Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age.

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“Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana.

The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry.

CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson.

CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.”

https://www.ncbi.nlm.nih.gov/pubmed/30298064

https://www.frontiersin.org/articles/10.3389/fimmu.2018.02009/full

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Chemometric Analysis of Cannabinoids: Chemotaxonomy and Domestication Syndrome

Scientific Reports

“Cannabis is an interesting domesticated crop with a long history of cultivation and use. Strains have been selected through informal breeding programs with undisclosed parentage and criteria. The term “strain” refers to minor morphological differences and grower branding rather than distinct cultivated varieties.

The “sativa” and “indica” lineages used to describe cannabis throughout the industry are based on postulation that sativa strains originated from European hemp cultivars, while indica are from potent, resinous Indian cannabis but given the use and trade of the plant in ancient times, the exact origin is unknown and these may not be distinct species. Comparisons of cannabinoid contents of these classifications have shown that the THC content can be identical between these two classification groups.”   https://www.nature.com/articles/s41598-018-31120-2

“THC amounts identical in most cannabis strains, study finds. Newly published research from UBC’s Okanagan campus has determined that many strains of cannabis have virtually identical levels of tetrahydrocannabinol (THC) and cannabidiol (CBD), despite their unique street names. The research shows that most strains, regardless of their origin or name, had the same amount of THC and CBD” https://phys.org/news/2018-10-thc-amounts-identical-cannabis-strains.html
“UBC Okanagan study: THC amounts identical in most cannabis strains. B.C. Kush. Platinum GSC. Blueberry Cookies. Blue Sapphire. Death Bubba. Oregon Golden Coat. Those are just some of the many, many types of marijuana available for purchase. Yet, according to newly published research from UBC Okanagan, many strains of cannabis have virtually identical levels of tetrahydrocannabinol (THC) and cannabidiol (CBD) despite their unique street names.” https://globalnews.ca/news/4533548/ubc-okanagan-study-thc-amounts-identical-in-most-cannabis-strains/
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Single center experience with medical cannabis in Gilles de la Tourette syndrome.

Parkinsonism and Related Disorders Home

“Patients with Gilles de la Tourette syndrome (GTS) experience reduced function and impaired quality of life. The current medical treatments for this syndrome can cause significant side effects and offer partial symptomatic relief.

In a few small trials medical cannabis (MC) has been suggested to offer symptomatic relief with a relatively benign side effect profile.

We conducted a real-life assessment of clinical benefit and adverse effects of chronic MC treatment among patients with GTS.

CONCLUSION:

MC seems to hold promise in the treatment of GTS as it demonstrated high subjective satisfaction by most patients however not without side effects and should be further investigated as a treatment option for this syndrome.”

https://www.ncbi.nlm.nih.gov/pubmed/30292733

https://www.prd-journal.com/article/S1353-8020(18)30429-2/fulltext

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Avidekel Cannabis extracts and cannabidiol are as efficient as Copaxone in suppressing EAE in SJL/J mice.

“Multiple sclerosis (MS) is an autoimmune disease leading to the destruction of myelin with consequent axonal degeneration and severe physical debilitation. The disease can be treated with immunosuppressive drugs that alleviate the symptoms and retard disease aggravation. One such drug in clinical use is glatiramer acetate (Copaxone).

The non-psychotropic immunosuppressive cannabinoid compound cannabidiol (CBD) has recently been shown to have beneficial effects on experimental autoimmune encephalomyelitis (EAE). The aim of our study was to compare the efficacy of CBD and standardized extracts from a CBD-rich, ∆9-THClow Cannabis indica subspecies (Avidekel) with that of Copaxone.

Our data show that CBD and purified Avidekel extracts are as efficient as Copaxone to alleviate the symptoms of proteolipid protein (PLP)-induced EAE in SJL/J mice. No synergistic effect was observed by combining CBD or Avidekel extracts with Copaxone.

Our data support the use of Avidekel extracts in the treatment of MS symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/30291491

https://link.springer.com/article/10.1007%2Fs10787-018-0536-3

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The relationship between cannabis use and diabetes: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III.

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“The relationship between cannabis use and diabetes is puzzling. Although cannabis users versus non-users should theoretically have a higher likelihood of diabetes, epidemiological studies suggest otherwise. However, previous epidemiological studies have not considered the potential confounding effects of mental health disorders. As such, the relationship between cannabis use and diabetes was examined while accounting for a range of potential confounders, including mental health disorders.

RESULTS:

Although there was a considerable attenuation in the magnitude of the odds ratios after adjustment for confounders, there was still a decreased likelihood of diabetes for cannabis users versus non-users. The corresponding odds ratios of diabetes were 0.81 (95% confidence interval 0.70, 0.94) and 0.51 (95% confidence interval 0.41, 0.63) for lifetime and 12-month cannabis use, respectively.

DISCUSSION AND CONCLUSIONS:

A decreased likelihood of diabetes for cannabis users versus non-users was indicated after accounting for a range of potential confounders, including mental health disorders. Before the protective effects of cannabis use for diabetes can be suggested, further epidemiological studies are needed that incorporate prospective designs, as well as feature innovative exposure measurements and statistical analyses.”

https://www.ncbi.nlm.nih.gov/pubmed/30288813

https://onlinelibrary.wiley.com/doi/abs/10.1111/dar.12867

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Cannabinoids in depressive disorders.

 Life Sciences “Cannabis sativa is one of the most popular recreational and medicinal plants. Benefits from use of cannabinoid agents in epilepsy, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and others have been suggested. It seems that the endocannabinoid system is also involved in the pathogenesis and treatment of depression, though its role in this mental disease has not been fully understood yet. Both the pro- and antidepressant activity have been reported after cannabis consumption and a number of pre-clinical studies have demonstrated that both agonist and antagonist of the endocannabinoid receptors act similarly to antidepressants. Responses to the cannabinoid agents are relatively fast, and most probably, the noradrenergic, serotoninergic, glutamatergic neurotransmission, neuroprotective activity, as well as modulation of the hypothalamic-pituitary-adrenal axis are implicated in the observed effects. Based on the published data, the endocannabinoid system evidently gives novel ideas and options in the field of antidepressant treatment, however further studies are needed to determine which group of patients could benefit from this type of therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/30290188

https://www.sciencedirect.com/science/article/pii/S0024320518306040?via%3Dihub

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Endocannabinoid Virodhamine is an Endogenous Inhibitor of Human Cardiovascular CYP2J2 Epoxygenase.

 Biochemistry

“The human body contains endogenous cannabinoids (endocannabinoids) that elicit similar effects as Δ9-tetrahydrocanabinol, the principal bioactive component of cannabis.

The endocannabinoid virodhamine (O-AEA) is the constitutional isomer of the well-characterized cardioprotective and anti-inflammatory endocannabinoid anandamide (AEA).

The chemical structures of O-AEA and AEA contain arachidonic acid (AA) and ethanolamine, however AA in O-AEA is connected to ethanolamine via an ester linkage whereas AA in AEA is connected through an amide linkage. We show that O-AEA is found at 9.6 fold higher levels than AEA in porcine left ventricle and is involved in regulating blood pressure and cardiovascular function.

On a separate note, the cytochrome P450 (CYP) epoxygenase CYP2J2 is the most abundant CYP in the heart where it catalyzes the metabolism of AA and AA-derived eCBs to bioactive epoxides that are involved in diverse cardiovascular functions. Herein, using competitive binding studies, kinetic metabolism measurements, molecular dynamics and wound healing assays we have shown that O-AEA is an endogenous inhibitor of CYP2J2 epoxygenase.

Together, the role of O-AEA as an endogenous eCB inhibitor of CYP2J2 may provide a new mode of regulation to control the activity of cardiovascular CYP2J2 in vivo and suggests a potential cross talk between the cardiovascular endocannabinoids and cytochrome P450 system.”

https://www.ncbi.nlm.nih.gov/pubmed/30285425

https://pubs.acs.org/doi/10.1021/acs.biochem.8b00691

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Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A randomized, double-blind, controlled trial.

“Treatment with a highly purified oral solution of cannabidiol (CBD), derived from the plant Cannabis sativa L., demonstrated some evidence of central nervous system (CNS)-related adverse events in patients enrolled in phase 3 trials for treatment of childhood-onset epilepsy. Cannabidiol was categorized as a Schedule 1 substance by the United States Drug Enforcement Administration; therefore, it was important to test CBD for human abuse potential.

Administration of a therapeutic dose of CBD (750 mg) showed significantly low abuse potential in a highly sensitive population of polydrug users. Although high and supratherapeutic doses of CBD (1500 mg and 4500 mg, respectively) had detectable subjective effects compared with placebo; the effects were significantly lower than those observed with alprazolam and dronabinol.

The majority of adverse events reported during the trial were of mild or moderate severity; no serious adverse events or deaths were reported.”

https://www.ncbi.nlm.nih.gov/pubmed/30286443

https://www.epilepsybehavior.com/article/S1525-5050(18)30483-9/fulltext

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A systematic review on the neuroprotective perspectives of beta-caryophyllene.

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“Beta (β)-caryophyllene (BCAR) is a major sesquiterpene of various plant essential oils reported for several important pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, antimicrobial, and immune-modulatory activity. Recent studies suggest that it also possesses neuroprotective effect.

This study reviews published reports pertaining to the neuropharmacological activities of BCAR. Databases such as PubMed, Scopus, MedLine Plus, and Google Scholar with keywords “beta (β)-caryophyllene” and other neurological keywords were searched. Data were extracted by referring to articles with information about the dose or concentration/route of administration, test system, results and discussion, and proposed mechanism of action.

A total of 545 research articles were recorded, and 41 experimental studies were included in this review, after application of exclusion criterion. Search results suggest that BCAR exhibits a protective role in a number of nervous system-related disorders including pain, anxiety, spasm, convulsion, depression, alcoholism, and Alzheimer’s disease.

Additionally, BCAR has local anesthetic-like activity, which could protect the nervous system from oxidative stress and inflammation and can act as an immunomodulatory agent. Most neurological activities of this natural product have been linked with the cannabinoid receptors (CBRs), especially the CB2R. This review suggests a possible application of BCAR as a neuroprotective agent.”

https://www.ncbi.nlm.nih.gov/pubmed/30281175

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

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New Perspectives on the Use of Cannabis in the Treatment of Psychiatric Disorders.

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“Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and cannabidiol are the most abundant phytocannabinoids found in cannabis extracts, as well as the most studied. The present review aims to provide an overview of the current evidence for their beneficial effects in treating psychiatric disorders, including schizophrenia, anxiety, and depression. Nevertheless, further investigations are required to clarify many pending issues, especially those relative to the assessment of benefits and risks when using cannabis for therapeutic purposes, thereby also helping national and federal jurisdictions to remain updated.”

https://www.ncbi.nlm.nih.gov/pubmed/30279403

https://www.mdpi.com/2305-6320/5/4/107

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