Cannabinoids prevent depressive-like symptoms and alterations in BDNF expression in a rat model of PTSD.

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“Posttraumatic stress disorder (PTSD) is a debilitating condition highly comorbid with depression. The endocannabinoid (eCB) system and brain-derived neurotrophic factor (BDNF) are suggestively involved in both disorders.

We examined whether cannabinoids can prevent the long-term depressive-like symptoms induced by exposure to the shock and situational reminders (SRs) model of PTSD. The CB1/2 receptor agonist WIN55,212-2 (0.5 mg/kg; i.p.), the fatty acid hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg, i.p.) or vehicle were administered 2 h after severe shock.

Cannabinoids prevented the shock/SRs-induced alterations in social recognition memory, locomotion, passive coping, anxiety-like behavior, anhedonia, fear retrieval, fear extinction and startle response as well as the decrease in BDNF levels in the hippocampus and prefrontal cortex (PFC). Furthermore, significant correlations were found between depressive-like behaviors and BDNF levels in the brain.

The findings suggest that cannabinoids may prevent both depressive- and PTSD-like symptoms following exposure to severe stress and that alterations in BDNF levels in the brains’ fear circuit are involved in these effects.”

https://www.ncbi.nlm.nih.gov/pubmed/29458190

https://www.sciencedirect.com/science/article/pii/S027858461731000X

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Role of the Endocannabinoid System in the Neurobiology of Suicide

Cover of The Neurobiological Basis of Suicide

“In the past decade, remarkable advances have been made in cannabinoid (CB) research. The brain endocannabinoid (eCB) system modulates several neurobiological processes and its dysfunction is suggested to be involved in the pathophysiology of mood and drug use disorders.

The CB1 receptor–mediated signaling, in particular, has been shown to play a critical role in the neural circuitry that mediates mood, motivation, and emotional behaviors. This chapter presents the data pertaining to the involvement of the eCB system in depression, suicide, and alcohol addiction.

It appears that the eCB system might have a critical role in the regulation of mood and emotional responses that are impaired in patients with depression and suicidal behavior.

The data provided in this chapter support the notion that the eCB system might be an additional target for the development of a drug against alcohol use, depression, and suicidal behavior.

Among therapeutic agents, antidepressants are the most widely used drugs for the treatment of depression-related disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/23035286

https://www.ncbi.nlm.nih.gov/books/NBK107200/

“Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from cannabis sativa L. The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. Results of this study show that Δ9-THC and other cannabinoids exert anti-depressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/

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The Cannabinoids Δ8THC, CBD, and HU-308 Act via Distinct Receptors to Reduce Corneal Pain and Inflammation

Mary Ann Liebert, Inc. publishers

“Corneal injury can result in dysfunction of corneal nociceptive signaling and corneal sensitization.

Activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory.

The purpose of this research was to investigate the antinociceptive and anti-inflammatory effects of cannabinoids with reported actions at cannabinoid 1 (CB1R) and cannabinoid 2 (CB2R) receptors and/or noncannabinoid receptors in an experimental model of corneal hyperalgesia.

Topical cannabinoids reduce corneal hyperalgesia and inflammation.

The antinociceptive and anti-inflammatory effects of Δ8THC are mediated primarily via CB1R, whereas that of the cannabinoids CBD and HU-308, involve activation of 5-HT1A receptors and CB2Rs, respectively.

Cannabinoids could be a novel clinical therapy for corneal pain and inflammation resulting from ocular surface injury.”

https://www.ncbi.nlm.nih.gov/pubmed/29450258

http://online.liebertpub.com/doi/abs/10.1089/can.2017.0041

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The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.

Current Neurology and Neuroscience Reports

“Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms.

This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects.

We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs.

Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms.

Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.”

https://www.ncbi.nlm.nih.gov/pubmed/29442178

https://link.springer.com/article/10.1007%2Fs11910-018-0814-x

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Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.

Journal of Physiology and Biochemistry

“Among a variety of phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells.

Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death.

The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability.

These data indicate that cannabinoids modulate endometrial cancer cell death.

Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma.

Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/29441458

https://link.springer.com/article/10.1007%2Fs13105-018-0611-7

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The Association of Unfavorable Traffic Events and Cannabis Usage: A Meta-Analysis

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“In the last years were published many epidemiological articles aiming to link driving under the influence of cannabis (DUIC) with the risk of various unfavorable traffic events (UTEs), with sometimes contradictory results.

The primary objective of this study was to analyze whether there is a significant association between DUIC and UTEs.

Our analysis suggests that the overall effect size for DUIC on UTEs is not statistically significant, but there are significant differences obtained through subgroup analysis. This result might be caused by either methodological flaws (which are often encountered in articles on this topic), the indiscriminate employment of the term “cannabis use,” or an actual absence of an adverse effect.

A positive test for cannabis (i.e., blood) does not necessarily imply that drivers were impaired, as THC/metabolites might be detected in blood a long time after impairment, especially in chronic cannabis users, which could also induce an important bias in the analysis of the results.

When a driver is found, in traffic, with a positive reaction suggesting cannabis use, the result should be corroborated by either objective data regarding marijuana usage (like blood analyses, with clear cut-off values), or a clinical assessment of the impairment, before establishing his/her fitness to drive.”

https://www.frontiersin.org/articles/10.3389/fphar.2018.00099/full

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Ultrasound-Assisted Extraction of Cannabinoids from Cannabis Sativa L. Optimized by Response Surface Methodology.

Journal of Food Science

“Ultrasonication was used to extract bioactive compounds from Cannabis sativa L. such as polyphenols, flavonoids, and cannabinoids.

On comparing the ultrasonic process with the control extraction, noticeably higher values were obtained for each of the responses.

Additionally, ultrasound considerably improved the extraction of cannabinoids present in Cannabis.

PRACTICAL APPLICATION:

Low frequency ultrasound was employed to extract bioactive compounds from the inflorescence part of Cannabis. The responses evaluated were-total phenols, flavonoids, ferric reducing assay and yield. The solvent composition and time significantly influenced the extraction process. Appreciably higher extraction of cannabinoids was achieved on sonication against control.”

https://www.ncbi.nlm.nih.gov/pubmed/29437231

http://onlinelibrary.wiley.com/doi/10.1111/1750-3841.14075/abstract

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Cannabis use is associated with lower rates of initiation of injection drug use among street-involved youth: A longitudinal analysis.

Drug and Alcohol Review

“Street-involved youth are known to be at elevated risk of initiating injection drug use. However, the impact of so-called ‘gateway’ drugs, such as cannabis, on injection initiation is unknown.

The objective of this study was to examine the association between cannabis use and initiation of injection drug use among a prospective cohort of street-involved youth in Vancouver, Canada.

In a multivariable analysis, ≥daily cannabis use was associated with slower rates of injection initiation (adjusted relative hazard 0.66, 95% confidence interval 0.45-0.98; P = 0.038). Sub-analyses revealed that cannabis use was negatively associated with initiation of injection stimulants but not initiation of injection opioids.

DISCUSSION AND CONCLUSIONS:

Given the expansion of cannabis legalisation throughout North America, it is encouraging that cannabis use was associated with slower time to initiation of injection drug use in this cohort. This finding challenges the view of cannabis as a gateway substance that precipitates the progression to using harder and more addictive drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/29430806

http://onlinelibrary.wiley.com/doi/10.1111/dar.12667/abstract

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Chronic High Doses of Cannabinoids Promote Hippocampal Neurogenesis

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“Hippocampal neurogenesis is suppressed following chronic administration of the major drugs of abuse (including opiates, alcohol, nicotine, and cocaine). However, CB1-knockout mice display significantly decreased hippocampal neurogenesis, suggesting that CB1 receptors activated by endogenous, plant-derived, or synthetic cannabinoids may promote hippocampal neurogenesis.

Cannabinoids can regulate the proliferation of hippocampal NS/PCs by acting on CB1 receptors. They found that both the synthetic cannabinoid HU210 and the endocannabinoid anandamide profoundly promote embryonic hippocampal NS/PC proliferation. Chronic, but not acute, HU210 significantly increases the number of newborn hippocampal neurons in adult rats by promoting NS/PC proliferation.

A significant increase was observed in the hipoppocampal newborn neurons of mice following twice-daily HU210 injection for 10 days.

This suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic  administration.”

Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.” https://www.jci.org/articles/view/25509

http://www.science20.com/science_why_not/blog/chronic_high_doses_cannabinoids_promote_hippocampal_neurogenesis

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Role for neuronal nitric-oxide synthase in cannabinoid-induced neurogenesis.

Role for neuronal nitric-oxide synthase in cannabinoid-induced neurogenesis.“Cannabinoids, acting through the CB1 cannabinoid receptor (CB1R), protect the brain against ischemia and related forms of injury.

This may involve inhibiting the neurotoxicity of endogenous excitatory amino acids and downstream effectors, such as nitric oxide (NO).

Cannabinoids also stimulate neurogenesis in the adult brain through activation of CB1R.

Because NO has been implicated in neurogenesis, we investigated whether cannabinoid-induced neurogenesis, like cannabinoid neuroprotection, might be mediated through alterations in NO production.” https://aggregator.leafscience.org/role-for-neuronal-nitric-oxide-synthase-in-cannabinoid-induced-neurogenesis/

“Nitric oxide negatively regulates mammalian adult neurogenesis.”  http://www.pnas.org/content/100/16/9566.long

“Thus, cannabinoids appear to stimulate adult neurogenesis by opposing the antineurogenic effect of NO.” http://jpet.aspetjournals.org/content/jpet/319/1/150.full.pdf

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