CBD - 30 RESEARCH REPORTS WORLDWIDE
CBD - THE MIRACLE MOLECULE
The following thirty hand picked research reports and clinical trials are profided for practitioners, patients that are taking CBD now, or for anyone that is serviously researching the use of CBD to treat the themselves or a loved one.
Our research papers abstracts include key point summaries on the efficacy of CBD, how it works, clinical trial results, animal trials, and links to the original papers.
Over the past years, several lines of evidence support a therapeutic potential of Marijuana derivatives and in particular phytocannabinoids. d9THC and Cannabidiol-CBD are the most abundant phyto cannabinoids in Marijuana plants and therapeutic application for both substances have been suggested. But, Cannabidiol-CBD is recently emerging as a therapeutic agent in numerous pathological conditions since devoid of the psychoactive toxic side effects resulted instead by d9THC.
In this review, we highlight the pharmacological activities of Cannabidiol-CBD, its cannabinoid receptor-dependent and -independent action, its biological effects targeting on immunomodulation, angiogenic properties, and modulation of neuronal and cardiovascular function. Furthermore, the therapeutic potential of Cannabidiol-CBD is also highlighted, in particular in neurological conditions and cancer.
Four patients had data through wk. 14, one of whom initially withdrew for lack of effectiveness, but because of other benefits re-enrolled with a lesser dose. Two patients at wk. 14 and three patients with bilateral brain involvement had at the last visit a greater than 50 percent spasm and seizure reduction, reported an improved quality of life, and remained on Cannabidiol-CBD 63-80 weeks after starting the drug. Three patients reported mild side effects considered related to cannabidiol.
This inquiry suggests that Cannabidiol-CBD may be well tolerated as an adjunctive medication for spasm and seizure management and provides initial data supporting further inquiry of Cannabidiol-CBD in individuals with Sturge-Weber syndrome.
*The endocannabinoid- body's own system plays a pivotal role in modifying central synaptic transmission.
*CB1 agonism generally exerts anti-convulsant, antiepileptic and antiepileptogenic effects, but with several important exceptions.
*CB1 antagonists may be proconvulsant, but exhibit anti-epileptogenic effects if employed during a precise time window.
*Cannabidiol-CBD consistently exerts CB1/CB2R-independent anti-seizure and anti-epileptogenic properties.
*The phyto-cannabinoids’ therapeutic domain in epilepsy includes neuroprotective effects.
*CBD may prolong d9THC-induced antinociception and hyperlocomotion in rodents.
*CBD-THC interactions on behavior do not appear to be sex-dependent.
*CBD alters d9THC metabolite production to a greater extent in females than males.
We highlight components of the eCB system that offer potential ‘druggable’ targets for new anxiolytic medications.
*Amplifying eCBs by attenuating eCB-degradation, via fatty acid amide hydrolase or monoacylglycerol lipase, reduces anxiety.
*A non-canonical route to regulate eCM degradation and anxiety involves interfering with cyclooxygenase-2 -COX-2.
*Anxiety-stress may be affected by targeting the CB2R subtype and the transient receptor potential vanilloid receptor type 1 -TRPV1.
*Cannabidiol-CBD represents another plausible path to modulating eCBs to alleviate anxiety.
This article summarizes the available scientific data of pharmacology from human and animal studies on the major phyto-cannabinoids, which have been of interest in the management of epilepsy, including d9-tetrahydrocannabinol -d9THC, Cannabidiol-CBD, d9-tetrahydrocannabivarin -9 THCV, cannabidivarin -CBDV, and d9-tetrahydrocannabinolic acid -d9 THCA.
The adult male rodents were exposed to surgical transection of the cord and treated with Cannabidiol-CBD for consecutive 14 days. It was found that Cannabidiol-CBD management elevated the serum levels of osteocalcin, reduced the serum levels of collagen type I cross-linked C-telopeptide, and enhanced bone mineral density of tibiae and femurs.
Treatment of SCI rodents with Cannabidiol-CBD enhanced bone volume, trabecular thickness, and trabecular number, and reduced trabecular separation in proximal tibiae, and increased ultimate compressive load, stiffness, and energy to max force of femoral diaphysis.
Treatment of SCI rodents with Cannabidiol-CBD upregulated mRNA expression of alkaline phosphatase and osteoprotegerin and downregulated mRNA expression of receptor activator of NF-κB ligand and tartrate-resistant acid phosphatase in femurs. Furthermore, therapy of SCI rodents with Cannabidiol-CBD enhanced mRNA expression of wnt3a, Lrp5 and ctnnb1 in femurs. In conclusion, Cannabidiol-CBD dosing attenuated SCI-induced sublesional cancellous bone loss.
*Cannabidiol increased melanin content in human melanocytes.
*Cannabidiol upregulated mRNA levels of MITF, tyrosinase, TRP-1, and TRP-2.
*Cannabidiol led to a activation of p38 MAPK and p42/44 MAPK.
*Cannabidiol effects were dependent on cannabinoid CB1 receptor, not by CB2 receptor.
*Cannabidiol effects were mediated by activation of the p38 MAPK and p42/44 MAPK.
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*An historical perspective of cannabinoid studies in the hippocampus is presented.
*The effects of phyto-cannabinoids on synchronous hippocampal activity is discussed.
*Cannabinoid-altered hippocampal synchrony in memory impairment is examined.
*Cannabinoid-altered hippocampal synchrony in psychiatric disorders is examined.
*The therapeutic potential of phyto-cannabinoids in epilepsy therapy is discussed.
Cannabidiol-CBD is a non-psychotomimetic phytocannabinoid derived from Marijuana sativa. It has possible therapeutic effects over a broad range of neuropsychiatric disorders. Cannabidiol-CBD attenuates brain damage associated with neurodegenerative and/or ischemic conditions.
It also has positive effects on attenuating psychotic-, anxiety- and depressive-like behaviors. Moreover, Cannabidiol-CBD affects synaptic plasticity and facilitates neurogenesis. The mechanisms of these effects are still not entirely obvious, but seem to involve multiple pharmacological targets. In the present review, we have summarized the main biochemical and molecular mechanisms that have been associated with the therapeutic effects of Cannabidiol-CBD, targeting on their relevance to brain function, neuroprotection and neuropsychiatric disorders.
*The Changing Sociopolitical Pendulum of Medicinal Marijuana
*Making the Case for Cannabidiol-CBD As a Treatment for Opioid Addiction
*CBD to Treat Opioid Addiction: Neurobiological Considerations
*The Crosstalk between Cannabidiol-CBD and Opioid Addiction
*Concluding Remarks … So Where Do We Go from Here?
This inquiry reveals a mechanism of action of Cannabidiol-CBD at GABAA receptors, in particular at α2-containing receptors that may be relevant to the anticonvulsant and anxiolytic effects of the substance.
First isolated from Marijuana in 1940 by Roger Adams, the structure of Cannabidiol-CBD was not completely elucidated until 1963. Subsequent studies resulted in the pronouncement that d9THC was the ‘active’ principle of Marijuana and research, then focused primarily on it to the virtual exclusion of Cannabidiol-CBD. This was no doubt due to the belief that activity meant psychoactivity that was shown by d9THC and not by Cannabidiol-CBD.
In retrospect, this must be seen as unfortunate since a number of actions of Cannabidiol-CBD with potential therapeutic benefit were downplayed for many years. In this review, attention will be focused on the effects of Cannabidiol-CBD in the broad area of inflammation where such benefits seem likely to be developed. Topics covered in this summarize are; the medicinal chemistry of Cannabidiol-CBD, CBD receptor binding involved in controlling Inflammation, signaling events generated by CBD, downstream events affected by Cannabidiol-CBD -gene expression and transcription, functional effects reported for Cannabidiol-CBD and combined d9THC plus Cannabidiol-CBD therapy.
Once a widely ignored phytocannabinoid, Cannabidiol-CBD now attracts great therapeutic interest, especially in epilepsy and cancer. As with many rising trends, various myths and misconceptions have accompanied this heightened public interest and intrigue. This forum article examines and attempts to clarify some areas of contention.
*Misconception: Cannabidiol Is Non-psychoactive and Non-psychotropic
*Misconception: Cannabidiol-CBD Is Sedating
*Misconception: Cannabidiol-CBD Is a CB1 Antagonist Like Rimonabant
*Misconception: Cannabidiol-CBD Is Legal in All 50 States
*Misconception: Cannabidiol-CBD Turns into d9THC in the Body
*The activities of various phyto-cannabinoids were tested on orphan receptors GPR3/GPR6.
*Cannabidiol-CBD behaves as a new inverse agonist for GPR3 and GPR6.
*GPR3 and GPR6 are novel molecular targets for Cannabidiol-CBD.
*The potential therapeutic effects of Cannabidiol-CBD may be mediated in part through GPR3/GPR6.
*In the context of recent legalization, many cannabis users tried new products.
*Trial of new cannabis products was associated with greater odds of an unexpected high.
*Use of cannabis edibles was associated with greater odds of an unexpected high.
*Research is needed on consumer perceptions of cannabis product packaging.
*Cannabidiol-CBD significantly attenuates spasm and seizure induced by acute pentylenetetrazol in rodents.
*Pre-therapy with a 5HT1A and 5HT2A receptor antagonist does not interfere with Cannabidiol-CBD anticonvulsant effects.
*This suggests that Cannabidiol-CBD anticonvulsant mechanism of action is not mediated by these specific serotonergic receptors.
Short-term Cannabidiol-CBD 10 mg/kg therapy prevented the cognitive and emotional impairments, attenuated hippocampal neurodegeneration and white matter -WM injury, and reduced glial response that were induced by BCCAO. Furthermore, ischemic rodents treated with Cannabidiol-CBD showed an improvement in the hippocampal brain derived neurotrophic factor -BDNF protein levels. Cannabidiol-CBD also stimulated neurogenesis and promoted dendritic restructuring in the hippocampus of BCCAO animals. Collectively, the present results demonstrate that short-term Cannabidiol-CBD therapy results in global functional recovery in ischemic rodents and impacts multiple and distinct targets involved in the pathophysiology of brain ischemic injury.
*Cannabinoid substances found in cannabis have complex effects on neuropsychiatric disorders.
*Evidence demonstrates differential roles for delta-9-tetrahydrocannabinol -THC and. Cannabidiol-CBD in regulating the mesolimbic dopamine system.
*THC and Cannabidiol-CBD produce opposing molecular and neuronal effects on the mesolimbic dopamine system.
*The differential effects of d9THC and Cannabidiol-CBD may underlie their pro vs. antipsychotic clinical properties.
*Cannabidiol-CBD is presently being explored for numerous disease conditions.
*CBD is a Schedule I drug; however, abuse liability assessments have not been conducted.
*CBD effects were not similar to mono-THC cannabis ; Cannabidiol-CBD was placebo-like on all measures.
*CBD did not produce a signal for abuse liability on any measure.
*These data may help inform regulatory decisions relating to the scheduling status of Cannabidiol-CBD.
But, the non-psychotropic, plant-derived cannabinoid agent Cannabidiol-CBD may have antipsychotic properties, and thus may be a promising new agent in the therapy of schizophrenia. Here we summarize studies that investigated the antipsychotic properties of Cannabidiol-CBD in human patients. Results show the ability of Cannabidiol-CBD to counteract psychotic symptoms and cognitive impairment associated with marijuana use as well as with acute d9THC dosing. Furthermore, Cannabidiol-CBD may lesser the risk for developing psychosis that is related to marijuana use.
These effects are possibly mediated by opposite effects of Cannabidiol-CBD and d9THC on brain activity patterns in key regions implicated in the pathophysiology of schizophrenia, such as the striatum, hippocampus and prefrontal cortex. The first small-scale clinical studies with Cannabidiol-CBD therapy of subjects with psychotic symptoms further confirm the potential of Cannabidiol-CBD as an effective, safe and well-tolerated antipsychotic substance, although large randomised clinical trials will be needed before this novel therapy may be introduced into clinical practice.
In The Lancet Neurology, Orrin Devinsky and colleagues 6 present findings from the first large-scale prospective multicentre inquiry examining the use of Cannabidiol-CBD in subjects with therapy-resistant epilepsy. 162 children and young adults -aged 1–30 years with refractory epilepsy of multiple types were given a 99 percent purified
oil-based form of Cannabidiol-CBD as an add-on therapy to their existing antiepileptic medications. Seizure frequency and adverse events were monitored for a minimum of.....
*Cannabidiol appears often in Norwegian d9THC-positive blood samples.
*Cannabidiol does not appear to protect against d9THC-induced impairment.
*Cannabidiol may be detected in blood for more than 2 h after marijuana intake.
*Hashish has revealed far lesser d9THC/Cannabidiol-CBD ratios than cannabis in Norway.
Selective post-training time window for memory consolidation interference of Cannabidiol-CBD into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits
*Cannabidiol infusion into the prefrontal cortex impairs fear memory consolidation when applied 5 h after conditioning, but not when applied immediately after training.
*Cannabidiol decreases dopamine release in the prefrontal cortex following memory retrieval 5 days after training.
*Post-training infusion of Cannabidiol-CBD reduces c-fos and zif268 gene expression in cortico-limbic circuits following memory retrieval.
In this commentary, we address the contrasting properties of tetrahydrocannabinol -THC and Cannabidiol-CBD and their opposing effects on cognitive function. Furthermore, we address the improvement in marijuana potency throughout the past two decades and how that impacts generalizability of early data to evaluations of contemporary public health. We underscore the urgent need for future research to disaggregate examination of d9THC from Cannabidiol-CBD, along with the importance of measuring marijuana potency to more effectively unravel its influence on cognitive function and other health issues.
*CBD has properties that are common to classic antidepressants in the tail suspension test -TST in Swiss non-stressed rodents.
*CBD presents dose-dependent effects on cell proliferation and neurogenesis in the hippocampus and subventricular zone -SVZ.
*The behavioral effects of repeated Cannabidiol-CBD dosing may be independent of neurogenesis.
In particular, the non psychoactive substance Cannabidiol-CBD has shown anticonvulsant properties, both in preclinical and clinical studies, with a yet not completely clarified mechanism of action. But, it should be made obvious that most phytocannabinoids do not act on the endocannabinoid- body's own system as in the case of Cannabidiol-CBD. In in vivo preclinical studies.
Cannabidiol-CBD has shown significant anticonvulsant effects mainly in acute animal models of spasms and seizures, whereas restricted data exist in chronic models of epilepsy as well as in animal models of epileptogenesis. Likewise, clinical evidence seems to indicate that Cannabidiol-CBD is able to manage epilepsy both in adults and children affected by refractory spasms and seizures, with a favourable side effect profile.
This co-localization provides an improvement in Cannabidiol-CBD and d9THC bioavailability by its consequence at the pre-enterocyte and the enterocyte levels of the absorption process. The extra augmentation in the absorption of Cannabidiol-CBD and d9THC by incorporating piperine into PNL is attributed to the inhibition of Phase I and phase II metabolism by piperine in addition to the Phase I metabolism and P-gp inhibition by PNL. These novel results pave the way to utilize piperine-PNL delivery system for other poorly soluble, highly metabolized substances that presently cannot be administered orally.
*Review of Cannabidiol-CBD in open-label studies and randomized control trials
*Safety and effectiveness data and findings support use in therapy-resistant epilepsy.
*More research needed into medical cannabis and its derivatives
*Cannabidiol-CBD attenuated haloperidol-induced catalepsy.
*CBD reduced c-Fos protein expression in the dorsal striatum induced by haloperidol.
*CBD effects were blocked by 5-HT1A receptor antagonist.
*CBD-enriched medical marijuana is a promising therapy for intractable epilepsy.
*Only minor and infrequent toxic side effects were reported.
*Epileptic encephalopathies respond better to Cannabidiol-CBD-enriched medical marijuana.
*Cannabidiol-CBD and tetrahydrocannabinol -THC act via different mechanisms.
*THC acts via the endocannabinoid- body's own - CB1 receptor.
*CBD appears to act synergistically with d9THC, but the mechanism is not obvious.
*There are anecdotal data in support of marijuana's effectiveness for spasm and spasm and seizure control.
*Major Marijuana use produces long-term cognitive and constitutional effects.
*Cannabidiol exerts fast antidepressant-like actions in bulbectomized rodents.
*Cannabidiol enhances 5-HT and glutamate levels in prefrontal cortex.
*5-HT1A receptor mediates cannabidiol-induced antidepressant-like effects.
*5-HT1A receptor mediates cannabidiol-induced improvement of 5-HT/glutamate levels.
*CBD disrupts the consolidation of specific and generalized fear memories.
*CBD reduces generalized fear and 22-kHz calls, and accelerates extinction.
*Inhibiting the FAAH activity with URB597 induces similar effects.
*The Cannabidiol-CBD consequences rely on the activation of dorsal hippocampus CB1 and CB2 receptors.
*CBD inhibits TNBC proliferation, migration and invasion.
*CBD inhibits EGF/EGFR signaling pathway and its downstream targets.
*CBD inhibits GM-CSF, CCL3 and MIP-2 secretion from cancer cells.
*CBD inhibits breast cancer growth and metastasis in two mouse models.
*CBD inhibit M2 macrophage recruitment to the tumor stroma.
Our data and findings suggest that Cannabidiol-CBD might reduce spasm and spasm and seizure frequency and might have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy. Randomised controlled trials are warranted to characterise the safety profile and true effectiveness of this substance.
*Post-stroke dosing of Cannabidiol-CBD is neuroprotective in neonatal rodents.
*Cannabidiol-CBD neuroprotection is sustained in the long term.
*Cannabidiol-CBD therapy led to functional recovery in both motor and sensorimotor domains.
*Cannabidiol-CBD modulated excitotoxicity, astrocyte dysfunction and microglial activation.
Our survey shows that parents are using cannabidiol-enriched marijuana as a therapy for their children with therapy-resistant epilepsy. Because of the increasing number of states that allow access to medical marijuana, its use will likely be a growing concern for the epilepsy community. Safety and tolerability data for cannabidiol-enriched marijuana use among children are not available. Objective determinations of a standardized preparation of pure Cannabidiol-CBD are needed to determine whether it is safe, well tolerated, and efficacious at controlling seizures in this pediatric population with difficult-to-treat spasms and seizures.
*In the United States, federal and state laws relating the medical use of marijuana and phyto-cannabinoids are confusing
*Many states allow marijuana products high in Cannabidiol-CBD and low in tetrahydrocannabinol to be sold for medical use
*The legal aspects of marijuana' and cannabidiol cultivation, manufacture, distribution, and medical use are reviewed