Tag Archives: Cannabinoids

Enhancing Endocannabinoid Neurotransmission Augments The Efficacy of Extinction Training and Ameliorates Traumatic Stress-Induced Behavioral Alterations in Rats.

Posted on by
Reply

Image result for neuropsychopharmacology

“Exposure to a traumatic event may result in the development of Post-Traumatic Stress Disorder (PTSD).

Endocannabinoids are crucial modulators of the stress response, interfere with excessive retrieval and facilitate the extinction of traumatic memories. Exposure therapy, combined with pharmacotherapy, represents a promising tool for PTSD treatment.

We investigated whether pharmacological manipulations of the endocannabinoid system during extinction learning ameliorates the behavioral changes induced by trauma exposure.

Our findings suggest that drugs potentiating endocannabinoid neurotransmission may represent promising tools when combined to exposure-based psychotherapies in the treatment of PTSD.”

https://www.ncbi.nlm.nih.gov/pubmed/29265107

https://www.nature.com/articles/npp2017305

Role of the endogenous cannabinoid receptor 1 in brain injury induced by chronic intermittent hypoxia in rats.

Posted on by
Reply

Publication Cover

“This study investigated the effect of rimonabant, a cannabinoid receptor type 1 (CB1) antagonist, on calcium/calmodulin dependent protein kinase II (CaMKII) and CB1 in chronic intermittent hypoxia (CIH).

Rimonabant had a protective effect against CIH.” https://www.ncbi.nlm.nih.gov/pubmed/29264962

http://www.tandfonline.com/doi/abs/10.1080/00207454.2017.1420069

 

Restoration of osteogenic differentiation by overexpression of cannabinoid receptor 2 in bone marrow mesenchymal stem cells isolated from osteoporotic patients.

Posted on by
1

 Journal Cover

“Cannabinoid receptor 2 (CNR2) has a critical role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). CNR2 expression was found to be downregulated in osteoporotic patients.

The present study aimed to investigate the functionality of CNR2 in restoring osteogenic differentiation and mineralization of BMSCs isolated from osteoporotic patients.

The results demonstrated that overexpression of CNR2 in osteoporotic BMSCs increased ALP activity, promoted expression of osteogenic genes and enhanced deposition of mineralized extracellular matrix. In addition, phosphorylation of p38 MAPK was found to be increased by overexpression of CNR2.

In conclusion, the present study indicated that restoration of CNR2 recovered the osteogenic differentiation of BMSCs isolated from osteoporotic patients. This finding may provide a novel strategy for a treatment approach for osteoporosis.”

https://www.ncbi.nlm.nih.gov/pubmed/29250156

https://www.spandidos-publications.com/10.3892/etm.2017.5369

Cannabinoids for the treatment of neuropsychiatric symptoms, pain and weight loss in dementia.

Posted on by
Reply

“Efficacious treatment for neuropsychiatric symptoms (NPS), pain and weight loss for dementia patients is desperately needed.

This review presents an up-to-date look at the literature investigating the use of cannabinoid for these symptoms in dementia.

RECENT FINDINGS:

We searched electronically for publications regarding cannabinoid use in dementia, with a focus on Alzheimer’s disease. Seven studies and one case report have been conducted to examine the use of cannabinoids for the treatment of NPS of dementia, and three of these trials reported on the effect of cannabinoids on weight. Five studies reported decreased agitation or improvements in sleep with cannabinoid use. One crossover trial found that cannabinoids positively impacted weight, whereas a chart review study found no impact on weight with cannabinoids, but an increase in food intake. There were no trials examining the use of cannabinoids for pain in dementia.

SUMMARY:

Findings from trials with small sample sizes and various clinical populations suggest that cannabinoid use may be well tolerated and effective for treatment of NPS such as agitation as well as weight and pain management in patients with dementia. Additional studies are necessary to further elucidate the relative risks and benefits of this treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/29256923
https://insights.ovid.com/crossref?an=00001504-900000000-99303
http://journals.lww.com/co-psychiatry/Abstract/publishahead/Cannabinoids_for_the_treatment_of_neuropsychiatric.99303.aspx

Provider Perspectives on Use of Medical Marijuana in Children With Cancer.

Posted on by
Reply

Home

“Although medical marijuana (MM) may have utility in the supportive care of children with serious illness, it remains controversial.

We investigated interdisciplinary provider perspectives on legal MM use in children with cancer.

Most pediatric oncology providers are willing to consider MM use in children with cancer and receive frequent inquiries.” https://www.ncbi.nlm.nih.gov/pubmed/29233937

http://pediatrics.aappublications.org/content/early/2017/12/08/peds.2017-0559.long

“Medical Marijuana For Children With Cancer Broadly Supported By Doctors. An overwhelming majority of health care professionals who care for children with cancer would be willing to help those children get medical marijuana” https://www.forbes.com/sites/tarahaelle/2017/12/12/medical-marijuana-for-children-with-cancer-broadly-supported-by-doctors/#3d31cf08795d

“Most doctors would allow medical marijuana for children with cancer, study finds. A considerable majority of medical physicians would help children treat cancer with medical cannabis, a new study suggests.” http://blog.sfgate.com/smellthetruth/2017/12/12/most-doctors-would-allow-medical-marijuana-for-children-with-cancer-study-finds/

“Clinicians Support Medical Marijuana Use in Children With Cancer, But Lack Knowledge” https://jamanetwork.com/journals/jama/fullarticle/2672986

Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.

Posted on by
Reply

 SAGE Journals

“Clostridium difficile toxin A is responsible for colonic damage observed in infected patients.

Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity.

The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A.

RESULTS:

Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251.

CONCLUSIONS:

Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.”

https://www.ncbi.nlm.nih.gov/pubmed/29238589

“In the last decade, cannabinoids extracted from the marijuana plant (Cannabis sativa) and synthetic cannabinoids have shown numerous beneficial effects on gastrointestinal (GI) functions. Non-psychotropic phytocannabinoid cannabidiol (CBD) is one of the most interesting compounds, since it exerts a wide range of beneficial pharmacological actions on GI functions, ranging from antioxidant to antinflammatory activities. CBD has been shown to act as a non-competitive negative allosteric modulator of CB1 receptors. Notably, CBD is able to restore in vitro intestinal permeability increased by ethylenediaminetetraacetic acid (EDTA) or pro-inflammatory stimuli.

Conclusion

Clostridium difficile infection is the leading cause of hospital-acquired diarrhoea and pseudomembranous colitis. Clostridium difficile-Toxin A significantly affects enterocytes permeability leading to apoptosis and colonic mucosal damage.

In the present study, we showed that Cannabidiol, a non-psychotropic component of Cannabis sativa significantly inhibit the apoptosis rate in TcdA-exposed cells and restores barrier function by a significant RhoA GTP rescue.

We also provide evidence that the effects of Cannabidiol are mediated by CB-1 receptor.

Given the absence of any significant toxic effect in humans, cannabidiol may ideally represent an effective adjuvant treatment for Clostridium difficile-associated colitis.”   http://journals.sagepub.com/doi/10.1177/2050640617698622

HIV-infected cannabis users have lower circulating CD16+ monocytes and IP-10 levels compared to non-using HIV patients.

Posted on by
Reply

Related image

“Chronic immune activation and elevated numbers of circulating activated monocytes (CD16) are implicated in HIV-associated neuroinflammation.

The objective was to compare the level of circulating CD16 monocytes and interferon-γ-inducible protein 10 (IP-10) between HIV-infected cannabis users (HIV+MJ+) and non-cannabis users (HIV+MJ-), and determine whether in vitro Δ-Tetrahydrocannabinol (THC), a constituent of cannabis, affected CD16 expression as well as IP-10 production by monocytes.

RESULTS:

HIV+MJ+ donors possessed a lower level of circulating CD16 monocytes and serum IP-10, compared to HIV+MJ- donors. Further, monocytes from HIV+MJ+ donors were unable to induce CD16 expression when treated with in vitro IFNα, while HIV-MJ- and HIV+MJ- donors displayed pronounced CD16 induction, suggesting anti-inflammatory effects by cannabis.

CONCLUSIONS:

Components of cannabis, including THC, may decelerate peripheral monocyte processes that are implicated in HIV-associated neuroinflammation.”   https://www.ncbi.nlm.nih.gov/pubmed/29194121

http://journals.lww.com/aidsonline/Abstract/publishahead/HIV_infected_cannabis_users_have_lower_circulating.97348.aspx

“Medical Cannabis May Improve Neurocognitive Disorder in Patients With HIV. Medical marijuana could help prevent the development of neurocognitive disorders in patients with HIV, according to a new study. Tetrahydrocannabinol (THC), the prominent compound in marijuana, was found to slow the process of neurodegeneration — a condition common in about half of all patients with HIV — according to a study from researchers at Michigan State University (MSU).” https://www.specialtypharmacytimes.com/news/medical-cannabis-may-improve-neurocognitive-disorder-in-patients-with-hiv

“Marijuana may help HIV patients keep mental stamina longer. Norbert Kaminski, director of Michigan State University‘s Institute for Integrative Toxicology, has found that a chemical in marijuana, known as THC, can potentially slow the process of mental decline that can occur in up to 50 percent of HIV patients.” https://medicalxpress.com/news/2017-12-marijuana-hiv-patients-mental-stamina.html

“New Research Says A Chemical in Marijuana May Help HIV Patients Maintain Their Mental Fortitude. “The patients who didn’t smoke marijuana had a very high level of inflammatory cells compared to those who did use. In fact, those who used marijuana had levels pretty close to a healthy person not infected with HIV.”” http://game360.co/2017/12/new-research-says-chemical-marijuana-may-help-hiv-patients-maintain-mental-fortitude/

“Cannabis could prevent mental decline in up to 50 percent of HIV sufferers, new research reveals. Patients who use marijuana have fewer inflammatory white blood cells, which are involved in the immune system, a study found. This could save infected people from mental decline, which affects up to 50 percent of sufferers due to ongoing inflammation in the brain as a result of the immune system constantly fighting the virus. Lead author Professor Norbert Kaminski from Michigan State University, said: ‘Those who used marijuana had [inflammatory cell] levels pretty close to a healthy person not infected with HIV.'” http://www.dailymail.co.uk/health/article-5174379/Cannabis-prevent-mental-decline-HIV-sufferers.html

“Marijuana may help increase mental strength in HIV patients”  http://www.timesnownews.com/health/article/marijuana-may-help-increase-mental-strength-in-hiv-patients/145504

Medical marijuana laws and adolescent use of marijuana and other substances: Alcohol, cigarettes, prescription drugs, and other illicit drugs

Posted on by
Reply

Drug and Alcohol Dependence Home

“Historical shifts have taken place in the last twenty years in marijuana policy. The impact of medical marijuana laws (MML) on use of substances other than marijuana is not well understood. We examined the relationship between state MML and use of marijuana, cigarettes, illicit drugs, nonmedical use of prescription opioids, amphetamines, and tranquilizers, as well as binge drinking.

Among 8th graders, the prevalence of marijuana, binge drinking, cigarette use, non-medical use of opioids, amphetamines and tranquilizers, and any non-marijuana illicit drug use decreased after MML enactment.

Among 10th graders, the prevalence of substance use did not change after MML enactment.

Among 12th graders, non-medical prescription opioid and cigarette use increased after MML enactment.

Conclusions

MML enactment is associated with decreases in marijuana and other drugs in early adolescence in those states.

  • •Substance use decreased among 8th graders after medical marijuana use was legalized.
  • •Substance use did not change among 10th graders following legalization.
  • •Prescription drug and cigarette use increased among 12th graders after legalization.”

http://www.drugandalcoholdependence.com/article/S0376-8716(17)30569-0/abstract

From “Azalla” to Anandamide: Distilling the Therapeutic Potential of Cannabinoids

Posted on by
Reply

Biological Psychiatry Home

“Cannabis has held a unique place in the hearts and minds of people since time immemorial: some have exalted its properties and considered it to be sacred; others have reviled it, considering it a root cause of social evil.

The Assyrians, who lived about 3000 years ago, documented the effects of cannabis on clay tablets. They referred to the plant according to its various uses: as “azalla,” when used as a medical agent; as hemp; and as “gan-zi-gun-nu”—“the drug that takes away the mind”   These seemingly contradictory properties—a substance that can be both a therapeutic agent and a corrupting psychoactive drug—have continued to puzzle us over the ensuing centuries.

As early as the 11th century, excessive cannabis use was suggested to be a cause of “moral degeneracy.”  On the other hand, the ostensible therapeutic value of cannabis was documented extensively in the early 19th century by Sir William B. O’Shaughnessy, an Irish physician working in Calcutta, India.

Given the critical role of the endocannabinoid system in modulating anxiety, it is clear that compounds that can modulate this system offer great promise as therapeutic agents for psychiatric disorders. It is therefore not surprising that the concept of medical marijuana is compelling to laypersons, clinicians, and researchers alike.

While there is not yet a robust body of literature supporting any specific psychiatric indication (despite the regulatory approval in some states of medical marijuana for specific psychiatric disorders), active lines of investigation of therapeutic targets within the endocannabinoid system offer hope for better treatment options.

The evidence at present suggests that the question of whether cannabinoids are good or bad is not dichotomous—it is likely both good and bad depending on the context of use, including dose, duration of exposure, and an individual’s genetic vulnerabilities. Therefore, the challenge that remains is to distill the good therapeutic effects of cannabinoids and thus weed out “gan-zi-gun-nu” from “azalla.””

http://www.biologicalpsychiatryjournal.com/article/S0006-3223(17)32207-2/fulltext

 

Neuroprotective Properties of Endocannabinoids N-Arachidonoyl Dopamine and N-Docosahexaenoyl Dopamine Examined in Neuronal Precursors Derived from Human Pluripotent Stem Cells.

Posted on by
Reply

Biochemistry (Moscow)

“Neuroprotective properties of endocannabinoids N-arachidonoyl dopamine (NADA) and N-docosahexaenoyl dopamine (DHDA) were examined in neuronal precursor cells differentiated from human induced pluripotent stem cells and subjected to oxidative stress. Both compounds exerted neuroprotective activity, which was enhanced by elevating the concentration of the endocannabinoids within the 0.1-10 µM range. However, both agents at 10 µM concentration showed a marked toxic effect resulting in death of ~30% of the cells. Finally, antagonists of cannabinoid receptors as well as the receptor of the TRPV1 endovanilloid system did not hamper the neuroprotective effects of these endocannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/29223163

https://link.springer.com/article/10.1134%2FS0006297917110141