“Endocannabinoids and opioids play a vital role in mediating pain-induced analgesia. The specific effects of these compounds within orofacial region are largely unknown. In this study we tried to determine whether the increase of cannabinoid and opioid concentration in cerebrospinal fluid affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles.
Tag Archives: Cannabinoids
Blunted stress reactivity in chronic cannabis users
“One of the most commonly cited reasons for chronic cannabis use is to cope with stress. Consistent with this, cannabis users have shown reduced emotional arousal and dampened stress reactivity in response to negative imagery. Chronic cannabis use is associated with blunted stress reactivity.” https://link.springer.com/article/10.1007/s00213-017-4648-z?no-access=true
“WSU study: Regular marijuana users more calm under stress” http://komonews.com/news/local/wsu-study-regular-marijuana-users-more-calm-under-stress
“Potheads don’t stress easily, say WSU researchers” http://www.spokesman.com/stories/2017/jul/31/potheads-dont-stress-easily-say-wsu-researchers/
Modeling Neurodegenerative Disorders for Developing Cannabinoid-Based Neuroprotective Therapies.
“The increase in lifespan during the last 50 years, mainly in developed countries, has originated a progressive elevation in the incidence of chronic neurodegenerative disorders, for which aging is the key risk factor. This fact will definitively become the major biomedical challenge during the present century, in part because the expectation of a persisting elevation in the population older than 65 years over the whole population and, on the other hand, because the current lack of efficacious therapies to control these disorders despite years of intense research. This chapter will address this question and will stress the urgency of developing better neuroprotective and neurorepair strategies that may delay/arrest the progression of these disorders, reviewing the major needs to solve the causes proposed for the permanent failures experienced in recent years, e.g., to develop multitarget strategies, to use more predictive experimental models, and to identify early disease biomarkers. This chapter will propose the cannabinoids and their classic (e.g., endocannabinoid receptors and enzymes) and nonclassic (e.g., peroxisome proliferator-activated receptors, transcription factors) targets as a useful strategy for developing novel therapies for these disorders, based on their broad-spectrum neuroprotective profile, their activity as an endogenous protective system, the location of the endocannabinoid targets in cell substrates critical for neuronal survival, and their ability to serve for preservation and rescue, but also for repair and/or replacement, of neurons and glial cells against cytotoxic insults.” https://www.ncbi.nlm.nih.gov/pubmed/28750802 http://www.sciencedirect.com/science/article/pii/S0076687917301787?via%3Dihub]]>
Combined deficiency of the Cnr1 and Cnr2 receptors protects against age-related bone loss by osteoclast inhibition.
“The endocannabinoid system plays a role in regulating bone mass and bone cell activity and inactivation of the type 1 (Cnr1) or type 2 (Cnr2) cannabinoid receptors influences peak bone mass and age-related bone loss. As the Cnr1 and Cnr2 receptors have limited homology and are activated by different ligands, we have evaluated the effects of combined deficiency of Cnr1 and 2 receptors (Cnr1/2-/- ) on bone development from birth to old age and studied ovariectomy induced bone loss in female mice. The Cnr1/2-/- mice had accelerated bone accrual at birth when compared with wild type littermates, and by 3 months of age, they had higher trabecular bone mass. They were also significantly protected against ovariectomy-induced bone loss due to a reduction in osteoclast number. The Cnr1/2-/- mice had reduced age-related bone loss when compared with wild-type due to a reduction in osteoclast number. Although bone formation was reduced and bone marrow adiposity increased in Cnr1/2-/- mice, the osteoclast defect outweighed the reduction in bone formation causing preservation of bone mass with aging. This contrasts with the situation previously reported in mice with inactivation of the Cnr1 or Cnr2 receptors individually where aged-related bone loss was greater than in wild-type. We conclude that the Cnr1 and Cnr2 receptors have overlapping but nonredundant roles in regulating osteoclast and osteoblast activities. These observations indicate that combined inhibition of Cnr1 and Cnr2 receptors may be beneficial in preventing age-related bone loss, whereas blockade of individual receptors may be detrimental.” https://www.ncbi.nlm.nih.gov/pubmed/28752643 http://onlinelibrary.wiley.com/doi/10.1111/acel.12638/abstract]]>
Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder.
“Exposure to stress is an undeniable, but in most cases surmountable, part of life. However, in certain individuals, exposure to severe or cumulative stressors can lead to an array of pathological conditions including posttraumatic stress disorder (PTSD), characterized by debilitating trauma-related intrusive thoughts, avoidance behaviors, hyperarousal, as well as depressed mood and anxiety. In the context of the rapidly changing political and legal landscape surrounding use of cannabis products in the United States, there has been a surge of public and research interest in the role of cannabinoids in the regulation of stress-related biological processes and in their potential therapeutic application for stress-related psychopathology. Here we review the current state of knowledge regarding the effects of cannabis and cannabinoids in PTSD and the preclinical and clinical literature on the effects of cannabinoids and endogenous cannabinoid signaling systems in the regulation of biological processes related to the pathogenesis of PTSD. Potential therapeutic implications of the reviewed literature are also discussed. Lastly, we propose that a state of endocannabinoid deficiency could represent a stress-susceptibility endophenotype predisposing to the development of trauma-related psychopathology and provide biologically plausible support for the self-medication hypotheses used to explain high rates of cannabis use in patients with trauma-related disorders.” https://www.ncbi.nlm.nih.gov/pubmed/28745306 https://www.nature.com/npp/journal/vaop/naam/abs/npp2017162a.html]]>
Cannabidiol reduces seizure frequency in Dravet syndrome
“Cannabidiol is effective in treating drug-resistant seizures in Dravet syndrome, according to a new clinical trial. For the first time, a multinational, randomized, double-blind, placebo-controlled trial has confirmed controversial anecdotal evidence supporting the efficacy of cannabinoids in epilepsy.” https://www.nature.com/nrneurol/journal/v13/n7/full/nrneurol.2017.86.html
“Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome” http://www.nejm.org/doi/10.1056/NEJMoa1611618
“Cannabinoids for Epilepsy — Real Data, at Last” http://www.nejm.org/doi/full/10.1056/NEJMe1702205
]]>The effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model.
“The lipophilic phytocannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) show therapeutic efficacy in various medical conditions. Both molecules are poorly water soluble and subjected to extensive first pass metabolism in the gastrointestinal tract, leading to a limited oral bioavailability of approximately 9%. We have developed an advanced lipid based Self-Emulsifying Drug Delivery System termed Advanced Pro-NanoLiposphere (PNL) pre-concentrate. The PNL is composed of lipid and emulsifying excipients of GRAS status and are known to increase solubility and reduce Phase I metabolism of lipophilic active compounds. Advanced PNLs are PNLs with an incorporated natural absorption enhancers. These molecules are natural alkaloids and phenolic compounds which were reported to inhibit certain phase I and phase II metabolism processes. Here we use piperine, curcumin and resveratrol to formulate the Advanced-PNL formulations. Consequently, we have explored the utility of these Advanced-PNLs on CBD and THC oral bioavailability. Oral administration of CBD-piperine-PNL resulted in 6-fold in AUC compared to CBD solution, proving to be the most effective of the screened formulations. The same trend was found in pharmacokinetic experiments of THC-piperine-PNL with resulted in a 9.3-fold increase in AUC as compared to THC solution. Our Piperine-PNL can be used as a platform for synchronized delivery of piperine and CBD or THC to the enterocyte site. This co-localization provides an increase in CBD and THC bioavailability by its effect at the pre-enterocyte and the enterocyte levels of the absorption process. The extra augmentation in the absorption of CBD and THC by incorporating piperine into PNL is attributed to the inhibition of Phase I and phase II metabolism by piperine in addition to the Phase I metabolism and P-gp inhibition by PNL. These novel results pave the way to utilize piperine-PNL delivery system for other poorly soluble, highly metabolized compounds that currently cannot be administered orally.” https://www.ncbi.nlm.nih.gov/pubmed/28736128 http://www.sciencedirect.com/science/article/pii/S0928098717304025]]>
Longitudinal study of hippocampal volumes in heavy cannabis users.
“Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes.
Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes.
Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.”Compared to high and low cannabis use, moderate use is associated with fewer cognitive deficits in psychosis.
“Literature on the relationship of cannabis use and cognition in schizophrenia provides the paradoxical view that cannabis use is sometimes linked with less severe impairment in neurocognition.
This paper explored the possibility that this is a reflection of a dose related response between lifetime cannabis use and two forms of cognition, neurocognition and metacognition, in schizophrenia. It was hypothesized that three groups of patients could be differentiated, those with (1) little to no cannabis use with poor levels of cognition, (2) moderate cannabis use and relatively better levels of cognition and (3) high cannabis use with relatively poorer levels of cognition.
Consistent with our hypothesis, participants with high and moderate lifetime cannabis use had lesser impairment of neurocognition and metacognition compared to low lifetime cannabis use. Participants with moderate lifetime cannabis use also had lesser impairment of metacognition compared to low and heavy use.
These findings suggest that a dose related relationship exists between cannabis use and cognition. Results could be due to an influence of pre-existing cognitive level on likelihood of lifetime cannabis use, or to an interaction between use and cognitive function.”
https://www.ncbi.nlm.nih.gov/pubmed/28740820
http://www.sciencedirect.com/science/article/pii/S2215001316300166?via%3Dihub