of post-traumatic nightmares.

This essay examines how a traumatic event is captured in the mind after just a single exposure and repeatedly replicated during the nights that follow.

The adaptive neurophysiological, endocrine and inflammatory changes that are triggered by the trauma and that alter personality and behavior are surveyed. These adaptive changes, once established, can be difficult to reverse. But cannabinoids, uniquely, have been shown to interfere with all of these post-traumatic somatic adaptations.

While cannabinoids can suppress nightmares and other symptoms of the post-traumatic stress disorder, they are not a cure. There may be no cure.

The cannabinoids may best be employed, alone, but more likely in conjunction with other agents, in the immediate aftermath of a trauma to mitigate or even abort the metabolic changes which are set in motion by the trauma and which may permanently alter the reactivity of the nervous system. Steps in this direction have already been taken.”

https://www.ncbi.nlm.nih.gov/pubmed/31934840

http://www.eurekaselect.com/178302/article

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

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

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

[Cannabidiol in cancer treatment].

Image result for springer link journals“Cannabis was used for cancer patients as early as about 2500 years ago.

Experimental studies demonstrated tumor-inhibiting activities of various cannabinoids more than 40 years ago.

In view of the status of tetrahydrocannabinol (THC) as a regulated substance, non-psychotomimetic cannabidiol (CBD) is of particular importance.

RESULTS:

Preclinical studies, particularly recent ones, including numerous animal models of tumors, unanimously suggest the therapeutic efficacy of CBD. In isolated combination studies, synergistic effects were generally observed. In addition, CBD may potentially play a role in the palliative care of patients, especially concerning symptoms such as pain, insomnia, anxiety, and depression. Further human studies are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/31897700

https://link.springer.com/article/10.1007%2Fs00482-019-00438-9

Effect of combined doses of Δ9-tetrahydrocannabinol and cannabidiol or tetrahydrocannabinolic acid and cannabidiolic acid on acute nausea in male Sprague-Dawley rats.

 “This study evaluated the potential of combined cannabis constituents to reduce nausea.

CONCLUSION:

Combinations of very low doses of CBD + THC or CBDA + THCA robustly reduce LiCl-induced conditioned gaping. Clinical trials are necessary to determine the efficacy of using single or combined cannabinoids as adjunct treatments with existing anti-emetic regimens to manage chemotherapy-induced nausea.”

https://www.ncbi.nlm.nih.gov/pubmed/31897571

https://link.springer.com/article/10.1007%2Fs00213-019-05428-4

Therapeutic Uses of Cannabis on Sleep Disorders and Related Conditions.

 Related image“Marijuana generally refers to the dried mixture of leaves and flowers of the cannabis plant, and the term cannabis is a commonly used to refer to products derived from the Cannabis sativa L. plant. There has been an increasing interest in the potential medicinal use of cannabis to treat a variety of diseases and conditions. This review will provide the latest evidence regarding the medical risks and potential therapeutic benefits of cannabis in managing patients with sleep disorders or those with other medical conditions who commonly suffer with sleep disturbance as an associated comorbidity. Published data regarding the effects of cannabis compounds on sleep in the general population, as well as in patients with insomnia, chronic pain, posttraumatic stress disorder, and other neurological conditions, will be presented. Current trends for marijuana use and its effects on the economy and the implications that those trends and effects have on future research into medical cannabis are also presented.”

https://www.ncbi.nlm.nih.gov/pubmed/31895189

https://insights.ovid.com/crossref?an=00004691-202001000-00007

The Use of Cannabis as a Treatment for Epilepsy in Adult Patients: Are Side Effects a Limitation of Use?

 Related image“Marijuana is the dried leaves, stems, and flowers of a 1- to 5-m weed originating from Central Asia. The most common varieties are Cannabis sativa and Cannabis indica. It is usually inhaled as smoke but can also be used as a vapor, taken by mouth as a spray, ingested in tea or as butter in baked goods, or in capsule form and used as an oil. Cannabis has been widely used to treat many medical conditions such as multiple sclerosis symptoms, mood disorders, pain, sleep disorders, and seizures among others. Preclinical and clinical studies have been done over the past decade, among them there are few randomized placebo-controlled trials. In the last few years, Cannabis has been proposed as a potential therapy for patients with drug-resistant epilepsy. This review analyzes the best information about the use of cannabis in adult patients, reviewing aspects of efficacy and safety.”

https://www.ncbi.nlm.nih.gov/pubmed/31895185

https://insights.ovid.com/crossref?an=00004691-202001000-00003