THC Total Health Care

A comprehensive research archive dedicated to the science of cannabis

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

Posted on July 11, 2018 by David Worrell

“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.

Posted on July 11, 2018 by David Worrell

“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

]]>

Role of endocannabinoids in the hippocampus and amygdala in emotional memory and plasticity.

Posted on July 10, 2018 by David Worrell

Image result for neuropsychopharmacology

“Posttraumatic stress disorder (PTSD) is characterized by the reexperiencing of a traumatic event and is associated with slower extinction of fear responses. Impaired extinction of fearful associations to trauma-related cues may interfere with treatment response, and extinction deficits may be premorbid risk factors for the development of PTSD. We examined the effects of exposure to a severe footshock followed by situational reminders (SRs) on extinction, plasticity, and endocannabinoid (eCB) content and activity in the hippocampal CA1 area and basolateral amygdala (BLA). The findings suggest that targeting the eCB system before extinction may be beneficial in fear memory attenuation and these effects may involve metaplasticity in the CA1 and BLA.” https://www.ncbi.nlm.nih.gov/pubmed/29977073 https://www.nature.com/articles/s41386-018-0135-4

]]>

The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: a phase 1 dosage escalation study.

Posted on July 10, 2018 by David Worrell

“Initial studies suggest pharmaceutical grade cannabidiol (CBD) can reduce the frequency of convulsive seizures and lead to improvements in quality of life in children affected by epileptic encephalopathies. With limited access to pharmaceutical CBD, Cannabis extracts in oil are becoming increasingly available. The primary aims of the study presented in this protocol are (i) To determine whether CBD enriched Cannabis extract is safe and well-tolerated for pediatric patients with refractory epilepsy, (ii) To monitor the effects of CBD-enriched Cannabis extract on the frequency and duration of seizure types and on quality of life.

DISCUSSION:

This paper describes the study design of a phase 1 trial of CBD-enriched Cannabis herbal extract in children with treatment-resistant epileptic encephalopathy. This study will provide the first high quality analysis of safety of CBD-enriched Cannabis herbal extract in pediatric patients in relation to dosage and pharmacokinetics of the active cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/29981580 “Children with epileptic encephalopathies resistant to standard therapy are at considerable risk for long-term neurocognitive impairment and poor quality of life. CBD-enriched Cannabis based therapies have been shown in several studies to provide a reduction in seizure frequencies and improvements in sleep patterns, mood, and alertness.” https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-018-1191-y]]>

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

Posted on July 10, 2018 by David Worrell

“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]]>

Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation.

Posted on July 10, 2018 by David Worrell

“Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting side effect of cancer treatment that affects millions of cancer survivors throughout the world and current treatment options are extremely limited by their side effects. Cannabinoids are highly effective in suppressing pain symptoms of chemotherapy-induced and other peripheral neuropathies but their widespread use is limited by central nervous system (CNS)-mediated side effects. Here, we tested one compound from a series of recently developed synthetic peripherally restricted cannabinoids (PRCBs) in a rat model of cisplatin-induced peripheral neuropathy. Our results demonstrate that PRCBs exemplified by PrNMI may represent a viable option for the treatment of CIPN pain symptoms.” https://www.ncbi.nlm.nih.gov/pubmed/29981335 https://www.sciencedirect.com/science/article/pii/S0028390818303575?via%3Dihub

]]>

Anti-Proliferative Properties and Proapoptotic Function of New CB2 Selective Cannabinoid Receptor Agonist in Jurkat Leukemia Cells.

Posted on July 6, 2018 by David Worrell

“Several studies demonstrated that cannabinoids reduce tumor growth, inhibit angiogenesis, and decrease cancer cell migration. As these molecules are well tolerated, it would be interesting to investigate the potential benefit of newly synthesized compounds, binding cannabinoid receptors (CBRs). In this study, we describe the synthesis and biological effect of 2-oxo-1,8-naphthyridine-3-carboxamide derivative LV50, a new compound with high CB2 receptor (CB2R) affinity. We demonstrated that it decreases viability of Jurkat leukemia cells, evaluated by Trypan Blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), but mainly induces a proapoptotic effect. We observed an increase of a hypodiploid peak by propidium iodide staining and changes in nuclear morphology by Hoechst 33258. These data were confirmed by a significant increase of Annexin V staining, cleavage of the nuclear enzyme poly(ADP-ribose)-polymerase (PARP), and caspases activation. In addition, in order to exclude that LV50 non-specifically triggers death of all normal leukocytes, we tested the new compound on normal peripheral blood lymphocytes, excluding the idea of general cytotoxicity. To characterize the involvement of CB2R in the anti-proliferative and proapoptotic effect of LV50, cells were pretreated with a specific CB2R antagonist and the obtained data showed reverse results. Thus, we suggest a link between inhibition of cell survival and proapoptotic activity of the new compound that elicits this effect as selective CB2R agonist.” https://www.ncbi.nlm.nih.gov/pubmed/29973514 http://www.mdpi.com/1422-0067/19/7/1958

]]>

Hippocampal mammalian target of rapamycin is implicated in stress-coping behavior induced by cannabidiol in the forced swim test.

Posted on July 5, 2018 by David Worrell

Image result for journal of psychopharmacology

“Cannabidiol is a non-psychotomimetic compound with antidepressant-like effects. However, the mechanisms and brain regions involved in cannabidiol effects are not yet completely understood. Brain-derived neurotrophic factor/tropomyosin-receptor kinase B/mammalian target of rapamycin (BDNF-TrkB-mTOR) signaling, especially in limbic structures, seems to play a central role in mediating the effects of antidepressant drugs.

RESULTS:

Systemic cannabidiol administration induced antidepressant-like effects and increased BDNF levels in the dorsal hippocampus. Rapamycin, but not K252a, injection into the dorsal hippocampus prevented the antidepressant-like effect induced by systemic cannabidiol treatment (10 mg/kg). Differently, hippocampal administration of cannabidiol (10 nmol/0.2 µL) reduced immobility time, an effect that was blocked by both rapamycin and K252a local microinjection.

CONCLUSION:

Altogether, our data suggest that the hippocampal BDNF-TrkB-mTOR pathway is vital for cannabidiol-induced antidepressant-like effect when the drug is locally administered. However, other brain regions may also be involved in cannabidiol-induced antidepressant effect upon systemic administration.” https://www.ncbi.nlm.nih.gov/pubmed/29968502 http://journals.sagepub.com/doi/abs/10.1177/0269881118784877?journalCode=jopa

]]>

Preliminary evaluation of the efficacy, safety, and costs associated with the treatment of chronic pain with medical cannabis.

Posted on July 3, 2018 by David Worrell

College of Psychiatric and Neurologic Pharmacists

“Medical cannabis (MC) is commonly claimed to be an effective treatment for chronic or refractory pain. With interest in MC in the United States growing, as evidenced by the 29 states and 3 US districts that now have public MC programs, the need for clinical evidence supporting this claim has never been greater.

METHODS:

This was a retrospective, mirror-image study that investigated MC’s effectiveness in patients suffering from chronic pain associated with qualifying conditions for MC in New York State. The primary outcome was to compare European Quality of Life 5 Dimension Questionnaire (EQ-5D) and Pain Quality Assessment Scale (PQAS) scores at baseline and 3 months post-therapy. The secondary outcomes included comparisons of monthly analgesic prescription costs and opioid consumption pre- and post-therapy. Tolerability was assessed by side effect incidence.

RESULTS:

This investigation included 29 subjects. Quality of life and pain improved, measured by change in EQ-5D (Pre 36 - Post 64, P < .0001) and change in PQAS paroxysmal (Pre 6.76 - Post 2.04, P < .0001), surface (Pre 4.20 - Post 1.30, P < .0001), deep (Pre 5.87 - Post 2.03, P < .0001), unpleasant (Pre “miserable” - Post “annoying”, P < .0001). Adverse effects were reported in 10% of subjects.

DISCUSSION:

After 3 months treatment, MC improved quality of life, reduced pain and opioid use, and lead to cost savings. Large randomized clinical trials are warranted to further evaluate the role of MC in the treatment of chronic pain.” https://www.ncbi.nlm.nih.gov/pubmed/29955555

http://mhc.cpnp.org/doi/10.9740/mhc.2018.05.110

]]>

Modulation of the Cannabinoid System: A New Perspective for the Treatment of the Alzheimer's Disease.

Posted on July 3, 2018 by David Worrell

“The pathogenesis of Alzheimer’s disease (AD) is somewhat complex and has yet to be fully understood. As the effectiveness of the therapy currently available for AD has proved to be limited, the need for new drugs has become increasingly urgent. The modulation of the endogenous cannabinoid system (ECBS) is one of the potential therapeutic approaches that is attracting a growing amount of interest. The ECBS consists of endogenous compounds and receptors. The receptors CB1 and CB2 have already been well characterized: CB1 receptors, which are abundant in the brain, particularly in the hippocampus, basal ganglia and cerebellum, regulate memory function and cognition. It has been suggested that the activation of CB1 receptors reduces intracellular Ca concentrations, inhibits glutamate release and enhances neurotrophin expression and neurogenesis. CB2 receptors are expressed, though to a lesser extent, in the central nervous system, particularly in microglia and in immune system cells involved in the release of cytokines. CB2 receptors have been shown to be upregulated in neuritic plaque-associated migroglia in the hippocampus and entorhinal cortex of patients, which suggests that these receptors play a role in the inflammatory pathology of AD. The role of the ECBS in AD is supported by cellular and animal models. By contrast, few clinical studies designed to investigate therapies aimed at reducing behaviour disturbances, especially night-time agitation, eating behaviour and aggressiveness, have yielded positive results. In this review, we will describe how the manipulation of the ECBS offers a potential approach to the treatment of AD.”

https://www.ncbi.nlm.nih.gov/pubmed/29962346

http://www.eurekaselect.com/163401/article

]]>