“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.”
“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.”
“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.”
“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.”
“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…
“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/
“Cannabis-based medicines have recently been approved for the treatment of pain and spasticity in multiple sclerosis (MS).
This supports the original perceptions of people with MS, who were using illegal street cannabis for symptom control and pre-clinical testing in animal models of MS.
This activity is supported both by the biology of the disease and the biology of the cannabis plant and the endocannabinoid system.
MS results from disease that impairs neurotransmission and this is controlled by cannabinoid receptors and endogenous cannabinoid ligands. This can limit spasticity and may also influence the processes that drive the accumulation of progressive disability.”
http://www.ncbi.nlm.nih.gov/pubmed/25876933
http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/
“2-Arachidonoyl-glycerol (2-AG) and arachidonyl-ethanolamide (AEA) are endocannabinoids that have been implicated in many physiologic disorders, including obesity, metabolic syndromes, hepatic diseases, pain, neurologic disorders, and inflammation.
Their immunomodulatory effects are numerous and are not always mediated by cannabinoid receptors, reflecting the presence of an arachidonic acid (AA) molecule in their structure, the latter being the precursor of numerous bioactive lipids that are pro- or anti-inflammatory.
2-AG and AEA can thus serve as a source of AA but can also be metabolized by most eicosanoid biosynthetic enzymes, yielding additional lipids.
In this regard, enhancing endocannabinoid levels by using endocannabinoid hydrolysis inhibitors is likely to augment the levels of these lipids that could regulate inflammatory cell functions.
This review summarizes the metabolic pathways involved in the biosynthesis and metabolism of AEA and 2-AG, as well as the biologic effects of the 2-AG and AEA lipidomes in the regulation of inflammation.”
“Synaptic plasticity, a main substrate for learning and memory, is commonly assessed with prolonged stimulations. Since learning can arise from few or even a single trial, synaptic strength is expected to adapt rapidly. However, it remains elusive whether synaptic plasticity occurs in response to limited event occurrences. To answer this question, we investigated if a low number of paired stimulations can induce plasticity in a major synaptic learning rule, the spike-timing dependent plasticity (STDP). It is known that 100 pairings induce bidirectional STDP, i.e. spike-timing-dependent potentiation (tLTP) and depression (tLTD) at most central synapses. In rodent striatum, we found that tLTD progressively disappears when the number of paired stimulations is decreased (below 50 pairings) whereas tLTP displays a biphasic profile: tLTP is observed for 75-100 pairings, absent for 25-50 pairings and reemerges for 5-10 pairings. This tLTP, induced by very few pairings (∼5-10), depends on the endocannabinoid (eCB) system. This eCB-tLTP involves postsynaptic endocannabinoid synthesis, requires paired activity (post- and presynaptic) and the activation of type-1 cannabinoidreceptor (CB1R) and transient receptor potential vanilloid type-1 (TRPV1) activation. eCB-tLTP occurs in both striatopallidal and striatonigral MSNs and is dopamine-dependent. Lastly, we show that eCB-LTP and eCB-LTD can be induced sequentially in the same neuron, depending on the cellular conditioning paradigm. Thus, while usually considered as simply depressing synaptic function, endocannabinoids constitute a versatile system underlying bidirectional plasticity. Our results reveal a novel form of synaptic plasticity, eCB-tLTP, which may underlie rapid learning capabilities characterizing behavioral flexibility.”
“Alzheimer´s disease (AD), a neurodegenerative illness involving synaptic dysfunction with extracellular accumulation of Aβ1-42 toxic peptide, glial activation, inflammatory response and oxidative stress, can lead to neuronal death.
Endogenous cannabinoid system is implicated in physiological and physiopathological events in central nervous system (CNS), and changes in this system are related to many human diseases, including AD…
In conclusion cannabinoid WIN 55,212-2 increases cell viability and anti-inflammatory response in cultured astrocytes. Moreover, WIN 55,212-2 increases expression of anti-oxidant Cu/Zn SOD and is able to prevent inflammation induced by Aβ1-42 in cultured astrocytes.
Further studies would be needed to assess the possible beneficial effects of cannabinoids in Alzheimer’s disease patients.”
http://www.ncbi.nlm.nih.gov/pubmed/25874692
http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/