Category Archives: Uncategorized

Medical Cannabis Legalization and Opioid Prescriptions: Evidence on US Medicaid Enrollees during 1993-2014.

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“While the US has been experiencing an opioid epidemic, 29 states and Washington DC have legalized cannabis for medical use. This study examined whether statewide medical cannabis legalization was associated with reduction in opioids received by Medicaid enrollees.

FINDINGS:

For Schedule III opioid prescriptions, medical cannabis legalization was associated with a 29.6% (p=0.03) reduction in number of prescriptions, 29.9% (p=0.02) reduction in dosage, and 28.8% (p=0.04) reduction in related Medicaid spending. No evidence was found to support the associations between medical cannabis legalization and Schedule II opioid prescriptions. Permitting medical cannabis dispensaries was not associated with Schedule II or Schedule III opioid prescriptions after controlling for medical cannabis legalization. It was estimated that, if all the states had legalized medical cannabis by 2014, Medicaid annual spending on opioid prescriptions would be reduced by 17.8 million dollars.

CONCLUSION:

Statewide medical cannabis legalization appears to have been associated with reductions in both prescriptions and dosages of Schedule III (but not Schedule II) opioids received by Medicaid enrollees in the US.”

https://www.ncbi.nlm.nih.gov/pubmed/29989239

https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14382

In Vitro Model of Neuroinflammation: Efficacy of Cannabigerol, a Non-Psychoactive Cannabinoid.

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“Inflammation and oxidative stress play main roles in neurodegeneration. Interestingly, different natural compounds may be able to exert neuroprotective actions against inflammation and oxidative stress, protecting from neuronal cell loss.

Among these natural sources, Cannabis sativa represents a reservoir of compounds exerting beneficial properties, including cannabigerol (CBG), whose antioxidant properties have already been demonstrated in macrophages.

Here, we aimed to evaluate the ability of CBG to protect NSC-34 motor neurons against the toxicity induced from the medium of LPS-stimulated RAW 264.7 macrophages.

All together, these results indicated the neuroprotective effects of CBG, that may be a potential treatment against neuroinflammation and oxidative stress.”

https://www.ncbi.nlm.nih.gov/pubmed/29986533

http://www.mdpi.com/1422-0067/19/7/1992

Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol-dimethylheptyl at the type 1 and type 2 cannabinoid receptors.

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“We sought to understand why (-)-cannabidiol (CBD) and (-)-cannabidiol-dimethylheptyl (CBD-DMH) exhibit distinct pharmacology, despite near identical structures.

KEY RESULTS:

At CB1R, CBD was a negative allosteric modulator (NAM) and CBD-DMH was a mixed agonist/positive allosteric modulator. CBD and Org27569 shared multiple interacting residues in the antagonist-bound model of CB1R (5TGZ), but shared a binding site with CP55,940 in the agonist-bound model of CB1R (5XRA). The binding site for CBD-DMH in the CB1R models overlapped with CP55,940 and Org27569. At CB2R, CBD was a partial agonist, and CBD-DMH was a positive allosteric modulator of cAMP modulation, but a NAM of βarrestin1 recruitment. CBD, CP55,940, and SR144528 shared a binding site in the CB2R models that was separate from CBD-DMH.

CONCLUSION AND IMPLICATIONS:

The pharmacological activity of CBD and CBD-DMH in HEK293A cells and their modelled binding sites at CB1R and CB2R may explain their in vivo effects and illuminates the difficulties associated with the development of allosteric modulators for CB1R and CB2R.”

https://www.ncbi.nlm.nih.gov/pubmed/29981240

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14440

Evidence for the use of “medical marijuana” in psychiatric and neurologic disorders.

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College of Psychiatric and Neurologic Pharmacists

“Cannabis is listed as a Schedule I substance under the Controlled Substances Act of 1970, meaning the US federal government defines it as an illegal drug that has high potential for abuse and no established medical use; however, half of the states in the nation have enacted “medical marijuana” (MM) laws. Clinicians must be aware of the evidence for and against the use of MM in their patients who may consider using this substance.

RESULTS:

Publications were identified that included patients with dementia, multiple sclerosis, Parkinson disease, Huntington disease, schizophrenia, social anxiety disorder, depression, tobacco use disorder, and neuropathic pain.

DISCUSSION:

There is great variety concerning which medical conditions are approved for treatment with MM for either palliative or therapeutic benefit, depending on the state law. It is important to keep an evidence-based approach in mind, even with substances considered to be illegal under US federal law. Clinicians must weigh risks and benefits of the use of MM in their patients and should ensure that patients have tried other treatment modalities with higher levels of evidence for use when available and appropriate.”

https://www.ncbi.nlm.nih.gov/pubmed/29955495

““Medical marijuana” encompasses everything from whole-plant cannabis to synthetic cannabinoids available for commercial use approved by regulatory agencies. In determining whether MM is of clinical utility to our patients, it is important to keep in mind chemical constituents, dose, delivery, and indication. Selection of the patient appropriate for MM must be carefully considered because clinical guidelines and treatment options with stronger levels of evidence should be exhausted first in most cases. There seems to be strongest evidence for the use of MM in patients with MS and in patients with neuropathic pain; moderate evidence exists to support further research in social anxiety disorder, schizophrenia, PD, and tobacco use disorder; evidence is limited for use in patients with dementia, Huntington disease, depression, and anorexia.”

http://mhc.cpnp.org/doi/10.9740/mhc.2017.01.029?code=cpnp-site

Brain endocannabinoid signaling exhibits remarkable complexity.

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“The endocannabinoid (eCB) signaling system is one of the most extensive of the mammalian brain. Despite the involvement of only few specific ligands and receptors, the system encompasses a vast diversity of triggered mechanisms and driven effects. It mediates a wide range of phenomena, including the regulation of transmitter release, neural excitability, synaptic plasticity, impulse spread, long-term neuronal potentiation, neurogenesis, cell death, lineage segregation, cell migration, inflammation, oxidative stress, nociception and the sleep cycle. It is also known to be involved in the processes of learning and memory formation. This extensive scope of action is attained by combining numerous variables. In a properly functioning brain, the correlations of these variables are kept in a strictly controlled balance; however, this balance is disrupted in many pathological conditions. However, while this balance is known to be disrupted by drugs in the case of addicts, the stimuli and mechanisms influencing the neurodegenerating brain remain elusive. This review examines the multiple factors and phenomena affecting the eCB signaling system in the brain. It evaluates techniques of controlling the eCB system to identify the obstacles in their applications and highlights the crucial interdependent variables that may influence biomedical research outcomes.”

https://www.ncbi.nlm.nih.gov/pubmed/29953913

Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1–CB2 Heteroreceptor Complexes

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“Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L. that is attracting pharmacological interest because it is non-psychotropic and is abundant in some industrial hemp varieties.

The aim of this work was to investigate in parallel the binding properties of CBG to cannabinoid CB1 (CB1R) and CB2 (CB2R) receptors and the effects of the compound on agonist activation of those receptors and of CB1–CB2 heteroreceptor complexes.

The results indicate that CBG is indeed effective as regulator of endocannabinoid signaling.

In conclusion, the results presented in this study reveal that the non-psychotropic phytocannabinoid, CBG, may exert beneficial actions with therapeutic potential via cannabinoid receptors.”

https://www.frontiersin.org/articles/10.3389/fphar.2018.00632/full

“International Multi-Centre Collaboration Reveals that Cannabigerol Acts Directly on Cannabinoid Receptors CB1 and CB2” https://www.prnewswire.com/news-releases/international-multi-centre-collaboration-reveals-that-cannabigerol-acts-directly-on-cannabinoid-receptors-cb1-and-cb2-300671024.html

“Illogical” cannabis regulation blocks research into therapeutic uses, say doctors

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“Doctors should be able to prescribe cannabis legally and research its therapeutic use more easily, 20 prominent UK clinicians and academics have said.

In a letter to The Times on 20 June, they “strongly urge the government” to recategorise cannabis from schedule 1 to schedule 2 under the UK Misuse of Drugs Regulations 2001.

Schedule 1 is for illicit substances deemed to have no clinical application and which doctors cannot prescribe; schedule 2 drugs, including, for example, diamorphine (heroin), are subject to requirements relating to prescriptions.

Last week, Savid Javid, the home secretary, said that a panel would be set up to review the evidence for medical cannabis that could see the drug rescheduled.”

https://www.bmj.com/content/361/bmj.k2780.full

Driving Under the Influence of Cannabis: A Framework for Future Policy.

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“Marijuana is a commonly found illicit substance in motor vehicle operators driving under the influence of drugs. Current evidence shows that blood levels of tetrahydrocannabinol do not correlate well with the level of impairment. In addition, although acute infrequent use of cannabis typically leads to cognitive and psychomotor impairment, this is not consistently the case for chronic heavy use.”

https://www.ncbi.nlm.nih.gov/pubmed/29933274

https://insights.ovid.com/crossref?an=00000539-900000000-96658

Medicinal Cannabinoids in Palliative Care.

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“The treatment of symptoms in people with palliative diagnoses begins with meticulous clinical assessment with treatment choice (s) selected based on an understanding of the symptom aetiology and the evidence which underpins its treatment.

Increasingly the merits of palliative care have been established earlier in the disease trajectory where treatment outcomes may include increased survival and maintenance of function.

There is strong public support for the availability of medicinal cannabis, particularly for people with palliative diagnoses.

There are several areas where there is potential for symptom benefits through modulation of the endocannabinoid system, though clinical data to date has been inconclusive in key symptoms such as pain and nausea, and data from other settings such as chemotherapy-induced nausea and vomiting not readily extrapolated.

Ideally exploration of medicinal cannabinoids should occur within a clinical trial to accelerate the evidence base to inform practice. In people with refractory symptoms the consideration of unregistered products or off label prescribing should be guided by the potential influences of pharmacokinetic, pharmacodynamic and drug-drug interactions, supported by an informed discussion with the patient, and regular review of net clinical benefit.”

https://www.ncbi.nlm.nih.gov/pubmed/29923616

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.13671

Cannabidiol did not induce teratogenicity or neurotoxicity in exposed zebrafish embryos.

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“Cannabidiol (CBD) is a non-psychotomimetic compound of the Cannabis sativa that has been used for the treatment of severe epilepsy as well as other diseases of nervous system. However, toxicity studies of CBD have great relevance to guarantee the patients safety.

In this context, morphological analyses of zebrafish can contribute to evaluate the teratogenic potential, as well as evaluation of acetylcholinesterase activity and motor activity of zebrafish are valuable tools to verify the neurotoxicity potential. In the present work, we use this methodology to test the toxicity of CBD to zebrafish embryos.

No malformation was observed in morphological analysis of embryos exposed to all tested concentrations of CBD.

Embryos exposed to CBD did not show differences in acetylcholinesterase activity, but embryos exposed to CBD 20-300 μg/L were 1.4 up to 1.7-fold more active when compared to the control. Despite that, at 48 hpf, motor activity returned to control values.

Our results suggest that the effects observed after CBD exposure are intimately related to CB1 receptor that is present in zebrafish since early stages of development. The present work showed early light effects induced by CBD exposure in concentrations that did not alter biochemical activity.”

 https://www.ncbi.nlm.nih.gov/pubmed/29902416
https://www.sciencedirect.com/science/article/pii/S0009279718302163