Differential upregulation of the cannabinoid CB2 receptor in neurotoxic and inflammation-driven rat models of Parkinson’s disease.

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“The cannabinoid CB2 receptor has recently emerged as a potential anti-inflammatory target to break the self-sustaining cycle of neuroinflammation and neurodegeneration that is associated with neurodegenerative diseases.

…the aim of this study was to investigate and compare the changes that occur in the endocannabinoid system in neurotoxic and inflammation-driven models of Parkinson’s disease.

…this study has shown that the endocannabinoid system is dysregulated in animal models of Parkinson’s disease, and has also revealed significant differences in the level of dysregulation between the models themselves.

This study indicates that targeting the CB2 receptor may represent a viable target for anti-inflammatory disease modification in Parkinson’s disease.”

 http://www.ncbi.nlm.nih.gov/pubmed/25895887

http://www.thctotalhealthcare.com/category/parkinsons-disease/

Differential Pharmacological Regulation of Sensorimotor-Gating Deficit in CB1 Knockout Mice and Associated Neurochemical and Histological Alterations.

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“The endocannabinoid system has been widely involved in the pathophysiology of sensorimotor gating deficits. The present study is aimed to evaluate the pharmacological modulation of the sensorimotor gating impairment induced by cannabinoid CB1 receptor (CB1r) deletion…

These data further support the important role of CB1r in sensorimotor gating regulation and the therapeutic usefulness of methylphenidate for the treatment of psychiatric disorders with associated pre-attentional deficits.”

http://www.ncbi.nlm.nih.gov/pubmed/25895455

Attenuation of morphine antinociceptive tolerance by cannabinoid CB1 and CB2 receptor antagonists.

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“Cannabinoid CB1 and CB2 receptor antagonists may be useful for their potential to increase or prolong opioid analgesia while attenuating the development of opioid tolerance.

The aim of this study was to investigate the effects of AM251 (a selective CB1 antagonist) and JTE907 (a selective CB2 antagonist) on morphine analgesia and tolerance in rats…

In conclusion, we observed that co-injection of AM251 and JTE907 with morphine attenuated expression of tolerance to morphine analgesic effects and decreased the morphine analgesia.”

http://www.ncbi.nlm.nih.gov/pubmed/25894754

Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy.

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“Endocannabinoids are lipid-derived messengers, and both their synthesis and breakdown are under tight spatiotemporal regulation. As retrograde signalling molecules, endocannabinoids are synthesized postsynaptically but activate presynaptic cannabinoid receptor 1 (CB1) receptors to inhibit neurotransmitter release. In turn, CB1-expressing inhibitory and excitatory synapses act as strategically placed control points for activity-dependent regulation of dynamically changing normal and pathological oscillatory network activity. Here, we highlight emerging principles of cannabinoid circuit control and plasticity, and discuss their relevance for epilepsy and related comorbidities. New insights into cannabinoid signalling may facilitate the translation of the recent interest in cannabis-related substances as antiseizure medications to evidence-based treatment strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/25891509

http://www.thctotalhealthcare.com/category/epilepsy-2/

Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals.

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“The release of GABA from cholecystokinin-containing interneurons is modulated by type-1 cannabinoid receptors (CB1). Here we tested the hypothesis that the strength of CB1-mediated modulation of GABA release is related to the CB1 content of axon terminals.

Our data suggest that only a subpopulation of CB1s, within nanometre distances from their target Cav2.2 channels, are responsible for endocannabinoid-mediated modulation of GABA release.”

http://www.ncbi.nlm.nih.gov/pubmed/25891347

Cannabinoids Inhibit T-cells via Cannabinoid Receptor 2 in an in vitro Assay for Graft Rejection, the Mixed Lymphocyte Reaction

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“Cannabinoids are known to have anti-inflammatory and immunomodulatory properties.

Cannabinoid receptor 2 (CB2) is expressed mainly on leukocytes and is the receptor implicated in mediating many of the effects of cannabinoids on immune processes.

This study tested the capacity of Δ9-tetrahydrocannabinol (Δ9-THC) and of two CB2-selective agonists to inhibit the murine Mixed Lymphocyte Reaction (MLR), an in vitro correlate of graft rejection following skin and organ transplantation. Both CB2-selective agonists and Δ9-THC significantly suppressed the MLR in a dose dependent fashion…

Together, these data support the potential of this class of compounds as useful therapies to prolong graft survival in transplant patients.

Cannabinoids were reported to have effects on immune responses as early as the 1970s, but the basis for this activity was not understood until the cannabinoid receptors were cloned

Ideally, the anatomically disparate expression of CB1 and CB2 would allow for the use of compounds selective for CB2, and thus eliminate the unwanted psychoactive effects from CB1 activation, while maintaining the anti-inflammatory and immunosuppressive properties.

CB2-selective cannabinoids have been proposed as possible candidates to block graft rejection.

The results presented in this paper show that Δ9-THC, a mixed CB1/CB2 agonist, and two CB2-selective agonists can inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ and skin graft rejection.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864984/

Historical essay: An Arabic surgeon, Ibn al Quff’s (1232-1286) account on surgical pain relief.

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“This is a review of Ibn al Quff’s account of surgical pain relief in his surgical book Al Omdah, in which he mentioned the word anesthetic (Al moukhadder) and the involvement of physician (al tabbaaee) to give mixture of drugs to prevent pain in a surgical condition to relieve the patient from pain or to make surgical management possible.

Hich indicated one rare occasion to such description in Arabic medical texts. Methods of administration of these drugs were inhalation, ingestion and by rectal suppositories.

The drugs used in anesthetic sponges include all the drugs that are recorded in the modern literature of anesthesia. They are as follows: opium, mandrake, Hyocymus albus, belladonna, Cannabis sativus, Cannabisindica, wild lettuce.

The anesthetic sponge, mentioned in many references as an inhalation method, may be of symbolic value to surgery.”

http://www.ncbi.nlm.nih.gov/pubmed/25885079

“Ibn al-Quff (1233-1286 AD), a medieval Arab surgeon and physician. Abū’l-Faraj ibn Ya’qūb ibn Isāq Ibn al-Quff al-Karakī (1233-1286 AD), best known as Ibn al-Quff in the West, was a 13th century Arab physician-surgeon. During his lifetime, Ibn al-Quff made some important contributions to the art of healing. He authored several books and commentaries in the field of medicine, in particular surgery.”  http://www.ncbi.nlm.nih.gov/pubmed/24585631

http://www.thctotalhealthcare.com/category/pain-2/

Cannabis in medicine: a national educational needs assessment among Canadian physicians.

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“There is increasing global awareness and interest in the use of cannabis for therapeutic purposes (CTP).

It is clear that health care professionals need to be involved in these decisions, but often lack the education needed to engage in informed discussions with patients. This study was conducted to determine the educational needs of Canadian physicians regarding CTP…

 We have identified several key educational needs among Canadian physicians regarding CTP. These data can be used to develop resources and educational programs to support clinicians in this area, as well as to guide further research to inform these gaps.”
“History of cannabis as a medicine: a review” 

Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection.

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“Parkinson’s disease (PD) is a slow insidious neurological disorder characterized by a loss of dopaminergic neurons in the midbrain. Although several recent preclinical advances have proposed to treat PD, there is hardly any clinically proved new therapeutic for its cure.

Increasing evidence suggests a prominent modulatory function of the cannabinoid signaling system in the basal ganglia. Hence, use of cannabinoids as a new therapeutic target has been recommended as a promising therapy for PD.

The elements of the endocannabinoid system are highly expressed in the neural circuit of basal ganglia wherein they bidirectionally interact with dopaminergic, glutamatergic, and GABAergic signaling systems.

As the cannabinoid signaling system undergoes a biphasic pattern of change during progression of PD, it explains the motor inhibition typically observed in patients with PD.

Cannabinoid agonists such as WIN-55,212-2 have been demonstrated experimentally as neuroprotective agents in PD, with respect to their ability to suppress excitotoxicity, glial activation, and oxidative injury that causes degeneration of dopaminergic neurons.

Additional benefits provided by cannabinoid related compounds including CE-178253, oleoylethanolamide, nabilone and HU-210 have been reported to possess efficacy against bradykinesia and levodopa-induced dyskinesia in PD.

Despite promising preclinical studies for PD, use of cannabinoids has not been studied extensively at the clinical level. In this review, we reassess the existing evidence suggesting involvement of the endocannabinoid system in the cause, symptomatology, and treatment of PD. We will try to identify future threads of research that will help in the understanding of the potential therapeutic benefits of the cannabinoid system for treating PD.”

http://www.ncbi.nlm.nih.gov/pubmed/25888232

“To conclude, development of safe, effective cannabis-based medicines targeting different mechanisms may have a significant impact in PD therapy.”

Full-text: http://www.molecularneurodegeneration.com/content/10/1/17

http://www.thctotalhealthcare.com/category/parkinsons-disease/

Pure cannabidiol in the treatment of malignant migrating partial seizures in infancy: a case report.

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“Malignant migrating partial seizures in infancy is a devastating pharmacoresistent epileptic encephalopathy of unknown etiology characterized by onset in the first 6 months of life, continuous migrating focal seizures with corresponding multifocal electroencephalographic discharges, developmental deterioration, and early mortality.

Recent widespread interest in the nonpsychoactive component of the cannabis plant, cannabidiol, as a potential treatment for refractory devastating epilepsies has led to individual trials initiated by families or physicians in states that have legalized medical marijuana with anecdotal success.

We describe a now 10-month-old boy with malignant migrating partial seizures in infancy who made developmental gains and demonstrated sustained seizure reduction with the addition of cannabidiol to his antiepileptic regimen.

This report supports a role for cannabidiol in the treatment of malignant migrating partial seizures in infancy.”

http://www.ncbi.nlm.nih.gov/pubmed/25882081

http://www.thctotalhealthcare.com/category/epilepsy-2/