Tag Archives: CBD

Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay.

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Transplantation Proceedings Home

“Chronic pain is a major therapeutic problem in kidney transplant patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory drugs.

Benefits in chronic pain treatment with cannabidiol (CBD) have been reported.

This study assesses the effect, safety, and possible drug interactions in kidney transplant patients treated with CBD for chronic pain.

RESULTS:

We assessed 7 patients with a mean age of 64.5 years (range, 58-75 years). CBD initial dose was 100 mg/d, CBD dose reduction to 50 mg/d has been done on day 4 to patient 1 for persistent nausea. Tacrolimus dose reduction in patient 3 was undertaken on days 4, 7, and 21 owing to persisting elevated levels (even before CBD) and itching, and on day 21 in patient 5. Tacrolimus levels decreased in patient 2 but were normal in the control 1 week later. Patients on cyclosporine were stable. Adverse effects were nausea, dry mouth, dizziness, drowsiness, and intermittent episodes of heat. CBD dose decrease was required in 2 patients. Two patients had total pain improvement, 4 had a partial response in the first 15 days, and in 1 there was no change.

CONCLUSIONS:

During this follow-up, CBD was well-tolerated, and there were no severe adverse effects. Plasma levels of tacrolimus were variable. Therefore, longer follow-up is required.”

https://www.ncbi.nlm.nih.gov/pubmed/29579828

http://www.transplantation-proceedings.org/article/S0041-1345(17)30962-4/fulltext

Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model.

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“A non-psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy.

In an attempt to understand the mechanisms by which CBD exerts its anti-seizure effects, we investigated the effects of CBD at synaptic connections, and the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two major inhibitory interneurons: fast spiking, parvalbumin -expressing (PV) and adapting, cholecystokinin-expressing (CCK) interneurons.

CONCLUSIONS & IMPLICATIONS:

In conclusion, our data suggest CBD restores excitability and morphological impairment in epileptic models to pre-epilepsy control levels through multiple mechanisms to restore normal network function.”

https://www.ncbi.nlm.nih.gov/pubmed/29574880

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14202

Cannabidiol Reverses Deficits in Hippocampal LTP in a Model of Alzheimer’s Disease.

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Neurochemical Research

“Here we demonstrate for the first time that cannabidiol (CBD) acts to protect synaptic plasticity in an in vitro model of Alzheimer’s disease (AD).

The non-psycho active component of Cannabis sativa, CBD has previously been shown to protect against the neurotoxic effects of beta amyloid peptide (Aβ) in cell culture and cognitive behavioural models of neurodegeneration. Hippocampal long-term potentiation (LTP) is an activity dependent increase in synaptic efficacy often used to study cellular mechanisms related to memory.

Here we show that acute application of soluble oligomeric beta amyloid peptide (Aβ1-42) associated with AD, attenuates LTP in the CA1 region of hippocampal slices from C57Bl/6 mice. Application of CBD alone did not alter LTP, however pre-treatment of slices with CBD rescued the Aβ1-42 mediated deficit in LTP.

We found that the neuroprotective effects of CBD were not reversed by WAY100635, ZM241385 or AM251, demonstrating a lack of involvement of 5HT1A, adenosine (A2A) or Cannabinoid type 1 (CB1) receptors respectively. However in the presence of the PPARγ antagonist GW9662 the neuroprotective effect of CBD was prevented.

Our data suggests that this major component of Cannabis sativa, which lacks psychoactivity may have therapeutic potential for the treatment of AD”

https://www.ncbi.nlm.nih.gov/pubmed/29574668

https://link.springer.com/article/10.1007%2Fs11064-018-2513-z

Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle

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“Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders.

Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control. Here, we evaluated the “anti-relapse” potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity.

Rats with alcohol or cocaine self-administration histories received transdermal CBD at 24 h intervals for 7 days and were tested for context and stress-induced reinstatement, as well as experimental anxiety on the elevated plus maze. Effects on impulsive behavior were established using a delay-discounting task following recovery from a 7-day dependence-inducing alcohol intoxication regimen.

CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. Following treatment termination, reinstatement remained attenuated up to ≈5 months although plasma and brain CBD levels remained detectable only for 3 days. CBD also reduced experimental anxiety and prevented the development of high impulsivity in rats with an alcohol dependence history.

The results provide proof of principle supporting potential of CBD in relapse prevention along two dimensions CBD: beneficial actions across several vulnerability states, and long-lasting effects with only brief treatment. The findings also inform the ongoing medical marijuana debate concerning medical benefits of non-psychoactive cannabinoids and their promise for development and use as therapeutics.”

https://www.nature.com/articles/s41386-018-0050-8

“Non-psychoactive cannabis ingredient could help addicts stay clean. Preclinical study using rats shows that Cannabidiol can reduce the risk of relapse”  https://www.sciencedaily.com/releases/2018/03/180323104821.htm

“Non-psychoactive cannabis ingredient could reduce risk of relapse among recovering addicts. A preclinical study in rats has shown that there might be value in using a non-psychoactive and non-addictive ingredient of the Cannabis sativa plant to reduce the risk of relapse among recovering drug and alcohol addicts.”  https://www.news-medical.net/news/20180323/Non-psychoactive-cannabis-ingredient-could-reduce-risk-of-relapse-among-recovering-addicts.aspx

“Non-psychoactive cannabis ingredient could help addicts stay clean”  https://www.springer.com/gp/about-springer/media/research-news/all-english-research-news/non-psychoactive-cannabis-ingredient-could-help-addicts-stay-clean/15548156

“Non-psychoactive cannabinoid may enable drug addiction recovery”  https://www.drugabuse.gov/news-events/news-releases/2018/03/non-psychoactive-cannabinoid-may-enable-drug-addiction-recovery

Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model.

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SciELO - Scientific Electronic Library Online

“Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients.

Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol(CBD) has been used as a therapeutic agent in many diseases.

Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS.

Maternal use of CBD had a beneficial effect on the intestinal loops of GS with decreased nitrite/nitrate and iNOS expression.”

https://www.ncbi.nlm.nih.gov/pubmed/29561958

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018000500607&lng=en&tlng=en

“Is CBD Oil Safe To Use During Pregnancy? It’s Said To Relieve Pain & Your Body Is Hurting” https://www.romper.com/p/is-cbd-oil-safe-to-use-during-pregnancy-its-said-to-relieve-pain-your-body-is-hurting-8280324

Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome.

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“To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome.

Exposure to CBD and its metabolites increased proportionally with dose. An interaction with N-CLB was observed, likely related to CBD inhibition of cytochrome P450 subtype 2C19. CBD resulted in more AEs than placebo but was generally well-tolerated.

CLASSIFICATION OF EVIDENCE:

This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated.”

https://www.ncbi.nlm.nih.gov/pubmed/29540584

http://n.neurology.org/content/early/2018/03/14/WNL.0000000000005254

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis.

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“Cannabidiol (CBD) exhibits anti-inflammatory properties that could improve disease activity in inflammatory bowel disease.

This proof-of-concept study assessed efficacy, safety and tolerability of CBD-rich botanical extract in ulcerative colitis (UC) patients.

Although the primary endpoint was not reached, several signals suggest CBD-rich botanical extract may be beneficial for symptomatic treatment of UC.”

https://www.ncbi.nlm.nih.gov/pubmed/29538683

“Cannabinoid administration is associated with a number of beneficial effects in the gut including decreasing emesis, gastric acid secretion, inflammation and intestinal motility. Cannabis has been reported to produce symptom improvement in people with IBD and some patients self-medicate with cannabis.”

https://academic.oup.com/ibdjournal/advance-article/doi/10.1093/ibd/izy002/4925788

Clinical response to Nabiximols correlates with the down-regulation of immune pathways in Multiple Sclerosis.

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European Journal of Neurology

“Nabiximols (Sativex® ) is a cannabinoid-based compound used for the treatment of moderate to severe spasticity in multiple sclerosis (MS).

The aim of the study is to investigate the effect of the administration of Nabiximols on blood transcriptome profile of MS patients and to interpret it in the context of pathways and networks.

Our findings support the immunomodulatory activity of cannabinoids in MS patients. Further studies in more specific cell types are needed to refine these results.”

https://www.ncbi.nlm.nih.gov/pubmed/29528549

http://onlinelibrary.wiley.com/doi/10.1111/ene.13623/abstract

“Cannabinoid compounds suppress immune function, and while this could compromise one’s ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases.” https://www.ncbi.nlm.nih.gov/pubmed/29512125
“Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923447/

Cannabidiol for treatment of refractory childhood epilepsies: Experience from a single tertiary epilepsy center in Slovenia.

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“Refractory epilepsies in children present a major burden for patients and their families. Cannabidiol (CBD) has been suggested as a potential treatment for refractory epilepsies. The aim of this study was to evaluate the effectiveness of add-on therapy with CBD for the treatment of refractory childhood epilepsies.

METHOD:

Patients with childhood-onset refractory epilepsy, treated at the tertiary epilepsy center of the University Children’s Hospital Ljubljana, Slovenia, were included in the study. Add-on therapy with CBD was initiated once the child’s epilepsy was categorized as pharmacoresistant to other antiepileptic drugs/therapies. The dosage of CBD was gradually increased to at least 8mg/kg/day. The effect of CBD treatment was evaluated by the reduction in seizure burden and presence of side effects (positive and negative). Serial electroencephalography was performed in some children.

RESULTS:

Sixty-six patients were included in the analysis. Thirty-two (48.5%) patients had a more than 50% improvement regarding seizure burden, 14 of whom (21.2%) became seizure-free. None of the patients reported worsening of seizure frequency, but CBD had no effect in 15 (22.7%) patients. Some patients reported less vigorous seizures, shorter duration of seizures, shorter time to recovery, and other positive side effects of CBD treatment. Adverse effects were reported in 5/66 children.

CONCLUSIONS:

In our cohort of patients, CBD was found to have potential benefits as add-on therapy for refractory childhood epilepsies, mainly by reducing seizure burden.”

https://www.ncbi.nlm.nih.gov/pubmed/29526578

http://www.epilepsybehavior.com/article/S1525-5050(17)30942-3/fulltext

Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence.

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“Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy.

Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL).

Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5-55 years).

Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17).

CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs.

Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.”

https://www.ncbi.nlm.nih.gov/pubmed/29511052

http://jnnp.bmj.com/content/early/2018/02/05/jnnp-2017-317168

“Cannabis Compounds Reduce Epileptic Seizure Frequency In Children And Teenagers” http://www.iflscience.com/health-and-medicine/cannabis-compounds-reduce-epileptic-seizure-frequency-in-children-and-teenagers/

“Cannabis ingredient ‘reduces epilepsy seizures'”  https://www.webmd.boots.com/news/20180307/cannabis-ingredient-for-epilepsy-seizures

“Marijuana Derivative Successfully Treats Teen Epilepsy in New Experiments”  https://www.inverse.com/article/41985-cbd-marijuana-treat-seizures-epilepsy