The cannabinoid beta-caryophyllene (BCP) induces neuritogenesis in PC12 cells by a cannabinoid-receptor-independent mechanism.

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“Beta-caryophyllene (BCP) is a phytocannabinoid whose neuroprotective activity has been mainly associated with selective activation of cannabinoid-type-2 (CB2) receptors, inhibition of microglial activation and decrease of inflammation.

Here, we addressed the potential of BCP to induce neuritogenesis in PC12 cells, a model system for primary neuronal cells that express trkA receptors, respond to NGF and do not express CB2 receptors.

We demonstrated that BCP increases the survival and activates the NGF-specific receptor trkA in NGF-deprived PC12 cells, without increasing the expression of NGF itself. The neuritogenic effect of BCP in PC12 cells was abolished by k252a, an inhibitor of the NGF-specific receptor trkA. Accordingly, BCP did not induce neuritogenesis in SH-SY5Y neuroblastoma cells, a neuronal model that does not express trkA receptors and do not respond to NGF.

Additionally, we demonstrated that BCP increases the expression of axonal-plasticity-associated proteins (GAP-43, synapsin and synaptophysin) in PC12 cells. It is known that these proteins are up-regulated by NGF in neurons and neuron-like cells, such as PC12 cells.

Altogether, these findings suggest that BCP activates trka receptors and induces neuritogenesis by a mechanism independent of NGF or cannabinoid receptors. This is the first study to show such effects of BCP and their beneficial role in neurodegenerative processes should be further investigated.”

https://www.ncbi.nlm.nih.gov/pubmed/27871898

“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

“The oral intake of this dietary cannabinoid with vegetable food could be advantageous in the daily routine clinical practice over synthetic cannabinoid agonists.” http://www.europeanneuropsychopharmacology.com/article/S0924-977X(13)00302-7/fulltext

Cannabinoid Receptor 2 Functional Variant Contributes to the Risk for Pediatric Inflammatory Bowel Disease.

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“We conducted a case-control association analysis to establish the role of a common CB2 functional variant, Q63R, in the susceptibility to inflammatory bowel disease (IBD).

Endocannabinoids may limit intestinal inflammation through cannabinoid receptor 1 and/or 2 (CB1, CB2).

The CB2-Q63R variant contributes to the risk for pediatric IBD, in particular CD. The R63 variant is associated with a more severe phenotype in both UC and CD.

Taken together, our data point toward the involvement of the CB2 receptor in the pathogenesis and clinical features of pediatric IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/27875353

A systematic review of the effect of cannabidiol on cognitive function: Relevance to schizophrenia.

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“Cognitive impairment is a core symptom domain of schizophrenia, neurological disorders and substance abuse. It is characterised by deficits in learning, memory, attention and executive functioning and can severely impact daily living.

Antipsychotic drugs prescribed to treat schizophrenia provide limited cognitive benefits and novel therapeutic targets are required. Cannabidiol (CBD), a component of the cannabis plant, has anti-inflammatory and antipsychotic-like properties; however, its ability to improve cognitive impairment has not been thoroughly explored. The aim of this systematic review was to evaluate preclinical and clinical literature on the effects of CBD in cognitive domains relevant to schizophrenia.

CBD improves cognition in multiple preclinical models of cognitive impairment, including models of neuropsychiatric (schizophrenia), neurodegenerative (Alzheimer’s disease), neuro-inflammatory (meningitis, sepsis and cerebral malaria) and neurological disorders (hepatic encephalopathy and brain ischemia). To-date, there is one clinical investigation into the effects of CBD on cognition in schizophrenia patients, with negative results for the stroop test. CBD attenuates Δ9-THC-induced cognitive deficits.

 

The efficacy of CBD to improve cognition in schizophrenia cannot be elucidated due to lack of clinical evidence; however, given the ability of CBD to restore cognition in multiple studies of impairment, further investigation into its efficacy in schizophrenia is warranted. Potential mechanisms underlying the efficacy of CBD to improve cognition are discussed.”

https://www.ncbi.nlm.nih.gov/pubmed/27884751

Medical Cannabis – another piece in the mosaic of autoimmunity?

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“Legalization of cannabis’ medicinal use is rapidly increasing worldwide, raising the need to evaluate medical implications of cannabis. Currently evidence supports cannabis and its active ingredients as an immune-modulating agents, affecting T-cells, B-cells, Monocytes and Microglia-cells, causing an overall reduction in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokines. Due to the supporting evidence of cannabinoids as an immune-modulating agent, research focusing on cannabinoids and autoimmunity has emerged. Several clinical trials in multiple sclerosis, inflammatory bowel disease and fibromyalgia suggest cannabis’ effectiveness as an immune-modulator. However, contradicting results and lack of large scale clinical trials obscure these results. Though lacking clinical research, in-vitro and in-vivo experiments in rheumatoid arthritis, diabetes type 1 and systemic sclerosis, demonstrate a correlation between disease activity and cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/27859024

A Science Based Evaluation of Cannabis and Cancer

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“The irritant properties of all smoke will naturally tend to promote a pro-inflammatory immune response with the corresponding production of potentially carcinogenic free radicals. However, cannabis promotes immune deviation to an anti-inflammatory Th2 response via immune-system specific CB2 receptors. Thus, the natural pharmacological properties of marijuana’s cannabinoids, that are not present in tobacco smoke, would minimize potential irritant initiated carcinogenesis. In contrast, the pharmacological activities of tobacco smoke would tend to amplify its carcinogenic potential by inhibiting the death of genetically damaged cells. Together these observations support the epidemiological study of the Kaiser Foundation that did not find cannabis smoking to be associated with cancer incidence. Additionally, the demonstrated cancer killing activities of cannabinoids has been ignored. Cannabinoids have been shown to kill some leukemia and lymphoma, breast and prostate, pheochromocytoma, glioma and skin cancer cells in cell culture and in animals.” http://www.bmj.com/rapid-response/2011/10/29/science-based-evaluation-cannabis-and-cancer

Prevalence and Patterns of Marijuana Use in Young Adults with Inflammatory Bowel Disease.

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“Recent studies in adults report symptom relief with marijuana use in patients with inflammatory bowel disease (IBD).

We assessed the prevalence, pattern, effects and adverse effects of marijuana use in young adults with IBD.

We conducted a prospective questionnaire survey study at a pediatric IBD clinic. All patients (18 to 21 years of age) answered anonymous questionnaires about demographics, IBD, medications and marijuana use.

Overall, 98% of patients supported legalization of marijuana and 85% were interested in using medical marijuana if it became legally available.

We found a high rate of marijuana use in our cohort of young adults with IBD. Majority of users report symptom improvement but do not inform physicians. Future well controlled studies are necessary to assess role of marijuana in IBD therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/27846066

Survey of herbal cannabis (marijuana) use in rheumatology clinic attenders with a rheumatologist confirmed diagnosis.

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“Cannabinoids may hold potential for the management of rheumatic pain.

Arthritis, often self-reported, is commonly cited as the reason for the use of medicinal herbal cannabis (marijuana). We have examined the prevalence of marijuana use among 1000 consecutive rheumatology patients with a rheumatologist-confirmed diagnosis and compared in an exploratory manner the clinical characteristics of medicinal users and nonusers.

Current marijuana use, medicinal or recreational, was reported by 38 patients (3.8%; 95% CI: 2.8-5.2). Ever use of marijuana for medical purposes was reported by 4.3% (95% CI: 3.2-5.7), with 28 (2.8%; 95% CI: 1.9-4.0) reporting current medicinal use. Current medicinal users had a spectrum of rheumatic conditions, with over half diagnosed with osteoarthritis. Medicinal users were younger, more likely unemployed or disabled, and reported poorer global health. Pain report and opioid use was greater for users, but they had similar physician global assessment of disease status compared with nonusers.

Medicinal users were more likely previous recreational users, with approximately 40% reporting concurrent recreational use. Therefore, less than 3% of rheumatology patients reported current use of medicinal marijuana. This low rate of use in patients with a rheumatologist-confirmed diagnosis is in stark contrast to the high rates of severe arthritis frequently reported by medicinal marijuana users, especially in Canada. Familiarity with marijuana as a recreational product may explain use for some as disease status was similar for both groups.”

https://www.ncbi.nlm.nih.gov/pubmed/27842047

The combination of β-caryophyllene, baicalin and catechin synergistically suppresses the proliferation and promotes the death of RAW267.4 macrophages in vitro.

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“β-caryophyllene, which is a constituent of many essential oils, has been known to be a selective agonist of the cannabinoid receptor type-2 and to exert cannabimimetic anti-inflammatory effects in animals.

On the whole, this study demonstrates that the combination of β-caryophyllene, baicalin and (+)-catechin exerts synergistic suppressive effects on macrophages in vitro.

This composition may be a useful as an anti-inflammatory treatment strategy.”

https://www.ncbi.nlm.nih.gov/pubmed/27840942

Antagonism of cannabinoid receptor 1 attenuates the anti-inflammatory effects of electroacupuncture in a rodent model of migraine.

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“The anti-nociceptive effects of electroacupuncture (EA) in migraine have been documented in multiple randomised controlled trials.

Neurogenic inflammation plays a key role in migraine attacks, and the anti-inflammatory effects of acupuncture have been associated with the type 1 cannabinoid (CB1) receptor.

CB1 receptors appear to mediate anti-inflammatory effects of EA in a rat model of migraine.”

https://www.ncbi.nlm.nih.gov/pubmed/27834685

Cannabinoids in the Management of Musculoskeletal or Rheumatic Diseases.

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“The endocannabinoid system impacts pain and inflammation with potential for therapeutic effect on patients with rheumatic diseases. The current treatment options include the herbal product derived from the plant Cannabis sativa, as well as pharmaceutical preparations. The legalization of medicinal cannabis (marijuana) in many jurisdictions and widespread public advocacy has propelled an interest in use either by prescription or self-medication. In this review, we examine current evidence for efficacy and adverse effects of any cannabinoid product in rheumatic conditions. The evidence to date is scant and precludes making recommendations for the use of cannabinoid preparations in rheumatology patients. In particular, the risks of herbal cannabis in patients are not well defined. Anecdote and advocacy cannot supersede sound evidence.”

https://www.ncbi.nlm.nih.gov/pubmed/27832442