Biphasic Effects of THC in Memory and Cognition.

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“A generally undesired effect of cannabis smoking is a reversible disruption of short term memory induced by delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis.

However, this paradigm has been recently challenged by a group of scientists who have shown that THC is also able to improve neurological function in old animals when chronically administered at low concentrations.

Moreover, recent studies demonstrated that THC paradoxically promotes hippocampal neurogenesis, prevents neurodegenerative process occurring in Alzheimer Disease, protects from inflammation-induced cognitive damage and restores memory and cognitive function in old mice.

With the aim to reconcile these seemingly contradictory facts, the present work will show that such paradox can be explained within the framework of hormesis, defined as biphasic dose responses. ”

https://www.ncbi.nlm.nih.gov/pubmed/29574698

https://onlinelibrary.wiley.com/doi/abs/10.1111/eci.12920

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Targeting glial CB2 receptors to delay the progression of the pathological phenotype in TDP-43 (A315T) transgenic mice, a model of amyotrophic lateral sclerosis.

British Journal of Pharmacology banner

“CB2 receptors up-regulate in reactive microglia in the spinal cord of TDP-43(A315T) transgenic mice, an experimental model of ALS.

To determine whether such up-regulation may be pharmacologically exploited, we investigated different treatments modulating the CB2 receptor function.

CONCLUSIONS AND IMPLICATIONS:

Our study shows an important role for glial CB2 receptors in limiting the progression of the pathological phenotype in TDP-43(A315T) transgenic mice. Such benefits derived apparently from the activation of CB2 receptors concentrated in astrocytes and reactive microglia located in spinal dorsal and ventral horns.”

https://www.ncbi.nlm.nih.gov/pubmed/29574689

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14216

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Joint problems arising from lack of repair mechanisms: can cannabinoids help?

British Journal of Pharmacology banner

“Osteoarthritis (OA) is the most common disease of joints, which are complex organs where cartilage, bone and synovium cooperate to allow the range of movements. During the disease progression, the function of all three main components is jeopardized. Nevertheless, the involvement of each tissue in OA development is still not established and is the topic of the present review. The available OA therapies are symptomatic, largely targeting pain management rather than disease progression. The strong need to develop a treatment for cartilage degeneration, bone deformation and synovial inflammation has led to research on the involvement of the endocannabinoid system in the development of OA. The current review discusses the research on this topic to date and notes the advantages of exploiting endocannabinoid system modulation for cartilage, bone and synovium homeostasis, which could prevent the further progression of OA.”

https://www.ncbi.nlm.nih.gov/pubmed/29574720

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14204

“We provide experimental evidence to show that activation of the cannabinoid system enhances the survival, migration and chondrogenic differentiation of MSCs, which are three major tenets behind the success of a cell-based tissue-engineered cartilage repair strategy. These findings highlight the potential for cannabinoids to provide a dual function by acting as anti-inflammatory agents as well as regulators of MSC biology in order to enhance tissue engineering strategies aimed at cartilage repair.”

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Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model.

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“A non-psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy.

In an attempt to understand the mechanisms by which CBD exerts its anti-seizure effects, we investigated the effects of CBD at synaptic connections, and the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two major inhibitory interneurons: fast spiking, parvalbumin -expressing (PV) and adapting, cholecystokinin-expressing (CCK) interneurons.

CONCLUSIONS & IMPLICATIONS:

In conclusion, our data suggest CBD restores excitability and morphological impairment in epileptic models to pre-epilepsy control levels through multiple mechanisms to restore normal network function.”

https://www.ncbi.nlm.nih.gov/pubmed/29574880

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14202

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Cannabidiol Reverses Deficits in Hippocampal LTP in a Model of Alzheimer’s Disease.

Neurochemical Research

“Here we demonstrate for the first time that cannabidiol (CBD) acts to protect synaptic plasticity in an in vitro model of Alzheimer’s disease (AD).

The non-psycho active component of Cannabis sativa, CBD has previously been shown to protect against the neurotoxic effects of beta amyloid peptide (Aβ) in cell culture and cognitive behavioural models of neurodegeneration. Hippocampal long-term potentiation (LTP) is an activity dependent increase in synaptic efficacy often used to study cellular mechanisms related to memory.

Here we show that acute application of soluble oligomeric beta amyloid peptide (Aβ1-42) associated with AD, attenuates LTP in the CA1 region of hippocampal slices from C57Bl/6 mice. Application of CBD alone did not alter LTP, however pre-treatment of slices with CBD rescued the Aβ1-42 mediated deficit in LTP.

We found that the neuroprotective effects of CBD were not reversed by WAY100635, ZM241385 or AM251, demonstrating a lack of involvement of 5HT1A, adenosine (A2A) or Cannabinoid type 1 (CB1) receptors respectively. However in the presence of the PPARγ antagonist GW9662 the neuroprotective effect of CBD was prevented.

Our data suggests that this major component of Cannabis sativa, which lacks psychoactivity may have therapeutic potential for the treatment of AD”

https://www.ncbi.nlm.nih.gov/pubmed/29574668

https://link.springer.com/article/10.1007%2Fs11064-018-2513-z

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Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle

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“Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders.

Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control. Here, we evaluated the “anti-relapse” potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity.

Rats with alcohol or cocaine self-administration histories received transdermal CBD at 24 h intervals for 7 days and were tested for context and stress-induced reinstatement, as well as experimental anxiety on the elevated plus maze. Effects on impulsive behavior were established using a delay-discounting task following recovery from a 7-day dependence-inducing alcohol intoxication regimen.

CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. Following treatment termination, reinstatement remained attenuated up to ≈5 months although plasma and brain CBD levels remained detectable only for 3 days. CBD also reduced experimental anxiety and prevented the development of high impulsivity in rats with an alcohol dependence history.

The results provide proof of principle supporting potential of CBD in relapse prevention along two dimensions CBD: beneficial actions across several vulnerability states, and long-lasting effects with only brief treatment. The findings also inform the ongoing medical marijuana debate concerning medical benefits of non-psychoactive cannabinoids and their promise for development and use as therapeutics.”

https://www.nature.com/articles/s41386-018-0050-8

“Non-psychoactive cannabis ingredient could help addicts stay clean. Preclinical study using rats shows that Cannabidiol can reduce the risk of relapse”  https://www.sciencedaily.com/releases/2018/03/180323104821.htm

“Non-psychoactive cannabis ingredient could reduce risk of relapse among recovering addicts. A preclinical study in rats has shown that there might be value in using a non-psychoactive and non-addictive ingredient of the Cannabis sativa plant to reduce the risk of relapse among recovering drug and alcohol addicts.”  https://www.news-medical.net/news/20180323/Non-psychoactive-cannabis-ingredient-could-reduce-risk-of-relapse-among-recovering-addicts.aspx

“Non-psychoactive cannabis ingredient could help addicts stay clean”  https://www.springer.com/gp/about-springer/media/research-news/all-english-research-news/non-psychoactive-cannabis-ingredient-could-help-addicts-stay-clean/15548156

“Non-psychoactive cannabinoid may enable drug addiction recovery”  https://www.drugabuse.gov/news-events/news-releases/2018/03/non-psychoactive-cannabinoid-may-enable-drug-addiction-recovery

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Plasma anandamide concentrations are lower in children with autism spectrum disorder.

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“Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted, stereotyped behaviors and impairments in social communication.

Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD.

Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children with and without ASD (N = 112).

FINDINGS:

Anandamide concentrations significantly differentiated ASD cases (N = 59) from controls (N = 53), such that children with lower anandamide concentrations were more likely to have ASD (p = 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p = 0.034).

CONCLUSIONS:

These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD.”

https://www.ncbi.nlm.nih.gov/pubmed/29564080

https://molecularautism.biomedcentral.com/articles/10.1186/s13229-018-0203-y

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Cannabinoids for Treatment of Dystonia in Huntington’s Disease.

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“Motor symptoms in Huntington’s disease (HD) are heterogeneous with dystonia being described as a symptom with a very high prevalence not only in juvenile cases.

OBJECTIVE:

Treatment options for dystonia are limited. Cannabinoids have been described as a potential treatment for patients with dystonia of a different origin. Here, we present early onset HD patients with a marked improvement of motor symptoms mainly due to alleviation of dystonia due to treatment with cannabinoids. In addition we review the current literature concerning the use of cannabinoids in HD.

CONCLUSION:

Improvement of motor symptoms, mainly dystonia, led to several relevant improvements from a global clinical perspective such as improvement of care, gait and fine motor skills and weight gain. Moreover, we observed changes in behavior with less irritability and apathy, as well as less hypersalivation in some cases.”

https://www.ncbi.nlm.nih.gov/pubmed/29562549

https://content.iospress.com/articles/journal-of-huntingtons-disease/jhd170283

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Medical cannabis in the treatment of cancer pain and spastic conditions and options of drug delivery in clinical practice.

“The use of cannabis for medical purposes has been recently legalised in many countries including the Czech Republic. As a result, there is increased interest on the part of physicians and patients in many aspects of its application. This mini review briefly covers the main active substances of the cannabis plant and mechanisms of action. It focuses on two conditions, cancer pain and spasticity in multiple sclerosis, where its effects are well-documented. A comprehensive overview of a few cannabis-based products and the basic pharmacokinetics of marijuana’s constituents follows. The review concludes with an outline for preparing cannabis (dried inflorescence) containing drug dosage forms that can be produced in a hospital pharmacy.”

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Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model.

SciELO - Scientific Electronic Library Online

“Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients.

Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol(CBD) has been used as a therapeutic agent in many diseases.

Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS.

Maternal use of CBD had a beneficial effect on the intestinal loops of GS with decreased nitrite/nitrate and iNOS expression.”

https://www.ncbi.nlm.nih.gov/pubmed/29561958

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018000500607&lng=en&tlng=en

“Is CBD Oil Safe To Use During Pregnancy? It’s Said To Relieve Pain & Your Body Is Hurting” https://www.romper.com/p/is-cbd-oil-safe-to-use-during-pregnancy-its-said-to-relieve-pain-your-body-is-hurting-8280324

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