Category Archives: Uncategorized

Effect of chronic THC administration in the reproductive organs of male mice, spermatozoa and in vitro fertilization.

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Biochemical Pharmacology

“The increased use of cannabis as a therapeutic drug in recent years has raised some concerns due to its potential effects on reproductive health. With regards to the male, the endocannabinoid system is involved in the spermatogenesis and in the sperm function.

The chronic use of tetrahidrocannabinol (THC) has been associated with sperm anomalies, decreased sperm motility and structural changes in the testis. However, whether THC affects sperms ability to fertilize and to generate embryos remains unclear.

The aim of this study was to evaluate this effect using a mice model of THC chronic treatment. For this purpose, a chronic treatment with THC was carried out. Mice were randomly allocated into two groups: an experimental group treated with a daily dose of 10 mg/kg-body weight THC for a period of 30 days and a control group treated with a vehicle.

The THC-mice cortex showed a significant decrease of mRNA of Cnr1 compared to control-mice while, in the testis, the expression of Cnr1 was not affected. The weight of testis and epididymis and the histological analysis did not show any change between groups.

On the other hand, no changes were observed in the sperm motility or the sperm concentration. The chronic use of THC did not generate any methylation change in the three CpG regions of Cnn1 analysed, neither in the brain nor in the embryos generated by in vitro fertilization (IVF).

Finally, the embryo production by IVF was no different using spermatozoa from both THC and control mice. This work contradicts the belief that THC consumption has a negative effect on male reproductive processes.”

 https://www.ncbi.nlm.nih.gov/pubmed/30077641
https://www.sciencedirect.com/science/article/abs/pii/S0006295218303150

Cannabinoid pharmacology and therapy in gut disorders.

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Biochemical Pharmacology

“Cannabis sp and their products (marijuana, hashish…), in addition to their recreational, industrial and other uses, have a long history for their use as a remedy for symptoms related with gastrointestinal diseases.

After many reports suggesting these beneficial effects, it was not surprising to discover that the gastrointestinal tract expresses endogenous cannabinoids, their receptors, and enzymes for their synthesis and degradation, comprising the so-called endocannabinoid system.

This system participates in the control of tissue homeostasis and important intestinal functions like motor and sensory activity, nausea, emesis, the maintenance of the epithelial barrier integrity, and the correct cellular microenvironment. Thus, different cannabinoid-related pharmacological agents may be useful to treat the main digestive pathologies.

To name a few examples, in irritable bowel syndrome they may normalize dysmotility and reduce pain, in inflammatory bowel disease they may decrease inflammation, and in colorectal cancer, apart from alleviating some symptoms, they may play a role in the regulation of the cell niche.

This review summarizes the main recent findings on the role of cannabinoid receptors, their synthetic or natural ligands and their metabolizing enzymes in normal gastrointestinal function and in disorders including irritable bowel syndrome, inflammatory bowel disease, colon cancer and gastrointestinal chemotherapy-induced adverse effects (nausea/vomiting, constipation, diarrhea).”

 https://www.ncbi.nlm.nih.gov/pubmed/30076849
https://www.sciencedirect.com/science/article/abs/pii/S0006295218303186

Falling rates of marijuana dependence among heavy users.

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Drug and Alcohol Dependence Home

“Marijuana use has become increasingly popular in the United States since the turn of the century, and typical use patterns among past-month marijuana users have intensified, raising concerns for an increase in cannabis use disorders (CUDs). Yet the population prevalence of CUDs has mostly remained flat. We analyzed trends in DSM-IV marijuana dependence among Daily/Near-Daily (DND) users, both overall and by age and gender, and considered potential explanations.

RESULTS:

Dependence among DND users fell by 39% (26.5%-16.1%; p < .001), with significant trend. No significant change is detected at the population level. Sub-group analysis shows a steep gradient for age but not for gender. Declines are robust to sub-group analysis, except for users over 50 years old. Among dependence symptoms, most showed significant declines: reducing important activities (p < .001); use despite emotional, mental, or physical problems (p < .001); failing attempts to cutback (p < .001); lots of time getting, using, or getting over marijuana (p < .01); and failing to keep limits set on use (p < .05). Reported tolerance showed no significant change.

CONCLUSIONS:

Though it is unclear why, the risk of dependence formation among heavy marijuana users appear to have declined since 2002. Further research is warranted regarding explanations related to state marijuana policies, product forms, or social context.”

https://www.ncbi.nlm.nih.gov/pubmed/30077891

https://www.drugandalcoholdependence.com/article/S0376-8716(18)30389-2/fulltext

Elucidation of structure-function relationship of THCA and CBDA synthase from Cannabis sativa L.

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Journal of Biotechnology

“Cannabinoids are secondary natural products from the plant Cannabis sativa L.

Therapeutic indications of cannabinoids currently comprise a significant area of medicinal research.

We have expressed the Δ9-tetrahydrocannabinolic acid synthase (THCAS) and cannabidiolic acid synthase (CBDAS) recombinantly in Komagataella phaffii and could detect eight different products with a cannabinoid scaffold after conversion of the precursor cannabigerolic acid (CBGA).

Besides five products remaining to be identified, both enzymes were forming three major cannabinoids of C. sativa – Δ9-tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA).

These studies lay the groundwork for further research as well as biotechnological cannabinoid production.”

 https://www.ncbi.nlm.nih.gov/pubmed/30053500
https://www.sciencedirect.com/science/article/pii/S0168165618305698?via%3Dihub

Brain activity of anandamide: a rewarding bliss?

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“Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors. These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive ingredient in Cannabis sativa.

Several studies demonstrate that anandamide exerts an overall modulatory effect on the brain reward circuitry. Several reports suggest its involvement in the addiction-producing actions of other abused drugs, and it can also act as a behavioral reinforcer in animal models of drug abuse.

Importantly, all these effects of anandamide appear to be potentiated by pharmacological inhibition of its metabolic degradation. Enhanced brain levels of anandamide after treatment with inhibitors of fatty acid amide hydrolase, the main enzyme responsible for its degradation, seem to affect the rewarding and reinforcing actions of many drugs of abuse.

In this review, we will provide an overview from a preclinical perspective of the current state of knowledge regarding the behavioral pharmacology of anandamide, with a particular emphasis on its motivational/reinforcing properties. We will also discuss how modulation of anandamide levels through inhibition of enzymatic metabolic pathways could provide a basis for developing new pharmaco-therapeutic tools for the treatment of substance use disorders.”

 https://www.ncbi.nlm.nih.gov/pubmed/30050084
https://www.nature.com/articles/s41401-018-0075-x

Emerging strategies targeting cb2 cannabinoid receptor: biased agonism and allosterism.

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Biochemical Pharmacology

“During these last years, the CB2 cannabinoid receptor has emerged as a potential anti-inflammatory target in diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, ischemic stroke, autoimmune diseases, osteoporosis, and cancer. However, the development of clinically useful CB2 agonists reveals to be very challenging. Allosterism and biased-signaling mechanisms at CB2 receptor may offer new avenues for the development of improved CB2 receptor-targeted therapies. Although there has been some exploration of CB1 receptor activation by new CB1 allosteric or biased-signaling ligands, the CB2 receptor is still at initial stages in this domain. In an effort to understand the molecular basis behind these pharmacological approaches, we have analyzed and summarized the structural data reported so far at CB2 receptor.”

https://www.ncbi.nlm.nih.gov/pubmed/30055149
https://www.sciencedirect.com/science/article/abs/pii/S0006295218302995

Chronic treatment with the phytocannabinoid Cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome.

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Neuropharmacology

“Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms. RTT is caused by mutations in the MECP2 gene in about 95% of cases and to date no cure is available.

The endocannabinoid system modulates several physiological processes and behavioural responses that are impaired in RTT and its deregulation has been associated with neuropsychiatric disorders which have symptoms in common with RTT.

The present study evaluated the potential therapeutic efficacy for RTT of cannabidivarin (CBDV), a non-psychotropic phytocannabinoid from Cannabis sativa that presents antagonistic properties on the G protein-coupled receptor 55 (GPR55), the most recently identified cannabinoid receptor.

Present results demonstrate that systemic treatment with CBDV (2, 20, 100 mg/Kg ip for 14 days) rescues behavioural and brain alterations in MeCP2-308 male mice, a validated RTT model. The CBDV treatment restored the compromised general health status, the sociability and the brain weight in RTT mice. A partial restoration of motor coordination was also observed. Moreover, increased levels of GPR55 were found in RTT mouse hippocampus, suggesting this G protein-coupled receptor as new potential target for the treatment of this disorder.

Present findings highlight for the first time for RTT the translational relevance of CBDV, an innovative therapeutic agent that is under active investigation in the clinical setting.”

 https://www.ncbi.nlm.nih.gov/pubmed/30056123
https://www.sciencedirect.com/science/article/pii/S0028390818304131?via%3Dihub

Adolescent Marijuana Use, Marijuana-Related Perceptions, and Use of Other Substances Before and After Initiation of Retail Marijuana Sales in Colorado (2013-2015).

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“Due to the recentness of changes to marijuana policies in a number of states, the effect on adolescent use and perceptions is not yet well understood. This study examines change in adolescent marijuana use and related perceptions in Colorado, before and after the implementation of legal commercial sale of recreational marijuana for adults starting on January 1, 2014.

The data are from a repeated cross-sectional survey of a representative sample of Colorado high school students, with separately drawn samples surveyed in fall 2013 (prior to implementation) and fall 2015 (18 months after implementation). We examined change in the prevalence of adolescent marijuana use, measured by lifetime use, past 30-day use, frequent use, and use on school property. To consider the possibility of heterogeneity in the change in marijuana use, we examined change in past 30-day marijuana use by demographic characteristics (sex, grade, race/ethnicity), school characteristics (poverty, percent minority), urbanicity of the school district, and whether the city or county permitted retail marijuana stores.

There was an absence of significant effects for change in lifetime or past 30-day marijuana use. Among those reporting past 30-day use, frequent use and use on school property declined. There was a significant decline in the perceived harm associated with marijuana use, but we did not find a significant effect for perceived wrongfulness, perceived ease of access, or perceived parental disapproval. We did not find significant variability in past 30-day use by demographic characteristics or by school and community factors from 2013 to 2015.

We did not find a significant effect associated with the introduction of legal sales of recreational marijuana to adults in Colorado on adolescent (illegal) use, but ongoing monitoring is warranted, including consideration of heterogeneity in the effects of marijuana policies.”

https://www.ncbi.nlm.nih.gov/pubmed/30043198
https://link.springer.com/article/10.1007%2Fs11121-018-0933-2

Long-Term Heavy Recreational Cannabis Use and Serum Delta-9-Tetrahydrocannabinol Levels are not Associated with an Impaired Liver Function in Cannabis Dependents.

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Publication Cover

“To shed more light on the influence of chronic cannabis use on liver function, we performed a post-hoc analysis of routine lab data of 42 inpatient treatment-seeking (9 female, median: 27 years old) pure cannabis dependents. Serum liver function tests (LFT: transaminases, bilirubin), C-reactive protein (CRP), carbohydrate-deficient transferrin (CDT), and body mass index (BMI) were considered. The LFT were correlated with CDT, BMI, and cannabis-related clinical data (CR); i.e., the serum levels of delta-9-tetrahydrocannabinol (THC) and its major metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), plus the cannabis-history data. The LFT was normal in 32 (76.2%) patients. There was no significant association of LFT with BMI, CRP, CDT, and CR. No significant differences were found between the group with elevated LFT (N = 10) and the group without elevated LFT (N = 32) regarding BMI, CRP, CDT, and CR, except for THC-OH, which was even lower in the elevated-LFT group. These results argue against a relevant harmful impact of chronic cannabis inhalation on the liver function of relatively healthy humans (apart from nicotine dependence). Specifically, the liver function tests were not significantly influenced by THC and THC-COOH levels, both objective markers for the amount and duration of prior cannabis use.”

https://www.ncbi.nlm.nih.gov/pubmed/30052163

https://www.tandfonline.com/doi/abs/10.1080/02791072.2018.1482031?journalCode=ujpd20

Alcohol, Marijuana, and Dating Abuse Perpetration by Young Adults: Results of a Daily Call Study.

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SAGE Journals

“The purpose of this study was to investigate same-day alcohol or marijuana use and dating abuse (DA) perpetration in a sample of 60 noncollege-attending young adults. Participants reported daily data for 3 months. DA perpetration was more likely on days when participants also reported alcohol use (odds ratio [OR] = 2.17, 95% confidence interval [CI] = [1.38, 3.42]), but analyses of the temporal order indicated that alcohol use was not a proximal predictor of DA. Same day marijuana use was not associated with elevated risk of DA perpetration (OR = 1.40, 95% CI = [0.89, 2.21]). Results suggest the alcohol-DA relationship may vary by sample and context.”

https://www.ncbi.nlm.nih.gov/pubmed/30037318

http://journals.sagepub.com/doi/abs/10.1177/1077801218781959?journalCode=vawa