A pediatric patient with autism spectrum disorder and epilepsy using cannabinoid extracts as complementary therapy: a case report

 Journal of Medical Case Reports | Home page“The pharmacological treatment for autism spectrum disorders is often poorly tolerated and has traditionally targeted associated conditions, with limited benefit for the core social deficits.

We describe the novel use of a cannabidiol-based extract that incidentally improved core social deficits and overall functioning in a patient with autism spectrum disorder, at a lower dose than has been previously reported in autism spectrum disorder.

Case presentation: The parents of a 15-year-old boy, of South African descent, with autism spectrum disorder, selective mutism, anxiety, and controlled epilepsy, consulted a medical cannabis physician to trial cannabis extract to replace seizure medications. Incidentally, at a very low cannabidiol-based extract dose, he experienced unanticipated positive effects on behavioral symptoms and core social deficits.

Conclusion: This case report provides evidence that a lower than previously reported dose of a phytocannabinoid in the form of a cannabidiol-based extract may be capable of aiding in autism spectrum disorder-related behavioral symptoms, core social communication abilities, and comorbid anxiety, sleep difficulties, and weight control. Further research is needed to elucidate the clinical role and underlying biological mechanisms of action of cannabidiol-based extract in patients with autism spectrum disorder.”

https://pubmed.ncbi.nlm.nih.gov/32958062/

https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-020-02478-7

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Add-on cannabidiol significantly decreases seizures in 3 patients with SYNGAP1 developmental and epileptic encephalopathy

“Mutations in SYNGAP1 are associated with developmental delay, epilepsy, and autism spectrum disorder (ASD). Epilepsy is often drug-resistant in this syndrome with frequent drop attacks.

In a prospective study of add-on cannabidiol (CBD), we identified three patients with SYNGAP1 mutations: two boys and one girl. Seizure onset was at 3.5, 8, and 18 months (M), respectively, with numerous atypical absences per day associated with eyelid myoclonia (2/3 patients), upper limb myoclonic jerks (2/3 patients), and drop attacks (all patients). Seizures were resistant to at least 5 antiepileptic drugs (AEDs).

After CBD introduction, two patients were responders since M2 and achieve a seizure reduction of 90% and 80%, respectively, at M9 with disappearance of drop attacks. EEGs showed an improvement regarding background activity and interictal anomalies. The last patient showed a late response at M7 of treatment with an 80% decrease in seizure frequency. Caregiver in all three evaluated as much improved the status of their children. Treatment was well-tolerated in all, and no major adverse events (AEs) were reported.

CBD showed efficacy in patients with drug-resistant epilepsy due to SYNGAP1 mutations. Other patients with rare genetic developmental and epileptic encephalopathies with drug-resistant epilepsies might benefit from CBD.”

https://pubmed.ncbi.nlm.nih.gov/32913957/

“CBD add‐on therapy in patients with SYNGAP1 encephalopathy showed a good response in three patients with a good safety profile and a late response in one patient. This therapy should be included in the treatment algorithm of patients with SYNGAP1 mutations presenting drug resistance epilepsy and might be expanded to other rare genetic epilepsies that might not be included in formal trials.”

https://onlinelibrary.wiley.com/doi/full/10.1002/epi4.12411

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Insights on cannabidiol’s antiallodynic and anxiolytic mechanisms of action in a model of neuropathic pain

PAIN Impact Factor Increase to 6.029 - IASP“Recent studies have shown that cannabidiol (CBD) could have a great therapeutic potential for treating disorders such as chronic pain and anxiety. In the target article, the authors propose that CBD modulates serotonergic transmission and reverses allodynia and anxiety-like behaviour in a rat model of neuropathic pain. Furthermore, this study shows an antinociceptive effect mediated by TRPV1 and partially by 5-HT1A receptors, as well as an anxiolytic effect mediated by 5-HT1A receptors.”

https://pubmed.ncbi.nlm.nih.gov/32766463/

https://journals.lww.com/painrpts/Fulltext/2019/10000/Insights_on_cannabidiol_s_antiallodynic_and.10.aspx

“Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain”  https://pubmed.ncbi.nlm.nih.gov/30157131/

 

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Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer’s Disease

Frontiers in Pharmacology (@FrontPharmacol) | Twitter “Alzheimer’s disease (AD) is an irreversible chronic neurodegenerative disorder that occurs when neurons in the brain degenerate and die. Pain frequently arises in older patients with neurodegenerative diseases including AD. However, the presence of pain in older people is usually overlooked with cognitive dysfunctions. Most of the times dementia patients experience moderate to severe pain but the development of severe cognitive dysfunctions tremendously affects their capability to express the presence of pain. Currently, there are no effective treatments against AD that emphasize the necessity for increasing research to develop novel drugs for treating or preventing the disease process. Furthermore, the prospective therapeutic use of cannabinoids in AD has been studied for the past few years. In this regard, targeting the endocannabinoid system has considered as a probable therapeutic strategy to control several associated pathological pathways, such as mitochondrial dysfunction, excitotoxicity, oxidative stress, and neuroinflammation for the management of AD. In this review, we focus on recent studies about the role of cannabinoids for the treatment of pain and related neuropathological changes in AD.”

https://pubmed.ncbi.nlm.nih.gov/32792944/

“Cannabinoids act by targeting several signaling processes, such as pain, abnormal processing of Aβ and tau, neuroinflammation, excitotoxicity, oxidative stress, and mitochondrial dysfunction, which play a pivotal role in the management of AD. Cannabinoids also ameliorate behavioral and cognitive dysfunctions. Therefore, due to these extensive medical uses of cannabinoid compounds, it can be said that targeting the endocannabinoid system can be a promising strategy to develop an effective therapy for the management of AD. Furthermore, cannabinoids may demonstrate a safe and reliable low-cost therapy, with limited side effects.”

https://www.frontiersin.org/articles/10.3389/fphar.2020.01097/full

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Flavonoid and cannabinoid impact on the ocular surface

 Media Kit - Current Opinion in Allergy and Clinical Immunology | Lippincott  Audience Solutions | Wolters Kluwer“Purpose of review: To evaluate the impact of flavonoids and cannabinoids as anti-inflammatory and antiallergic treatments on the anterior surface of the eye.

Recent findings: Allergic conjunctivitis and dry eye syndrome are common ocular surface diseases that have been treated with traditional pharmacological measures, e.g. corticosteroids, antihistamines. Given the side-effect profiles of these medications and the growing interest in complementary treatment modalities as part of integrative medical interventions, well known flavonoids, such as quercetin and catechin, are under investigation for topical and systemic application methods for relief. As flavonoid derivatives, pycnogenol and epigallocatechin gallate have alleviated dry eye symptoms, including lacrimal gland inflammation, tear secretion, and the stability of the tear film. Research on ocular cannabinoid receptors and response to synthetic cannabinoids are also being considered for therapy of anterior ocular disorders. The expansion of herbal formulations provides a framework for future treatment regimens for ocular surface disorders.

Summary: Flavonoids and cannabinoids show promise as potential complementary treatment for allergic diseases because of their anti-inflammatory and antiallergic properties. Several studies implementing ocular and systemic application of these compounds show potential in becoming adjuvant treatment strategies for improving quality of life while also managing ocular surface disease processes.”

https://pubmed.ncbi.nlm.nih.gov/32796166/

https://journals.lww.com/co-allergy/Abstract/2020/10000/Flavonoid_and_cannabinoid_impact_on_the_ocular.11.aspx

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Cannabis, More Than the Euphoria: Its Therapeutic Use in Drug-Resistant Epilepsy

 See the source image“A significant number of epilepsy patients are refractory to conventional antiepileptic drugs. These patients experience considerable neurocognitive impairments that impact their quality of life and ability to function independently. This need for alternative treatment has generated increased interest in cannabis use as a therapeutic option in these patients.

This review seeks to analyze data presented on the pharmacology, safety, and efficacy of cannabis use in patients with drug-resistant epilepsy (DRE) and to propose any future recommendations regarding its use.

The two foremost phytocannabinoids of cannabis showing anticonvulsant properties are tetrahydrocannabinol (THC) and cannabidiol (CBD).

Due to the psychoactive properties of THC, most studies focused on CBD use in these patients. The use of CBD as an adjunct resulted in decreased seizure frequency, and secondary benefits observed included improvement in mood, alertness and sleep. Adverse events (AEs) reported were drowsiness, diarrhea, increased transaminases and worsening of seizures.

It can safely be concluded that there is a significant benefit in DRE patients using CBD as adjunctive therapy. However, further controlled and adequately powered studies are needed to assess the pharmacokinetics and impact of the long-term use of cannabis.”

https://pubmed.ncbi.nlm.nih.gov/32832296/

“The anticonvulsant properties of cannabis have been reported for several years; however, its use as adjunctive therapy in DRE has increased in recent years. Cannabis mediates the ECS, which affects neuronal excitability. This makes it a superior choice for the adjunctive treatment of DRE patients.”

https://www.cureus.com/articles/36299-cannabis-more-than-the-euphoria-its-therapeutic-use-in-drug-resistant-epilepsy

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The Effects of Cannabidiol and Prognostic Role of TRPV2 in Human Endometrial Cancer

ijms-logo“Several studies support, both in vitro and in vivo, the anti-cancer effects of cannabidiol (CBD), a transient receptor potential vanilloid 2 (TRPV2) ligand. TRPV2, often dysregulated in tumors, is associated with altered cell proliferation and aggressiveness.

Endometrial cancer (EC) is historically divided in type I endometrioid EC and type II non-endometrioid EC, associated with poor prognosis. Treatment options with chemotherapy and combinations with radiation showed only limited efficacy. Since no data are reported concerning TRPV2 expression as well as CBD potential effects in EC, the aim of this study was to evaluate the expression of TRPV2 in biopsies and cell lines as well as the effects of CBD in in vitro models. Overall survival (OS), progression-free survival (PFS), cell viability, migration, and chemo-resistance have been evaluated.

Results show that TRPV2 expression increased with the malignancy of the cancer tissue and correlated with shorter PFS (p = 0.0224). Moreover, in vitro TRPV2 over-expression in Ishikawa cell line increased migratory ability and response to cisplatin. CBD reduced cell viability, activating predominantly apoptosis in type I cells and autophagy in mixed type EC cells. The CBD improved chemotherapeutic drugs cytotoxic effects, enhanced by TRPV2 over-expression. Hence, TRPV2 could be considered as a marker for optimizing the therapy and CBD might be a useful therapeutic option as adjuvant therapy.”

https://pubmed.ncbi.nlm.nih.gov/32751388/

https://www.mdpi.com/1422-0067/21/15/5409

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Opioids/cannabinoids as a potential therapeutic approach in COVID-19 patients

Publication Cover“So far, no vaccine has been successfully developed and there is no effective treatment of COVID-19.

Since intensive inflammation leads to disease-induced morbidity and mortality, inhibition of the hyperinflammatory response is a definitive drug therapy objective.

Certainly, there is an urgent need for a substance that can potentially counter the effects of the virus and alleviate the symptoms and severity of the disease.

Could opioids/cannabinoids be an effective treatment for COVID-19?

Since opioids/cannabinoids receptors-based drugs can modulate immune cell migration and cytokine/chemokine secretion, they represent a promising pharmacological platform for developing anti-inflammatory therapeutics.

Therefore in the absence of effective treatments to decrease the damage associated with COVID-19 especially in those admitted to the ICU and suffer from exaggerated inflammatory response, opioids/cannabinoids receptor agonists might potentially open up an effective therapeutic approach in COVID-19 infection.

It is interesting to remember that physicians in the late 19th century used anodynes of opium tincture as a treatment of ‘bronchitis’ and other ailments in infants and children, as case reports and experience ‘demonstrated the efficacy’ of the concoction in controlling coughing and facilitating breathing.

Also, today some products of cannabinoids are used to modulate an inflammatory response. This permits us to rediscover the past and utilize the present, with hopes of finding the missing links in the pathophysiology of COVID-19, and raises the issue of opioids/cannabinoids utilization in the context of COVID-19.

It is suggested that clinical trials could be conducted on opioids/cannabinoids products with immunomodulatory activity. We hope that, with great efforts, scientific support, and sharing of information, the overcoming of COVID-19 will come soon.”

https://www.tandfonline.com/doi/full/10.1080/17476348.2020.1787836

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Evaluation of the Potential Use of Cannabidiol in the Treatment of Cocaine Use Disorder: A Systematic Review

 Pharmacology Biochemistry and BehaviorCannabinoids may have an important therapeutic potential for the treatment of dependence on crack cocaine.

Cannabidiol (CBD), in particular, has anxiolytic, antipsychotic and anticonvulsant properties and plays a role in regulating motivation circuitry and controlling sleep disorders. Several studies were performed evaluating CBD in experimental models for cocaine.

This systematic review aims evaluate the potential use of CBD in the treatment of cocaine use disorder.

Major findings: Fifty-one studies were analyzed, and 14 were selected. No studies conducted with humans were found; only one clinical trial was ongoing. The results were grouped into the following categories: cocaine self-administration, brain-stimulation reward, conditioned place preference, neuronal proliferation, anxiety, hepatic protection, anticonvulsant effect and locomotor sensitization response Only four studies had a low risk of bias. CBD promotes reduction on cocaine self-administration. Also, it interferes in cocaine induce brain reward stimulation and dopamine release. CBD promotes alteration in contextual memory associated with cocaine and in the neuroadaptations, hepatotoxicity and seizures induced by cocaine.

Conclusion: The evidence indicates that CBD is a promising adjunct therapy for the treatment of cocaine dependence due to its effect on: cocaine reward effects, cocaine consumption, behavioral responses, anxiety, neuronal proliferation, hepatic protection and safety. Moreover, clinical trials are strongly required to determine whether the findings in animal models occur in humans diagnosed for cocaine or crack cocaine use disorder.”

https://pubmed.ncbi.nlm.nih.gov/32645315/

“CBD is a promising adjunct therapy for the treatment of cocaine dependence. CBD promotes reduction on cocaine self-administration.”

https://www.sciencedirect.com/science/article/pii/S0091305720300307?via%3Dihub

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Cannabis, the Endocannabinoid System and Immunity-the Journey From the Bedside to the Bench and Back

ijms-logo“The Cannabis plant contains numerous components, including cannabinoids and other active molecules. The phyto-cannabinoid activity is mediated by the endocannabinoid system. Cannabinoids affect the nervous system and play significant roles in the regulation of the immune system.

While Cannabis is not yet registered as a drug, the potential of cannabinoid-based medicines for the treatment of various conditions has led many countries to authorize their clinical use. However, the data from basic and medical research dedicated to medical Cannabis is currently limited.

A variety of pathological conditions involve dysregulation of the immune system. For example, in cancer, immune surveillance and cancer immuno-editing result in immune tolerance. On the other hand, in autoimmune diseases increased immune activity causes tissue damage.

Immuno-modulating therapies can regulate the immune system and therefore the immune-regulatory properties of cannabinoids, suggest their use in the therapy of immune related disorders.

In this contemporary review, we discuss the roles of the endocannabinoid system in immunity and explore the emerging data about the effects of cannabinoids on the immune response in different pathologies. In addition, we discuss the complexities of using cannabinoid-based treatments in each of these conditions.”

https://pubmed.ncbi.nlm.nih.gov/32585801/

https://www.mdpi.com/1422-0067/21/12/4448

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