Cannabis as an anticonvulsant

BMJ Journals“There are records of the cannabis plant being used for medicinal purposes in ancient times, and in the 19th century it was used as an effective anti-epileptic drug (AED) in children.

However, because of its abuse potential, most countries imposed laws restricting its cultivation and use, and this has greatly inhibited research into possible therapeutic uses.

Things are now changing, and cannabis derivatives are now used legally to treat, for example, pain, nausea and spasticity.

The plant contains over 100 biologically active compounds, and recently it has been possible to isolate these and identify the neurochemical mechanisms by which some of them operate: one in particular, cannabidiol”

https://www.ncbi.nlm.nih.gov/pubmed/29449212

http://adc.bmj.com/content/early/2018/02/15/archdischild-2018-314921

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Cannabis for paediatric epilepsy: challenges and conundrums.

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“Research is expanding for the use of cannabidiol as an anticonvulsant drug. The mechanism of cannabidiol in paediatric epilepsy is unclear but is thought to play a role in modulation of synaptic transmission. Evidence for its efficacy in treating epilepsy is limited but growing, with a single pharmaceutical company-funded randomised double-blind controlled trial in children with Dravet syndrome. Progress towards the use of medicinal cannabinoids incorporates a complex interplay of social influences and political and legal reform. Access to unregistered but available cannabidiol in Australia outside of clinical trials and compassionate access schemes is state dependent and will require Therapeutic Goods Administration approval, although the cost may be prohibitive. Further clinical trials are needed to clearly define efficacy and safety, particularly long term.”

https://www.ncbi.nlm.nih.gov/pubmed/29438649

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Identification of a sustainable two-plant diet that effectively prevents age-related metabolic syndrome and extends lifespan in aged mice.

The Journal of Nutritional Biochemistry

“The current system of food production is linked to both the increasing prevalence of chronic disease and the deterioration of the environment, and thereby calls for novel ways of producing nutritious foods in a sustainable manner.

In the “longevity village” of Bama, China, we have identified two plant foods, hemp seed and bitter vegetable (Sonchus oleraceus), that are commonly consumed by its residents and grow abundantly in unfarmed land without fertilizers or pesticides.

Here, we show that a diet composed of these two foods (the “HB diet”) provides a sufficient variety of nutrients and confers significant health benefits.

Aged mice allowed ad libitum access to the HB diet not only had longer life spans and improved cognitive function but were also protected against age-related metabolic syndrome, fatty liver, gut dysbiosis and chronic inflammation compared to aged mice fed a control Western diet.

Furthermore, longevity-related genes (including 5’adenosine monophosphate-activated protein kinase, sirtuin 1, nuclear respiratory factor 1 and forkhead box O3) were significantly up-regulated, while aging-related genes (including mammalian target of rapamycin and nuclear factor kappa B) were down-regulated.

These results demonstrate that the HB diet is capable of promoting health and longevity, and present a sustainable source of healthy foods that can help control the prevalence of chronic diseases and reduce agricultural impact on the environment.”

https://www.ncbi.nlm.nih.gov/pubmed/29080417

https://www.sciencedirect.com/science/article/pii/S0955286316303461?via%3Dihub

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The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.

Current Neurology and Neuroscience Reports

“Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms.

This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects.

We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs.

Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms.

Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.”

https://www.ncbi.nlm.nih.gov/pubmed/29442178

https://link.springer.com/article/10.1007%2Fs11910-018-0814-x

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The Association of Unfavorable Traffic Events and Cannabis Usage: A Meta-Analysis

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“In the last years were published many epidemiological articles aiming to link driving under the influence of cannabis (DUIC) with the risk of various unfavorable traffic events (UTEs), with sometimes contradictory results.

The primary objective of this study was to analyze whether there is a significant association between DUIC and UTEs.

Our analysis suggests that the overall effect size for DUIC on UTEs is not statistically significant, but there are significant differences obtained through subgroup analysis. This result might be caused by either methodological flaws (which are often encountered in articles on this topic), the indiscriminate employment of the term “cannabis use,” or an actual absence of an adverse effect.

A positive test for cannabis (i.e., blood) does not necessarily imply that drivers were impaired, as THC/metabolites might be detected in blood a long time after impairment, especially in chronic cannabis users, which could also induce an important bias in the analysis of the results.

When a driver is found, in traffic, with a positive reaction suggesting cannabis use, the result should be corroborated by either objective data regarding marijuana usage (like blood analyses, with clear cut-off values), or a clinical assessment of the impairment, before establishing his/her fitness to drive.”

https://www.frontiersin.org/articles/10.3389/fphar.2018.00099/full

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Learning and Memory is Modulated by Cannabidiol When Administered During Trace Fear-Conditioning.

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“Cannabidiol (CBD) is thought to have therapeutic potential for treating psychiatric conditions that affect cognitive aspects of learning and memory, including anxiety and post-traumatic stress disorder (PTSD).

Studies have shown that CBD enhances extinction of fear memory when given after conditioning. This led us to hypothesize that CBD, if administered prior to fear conditioning, might modulate cognitive learning and memory processes in additional ways that would further guide its potential use for treating PTSD.

Therefore, we designed a study to investigate effects of CBD on fear learning and memory when administered to mice prior to administering a trace fear conditioning protocol which imposes cognitive demands on the learning and memory process.

Overall, the memory-modulating effects of a single pre-conditioning dose of CBD, which we show here, demonstrate the need to more fully characterize its basic effects on memory, suggest caution when using it clinically as an anxiolytic, and point to a need for more research into its potential as a therapeutic for treating memory-loss disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/29432803

https://www.sciencedirect.com/science/article/pii/S1074742718300224

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Ultrasound-Assisted Extraction of Cannabinoids from Cannabis Sativa L. Optimized by Response Surface Methodology.

Journal of Food Science

“Ultrasonication was used to extract bioactive compounds from Cannabis sativa L. such as polyphenols, flavonoids, and cannabinoids.

On comparing the ultrasonic process with the control extraction, noticeably higher values were obtained for each of the responses.

Additionally, ultrasound considerably improved the extraction of cannabinoids present in Cannabis.

PRACTICAL APPLICATION:

Low frequency ultrasound was employed to extract bioactive compounds from the inflorescence part of Cannabis. The responses evaluated were-total phenols, flavonoids, ferric reducing assay and yield. The solvent composition and time significantly influenced the extraction process. Appreciably higher extraction of cannabinoids was achieved on sonication against control.”

https://www.ncbi.nlm.nih.gov/pubmed/29437231

http://onlinelibrary.wiley.com/doi/10.1111/1750-3841.14075/abstract

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Cannabis use is associated with lower rates of initiation of injection drug use among street-involved youth: A longitudinal analysis.

Drug and Alcohol Review

“Street-involved youth are known to be at elevated risk of initiating injection drug use. However, the impact of so-called ‘gateway’ drugs, such as cannabis, on injection initiation is unknown.

The objective of this study was to examine the association between cannabis use and initiation of injection drug use among a prospective cohort of street-involved youth in Vancouver, Canada.

In a multivariable analysis, ≥daily cannabis use was associated with slower rates of injection initiation (adjusted relative hazard 0.66, 95% confidence interval 0.45-0.98; P = 0.038). Sub-analyses revealed that cannabis use was negatively associated with initiation of injection stimulants but not initiation of injection opioids.

DISCUSSION AND CONCLUSIONS:

Given the expansion of cannabis legalisation throughout North America, it is encouraging that cannabis use was associated with slower time to initiation of injection drug use in this cohort. This finding challenges the view of cannabis as a gateway substance that precipitates the progression to using harder and more addictive drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/29430806

http://onlinelibrary.wiley.com/doi/10.1111/dar.12667/abstract

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Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: Practical experiences in a tertiary medical center.

“Medically refractory epilepsy continues to be a challenge worldwide, and despite an increasing number of medical therapies, approximately 1 in 3 patients continues to have seizures.

Cannabidiol (CBD), one of many constituents of the Cannabis sativa or marijuana plant, has received renewed interest in the treatment of epilepsy. While highly purified CBD awaits Food and Drug Administration (FDA) approval, artisanal formulations of CBD are readily available and are seeing increased use in our patient population.

Although randomized controlled trials of CBD are ongoing and promising, data regarding artisanal formulations of CBD are minimal and largely anecdotal. Here, we report a retrospective study to define the efficacy of artisanal CBD preparations in children with epilepsy.

Given the known interaction between CBD and clobazam, we also conducted a subgroup comparison to determine if clobazam use was related to any beneficial effects of CBD. Additionally, we compared response rates with CBD and with clobazam alone within an overlapping patient cohort. A pediatric cohort with epilepsy of 108 patients was identified through a medical record search for patients using CBD oil.

The addition of CBD resulted in 39% of patients having a >50% reduction in seizures, with 10% becoming seizure-free. The responder rate for clobazam was similar. No patients achieved CBD monotherapy, although the weaning of other antiepileptic drugs (AEDs) became possible in 22% of patients. A comparable proportion had AED additions during CBD therapy. With concomitant use of clobazam, 44% of patients had a 50% reduction in seizures upon addition of CBD compared with 33% in the population not taking clobazam; this difference was not statistically significant. The most common reported side effect of CBD was sedation in less than 4% of patients, all of whom were also taking clobazam.

Increased alertness and improved verbal interactions were reported in 14% of patients in the CBD group and 8% of patients in the CBD and clobazam group. Benefits were more marked in the CBD alone group, in contrast to the CBD and clobazam group, but this difference was not statistically significant.

In summary, these findings support efficacy of artisanal CBD preparations in seizure reduction with few significant side effects. The response to CBD was independent of concurrent clobazam use, although clobazam may contribute to the sedation seen with concurrent CBD use.”

“In this retrospective study, we report that artisanal CBD is helpful in the treatment of medically refractory seizures.”
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