Prolonged Cannabidiol Treatment Lacks on Detrimental Effects on Memory, Motor Performance and Anxiety in C57BL/6J Mice.

Image result for frontier in behavioral neuroscience“The Cannabis plant contains more than 100 currently known phytocannabinoids. Regarding the rising consumption of the non-psychotropic phytocannabinoid cannabidiol (CBD) in people’s everyday life (e.g., beauty products, food and beverages), the importance of studies on the influence of CBD on healthy humans and rodents is evident. Therefore, the behavioral profile of CBD was investigated with a battery of behavioral tests, including motor, anxiety, and memory tests after prolonged CBD treatment. Adult C57Bl/6J wildtype (WT) mice were daily intraperitoneally injected with 20 mg/kg CBD for 6 weeks starting at two different points of ages (3 months and 5 months) to compare the influence of prolonged CBD treatment with a washout period (former group) to the effects of long term CBD treatment (current group). Our results show that CBD treatment does not influence motor performance on an accelerating Rotarod test, while it also results in a lower locomotor activity in the open field (OF). No influence of CBD on spatial learning and long term memory in the Morris Water Maze (MWM) was observed. Memory in the Novel Object Recognition test (NORT) was unaffected by CBD treatment. Two different anxiety tests revealed that CBD does not affect anxiety behavior in the Dark-Light Box (DLB) and OF test. Although, anxiety is altered by current CBD treatment in the Elevated Plus Maze (EPM). Moreover, CBD-treated C57Bl/6J mice showed an unaltered acoustic startle response (ASR) compared to vehicle-treated mice. However, current CBD treatment impairs prepulse inhibition (PPI), a test to analyze sensorimotor gating. Furthermore, prolonged CBD treatment did not affect the hippocampal neuron number. Our results demonstrate that prolonged CBD treatment has no negative effect on the behavior of adult C57Bl/6J mice.”

https://www.ncbi.nlm.nih.gov/pubmed/31133833

https://www.frontiersin.org/articles/10.3389/fnbeh.2019.00094/full

Retrograde activation of CB1R by muscarinic receptors protects against central organophosphorus toxicity.

Neuropharmacology“The acute toxicity of organophosphorus-based compounds is primarily a result of acetylcholinesterase inhibition in the central and peripheral nervous systems. The resulting cholinergic crisis manifests as seizure, paralysis, respiratory failure and neurotoxicity. Though overstimulation of muscarinic receptors is the mechanistic basis of central organophosphorus (OP) toxicities, short-term changes in synapse physiology that precede OP-induced seizures have not been investigated in detail. To study acute effects of OP exposure on synaptic function, field excitatory postsynaptic potentials (fEPSPs) were recorded from Schaffer collateral synapses in the mouse hippocampus CA1 stratum radiatum during perfusion with various OP compounds. Administration of the OPs paraoxon, soman or VX rapidly and stably depressed fEPSPs via a presynaptic mechanism, while the non-OP proconvulsant tetramethylenedisulfotetramine had no effect on fEPSP amplitudes. OP-induced presynaptic long-term depression manifested prior to interictal spiking, occurred independent of recurrent firing, and did not require NMDA receptor currents, suggesting that it was not mediated by activity-dependent calcium uptake. Pharmacological dissection revealed that the presynaptic endocannabinoid type 1 receptor (CB1R) as well as postsynaptic M1 and M3 muscarinic acetylcholine receptors were necessary for OP-LTD. Administration of CB1R antagonists significantly reduced survival in mice after a soman challenge, revealing an acute protective role for endogenous CB1R signaling during OP exposure. Collectively these data demonstrate that the endocannabinoid system alters glutamatergic synaptic function during the acute response to OP acetylcholinesterase inhibitors.”

https://www.ncbi.nlm.nih.gov/pubmed/31132436

“CB1R activation represents a novel therapy to mitigate acute OP toxicity”

https://www.sciencedirect.com/science/article/pii/S002839081930190X?via%3Dihub

Activation of cannabinoid type 2 receptor protects skeletal muscle from ischemia-reperfusion injury partly via Nrf2 signaling.

Life Sciences“Cannabinoid type 2 (CB2) receptor activation has been shown to attenuate IRI in various organs. NF-E2-related factor (Nrf2) is an anti-oxidative factor that plays multiple roles in regulating cellular redox homeostasis and modulating cell proliferation and differentiation. The protective effects of CB2 receptor activation on skeletal muscle IRI and the underlying mechanism that involves Nrf2 signaling remain unknown.

Our results showed that CB2 receptor activation reduced IR-induced histopathological lesions, edema, and oxidative stress 1 day post-injury and accelerated early myogenesis 4 days post-injury in mice. Nrf2 knockout mice that were treated with AM1241 exhibited deteriorative skeletal muscle oxidative damage and myogenesis. In vitro, pretreatment with AM1241 significantly increased the expression of Nrf2 and its nuclear translocation, attenuated the decrease in H2O2-induced C2C12 cell viability, and decreased reactive oxygen species generation and apoptosis. CB2 receptor activation also significantly enhanced C2C12 myoblasts differentiation, which was impaired by silencing Nrf2.

Overall, CB2 receptor activation protected skeletal muscle against IRI by ameliorating oxidative damage and promoting early skeletal muscle myogenesis, which was partly via Nrf2 signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/31128135

https://www.sciencedirect.com/science/article/abs/pii/S0024320519304126?via%3Dihub

The New Runner’s High? Examining Relationships Between Cannabis Use and Exercise Behavior in States With Legalized Cannabis.

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“Scientific literature examining cannabis use in the context of health behaviors, such as exercise engagement, is extremely sparse and has yielded inconsistent findings. This issue is becoming increasingly relevant as cannabis legalization continues, a situation that has been associated with increased initiation of use among adults, and increased potency of available products in legalized states.

Physical activity is among the most important health behaviors, but many Americans do not meet minimum exercise recommendations for healthy living. Common issues surrounding low exercise rates include inadequate enjoyment of and motivation to exercise, and poor recovery from exercise.

It is unclear whether cannabis use shortly before and/or after exercise impacts these issues, and whether this co-use affects exercise performance. The present online survey study examines attitudes and behaviors regarding cannabis use with exercise among adult cannabis users living in states with full legal access (N = 605).

Results indicated that the majority (81.7%) of participants endorsed using cannabis concurrently with exercise, and those who did tended to be younger and more likely to be males (p < 0.0005 for both). Even after controlling for these differences, co-users reported engaging in more minutes of aerobic and anaerobic exercise per week (p < 0.01 and p < 0.05, respectively). In addition, the majority of participants who endorsed using cannabis shortly before/after exercise reported that doing so enhances their enjoyment of and recovery from exercise, and approximately half reported that it increases their motivation to exercise.

This study represents an important step in clarifying cannabis use with exercise among adult users in states with legal cannabis markets, and provides guidance for future research directions.”

“A runner’s high depends on cannabinoid receptors in mice.”   http://www.ncbi.nlm.nih.gov/pubmed/26438875

“Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high’”  http://jeb.biologists.org/content/215/8/1331.long

Cannabis use as a risk factor for causing motor vehicle crashes: a prospective study.

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“We conducted a responsibility analysis to determine whether drivers injured in motor vehicle collisions who test positive for Δ-9-tetrahydrocannabinol (THC) or other drugs are more likely to have contributed to the crash than those who test negative.

There was no increased risk of crash responsibility in drivers with THC<2ng/mL or 2≤THC<5ng/mL.

In this sample of non-fatally injured motor vehicle drivers in British Columbia, Canada, there was no evidence of increased crash risk in drivers with THC<5ng/mL and a statistically non-significant increased risk of crash responsibility (OR=1.74) in drivers with THC≥5ng/mL.”

https://www.ncbi.nlm.nih.gov/pubmed/31106494

https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14663

Supplementation of Cannabis sativa L. leaf powder accelerates functional recovery and ameliorates haemoglobin level following an induced injury to sciatic nerve in mouse model.

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“Peripheral nerve injury is a common condition with a multitude of signs and symptoms. The major consequence of injury is limited physical activity. Presently, we are lacking effective therapies for PNI and it is need of the hour is to explore potential remedies for the recovery of functional loss.

Here, we have investigated the role of crude Cannabis sativa L. leaf powder in promoting functions recovery, in mouse model subjected to a traumatic sciatic nerve injury.

A dose of 200mg/kg of the body weight per day was administered orally from the day of nerve crush till the end of the experiment. The motor functions were evaluated by measuring sciatic functional index, muscle grip strength and muscle mass; whereas the sensory functions were assessed by hotplate test. The haematology and serum analyses were carried out to estimate the effect of treatment on the systemic index and oxidative stress.

The gain of motor functions was significantly improved and was early noticed in the treated mice. Restoration of muscle mass and elevated haemoglobin level were statistically significant in the treatment group.

This study indicates that Cannabis sativa L. supplementation accelerates the motor functions recovery after nerve compression injury.”

https://www.ncbi.nlm.nih.gov/pubmed/31103973

CBD: A New Hope?

 ACS Medicinal Chemistry Letters“The nonpsychoactive phytocannabinoid, CBD, was recently approved by the Food and Drug Administration for the treatment of children with drug-resistant epilepsy. This milestone opens new avenues for cannabinoid research. In this Viewpoint, we provide an overview of recent progress in the field highlighting molecular insights into CBD’s mechanism of action, as well as its therapeutic potential.”

https://www.ncbi.nlm.nih.gov/pubmed/31097982

https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00127

Diverse TRPV1 responses to cannabinoids.

 Publication Cover“Cannabinoid compounds are potential analgesics. Users of medicinal Cannabis report efficacy for pain control, clinical studies show that cannabis can be effective and opioid sparing in chronic pain, and some constituent cannabinoids have been shown to target nociceptive ion channels. Here, we explore and compare a suite of cannabinoids for their impact upon the physiology of TRPV1. The cannabinoids tested evoke differential responses in terms of kinetics of activation and inactivation. Cannabinoid activation of TRPV1 displays significant dependence on internal and external calcium levels. Cannabinoid activation of TRPV1 does not appear to induce the highly permeant, pore-dilated channel state seen with Capsaicin, even at high current amplitudes. Finally, we analyzed cannabinoid responses at nocioceptive channels other than TRPV1 (TRPV2, TRPM8 and TRPA1), and report that cannabinoids differentially activate these channels. On the basis of response activation and kinetics, state-selectivity and receptor selectivity, it may be possible to rationally design approaches to pain using single or multiple cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/31096838

https://www.tandfonline.com/doi/full/10.1080/19336950.2019.1619436

Cannabidivarin completely rescues cognitive deficits and delays neurological and motor defects in male Mecp2 mutant mice.

SAGE Journals“Recent evidence suggests that 2-week treatment with the non-psychotomimetic cannabinoid cannabidivarin (CBDV) could be beneficial towards neurological and social deficits in early symptomatic Mecp2 mutant mice, a model of Rett syndrome (RTT). The aim of this study was to provide further insights into the efficacy of CBDV in Mecp2-null mice using a lifelong treatment schedule to evaluate its effect on recognition memory and neurological defects in both early and advanced stages of the phenotype progression. CBDV rescues recognition memory deficits in Mecp2 mutant mice and delays the appearance of neurological defects. CBDV administration exerts an enduring rescue of memory deficits in Mecp2 mutant mice. CBDV delays neurological defects but this effect is only transient.” https://www.ncbi.nlm.nih.gov/pubmed/31084246

“Chronic treatment with the phytocannabinoid Cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome.”  https://www.ncbi.nlm.nih.gov/pubmed/30056123

Terpenes in Cannabis sativa – From plant genome to humans.

Plant Science“Cannabis sativa (cannabis) produces a resin that is valued for its psychoactive and medicinal properties. Despite being the foundation of a multi-billion dollar global industry, scientific knowledge and research on cannabis is lagging behind compared to other high-value crops. This is largely due to legal restrictions that have prevented many researchers from studying cannabis, its products, and their effects in humans. Cannabis resin contains hundreds of different terpene and cannabinoid metabolites. Our understanding of the genomic and biosynthetic systems of these metabolites in cannabis, and the factors that affect their variability, is rudimentary. As a consequence, there is concern about lack of consistency with regard to the terpene and cannabinoid composition of different cannabis ‘strains’. Likewise, claims of some of the medicinal properties attributed to cannabis metabolites would benefit from thorough scientific validation.”
https://www.ncbi.nlm.nih.gov/pubmed/31084880 

https://www.sciencedirect.com/science/article/pii/S0168945219301190?via%3Dihub

“Medicinal properties of terpenes found in Cannabis sativa”   https://www.ncbi.nlm.nih.gov/pubmed/30096653

“Terpene synthases from Cannabis sativa”   https://www.ncbi.nlm.nih.gov/pubmed/28355238