Monthly Archives: April 2018

Cannabidiol regulates behavioural alterations and gene expression changes induced by spontaneous cannabinoid withdrawal.

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“Cannabidiol (CBD) represents a promising therapeutic tool for treating cannabis use disorder (CUD).

This study aimed to evaluate the effects of CBD on the behavioural and gene expression alterations induced by spontaneous cannabinoid withdrawal.

CONCLUSION AND IMPLICATIONS:

The results suggest that CBD alleviates spontaneous cannabinoid withdrawal and normalises associated gene expression changes. Future studies are needed to determine the relevance of CBD as a potential therapeutic tool for treating CUD.”

https://www.ncbi.nlm.nih.gov/pubmed/29624642

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14226

Suppression of Cisplatin-Induced Vomiting by Cannabis sativa in Pigeons: Neurochemical Evidences.

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“Cannabis sativa (CS, family Cannabinaceae) has been reported for its anti-emetic activity against cancer chemotherapy-induced emesis in animal models and in clinics. The current study was designed to investigate CS for potential effectiveness to attenuate cisplatin-induced vomiting in healthy pigeons and to study the impact on neurotransmitters involved centrally and peripherally in the act of vomiting.

High-performance liquid chromatography system coupled with electrochemical detector was used for the quantification of neurotransmitters 5-hydroxytryptamine (5HT), dopamine (DA) and their metabolites; Di-hydroxy Phenyl Acetic acid (Dopac), Homovanillic acid (HVA), and 5-hydroxy indole acetic acid (5HIAA) centrally in specific brain areas (area postrema and brain stem) while, peripherally in small intestine. Cisplatin (7 mg/kg i.v.) induce emesis without lethality across the 24 h observation period.

CS hexane fraction (CS-HexFr; 10 mg/kg) attenuated cisplatin-induced emesis ∼ 65.85% (P < 0.05); the reference anti-emetic drug, metoclopramide (MCP; 30 mg/kg), produced ∼43.90% reduction (P < 0.05). At acute time point (3rd h), CS-HexFr decreased (P < 0.001) the concentration of 5HT and 5HIAA in the area postrema, brain stem and intestine, while at 18th h (delayed time point) CS-HexFr attenuated (P < 0.001) the upsurge of 5HT caused by cisplatin in the brain stem and intestine and dopamine in the area postrema. CS-HexFr treatment alone did not alter the basal neurotransmitters and their metabolites in the brain areas and intestine except 5HIAA and HVA, which were decreased significantly.

In conclusion the anti-emetic effect of CS-HexFr is mediated by anti-serotonergic and anti-dopaminergic components in a blended manner at the two different time points, i.e., 3rd and 18th h in pigeons.”

 https://www.ncbi.nlm.nih.gov/pubmed/29615907
https://www.frontiersin.org/articles/10.3389/fphar.2018.00231/full

Endocannabinoid System and Migraine Pain: An Update.

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“The trigeminovascular system (TS) activation and the vasoactive release from trigeminal endings, in proximity of the meningeal vessels, are considered two of the main effector mechanisms of migraine attacks. Several other structures and mediators are involved, however, both upstream and alongside the TS.

Among these, the endocannabinoid system (ES) has recently attracted considerable attention. Experimental and clinical data suggest indeed a link between dysregulation of this signaling complex and migraine headache.

Clinical observations, in particular, show that the levels of anandamide (AEA)-one of the two primary endocannabinoid lipids-are reduced in cerebrospinal fluid and plasma of patients with chronic migraine (CM), and that this reduction is associated with pain facilitation in the spinal cord.

AEA is produced on demand during inflammatory conditions and exerts most of its effects by acting on cannabinoid (CB) receptors. AEA is rapidly degraded by fatty acid amide hydrolase (FAAH) enzyme and its levels can be modulated in the peripheral and central nervous system (CNS) by FAAH inhibitors.

Inhibition of AEA degradation via FAAH is a promising therapeutic target for migraine pain, since it is presumably associated to an increased availability of the endocannabinoid, specifically at the site where its formation is stimulated (e.g., trigeminal ganglion and/or meninges), thus prolonging its action.”

https://www.ncbi.nlm.nih.gov/pubmed/29615860

https://www.frontiersin.org/articles/10.3389/fnins.2018.00172/full

Medical cannabis for paediatric developmental–behavioural and psychiatric disorders

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“Humans have used marijuana for millennia, variously as a spiritual sacrament, herbal medicine, dietary supplement or psychoactive inebriant. Use of Medical Cannabis (MC) is advocated for an increasing range of medical indications. Anecdotally, use of naturally occurring cannabis (phytocannabinoids) is said to have a calming effect in some children. There has been little drug discovery work in the field of child and adolescent mental health for many years, and there is an urgent need to develop safe and effective therapeutics for this vulnerable patient group. Medical cannabis may be one such treatment. In summary, MC has potential as a therapeutic option in the management of paediatric mental health symptoms; however, the evidence to support its use for these patients is not yet in. ” https://onlinelibrary.wiley.com/doi/full/10.1111/jpc.13902

The Role of Cannabis Legalization in the Opioid Crisis

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“The United States remains gripped by the opioid crisis. Each day, 90 Americans die from opioid overdoses. Owing to the incredible reach of the opioid crisis—it has affected people of every race, sex, and age across our country—many stakeholders are trying to combat the crisis using multipronged approaches emphasizing prevention, treatment, and law enforcement.

In this issue of JAMA Internal Medicine, Bradford et al and Wen and Hockenberry report results suggesting that cannabis legalization may play a beneficial role in the opioid crisis.”

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2676997

Association of Medical and Adult-Use Marijuana Laws With Opioid Prescribing for Medicaid Enrollees

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“In this population-based, cross-sectional study using the all-capture Medicaid prescription data for 2011 to 2016, medical marijuana laws and adult-use marijuana laws were associated with lower opioid prescribing rates (5.88% and 6.38% lower, respectively).

Medical and adult-use marijuana laws have the potential to lower opioid prescribing for Medicaid enrollees, a high-risk population for chronic pain, opioid use disorder, and opioid overdose, and marijuana liberalization may serve as a component of a comprehensive package to tackle the opioid epidemic.

These findings suggest that medical and adult-use marijuana laws have the potential to reduce opioid prescribing for Medicaid enrollees, a segment of population with disproportionately high risk for chronic pain, opioid use disorder, and opioid overdose.

Marijuana is one of the potential nonopioid alternatives that can relieve pain at a relatively lower risk of addiction and virtually no risk of overdose.”

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2677000

“Medicare, Medicaid Opioid Scripts Decline in Medical Marijuana States”  https://www.medpagetoday.com/neurology/opioids/72105

Association Between US State Medical Cannabis Laws and Opioid Prescribing in the Medicare Part D Population

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“In this study, we investigated whether medical cannabis access was associated with prescription opioid prescribing in Medicare Part D. We found that overall opioid prescribing in Part D was lower when states permit access to medical cannabis. When examining data by individual drug classes, we found that prescriptions for hydrocodone and morphine had statistically significant negative associations with medical cannabis access via dispensaries; while not statistically significant, there were also negative associations between dispensary MCLs and fentanyl and “other opioid” use. Combined with previously published studies suggesting cannabis laws are associated with lower opioid mortality, these findings further strengthen arguments in favor of considering medical applications of cannabis as one tool in the policy arsenal that can be used to diminish the harm of prescription opioids.”

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2676999

“Rise of medical marijuana eases abuse of opioids, study says”   https://www.ajc.com/news/rise-medical-marijuana-eases-abuse-opioids-study-says/uyXDks4G81MMIsrmq2mkeL/

Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.

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“Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ9-tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition.

Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users.

Conclusions:Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence.”

 https://www.ncbi.nlm.nih.gov/pubmed/29607408
https://www.liebertpub.com/doi/10.1089/can.2017.0043