GPR55 – a putative “type 3” cannabinoid receptor in inflammation.

“G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor. Therefore, GPR55 has emerged as a putative “type 3″ cannabinoid receptor, establishing a novel class of cannabinoid receptor. Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/26669245

https://www.degruyter.com/view/j/jbcpp.2016.27.issue-3/jbcpp-2015-0080/jbcpp-2015-0080.xml

The Effect of Medical Marijuana Laws on the Health and Labor Supply of Older Adults: Evidence from the Health and Retirement Study

 Journal of Policy Analysis and Management banner

“Older adults are at elevated risk of reducing labor supply due to poor health, partly because of high rates of symptoms that may be alleviated by medical marijuana. Yet, surprisingly little is known about how this group responds to medical marijuana laws (MMLs). We quantify the effects of state medical marijuana laws on the health and labor supply of adults age 51 and older, focusing on the 55 percent with one or more medical conditions with symptoms that may respond to medical marijuana. We use longitudinal data from the Health and Retirement Study to estimate event study and differences‐in‐differences regression models. Three principle findings emerge from our analysis. First, active state medical marijuana laws lead to lower pain and better self‐assessed health among older adults. Second, state medical marijuana laws lead to increases in older adult labor supply, with effects concentrated on the intensive margin. Third, the effects of MMLs are largest among older adults with a health condition that would qualify for legal medical marijuana use under current state laws. Findings highlight the role of health policy in supporting work among older adults and the importance of including older adults in assessments of state medical marijuana laws.”

https://onlinelibrary.wiley.com/doi/10.1002/pam.22122

https://www.jhsph.edu/news/news-releases/2019/medical-marijuana-laws-linked-to-health-and-labor-supply-benefits-in-older-adults.html?fbclid=IwAR2X_qV1jKU4Hj41KBHAr25o20CBZrWEIqfkcxCxzepC_2NLvsSRxeCNA9g

“Medical marijuana may increase productivity in older adults, Johns Hopkins study suggests” https://www.news5cleveland.com/news/national/medical-marijuana-may-increase-productivity-in-older-adults-johns-hopkins-study-suggests

Daily Practice Managing Resistant Multiple Sclerosis Spasticity With Delta-9-Tetrahydrocannabinol: Cannabidiol Oromucosal Spray: A Systematic Review of Observational Studies.

 Image result for journal of central nervous system disease“Spasticity is one of the most common symptoms in people with multiple sclerosis (MS). Conventional anti-spasticity agents have limitations in their efficacy and tolerability.

Delta-9-tetrahydrocannabinol: cannabidiol (THC:CBD) spray, a cannabinoid-based medicine, is approved as an add-on therapy for MS spasticity not adequately controlled by other anti-spasticity medications. The results from randomized controlled trials (RCTs) have demonstrated a reduction in the severity of spasticity and associated symptoms. However, RCTs do not always reflect real-life outcomes. We systematically reviewed the complementary evidence from non-interventional real-world studies.

METHODS:

A systematic literature review was conducted to identify all non-RCT publications on THC:CBD spray between 2011 and 2017. Data on study design, patient characteristics, effectiveness, and safety outcomes were extracted from those publications meeting our inclusion criteria.

RESULTS:

In total, we reviewed 14 real-world publications including observational studies and treatment registries. The proportion of patients reaching the threshold of minimal clinical important difference (MCID), with at least a 20% reduction of the spasticity Numeric Rating Scale (NRS) score after 4 weeks ranged from 41.9% to 82.9%. The reduction in the mean NRS spasticity score after 4 weeks was maintained over 6-12 months. The average daily dose was five to six sprays. Delta-9-tetrahydrocannabinol: cannabidiol was well tolerated in the evaluated studies in the same way as in the RCTs. No new or unexpected adverse events or safety signals were reported in everyday clinical practice.

CONCLUSIONS:

The data evaluated in this systematic review provide evidence for the efficacy and safety of THC:CBD in clinical practice and confirm results obtained in RCTs.”

https://www.ncbi.nlm.nih.gov/pubmed/30886530

https://journals.sagepub.com/doi/10.1177/1179573519831997

Cannabimimetic plants: are they new cannabinoidergic modulators?

“Phytochemicals and secondary metabolites able to interact with the endocannabinoid system (Cannabimimetics) have been recently described in a broad range of plants and fruits. These findings can open new alternative avenues to explore for the development of novel therapeutic compounds. The cannabinoids regulate many physiological and pathological functions in both animals and plants. Cannabis sativa is the main plant that produces phytocannabinoids inside resins capable to defend the plant from the aggression of parasites and herbivores. Animals produce anandamide and 2-arachidonoyl glycerol, which thanks to binding with main receptors such as type-1 cannabinoid receptor (CB1R) and the type-2 cannabinoid receptor (CB2R) are involved in inflammation processes and several brain functions. Endogenous cannabinoids, enzymes for synthesis and degradation of cannabinoids, and CB1R and CB2R constitute the endocannabinoid system (ECS). Other plants can produce cannabinoid-like molecules such as perrottetinene extracted from Radula perrottetii, or anandamide and 2-arachidonoyl glycerol extracted from some bryophytes. Moreover, several other secondary metabolites can also interact with the ECS of animals and take the name of cannabimimetics. These phytoextracts not derived from Cannabis sativa can act as receptor agonists or antagonist, or enzyme inhibitors of ECS and can be involved in the inflammation, oxidative stress, cancer, and neuroprotection. Finally, given the evolutionary heterogeneity of the cannabimimetic plants, some authors speculated on the fascinating thesis of the evolutionary convergence between plants and animals regarding biological functions of ECS. The review aims to provide a critical and complete assessment of the botanical, chemical and therapeutic aspects of cannabimimetic plants to evaluate their spread in the world and medicinal potentiality.”

https://www.ncbi.nlm.nih.gov/pubmed/30877436

https://link.springer.com/article/10.1007%2Fs00425-019-03138-x

Beneficial and deleterious effects of cannabinoids in the brain: the case of ultra-low dose THC.

Publication Cover

“This article reviews the neurocognitive advantages and drawbacks of cannabinoid substances, and discusses the possible physiological mechanisms that underlie their dual activity. The article further reviews the neurocognitive effects of ultra-low doses of ∆9-tetrahydrocannabinol (THC; 3-4 orders of magnitude lower than the conventional doses) in mice, and proposes such low doses of THC as a possible remedy for various brain injuries and for the treatment of age-related cognitive decline.”

https://www.ncbi.nlm.nih.gov/pubmed/30864864

https://www.tandfonline.com/doi/abs/10.1080/00952990.2019.1578366?journalCode=iada20

Cannabinoid Use in Patients With Gastroparesis and Related Disorders: Prevalence and Benefit.

 

Image result for Am J Gastroenterol.

“Gastroparesis (Gp) can be a challenging disorder to manage due to the paucity of treatment options. We do not know how frequently patients with Gp symptoms resort to cannabinoids to address their symptoms. This study (i) determines the prevalence of cannabinoid use in patients with Gp symptoms, (ii) describes the patients with Gp symptoms using cannabinoids, and (iii) assesses the patients’ perceived benefit of cannabinoids for Gp symptoms.

METHODS:

Consecutive outpatients with symptoms suggestive of Gp seen on follow-up at our academic center from June 2018 to September 2018 filled out questionnaires on their symptoms and the current treatments.

RESULTS:

Of 197 patients, nearly half (n = 92, 46.7%) reported current (35.5%) or past (11.2%) use of cannabinoids, including tetrahydrocannabinol (n = 63), dronabinol (n = 36), and/or cannabidiol (n = 16). Of these, most perceived improvement in Gp symptoms from cannabinoids (93.5% with tetrahydrocannabinol, 81.3% with cannabidiol, and 47.2% with dronabinol). Cannabinoids were used most commonly via smoking (n = 46). Patients taking cannabinoids were younger (41.0 ± 15.4 vs 48.0 ± 15.9 years; P < 0.01) and had a higher Gastroparesis Cardinal Symptom Index total score (3.4 ± 1.0 vs 2.8 ± 1.3; P < 0.01) compared with patients with no history of cannabinoid use.

CONCLUSIONS:

A third of patients with Gp symptoms actively use cannabinoids for their chronic symptoms. Most of these patients perceive improvement in their symptoms with cannabinoids. Patients taking cannabinoids were younger and more symptomatic than those not taking cannabinoids. Further studies on the efficacy and safety of cannabinoids in Gp will be useful.”

https://www.ncbi.nlm.nih.gov/pubmed/30865015

https://journals.lww.com/ajg/Abstract/2019/06000/Cannabinoid_Use_in_Patients_With_Gastroparesis_and.23.aspx

Does morning affect contribute to daily Cannabis use?

Addictive Behaviors

“Several theories posit that cannabis and other substances are used to reduce negative affect. This daily report study considered whether variations in positive and negative affect, reported each morning, contributed to the likelihood of cannabis use later that day. We also explored whether levels of positive and negative affect reported immediately after cannabis use improved, relative to that day’s morning levels. The sample included 183 men and 183 women representing heterosexual, cannabis-using couples from the community. Participants made independent, daily reports of affect and cannabis use episodes for 30 consecutive days. Using multilevel modeling, we modeled men’s and women’s use of cannabis on a given day as a function of morning levels of positive, hostile, and anxious affect, accounting for partner cannabis use that day, and mean levels of positive and negative affect. Men and women were more likely to use cannabis on a given day when morning positive affect was lower than typical for the person and when partner used cannabis that day. Neither hostile nor anxious affect contributed to later use of cannabis. Immediately after cannabis use, positive affect increased, and hostile and anxious affect decreased relative to that day’s morning levels. The improved affect immediately after use suggests a mechanism of positive reinforcement.”

https://www.ncbi.nlm.nih.gov/pubmed/30856545

https://www.sciencedirect.com/science/article/abs/pii/S030646031831339X?via%3Dihub

Characterization of Cancer-Induced Nociception in a Murine Model of Breast Carcinoma.

“Severe and poorly treated pain often accompanies breast cancer. Thus, novel mechanisms involved in breast cancer-induced pain should be investigated. Then, it is necessary to characterize animal models that are reliable with the symptoms and progression of the disease as observed in humans. Explaining cancer-induced nociception in a murine model of breast carcinoma was the aim of this study. 4T1 (104) lineage cells were inoculated in the right fourth mammary fat pad of female BALB/c mice; after this, mechanical and cold allodynia, or mouse grimace scale (MGS) were observed for 30 days. To determine the presence of bone metastasis, we performed the metastatic clonogenic test and measure calcium serum levels. At 20 days after tumor induction, the antinociceptive effect of analgesics used to relieve pain in cancer patients (acetaminophen, naproxen, codeine or morphine) or a cannabinoid agonist (WIN 55,212-2) was tested. Mice inoculated with 4T1 cells developed mechanical and cold allodynia and increased MGS. Bone metastasis was confirmed using the clonogenic assay, and hypercalcemia was observed 20 days after cells inoculation. All analgesic drugs reduced the mechanical and cold allodynia, while the MGS was decreased only by the administration of naproxen, codeine, or morphine. Also, WIN 55,212-2 improved all nociceptive measures. This pain model could be a reliable form to observe the mechanisms of breast cancer-induced pain or to observe the efficacy of novel analgesic compounds.”

https://www.ncbi.nlm.nih.gov/pubmed/30850915

https://link.springer.com/article/10.1007%2Fs10571-019-00666-8

Promoting cannabis products to pharmaceutical drugs.

European Journal of Pharmaceutical Sciences

“Cannabis sativa is widely used for medical purposes. However, to date, aroma, popular strain name or the content of two phytocannabinoids-Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are mostly considered for therapeutic activity. This is despite the hundreds of compounds in this plant and their potential synergistic interactions in mixtures. New, specific and effective cannabis-based drugs must be developed to achieve adequate medical standards for the use of cannabis. To do this, the comprehensive molecular profile of cannabis-based drugs must be defined, and mixtures of compounds should be tested for superior therapeutic activity due to synergistic effects compared to individually isolated cannabis compounds. The biological pathways targeted by these new drugs should also be characterized more accurately. For drug development and design, absorption, distribution, metabolism and elimination versus toxicity (ADME/Tox) must be characterized, and therapeutic doses identified. Promoting the quality and therapeutic activity of herbal or synthetic cannabis products to pharma grade is a pressing need worldwide.”

https://www.ncbi.nlm.nih.gov/pubmed/30851400

https://www.sciencedirect.com/science/article/pii/S0928098719300880?via%3Dihub

The Relationship between Marijuana Use Prior to Sex and Sexual Function in Women.

Sexual Medicine Open Access - Click here to go back to the homepage

“Scientific research on the effects of marijuana on sexual functioning in women, including libido, arousal, orgasm, and satisfaction, is limited.

AIM:

To evaluate women’s perceptions of the effect of marijuana use before sexual activity.

METHODS:

A cross-sectional design, from March 2016-February 2017, within a single, academic, obstetrics and gynecology practice, was performed. Patients were given a questionnaire at their visit and asked to complete it anonymously and place it in a locked box after their visit.

MAIN OUTCOME MEASURES:

The primary outcome was satisfaction in the sexual domains of drive, orgasm, lubrication, dyspareunia, and overall sexual experience. The secondary outcome was the effect of the frequency of marijuana use on satisfaction.

RESULTS:

Of the 373 participants, 34.0% (n = 127) reported having used marijuana before sexual activity. Most women reported increases in sex drive, improvement in orgasm, decrease in pain, but no change in lubrication. After adjusting for race, women who reported marijuana use before sexual activity had 2.13 higher odds of reporting satisfactory orgasms (adjusted odds ratio = 2.13; 95% CI = 1.05, 4.35) than women who reported no marijuana use. After adjusting for race and age, women with frequent marijuana use, regardless of use before sex or not, had 2.10 times higher odds of reporting satisfactory orgasms than those with infrequent marijuana use (adjusted odds ratio = 2.10; 95% CI = 1.01-4.44).

CONCLUSION:

Marijuana appears to improve satisfaction with orgasm. A better understanding of the role of the endocannabinoid system in women is important, because there is a paucity of literature, and it could help lead to development of treatments for female sexual dysfunction. ”

https://www.ncbi.nlm.nih.gov/pubmed/30833225

https://www.smoa.jsexmed.org/article/S2050-1161(19)30009-1/fulltext