The influence of THC:CBD oromucosal spray on driving ability in patients with multiple sclerosis-related spasticity.

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“Driving ability is a key function for the majority of patients with multiple sclerosis (MS) to help maintain daily interactions. Both physical and cognitive disability, as well as treatments, may affect the ability to drive. Spasticity is a common symptom associated with MS, and it may affect driving performance either directly or via the medications used to treat it.

In this article, we review the evidence relating the antispasticity medicine, Δ9-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®), and its potential impact on driving performance.

The results from THC:CBD oromucosal spray driving studies and real-world registries did not show any evidence of an increase in motor vehicle accidents associated with THC:CBD oromucosal spray. The majority of patients reported an improvement in driving ability after starting THC:CBD oromucosal spray, and it was speculated that this may be related to reduced spasticity and/or better cognitive function.

THC:CBD oromucosal spray was shown not to impair driving performance.”

https://www.ncbi.nlm.nih.gov/pubmed/29761015

https://onlinelibrary.wiley.com/doi/abs/10.1002/brb3.962

The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function.

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“Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine.

Cannabidiol is a nonpsychotropic plant constituent of Cannabis sativa.

As we hypothesized that non-CB receptor mechanisms of cannabidiol might contribute to its anti-inflammatory and neuroprotective effects, we investigated the interaction of cannabidiol with strychnine-sensitive alpha(1 )and alpha(1)beta glycine receptors by using the whole-cell patch clamp technique.

Cannabidiol showed a positive allosteric modulating effect in a low micromolar concentration range (EC(50) values: alpha(1) = 12.3 +/- 3.8 micromol/l and alpha(1)beta = 18.1 +/- 6.2 micromol/l). Direct activation of glycine receptors was observed at higher concentrations above 100 micromol/l (EC(50) values: alpha(1) = 132.4 +/- 12.3 micromol/l and alpha(1)beta = 144.3 +/- 22.7 micromol/l).

These in vitro results suggest that strychnine-sensitive glycine receptors may be a target for cannabidiol mediating some of its anti-inflammatory and neuroprotective properties.”

https://www.ncbi.nlm.nih.gov/pubmed/19204413

https://www.karger.com/Article/Abstract/201556

A Critical Systematic Review of Evidence for Cannabinoids in the Treatment of Schizophrenia

Psychiatric Annals

“Cannabinoids have an emerging evidence base as an effective treatment option in a number of medical conditions, including anorexia and intractable vomiting.

It is well known that patients with schizophrenia are more likely to use cannabis; it has also been argued that this could be a way of self-treating adverse side effects (secondary to antipsychotics) in a group of people with schizophrenia. Therefore, studies have attempted to examine the use of cannabinoids in schizophrenia.

Given the recent interest in the use of cannabinoids in general and the ensuing ethical debates, we systematically review the available literature on the use of four cannabinoids, namely delta-9-tetrahydrocannabinol, dronabinol, rimonabant, and cannabidiol, in the management of schizophrenia. We also offer suggestions for future research in this area.”

https://www.healio.com/psychiatry/journals/psycann/2018-5-48-5/%7B04639e36-7fd1-4e31-aff2-7cea85ea3bc3%7D/a-critical-systematic-review-of-evidence-for-cannabinoids-in-the-treatment-of-schizophrenia

Pharmacotherapeutic considerations for use of cannabinoids to relieve pain in patients with malignant diseases.

 

“The aim of this review was to assess the efficacy of cannabis preparations for relieving pain in patients with malignant diseases, through a systematic review of randomized controlled trials (RCTs), which were predominantly double-blind trials that compared cannabis preparation to a placebo.

RESULTS:

Fifteen of the 18 trials demonstrated a significant analgesic effect of cannabinoids as compared to placebo. The most commonly reported adverse effects were generally well tolerated, mild to moderate. The main side effects were drowsiness, nausea, vomiting and dry mouth. There is evidence that cannabinoids are safe and modestly effective in neuropathic pain and also for relieving pain in patients with malignant diseases. The proportion of “responders” (patients who at the end of 2 weeks of treatment reported ≥30% reduction in pain intensity on a scale of 0-10, which is considered to be clinically important) was 43% in comparison with placebo (21%).

CONCLUSION:

The target dose for relieving pain in patients with malignant diseases is most likely about 10 actuations per day, which is about 27 mg tetrahydrocannabinol (THC) and 25 mg cannabidiol (CBD), and the highest approved recommended dose is 12 actuations per day (32 mg THC/30 mg CBD). Further large studies of cannabinoids in homogeneous populations are required.”

https://www.ncbi.nlm.nih.gov/pubmed/29719417

https://www.dovepress.com/pharmacotherapeutic-considerations-for-use-of-cannabinoids-to-relieve–peer-reviewed-article-JPR

Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal.

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“Cannabidiol (CBD), a non-intoxicating cannabinoid, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side-effects and research showing it may modify drug cue salience.

We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette-related stimuli and increased craving and withdrawal; (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette-related stimuli, craving and withdrawal and not produce any side-effects.

FINDINGS:

When participants received placebo, tobacco abstinence increased AB (p=.001, d =.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (p=.007, d= .704) and no longer differed from satiety (p=.82). Compared with placebo, CBD also reduced explicit pleasantness of cigarette images (p=.011; d=.514). Craving (Bayes Factor: 7.07) and withdrawal (Bayes Factor: 6.48) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence.

CONCLUSIONS:

A single 800mg oral dose of cannabidiol (CBD) reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. CBD did not influence tobacco craving or withdrawal or any subjectively rated side-effects.”

https://www.ncbi.nlm.nih.gov/pubmed/29714034

https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14243

“Cannabidiol reduces attentional bias to cigarette cues in nicotine addicts, study finds” http://www.psypost.org/2018/06/cannabidiol-reduces-attentional-bias-cigarette-cues-nicotine-addicts-study-finds-51351

Cannabis, from Plant to Pill.

British Journal of Clinical Pharmacology banner

“The therapeutic application of Cannabis is attracting substantial public and clinical interest. The Cannabis plant has been described as a veritable ‘treasure trove’, producing more than a hundred different cannabinoids, although the focus to date has been on the psychoactive molecule delta-9-tetraydrocannabinol (THC) and cannabidiol (CBD).

Other numerous secondary metabolites of Cannabis the terpenes, some of which share the common intermediary geranyl diphosphate (GPP) with the cannabinoids, are hypothesised to contribute synergistically to their therapeutic benefits, an attribute that has been described as the ‘entourage effect’.

The effective delivery of such a complex multicomponent pharmaceutical relies upon the stable genetic background and standardised growth of the plant material, particularly if the raw botanical product in the form of the dried pistillate inflorescence (flos) is the source.

Following supercritical CO2 extraction of the inflorescence (and possibly bracts), the secondary metabolites can be blended to provide a specific ratio of major cannabinoids (THC:CBD) or individual cannabinoids can be isolated, purified and supplied as the pharmaceutical. Intensive breeding strategies will provide novel cultivars of Cannabis possessing elevated levels of specific cannabinoids or other secondary metabolites.”

https://www.ncbi.nlm.nih.gov/pubmed/29701252

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.13618

Palatability and oral cavity tolerability of THC:CBD oromucosal spray and possible improvement measures in multiple sclerosis patients with resistant spasticity: a pilot study.

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“Complaints about Δ9-tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®; GW Pharma Ltd, Sailsbury, UK) in the management of multiple sclerosis spasticity include unpleasant taste and oral mucosal anomalies.

This pilot study assessed the use of sugar-free chewing gum and/or a refrigerated bottle of THC:CBD oromucosal spray to mitigate these effects.

RESULTS:

Taste perception in patients receiving chewing gum ± cold bottle intervention (Groups A and C combined) was significantly (p = 0.0001) improved from baseline to week 4 while maintaining spasticity control.

CONCLUSION:

Patient comfort, satisfaction and treatment adherence may benefit from these interventions.”

https://www.ncbi.nlm.nih.gov/pubmed/29683408

https://www.futuremedicine.com/doi/10.2217/nmt-2017-0056

Paraneoplastic cerebellar degeneration: Yo antibody alters mitochondrial calcium buffering capacity.

Neuropathology and Applied Neurobiology banner

“Neurodegeneration is associated with dysfunction of calcium buffering capacity and thereby sustained cellular and mitochondrial calcium overload. Paraneoplastic cerebellar degeneration (PCD), characterized by progressive Purkinje neuron degeneration following paraneoplastic Yo antibody internalisation and binding to cerebellar degeneration-related protein CDR2 and CDR2L, has been linked to intracellular calcium homeostasis imbalance due to calbindin D28k malfunction. Therefore, we hypothesized that Yo antibody internalisation affects not only calbindin calcium binding capacity but also calcium-sensitive mitochondrial-associated signalling, causing mitochondrial calcium overload and thereby Purkinje neuron death.

CONCLUSION:

These findings suggest that minimising intracellular calcium overload toxicity either directly with cyclosporin-A or indirectly with cannabidiol or the ROS scavenger butylated hydroxytoluene promotes mitochondrial calcium homeostasis and may therefore be used as future neuroprotective therapy for PCD patients.”

https://www.ncbi.nlm.nih.gov/pubmed/29679372

https://onlinelibrary.wiley.com/doi/abs/10.1111/nan.12492

Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users.

Cannabis and Cannabinoid Research cover image

“Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. While adverse impacts of cannabis use are generally attributed to Δ9-tetrahydrocannabinol, emerging naturalistic evidence suggests cannabidiol (CBD) is neuroprotective and may ameliorate brain harms associated with cannabis use, including protection from hippocampal volume loss. This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use.

Results: No change was observed in left or right hippocampus as a whole. However, left subicular complex (parasubiculum, presubiculum, and subiculum) volume significantly increased from baseline to post-treatment (p=0.017 uncorrected) by 1.58% (Cohen’s d=0.63; 2.83% in parasubiculum). Heavy cannabis users demonstrated marked growth in the left subicular complex, predominantly within the presubiculum, and right cornu ammonis (CA)1 compared to lighter users. Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users.

Conclusions: Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis. While replication is required in a larger, placebo-controlled trial, these findings support a protective role of CBD against brain structural harms conferred by chronic cannabis use. Furthermore, these outcomes suggest that CBD may be a useful adjunct in treatments for cannabis dependence and may be therapeutic for a range of clinical disorders characterized by hippocampal pathology (e.g., schizophrenia, Alzheimer’s disease, and major depressive disorder).”

https://www.ncbi.nlm.nih.gov/pubmed/29682609

“In conclusion, our findings are the first to demonstrate an ameliorating effect of CBD treatment upon brain structural harms characteristic of regular cannabis use. Furthermore, these results speak to the potential for CBD treatment to restore hippocampal pathology in a range of clinical populations (e.g., schizophrenia, Alzheimer’s disease, and major depressive disorder).”

https://www.liebertpub.com/doi/10.1089/can.2017.0047

Hemp shows potential for treating ovarian cancer

“Researchers demonstrate hemp’s ability to slow cancer growth and uncover mechanism for its cancer-fighting ability.

Results from some of the first studies to examine hemp’s ability to fight cancer show that it might one day be useful as plant-based treatment for ovarian cancer. Hemp is part of the same cannabis family as marijuana but doesn’t have any psychoactive properties or cause addiction.

“Hemp, like marijuana, contains therapeutically valuable components such as cannabidiol, cannabinol, and tetrahydrocannabinol,”

“Our findings from this research as well as prior research show that KY hemp slows ovarian cancer comparable to or even better than the current ovarian cancer drug Cisplatin,” said Turner. “Since Cisplatin exhibits high toxicity, we anticipate that hemp would carry less side effects.”

https://www.sciencedaily.com/releases/2018/04/180423155046.htm

“Hemp Shows Potential for Treating Ovarian Cancer”  https://www.eurekalert.org/multimedia/pub/167927.php

“Hemp Can Fight Cancer Too, Reveal Scientists in New Cannabis Study”  https://www.inverse.com/article/44039-cancer-hemp-plant-based-treatment

“Studies show hemp’s potential for treating ovarian cancer”         https://www.news-medical.net/news/20180424/Studies-show-hemps-potential-for-treating-ovarian-cancer.aspx

“Hemp shows potential for treating ovarian cancer”  https://www.europeanpharmaceuticalreview.com/news/75103/hemp-treating-ovarian-cancer/

“Hemp portrays possibility for curing ovarian cancer”  https://ebuzzcommunity.com/2018/04/hemp-portrays-possibility-for-curing-ovarian-cancer/

“Hemp Extract Inhibits Growth Of Ovarian Cancer, Research Finds”  https://thefreshtoast.com/rx/hemp-extract-inhibits-growth-of-ovarian-cancer-research-finds/