Cannabinoids, Blood-Brain Barrier, and Brain Disposition.

Image result for pharmaceutics“Potential therapeutic actions of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are based on their activity as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds.

THC and CBD lipophilicity and their neurological actions makes them candidates as new medicinal approaches to treat central nervous system (CNS) diseases. However, they show differences about penetrability and disposition in the brain.

The present article is an overview about THC and CBD crossing the blood-brain barrier (BBB) and their brain disposition. Several findings indicate that CBD can modify the deleterious effects on BBB caused by inflammatory cytokines and may play a pivotal role in ameliorating BBB dysfunction consequent to ischemia. Thus supporting the therapeutic potential of CBD for the treatment of ischemic and inflammatory diseases of CNS.

Cannabinoids positive effects on cognitive function could be also considered through the aspect of protection of BBB cerebrovascular structure and function, indicating that they may purchase substantial benefits through the protection of BBB integrity. Delivery of these cannabinoids in the brain following different routes of administration (subcutaneous, oral, and pulmonary) is illustrated and commented. Finally, the potential role of cannabinoids in drug-resistance in the clinical management of neurological or psychiatric diseases such as epilepsy and schizophrenia is discussed on the light of their crossing the BBB.”

https://www.ncbi.nlm.nih.gov/pubmed/32183416

 

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Matched pilot study examining cannabis-based dronabinol for acute pain following traumatic injury.

BMJ Journals“To determine whether adjunctive dronabinol, a licensed form of delta-9-tetrahydrocannabinol, reduces opioid consumption when used off-label for managing acute pain following traumatic injury.

CONCLUSIONS:

The results of this study suggest adjunctive dronabinol reduces opioid consumption following traumatic injury.

The opioid-sparing effect of dronabinol may be greater in patients who are marijuana users.”

https://www.ncbi.nlm.nih.gov/pubmed/32154376

https://tsaco.bmj.com/content/5/1/e000391

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Marijuana use does not affect the outcomes of bariatric surgery.

 SpringerLink“The decriminalization of marijuana and legalization of derived products requires investigation of their effect on healthcare-related outcomes. Unfortunately, little data are available on the impact of marijuana use on surgical outcomes.

We aimed to determine the effect of marijuana use on 30-day complications and 1-year weight loss following laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG).

RESULTS:

Excess BMI lost did not differ between marijuana users and controls at 3 weeks (23.0% vs 18.9%, p = 0.095), 3 months (42.0% vs 38.1%, p = 0.416), 6 months (60.6% vs 63.1%, p = 0.631), 1 year (78.2% vs 77.3%, p = 0.789), or 2 years (89.1% vs 74.5%, p = 0.604). No differences in the rate of major 30-day postoperative complications, including readmission, infection, thromboembolic events, bleeding events and reoperation rates, were found between groups. Follow-up rate at two years was lower in marijuana users (12.3% vs 27.4%, p = 0.023).

CONCLUSION:

This study suggests marijuana use has no impact on 30-day complications or weight loss following bariatric surgery, and should not be a contraindication to bariatric surgery.”

https://www.ncbi.nlm.nih.gov/pubmed/32166550

https://link.springer.com/article/10.1007%2Fs00464-020-07497-5

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Cannabinoids Improve Gastrointestinal Symptoms in a Parenteral Nutrition-Dependent Patient With Chronic Intestinal Pseudo-Obstruction.

Journal of Parenteral and Enteral Nutrition“Chronic intestinal pseudo-obstruction (CIPO) is a rare and challenging cause of pediatric intestinal failure, requiring long-term parenteral nutrition in most cases. Despite optimal management, some patients experience chronic abdominal pain and recurrent obstructive episodes with a major impact on their quality of life.

Cannabinoids have been successfully used in some conditions. However, their use in CIPO has never been reported in the literature.

We report a case of successful use of medicinal cannabinoids in a patient with CIPO, resulting in a significant reduction of abdominal pain, vomiting, and subocclusive episodes and increased appetite and weight, without major adverse events.

Although further observations are required to consolidate these findings, this case may be helpful for other patients suffering from the same condition.”

https://www.ncbi.nlm.nih.gov/pubmed/32181915

https://onlinelibrary.wiley.com/doi/abs/10.1002/jpen.1821

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Cannabinoid modulation of corticolimbic activation to threat in trauma-exposed adults: a preliminary study.

 SpringerLink“Excessive fear and anxiety, coupled with corticolimbic dysfunction, are core features of stress- and trauma-related psychopathology, such as posttraumatic stress disorder (PTSD).

Interestingly, low doses of ∆9-tetrahydrocannabinol (THC) can produce anxiolytic effects, reduce threat-related amygdala activation, and enhance functional coupling between the amygdala and medial prefrontal cortex and adjacent rostral cingulate cortex (mPFC/rACC) during threat processing in healthy adults.

Together, these findings suggest the cannabinoid system as a potential pharmacological target in the treatment of excess fear and anxiety. However, the effects of THC on corticolimbic functioning in response to threat have not be investigated in adults with trauma-related psychopathology.

OBJECTIVE:

To address this gap, the present study tests the effects of an acute low dose of THC on corticolimbic responses to threat in three groups of adults: (1) non-trauma-exposed healthy controls (HC; n = 25), (2) trauma-exposed adults without PTSD (TEC; n = 27), and (3) trauma-exposed adults with PTSD (n = 19).

METHODS:

Using a randomized, double-blind, placebo-controlled, between-subjects design, 71 participants were randomly assigned to receive either THC or placebo (PBO) and subsequently completed a well-established threat processing paradigm during functional magnetic resonance imaging.

RESULTS:

In adults with PTSD, THC lowered threat-related amygdala reactivity, increased mPFC activation during threat, and increased mPFC-amygdala functional coupling.

CONCLUSIONS:

These preliminary data suggest that THC modulates threat-related processing in trauma-exposed individuals with PTSD, which may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology.”

https://www.ncbi.nlm.nih.gov/pubmed/32162103

https://link.springer.com/article/10.1007%2Fs00213-020-05499-8

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Antinociceptive and Immune Effects of Delta-9-tetrahydrocannabinol or Cannabidiol in Male Versus Female Rats with Persistent Inflammatory Pain.

Journal of Pharmacology and Experimental Therapeutics: 373 (1)

“Chronic pain is the most common reason reported for using medical cannabis.

The goal of this research was to determine if the two primary phytocannabinoids, THC and CBD, are effective treatments for persistent inflammatory pain.

These results suggest that THC may be more beneficial than CBD for reducing inflammatory pain, in that THC maintains its efficacy with short-term treatment in both sexes, and does not induce immune activation.

SIGNIFICANCE STATEMENT: CBDs and THCs pain-relieving effects are examined in male and female rats with persistent inflammatory pain to determine if individual phytocannabinoids could be a viable treatment for men and women with chronic inflammatory pain. Additionally, sex differences in the immune response to an adjuvant and to THC and CBD are characterized to provided preliminary insight into immune-related effects of cannabinoid-based therapy for pain.”

https://www.ncbi.nlm.nih.gov/pubmed/32179573

http://jpet.aspetjournals.org/content/early/2020/03/16/jpet.119.263319

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An overview of cannabis based treatment in Crohn’s disease.

 Publication Cover“Cannabis use among inflammatory bowel disease (IBD) patients is common. There are many studies of various laboratory models demonstrating the anti-inflammatory effect of cannabis, but their translation to human disease is still lacking.

Areas covered: The cannabis plant contains many cannabinoids, that activate the endocannabinoid system. The two most abundant phytocannabinoids are the psychoactive Tetrahydrocannabinol (THC), and the (mostly) anti-inflammatory cannabidiol (CBD). Approximately 15% of IBD patients use cannabis to ameliorate disease symptoms. Unfortunately, so far there are only three small placebo controlled study regarding the use of cannabis in active Crohns disease, combining altogether 93 subjects. Two of the studies showed significant clinical improvement but no improvement in markers of inflammation.

Expert opinion: Cannabis seems to have a therapeutic potential in IBD. This potential must not be neglected; however, cannabis research is still at a very early stage. The complexity of the plant and the diversity of different cannabis chemovars create an inherent difficulty in cannabis research. We need more studies investigating the effect of the various cannabis compounds. These effects can then be investigated in randomized placebo controlled clinical trials to fully explore the potential of cannabis treatment in IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/32149543

https://www.tandfonline.com/doi/abs/10.1080/17474124.2020.1740590?journalCode=ierh20

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High expectations: The landscape of clinical trials of medical marijuana in oncology.

Complementary Therapies in Medicine“Given the infancy and evolving complexity of medicinal marijuana, an evolving political landscape, and the growing frequency of its use in cancer care, it is important for oncologists to be actively engaged in developing and successfully implementing clinical trials focusing on medical marijuana.

The purpose of this study was to analyze and evaluate trends in clinical trials focused on medical marijuana in oncology.

CONCLUSION:

Our results indicate that across oncology, there is growing interest in clinical research in the use of medical marijuana.”

https://www.ncbi.nlm.nih.gov/pubmed/32147080

https://www.sciencedirect.com/science/article/abs/pii/S0965229919309306?via%3Dihub

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What Do You Know About Maryjane? A Systematic Review of the Current Data on the THC:CBD Ratio.

Publication Cover“Ratios of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact metabolism and therapeutic effects of cannabis.

The medical and scientific communities have not drawn substantive conclusions nor thoroughly explored THC:CBD ratios for “best practice” treatment of different disease processes and their sequelae.

While there is evidence that cannabis provides medical benefits, research is lacking on standardization of medical cannabis use in modern medical practices.”

https://www.ncbi.nlm.nih.gov/pubmed/32124675

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The effects of cannabinoids on glioblastoma growth: A systematic review with meta-analysis of animal model studies.

European Journal of Pharmacology“Glioblastoma multiforme (GBM) is the most frequent and aggressive malignant brain tumour, with a poor prognosis despite available surgical and radio-chemotherapy, rising the necessity for searching alternative therapies. Several preclinical studies evaluating the efficacy of cannabinoids in animal models of GBM have been described, but the diversity of experimental conditions and of outcomes hindered definitive conclusions about cannabinoids efficacy.

A search in different databases (Pubmed, Web of Science, Scopus and SciELO) was conducted during June 2019 to systematically identify publications evaluating the effects of cannabinoids in murine xenografts models of GBM. The tumour volume and number of animals were extracted, being a random effects meta-analysis of these results performed to estimate the efficacy of cannabinoids. The impact of different experimental factors and publication bias on the efficacy of cannabinoids was also assessed. Nine publications, which satisfied the inclusion criteria, were identified and subdivided in 22 studies involving 301 animals.

Overall, cannabinoid therapy reduced the fold of increase in tumour volume in animal models of GBM, when compared with untreated controls. The overall weighted standardized difference in means (WSDM) for the effect of cannabinoids was -1.399 (95% CI: -1.900 to -0.898; P-value<0.0001). Furthermore, treatment efficacy was observed for different types of cannabinoids, alone or in combination, and for different treatment durations.

Cannabinoid therapy was still effective after correcting for publication bias. The results indicate that cannabinoids reduce the tumour growth in animal models of GBM, even after accounting for publication bias.”

https://www.ncbi.nlm.nih.gov/pubmed/32145324

https://www.sciencedirect.com/science/article/abs/pii/S0014299920301473?via%3Dihub

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