Tag Archives: cannabinoid

Cannabidiol as a suggested candidate for treatment of autism spectrum disorder.

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 Progress in Neuro-Psychopharmacology and Biological Psychiatry “Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication, restricted and repetitive patterns of behavior, interests, or activities and often intellectual disabilities.

No effective treatment for the core symptoms of ASD is currently available.

There is increasing interest in cannabinoids, especially cannabidiol (CBD), as monotherapy or add-on treatment for the core symptoms and co-morbidities of ASD.

In this review we summarize the available pre-clinical and clinical data regarding the safety and effectiveness of medical cannabis, including CBD, in young ASD patients.

Cannabidiol seems to be a candidate for the treatment of ASD.”

https://www.ncbi.nlm.nih.gov/pubmed/30171992

https://www.sciencedirect.com/science/article/pii/S0278584618304445?via%3Dihub

Acute foot-shock stress decreased seizure susceptibility against pentylenetetrazole-induced seizures in mice: Interaction between endogenous opioids and cannabinoids.

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“Stressful conditions affect the brain’s neurotransmission and neural pathways that are involved in seizure susceptibility. Stress alters the intensity and/or frequency of seizures.

Although evidence indicates that chronic stress exerts proconvulsant effects and acute stress has anticonvulsant properties, the underlying mechanisms which mediate these effects are not well understood.

In the present study, we assessed the role of endogenous opioids, endocannabinoids, as well as functional interaction between opioid and cannabinoid systems in the anticonvulsant effects of acute foot-shock stress (FSS) against pentylenetetrazole (PTZ)-induced seizures in mice.

CONCLUSIONS:

Opioid and cannabinoid systems are involved in the anticonvulsant effects of acute FSS, and these neurotransmission systems interact functionally in response to acute FSS.”

https://www.ncbi.nlm.nih.gov/pubmed/30170259

https://www.epilepsybehavior.com/article/S1525-5050(17)30777-1/fulltext

Gut microbiota, cannabinoid system and neuroimmune interactions: New perspectives in multiple sclerosis.

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Biochemical Pharmacology

“The gut microbiota plays a fundamental role on the education and function of the host immune system.

Immunological dysregulation is the cause of numerous human disorders such as autoimmune diseases and metabolic disorders frequently associated with inflammatory processes therefore is critical to explore novel mechanisms involved in maintaining the immune system homeostasis.

The cannabinoid system and related bioactive lipids participate in multiple central and peripheral physiological processes that affect metabolic, gastrointestinal and neuroimmune regulatory mechanisms displaying a modulatory role and contributing to the maintenance of the organism’s homeostasis.

In this review, we gather the knowledge on the gut microbiota-endocannabinoids interactions and their impact on autoimmune disorders such as inflammatory bowel disease, rheumatoid arthritis and particularly, multiple sclerosis (MS) as the best example of a CNS autoimmune disorder.

Furthermore, we contribute to this field with new data on changes in many elements of the cannabinoid system in a viral model of MS after gut microbiota manipulation by both antibiotics and probiotics.

Finally, we highlight new therapeutic opportunities, under an integrative view, targeting the eCBS and the commensal microbiota in the context of neuroinflammation and MS.”

https://www.ncbi.nlm.nih.gov/pubmed/30171835

https://www.sciencedirect.com/science/article/abs/pii/S0006295218303630

When Orexins Meet Cannabinoids: Bidirectional Functional Interactions.

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Biochemical Pharmacology

“A growing body of evidence suggests the existence of biochemical and functional interactions between the endocannabinoid and orexin systems. Cannabinoid and orexin receptors have been shown to form heterodimers in agreement with the overlapping distribution of both receptors in several brain areas, and the activation of common intracellular signaling pathways, such as the MAP kinase cascade. The activation of orexin receptors induces the synthesis of the endocannabinoid 2-arachidonoyl glycerol suggesting that the endocannabinoid system participates in some physiological functions of orexins. Indeed, functional interactions between these two systems have been demonstrated in several behavioral responses including nociception, reward and food intake. The present review is focused on the latest developments in cannabinoid-orexin cross-modulation and the implications of this interesting interaction.”

https://www.ncbi.nlm.nih.gov/pubmed/30171834

https://www.sciencedirect.com/science/article/abs/pii/S0006295218303666

Should Cannabinoids Be Added to Multimodal Pain Regimens After Total Hip and Knee Arthroplasty?

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Journal of Arthroplasty Home

“This study investigated the effects of dronabinol on pain, nausea, and length of stay following total joint arthroplasty (TJA).

CONCLUSION:

These findings suggest that further investigation into the role of cannabinoid medications for non-opioid pain control in the post-arthroplasty patient may hold merit.”

https://www.ncbi.nlm.nih.gov/pubmed/30170713

“In conclusion, our study suggests that cannabinoids may have a role in post-arthroplasty pain management and may reduce patient’s need for opioid-containing pain medications. Further randomized, prospective clinical trials are warranted to shed more light onto the possible beneficial effects of cannabinoid medications in the orthopedic surgery patient population.” https://www.arthroplastyjournal.org/article/S0883-5403(18)30670-3/fulltext

Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis: A Randomized Clinical Trial.

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“Cannabidiol (CBD) has antipsychotic effects in humans, but how these are mediated in the brain remains unclear.

OBJECTIVE:

To investigate the neurocognitive mechanisms that underlie the therapeutic effects of CBD in psychosis.

CONCLUSIONS AND RELEVANCE:

Cannabidiol may partially normalize alterations in parahippocampal, striatal, and midbrain function associated with the CHR state. As these regions are critical to the pathophysiology of psychosis, the influence of CBD at these sites could underlie its therapeutic effects on psychotic symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/30167644

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2697762

“Psychosis: Cannabis extract normalizes brain function” https://www.medicalnewstoday.com/articles/322926.php
“Cannabis extract helps reset brain function in psychosis” https://medicalxpress.com/news/2018-08-cannabis-reset-brain-function-psychosis.html
“Cannabis extract helps reset brain function in psychosis” https://www.eurekalert.org/pub_releases/2018-08/kcl-ceh082818.php
“Cannabidiol Reduces Symptoms of Psychosis. A new study found that the chemical extracted from cannabis has antipsychotic effects.” https://www.usnews.com/news/health-care-news/articles/2018-08-29/one-dose-of-cannabidiol-reduces-symptoms-of-psychosis
“MEDICAL MARIJUANA: CANNABIS EXTRACT CBD USED TO SUCCESSFULLY TREAT PSYCHOSIS.” https://www.newsweek.com/cannabidiol-cannabis-extract-could-treat-symptoms-psychosis-1094353

 “Single dose of the cannabis compound CBD reduces psychotic symptoms by normalising brain activity” http://www.dailymail.co.uk/health/article-6110591/Single-dose-cannabis-compound-CBD-reduces-psychotic-symptoms-normalising-brain-activity.html

“British scientists have unraveled how a non-intoxicating component of cannabis acts in key brain areas to reduce abnormal activity in patients at risk of psychosis, suggesting the ingredient could become a novel anti-psychotic medicine.” https://www.theglobeandmail.com/cannabis/article-scientists-unravel-how-cannabis-component-may-fight-psychosis/

“Science proves component in weed actually helps fight psychosis” https://nypost.com/2018/08/29/science-proves-component-in-weed-actually-helps-fight-psychosis/
“We Now Have Evidence That a Marijuana Compound Can Help People With Psychosis” https://futurism.com/cbd-psychosis/

Anticonvulsant and Neuroprotective Effects of Cannabidiol During the Juvenile Period.

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“Anticonvulsant effects of cannabidiol (CBD), a nonpsychoactive cannabinoid, have not been investigated in the juvenile brain. We hypothesized that CBD would attenuate epileptiform activity at an age when the brain first becomes vulnerable to neurotoxicity and social/cognitive impairments.

To induce seizures, kainic acid (KA) was injected either into the hippocampus (KAih) or systemically (KAip) on postnatal (P) day 20. CBD was coadministered (KA + CBDih, KA + CBDip) or injected 30 minutes postseizure onset (KA/CBDih, KA/CBDip).

Hyperactivity, clonic convulsions, and electroencephalogram rhythmic oscillations were attenuated or absent after KA + CBDih and reduced after KA + CBDip. NeuN immunohistochemistry revealed neuroprotection.

Augmented reactive glia number and expression were reversed in CA1 but persisted deep within the dentate hilus. Parvalbumin-positive (PV+) interneurons were reduced in both models, whereas immunolabeling was dramatically increased within ipsilateral and contralateral dendritic/neuropilar fields following KA + CBDih. Cannabinoid receptor 1 (CB1) expression was minimally affected after KAih contrasting elevations observed after KAip.

Intracranial coadministration data suggest that CBD has higher efficacy in epilepsy with hippocampal focus rather than when extrahippocampal amygdala/cortical structures are triggered by systemic treatments. Inhibition of surviving PV+ and CB1+ interneurons may be facilitated by CBD implying a protective role in regulating hippocampal seizures and neurotoxicity at juvenile ages.”

https://www.ncbi.nlm.nih.gov/pubmed/30169677

Potential clinical benefits of CBD-rich Cannabis extracts over purified cannabidiol (CBD) in treatment-resistant epilepsy: observational data meta-analysis

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“This meta-analysis paper describes the analysis of observational clinical studies on the treatment of refractory epilepsy with cannabidiol (CBD)-based products. Beyond attempting to establish the safety and efficacy of such products, we also investigated if there is enough evidence to assume any difference in efficacy between CBD-rich extracts compared to purified CBD products.

The systematic search took place in February/2017 and updated in December/2017 using the keywords “epilepsy” or “Dravet” or “Lennox-Gastaut” or “CDKL5” combined with “Cannabis”, “cannabinoid”, “cannabidiol” or “CBD” resulting in 199 papers. The qualitative assessment resulted in 11 valid references, with an average impact factor of 8.1 (ranging from 1.4 to 47.8). The categorical data of a total of 670 patients were analyzed by Fischer test. The average daily dose ranged between 1 and 50 mg/kg, with treatment length from 3 to 12 months (mean 6.2 months).

Two thirds of patients reported improvement in the frequency of convulsive crisis (399/622, 64%). There were more reports of improvement from patients treated with CBD-rich extracts (318/447, 71%) than patients treated with purified CBD (81/223, 36%), with statistical significance (p<0.0001).

Nevertheless, when the standard clinical threshold of a “50% reduction or more in the frequency of convulsive crisis” was applied, only 39% of the individuals were considered “responders”, and there was no difference (p=0.56) between treatments with CBD-rich extracts (97/255, 38%) and purified CBD (94/223, 42%).

Patients treated with CBD-rich extracts reported lower average dose (6.1 mg/kg/day) than those using purified CBD (27.1 mg/kg/day). The reports of mild (109/285 vs 291/346, p<0.0001) and severe (23/285 vs 77/346, p<0.0001) adverse effects were more frequent in products containing purified CBD than in CBD-rich extracts.

CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy. The roots of this difference is likely due to synergistic effects of CBD with other phytocompounds (aka Entourage effect), but this remains to be confirmed in controlled clinical studies.”

https://www.frontiersin.org/articles/10.3389/fneur.2018.00759/abstract

Cannabidiol modulates serotonergic transmission and prevents allodynia and anxiety-like behavior in a model of neuropathic pain.

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“Clinical studies indicate that cannabidiol (CBD), the primary non-addictive component of cannabis that interacts with the serotonin (5-HT) 1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact in models of neuropathic pain are unknown.

Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Anti-allodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), while the anxiolytic effect was blocked only by WAY.

Overall, repeated treatment with low-dose CBD induces analgesia predominantly via TRPV1 activation, reduces anxiety via 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/30157131

https://insights.ovid.com/crossref?an=00006396-900000000-98870

“Cannabis pain relief without the ‘high’. Canadian researchers pinpoint the mechanism of cannabidiol for safe pain relief without side effects”  https://eurekalert.org/pub_releases/2018-10/muhc-cpr102418.php

“Effective dose of cannabidiol for safe pain relief without the typical ‘high'”  https://www.news-medical.net/news/20181025/Effective-dose-of-cannabidiol-for-safe-pain-relief-without-the-typical-high.aspx

Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science.

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“Comprehensive literature reviews of historical perspectives and evidence supporting cannabis/cannabinoids in the treatment of pain, including migraine and headache, with associated neurobiological mechanisms of pain modulation have been well described.

Most of the existing literature reports on the cannabinoids Δ9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), or cannabis in general. There are many cannabis strains that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce wide variations in benefits, side effects, and strain characteristics. Knowledge of the individual medicinal properties of the cannabinoids, terpenes, and flavonoids is necessary to cross-breed strains to obtain optimal standardized synergistic compositions. This will enable targeting individual symptoms and/or diseases, including migraine, headache, and pain.

OBJECTIVE:

Review the medical literature for the use of cannabis/cannabinoids in the treatment of migraine, headache, facial pain, and other chronic pain syndromes, and for supporting evidence of a potential role in combatting the opioid epidemic. Review the medical literature involving major and minor cannabinoids, primary and secondary terpenes, and flavonoids that underlie the synergistic entourage effects of cannabis. Summarize the individual medicinal benefits of these substances, including analgesic and anti-inflammatory properties.

CONCLUSION:

There is accumulating evidence for various therapeutic benefits of cannabis/cannabinoids, especially in the treatment of pain, which may also apply to the treatment of migraine and headache. There is also supporting evidence that cannabis may assist in opioid detoxification and weaning, thus making it a potential weapon in battling the opioid epidemic. Cannabis science is a rapidly evolving medical sector and industry with increasingly regulated production standards. Further research is anticipated to optimize breeding of strain-specific synergistic ratios of cannabinoids, terpenes, and other phytochemicals for predictable user effects, characteristics, and improved symptom and disease-targeted therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/30152161