Tag Archives: treatment

Cannabis Influences the Putative Cytokines-Related Pathway of Epilepsy among Egyptian Epileptic Patients.

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brainsci-logo“The study aims to investigate: (1) the prevalence of cannabis among epileptic patients seen at Mansoura University Hospital, (2) serum levels and gene expression of cytokines in epilepsy patients and the controls. and (3) the possibility that cannabis use affects the cytokine levels in epilepsy patients, triggering its future use in treatment.

We recruited 440 epilepsy patients and 200 controls matched for age, gender, and ethnicity. Of the epileptic patients, 37.5% demonstrated lifetime cannabis use with a mean duration of 15 ± 73 years. Serum levels of interleukin IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α), were analyzed and gene expression analysis was conducted only for those cytokines that were different between groups in the serum analysis.

The “Epilepsy-only” patients had significantly higher serum and mRNA levels of IL-1α, β, IL-2,6,8, and TNF-α compared to the controls and the “Cannabis+Epilepsy” group (p = 0.0001). IL-10 showed significantly lower levels in the “Epilepsy-only” patients compared to the controls and “Cannabis+Epilepsy” (p = 0.0001). Cannabis use is prevalent among epilepsy patients.

Epilepsy is characterized by a pro-inflammatory state supported by high serum and gene expression levels.

Cannabis users demonstrated significantly lower levels of inflammatory cytokines compared to epilepsy non-cannabis users which might contribute to its use in the treatment of resistant epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/31757102

https://www.mdpi.com/2076-3425/9/12/332

Association between cannabis and the eyelids: A comprehensive review.

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Publication cover image“Cannabis is the most consumed illicit drug worldwide. As more countries consider bills that would legalize adult use of cannabis, health care providers, including eye care professionals (ophthalmologists, optometrists), will need to recognize ocular effects of cannabis consumption in patients.

There are only 20 studies on the eyelid effects of cannabis usage as a medical treatment or a recreational drug.

These include: ptosis induction, an “eyelid tremor” appearance and blepharospasm attenuation.

Six articles describe how adequately dosed cannabis regimens could be promising medical treatments for blepharospasm induced by psychogenic factors.

The exact mechanism of cannabinoids connecting cannabis to the eyelids is unclear.

Further studies should be conducted to better understand the cannabinoid system in relation to the eyelid and eventually develop new, effective and safe therapeutic targets derived from cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/31747112

https://onlinelibrary.wiley.com/doi/abs/10.1111/ceo.13687

Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy.

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Image result for translational psychiatry“Autism spectrum disorder (ASD) is a high cost neurodevelopmental condition; and there are currently no effective pharmacological treatments for its core symptoms. This has led some families and researchers to trial alternative remedies – including the non-intoxicating Cannabis sativa-derived compound cannabidivarin (CBDV). However, how CBDV affects the human brain is unknown.

Previous (pre)clinical evidence suggests that CBDV may modulate brain excitatory-inhibitory systems, which are implicated in ASD. Hence, our main aim was to test, for the first time, if CBDV shifts glutamate and/or GABA metabolites – markers of the brain’s primary excitatory and inhibitory system – in both the ‘typical’ and autistic brain.

Our subsidiary aim was to determine whether, within ASD, brain responsivity to CBDV challenge is related to baseline biological phenotype. We tested this using a repeated-measures, double-blind, randomized-order, cross-over design.

We used magnetic resonance spectroscopy (MRS) to compare glutamate (Glx = glutamate + glutamine) and GABA + (GABA + macromolecules) levels following placebo (baseline) and 600 mg CBDV in 34 healthy men with (n = 17) and without (n = 17) ASD. Data acquisition from regions previously reliably linked to ASD (dorsomedial prefrontal cortex, DMPFC; left basal ganglia, BG) commenced 2 h (peak plasma levels) after placebo/CBDV administration. Where CBDV significantly shifted metabolite levels, we examined the relationship of this change with baseline metabolite levels. Test sessions were at least 13 days apart to ensure CBDV wash-out. CBDV significantly increased Glx in the BG of both groups. However, this impact was not uniform across individuals. In the ASD group, and not in the typically developing controls, the ‘shift’ in Glx correlated negatively with baseline Glx concentration. In contrast, CBDV had no significant impact on Glx in the DMPFC, or on GABA+ in either voxel in either group.

Our findings suggest that, as measured by MRS, CBDV modulates the glutamate-GABA system in the BG but not in frontal regions. Moreover, there is individual variation in response depending on baseline biochemistry. Future studies should examine the effect of CBDV on behaviour and if the response to an acute dose of CBDV could predict a potential clinical treatment response in ASD.”

https://www.ncbi.nlm.nih.gov/pubmed/31748505

“Here we report that CBDV can ‘shift’ subcortical levels of the brain’s primary excitatory metabolite glutamate (measured as Glx) both in the neurotypical and autistic brain; but that there may be significant response variability in ASD. These findings add to our understanding of the effects of CBDV in the adult human brain. Nonetheless, future studies will need to explore (i) the mechanisms of action of CBDV; (ii) the impact of CBDV on (ASD-related) cognition and behaviour; (iii) if single-dose responsivity could facilitate the identification of pharmacologically homogeneous sub-groups; and (iv) if acute CBDV effects are indicative of the impact of long-term treatment in ASD.”

https://www.nature.com/articles/s41398-019-0654-8

Medical Cannabis as an Effective Treatment for Refractory Symptoms of Paraneoplastic Stiff Person Syndrome.

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Journal of Pain and Symptom Management Home“Stiff person syndrome (SPS) is a disorder characterized by fluctuating, progressive and painful spasms of the limbs, trunk and face. The condition is frequently associated with other diseases, including malignancies1. Up to 10% of SPS cases are paraneoplastic (PSPS) and occur with various types of cancer 2. SPS is thought to be immune-mediated, with up to 60% of patients demonstrating antibodies to glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the production of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).” https://www.ncbi.nlm.nih.gov/pubmed/31743746

https://www.jpsmjournal.com/article/S0885-3924(19)30654-2/fulltext

“Successful cannabis derivatives oromucosal spray therapy for a seronegative stiff-person syndrome: a case report.”  https://ejhp.bmj.com/content/19/2/219.2

“Cannabis derivatives therapy for a seronegative stiff-person syndrome: a case report”   http://www.ncbi.nlm.nih.gov/pubmed/22726074

Effects of CBD-Enriched Cannabis sativa Extract on Autism Spectrum Disorder Symptoms: An Observational Study of 18 Participants Undergoing Compassionate Use.

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Image result for frontiers in neurology“Autism Spectrum Disorders comprise conditions that may affect cognitive development, motor skills, social interaction, communication, and behavior. This set of functional deficits often results in lack of independence for the diagnosed individuals, and severe distress for patients, families, and caregivers.

There is a mounting body of evidence indicating the effectiveness of pure cannabidiol (CBD) and CBD-enriched Cannabis sativa extract (CE) for the treatment of autistic symptoms in refractory epilepsy patients. There is also increasing data support for the hypothesis that non-epileptic autism shares underlying etiological mechanisms with epilepsy.

Here we report an observational study with a cohort of 18 autistic patients undergoing treatment with compassionate use of standardized CBD-enriched CE (with a CBD to THC ratio of 75/1).

Among the 15 patients who adhered to the treatment (10 non-epileptic and five epileptic) only one patient showed lack of improvement in autistic symptoms. Due to adverse effects, three patients discontinued CE use before 1 month.

After 6-9 months of treatment, most patients, including epileptic and non-epileptic, showed some level of improvement in more than one of the eight symptom categories evaluated: Attention Deficit/Hyperactivity Disorder; Behavioral Disorders; Motor Deficits; Autonomy Deficits; Communication and Social Interaction Deficits; Cognitive Deficits; Sleep Disorders and Seizures, with very infrequent and mild adverse effects.

The strongest improvements were reported for Seizures, Attention Deficit/Hyperactivity Disorder, Sleep Disorders, and Communication and Social Interaction Deficits. This was especially true for the 10 non-epileptic patients, nine of which presented improvement equal to or above 30% in at least one of the eight categories, six presented improvement of 30% or more in at least two categories and four presented improvement equal to or above 30% in at least four symptom categories.

Ten out of the 15 patients were using other medicines, and nine of these were able to keep the improvements even after reducing or withdrawing other medications.

The results reported here are very promising and indicate that CBD-enriched CE may ameliorate multiple ASD symptoms even in non-epileptic patients, with substantial increase in life quality for both ASD patients and caretakers.”

https://www.ncbi.nlm.nih.gov/pubmed/31736860

“The findings presented here, taken together, support the notion that many autism symptoms are associated to neuronal hyperexcitability, and indicate that CBD-enriched CE yields positive effects in multiple autistic symptoms, without causing the typical side effects found in medicated ASD patients. Most patients in this study had improved symptoms even after supervised weaning of other neuropsychiatric drugs.”

https://www.frontiersin.org/articles/10.3389/fneur.2019.01145/full

Efficacy and adverse event profile of cannabidiol and medicinal cannabis for treatment-resistant epilepsy: Systematic review and meta-analysis.

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“This paper aimed to systematically examine the efficacy and adverse event (AE) profile of cannabidiol and medicinal cannabis by analyzing qualitative and meta-analytic data.

According to the results, a statistically meaningful effect of cannabidiol compared with placebo was observed (p < 0.00001). When comparing treatment with cannabidiol or medicinal cannabis, significance was not found for the AE profile (p = 0.74). As AEs for cannabidiol were more common under short-term than under long-term treatment (p < 0.00001), this approach was favorable in the long term.

Furthermore, cannabidiol is more effective than placebo, regardless of the etiology of epileptic syndromes and dosage.

Overall, the AE profile did not differ across treatments with cannabidiol or medicinal cannabis, though it did differ favorably for long-term than for short-term treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/31731110

“CBD treatments were effective compared with placebo, regardless of the dose administered. •The safety analysis is related to tolerable SEs found in studies with both CBD and medicinal CNB. •There was a greater tendency for adverse events in short-term treatment compared with long-term treatment.”

https://www.epilepsybehavior.com/article/S1525-5050(19)30862-5/fulltext

Cannabidiol Protects Dopaminergic Neuronal Cells from Cadmium.

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ijerph-logo“The protective effect of cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, against neuronal toxicity induced by cadmium chloride (CdCl2 10 μM) was investigated in a retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cell line.

CBD (1 μM) was applied 24 h before and removed during cadmium (Cd) treatment. In differentiated neuronal cells, CBD significantly reduced the Cd-dependent decrease of cell viability, and the rapid reactive oxygen species (ROS) increase.

CBD significantly prevented the endoplasmic reticulum (ER) stress (GRP78 increase) and the subcellular distribution of the cytochrome C, as well as the overexpression of the pro-apoptotic protein BAX. Immunocytochemical analysis as well as quantitative protein evaluation by western blotting revealed that CBD partially counteracted the depletion of the growth associated protein 43 (GAP43) and of the neuronal specific class III β-tubulin (β3 tubulin) induced by Cd treatment.

These data showed that Cd-induced neuronal injury was ameliorated by CBD treatment and it was concluded that CBD may represent a potential option to protect neuronal cells from the detrimental effects of Cd toxicity.”

https://www.ncbi.nlm.nih.gov/pubmed/31718076

https://www.mdpi.com/1660-4601/16/22/4420

Study protocol for a randomised, double-blind, placebo-controlled study evaluating the Efficacy of cannabis-based Medicine Extract in slowing the disease pRogression of Amyotrophic Lateral sclerosis or motor neurone Disease: the EMERALD trial.

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Image result for bmj open“Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no known cure and with an average life expectancy of 3-5 years post diagnosis.

The use of complementary medicine such as medicinal cannabis in search for a potential treatment or cure is common in ALS.

Preclinical studies have demonstrated the efficacy of cannabinoids in extending the survival and slowing of disease progression in animal models with ALS.

There are anecdotal reports of cannabis slowing disease progression in persons with ALS (pALS) and that cannabis alleviated the symptoms of spasticity and pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31719072

https://bmjopen.bmj.com/content/9/11/e029449

Cannabidiol as a potential treatment for psychosis

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Image result for therapeutic advances in psychopharmacology“Accumulating evidence implicates the endocannabinoid system in the pathophysiology of psychosis.

If the endocannabinoid system plays a role in psychosis pathophysiology, it raises the interesting possibility that pharmacological compounds that modulate this system may have therapeutic value.

Cannabidiol (CBD), a phytocannabinoid constituent of Cannabis sativa, has been heralded as one such potential treatment.

Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, has emerged as a potential novel class of antipsychotic with a unique mechanism of action.

In this review, we set out the prospects of CBD as a potential novel treatment for psychotic disorders.

In sum, CBD currently represents a promising potential novel treatment for patients with psychosis.”

https://journals.sagepub.com/doi/10.1177/2045125319881916

https://www.ncbi.nlm.nih.gov/pubmed/31741731

Relieving tension: effects of cannabinoids on vagal afferent sensitivity.

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Publication cover image“Endocannabinoids are produced within the gastrointestinal (GI) tract and modulate energy homeostasis and food intake, at least in part, via vagally-dependent actions. The recent paper by Christie et al., [Christie, et al. J Physiol, 2019] demonstrate, for the first time, that cannabinoids exert biphasic effects on the mechanosensitivity of tension-sensitive gastric vagal afferents. At higher concentrations, anandamide increased vagal afferent sensitivity in a CB1 and TRPV1 receptor dependent manner. At lower concentrations, however, anandamide decreased afferent mechanosensitivity; while this was also dependent upon CB1 and TRPV1 receptors, it also appeared dependent upon signaling via the potent orexigenic neurohormone, ghrelin. These results provide further evidence to support the remarkable degree of neuroplasticity within vagal afferent signaling, and suggest that untangling the complex interactions of cannabinoid effects on food intake and energy homeostasis will require careful physiological and pharmacological investigations.”

https://www.ncbi.nlm.nih.gov/pubmed/31707736

https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP279173

“A clear understanding of the mechanisms which mediate these events may provide novel therapeutic targets for the treatment of gastrointestinal disorders due to vago-vagal pathway malfunctions.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318799/