Medical cannabis and automobile accidents: Evidence from auto insurance

“While many states have legalized medical cannabis, many unintended consequences remain under-studied. We focus on one potential detriment-the effect of cannabis legalization on automobile safety. We examine this relationship through auto insurance premiums.

Employing a modern difference-in-differences framework and zip code-level premium data from 2014 to 2019, we find that premiums declined, on average, by $22 per year following medical cannabis legalization. The effect is more substantial in areas near a dispensary and in areas with a higher prevalence of drunk driving before legalization.

We estimate that existing legalization has reduced health expenditures related to auto accidents by almost $820 million per year with the potential for a further $350 million reduction if legalized nationally.”

https://pubmed.ncbi.nlm.nih.gov/35691014/

https://onlinelibrary.wiley.com/doi/10.1002/hec.4553

Sex-Dependent Prescription Patterns and Clinical Outcomes Associated With the Use of Two Oral Cannabis Formulations in the Multimodal Management of Chronic Pain Patients in Colombia

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“To date, the therapeutic use of cannabinoids in chronic pain management remains controversial owing to the limited clinical evidence found in randomized clinical trials (RCTs), the heterogeneous nature of the clinical indication, and the broad range of cannabis-based medicinal products (CBMPs) used in both experimental and observational clinical studies.

Here we evaluate patient-reported clinical outcomes (PROMS) in a cohort of adult patients, diagnosed with chronic pain of diverse etiology, who received adjuvant treatment with oral, cannabis-based, magistral formulations between May and September 2021 at the Latin American Institute of Neurology and Nervous System (ILANS-Zerenia) in Bogotá, Colombia.

During this period, 2,112 patients completed a PROMS questionnaire aimed at capturing the degree of clinical improvement of their primary symptom and any potential side effects. Most participants were female (76.1%) with an average age of 58.7 years old, and 92.5% (1,955 patients) reported some improvement in their primary symptom (p < 0.001). Two monovarietal, full-spectrum, cannabis formulations containing either cannabidiol (CBD 30 mg/mL; THC <2 mg/mL) or a balanced composition (THC 12 mg/mL; CBD 14 mg/mL) accounted for more than 99% of all prescriptions (59.5 and 39.8%, respectively).

The degree of improvement was similar between both formulations, although males reported less effectiveness in the first 4 weeks of treatment. Sex-specific differences were also found in prescription patterns, with male patients increasing the intake of the balanced chemotype overtime. For many patients (71.7%) there were no adverse side effects associated to the treatment and those most reported were mild, such as somnolence (13.0%), dizziness (8.1%) and dry mouth (4.2%), which also appeared to fade over time.

Our results constitute the first real-world evidence on the clinical use of medicinal cannabis in Colombia and suggest that cannabis-based oral magistral formulations represent a safe and efficacious adjuvant therapeutic option in the management of chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/35399153/

“Cannabis sativa L. is one of the oldest plants cultivated by humanity and its medicinal and ethnobotanical properties have been exploited for centuries by many different ancient cultures. Medicinal cannabis in the form of oral magistral formulations may represent a valuable option for physicians as an adjuvant therapeutic intervention in the management of chronic pain and associated comorbidities. “

https://www.frontiersin.org/articles/10.3389/fpain.2022.854795/full


Cannabis-Based Products for Chronic Pain : A Systematic Review

Annals of Internal Medicine

“Background: Contemporary data are needed about the utility of cannabinoids in chronic pain.

Purpose: To evaluate the benefits and harms of cannabinoids for chronic pain.

Data sources: Ovid MEDLINE, PsycINFO, EMBASE, the Cochrane Library, and Scopus to January 2022.

Study selection: English-language, randomized, placebo-controlled trials and cohort studies (≥1 month duration) of cannabinoids for chronic pain.

Data extraction: Data abstraction, risk of bias, and strength of evidence assessments were dually reviewed. Cannabinoids were categorized by THC-to-CBD ratio (high, comparable, or low) and source (synthetic, extract or purified, or whole plant).

Data synthesis: Eighteen randomized, placebo-controlled trials (n = 1740) and 7 cohort studies (n = 13 095) assessed cannabinoids. Studies were primarily short term (1 to 6 months); 56% enrolled patients with neuropathic pain, with 3% to 89% female patients. Synthetic products with high THC-to-CBD ratios (>98% THC) may be associated with moderate improvement in pain severity and response (≥30% improvement) and an increased risk for sedation and are probably associated with a large increased risk for dizziness. Extracted products with high THC-to-CBD ratios (range, 3:1 to 47:1) may be associated with large increased risk for study withdrawal due to adverse events and dizziness. Sublingual spray with comparable THC-to-CBD ratio (1.1:1) probably is associated with small improvement in pain severity and overall function and may be associated with large increased risk for dizziness and sedation and moderate increased risk for nausea. Evidence for other products and outcomes, including longer-term harms, were not reported or were insufficient.

Limitation: Variation in interventions; lack of study details, including unclear availability in the United States; and inadequate evidence for some products.

Conclusion: Oral, synthetic cannabis products with high THC-to-CBD ratios and sublingual, extracted cannabis products with comparable THC-to-CBD ratios may be associated with short-term improvements in chronic pain and increased risk for dizziness and sedation. Studies are needed on long-term outcomes and further evaluation of product formulation effects.”

https://pubmed.ncbi.nlm.nih.gov/35667066/

https://www.acpjournals.org/doi/10.7326/M21-4520


Cannabis legalization and driving under the influence of cannabis in a national U.S. Sample

Preventive Medicine Reports

“The relationship between cannabis legalization and traffic safety remains unclear. Physiological measures of cannabis impairment remain imperfect. This analysis used self-report data to examine the relationship between cannabis legalization and driving under the influence of cannabis (DUIC). Using a cross-sectional national sample (2016-2017) of 1,249 past-30-day cannabis users, we regressed self-reported DUIC (driving within three hours of “getting high”) on cannabis legalization (recreational and medical (recreational), medical only (medical), or no legal cannabis), adjusting for demographics, days of use (past 30 days), days of use*legal status, calibration weights, and geographic clustering. The risk of DUIC in recreational (risk ratio [RR] = 0.41, 95% confidence interval (CI):0.23-0.72) and medical (RR = 0.39, 95% CI:0.20-0.79) states was lower than in states without legal cannabis, with one exception. Among frequent cannabis users (≥20 days per month), there was a significantly lower risk of DUIC for those living in recreational states (RR = 0.70, 95% CI: 0.49-0.99), but not for those living in medical states (RR = 0.87, 95% CI: 0.60-1.24), compared to users living in states without legal cannabis. The risk of self-reported DUIC was lower in recreational and medical cannabis states compared to states without legal cannabis. The only exception was for frequent users in medical states, for whom there was no difference in risk compared to frequent users living in states without legal cannabis.”

https://pubmed.ncbi.nlm.nih.gov/35656220/

“Users in medical cannabis states were less likely to report driving high.•

Users in recreational states were less likely to report driving high.”

https://www.sciencedirect.com/science/article/pii/S2211335522001061?via%3Dihub


Cannabinoid Receptor-1 suppresses M2 macrophage polarization in colorectal cancer by downregulating EGFR

Cell Death Discovery

“Cannabinoid receptors, CB1 and CB2, have been implicated as emerging targets for cancer therapy. Herein, we investigated the potential regulation mechanism of CB1 and its implications in colorectal cancer. CB1 and EGFR expression were examined in colorectal cancer cell lines. The effects of CB1 agonist ACEA and its antagonist AM251 on the proliferation, migration and invasion of colorectal cancer cells and the expression of M1 and M2 macrophage markers were examined. EGFR overexpression was performed with plasmids containing EGFR gene. Tumor xenografts were constructed to explore the effects of CB1 activation on tumorigenesis. We showed that CB1 was downregulated while EGFR was upregulated in colorectal cancer cells. The activation of CB1 suppressed the proliferation, migration and invasion of colorectal cancer cells and the differentiation of M2 macrophages, while CB1 inhibition had opposite effects. Moreover, the alterations in tumorigenesis and M2 macrophage activation induced by CB1 activation were counteracted by EGFR overexpression. Besides, CB1 silencing promoted tumor cell proliferation and M2 polarization which was counteracted by EGFR knockdown. In vivo, CB1 activation also repressed tumorigenesis and M2 macrophage activation. The present study demonstrated that CB1 activation suppressed M2 macrophage through EGFR downregulation in colorectal cancers. These findings first unveiled the potential avenue of CB1 as a targeted therapy for colorectal cancer.”

https://pubmed.ncbi.nlm.nih.gov/35641479/

“In conclusion, our study showed that CB1 activation suppressed tumor growth and M2 macrophage activation in colorectal cancer by downregulating EGFR. Our study provided the first evidence that CB1 activation was capable to suppress M2 macrophage activation. Since M2 macrophage are linked with immune evasion in various cancers, CB1 might be a promising target for cancer treatment.”

https://www.nature.com/articles/s41420-022-01064-8

“The use of THC, or selective targeting of the CB1 receptor, may represent a novel strategy for colorectal cancer therapy.”

https://pubmed.ncbi.nlm.nih.gov/17583570/

The Effectiveness of Common Cannabis Products for Treatment of Nausea

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“Background: Even though the Cannabis plant has been used to treat nausea for millennia, few studies have measured real-time effects of common and commercially available cannabis-based products.

Study: Using the Releaf App, 886 people completed 2220 cannabis self-administration sessions intended to treat nausea between June 6, 2016 and July 8, 2019. They recorded the characteristics of self-administered cannabis products and baseline symptom intensity levels before tracking real-time changes in the intensity of their nausea.

Results: By 1 hour postconsumption, 96.4% of people had experienced symptom relief with an average symptom intensity reduction of -3.85 points on a 0 to 10 visual analog scale (SD=2.45, d=1.85, P<0.001). Symptom relief was statistically significant at 5 minutes and increased with time. Among product characteristics, flower and concentrates yielded the strongest, yet similar results; products labeled as Cannabis indica underperformed those labeled as Cannabis sativa or hybrid; and joints were associated with greater symptom relief than pipes or vaporizers. In sessions using flower, higher tetrahydrocannbinol and lower cannabidiol were generally associated with greater symptom relief (eg, within 5 min).

Conclusions: The findings suggest that the vast majority of patients self-selecting into cannabis use for treatment of nausea likely experience relief within a relative short duration of time, but the level of antiemetic effect varies with the characteristics of the cannabis products consumed in vivo. Future research should focus on longer term symptom relief, including nausea-free intervals and dosing frequency; the risks of consumption of medical cannabis, especially among high-risk populations, such as pregnant women and children; and potential interactions between cannabis, conventional antiemetics, other medications, food, tobacco, alcohol, and street drugs among specific patient populations.”

https://pubmed.ncbi.nlm.nih.gov/35258504/

https://journals.lww.com/jcge/Abstract/2022/04000/The_Effectiveness_of_Common_Cannabis_Products_for.8.aspx


The Effectiveness and Safety of Medical Cannabis for Treating Cancer Related Symptoms in Oncology Patients

Frontiers in Pain Research (@FrontPain) / Twitter

“The use of medical cannabis (MC) to treat cancer-related symptoms is rising. However, there is a lack of long-term trials to assess the benefits and safety of MC treatment in this population. In this work, we followed up prospectively and longitudinally on the effectiveness and safety of MC treatment.

Oncology patients reported on multiple symptoms before and after MC treatment initiation at one-, three-, and 6-month follow-ups. Oncologists reported on the patients’ disease characteristics. Intention-to-treat models were used to assess changes in outcomes from baseline. MC treatment was initiated by 324 patients and 212, 158 and 126 reported at follow-ups.

Most outcome measures improved significantly during MC treatment for most patients (p < 0.005). Specifically, at 6 months, total cancer symptoms burden declined from baseline by a median of 18%, from 122 (82–157) at baseline to 89 (45–138) at endpoint (−18.98; 95%CI= −26.95 to −11.00; p < 0.001). Reported adverse effects were common but mostly non-serious and remained stable during MC treatment.

The results of this study suggest that MC treatment is generally safe for oncology patients and can potentially reduce the burden of associated symptoms with no serious MC-related adverse effects.

The main finding of the current study is that most cancer comorbid symptoms improved significantly during 6 months of MC treatment.

Additionally, we found that MC treatment in cancer patients was well tolerated and safe.”

https://pubmed.ncbi.nlm.nih.gov/35669038/

https://www.frontiersin.org/articles/10.3389/fpain.2022.861037/full?utm_source=fweb

“Cancer Pain Treatment Using Marijuana Safe and Effective, Large Study Finds”

https://www.newsweek.com/cannabis-medicinal-cancer-patient-symptoms-pain-relief-1711981


The Efficacy of Cannabis on Multiple Sclerosis-Related Symptoms

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“Multiple sclerosis (MS) is known as an autoimmune disease that damages the neurons in the central nervous system. MS is characterized by its most common symptoms of spasticity, muscle spasms, neuropathic pain, tremors, bladder dysfunction, dysarthria, and some intellectual problems, including memory disturbances. Several clinical studies have been conducted to investigate the effects of cannabis on the relief of these symptoms in MS patients. The efficacy of Cannabis sativa (C. Sativa) in the management of MS outcomes such as spasticity, pain, tremors, ataxia, bladder functions, sleep, quality of life, and adverse effects were assessed in this review.

Most clinical studies showed the positive effects of cannabinoids with their different routes of administration, such as oromucosal spray and oral form, in reducing most MS symptoms. The oromucosal spray Nabiximols demonstrated an improvement in reducing MS spasticity, pain, and quality of life with a tolerated adverse effect. Oral cannabinoids are significantly effective for treating MS pain and spasticity, while the other symptoms indicate slight improvement and the evidence is quite inconsistent. Oromucosal spray and oral cannabis are mainly used for treating patients with MS and have positive effects on treating the most common symptoms of MS, such as pain and spasticity, whereas the other MS symptoms indicated slight improvement, for which further studies are needed.”

https://pubmed.ncbi.nlm.nih.gov/35629350/

https://www.mdpi.com/2075-1729/12/5/682


Eye Tracking in Patients with Parkinson’s Disease Treated with Nabilone-Results of a Phase II, Placebo-Controlled, Double-Blind, Parallel-Group Pilot Study

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“The topic of the therapeutic use of cannabinoids in Parkinson’s disease (PD) is broadly discussed and frequently comes up in the outpatient clinic. So far, there are only a few randomized clinical trials assessing the effects of cannabinoids in PD. We are able to demonstrate a reduction in non-motor symptom (NMS) burden after the administration of nabilone. As impairment of attention and working memory have been described earlier as possible side effects, we assess cognitive performance using saccadic paradigms measured by an eye tracker. We do not observe a significant difference in any of the saccadic paradigms between PD patients on placebo versus those treated with nabilone. We, therefore, conclude that top-down inhibitory control is not affected by the tetrahydrocannabinol analogue. Nabilone did not significantly worsen cognitive performance and appears to be safe to use in selected PD patients who suffer from disabling NMS.”

https://pubmed.ncbi.nlm.nih.gov/35625047/

https://www.mdpi.com/2076-3425/12/5/661

Modulation of Endocannabinoid System Components in Depression: Pre-Clinical and Clinical Evidence

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“Depression is characterized by continuous low mood and loss of interest or pleasure in enjoyable activities. First-line medications for mood disorders mostly target the monoaminergic system; however, many patients do not find relief with these medications, and those who do suffer from negative side effects and a discouragingly low rate of remission.

Studies suggest that the endocannabinoid system (ECS) may be involved in the etiology of depression and that targeting the ECS has the potential to alleviate depression.

ECS components (such as receptors, endocannabinoid ligands, and degrading enzymes) are key neuromodulators in motivation and cognition as well as in the regulation of stress and emotions. Studies in depressed patients and in animal models for depression have reported deficits in ECS components, which is motivating researchers to identify potential diagnostic and therapeutic biomarkers within the ECS. By understanding the effects of cannabinoids on ECS components in depression, we enhance our understanding of which brain targets they hit, what biological processes they alter, and eventually how to use this information to design better therapeutic options.

In this article, we discuss the literature on the effects of cannabinoids on ECS components of specific depression-like behaviors and phenotypes in rodents and then describe the findings in depressed patients. A better understanding of the effects of cannabinoids on ECS components in depression may direct future research efforts to enhance diagnosis and treatment.”

https://pubmed.ncbi.nlm.nih.gov/35628337/

https://www.mdpi.com/1422-0067/23/10/5526