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Marijuana improves fertility in men, beats colorectal cancer, chronic pain

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Marijuana. Photo: Newshub

With the increased legalisation of cannabis, especially medical marijuana, researchers are interested in finding out more about its effects on health. One area that is currently under exploration is that of marijuana’s effect on fertility.

As recent research shows, men in Western countries are facing a fertility crisis. Sperm count in males of reproductive age more than halved between 1973 and 2011.

According to the Eunice Kennedy Shriver National Institute of Child Health and Human Development, approximately nine percent of men in the United States have faced infertility.

For this reason, researchers have been looking at how different modifiable factors, such as lifestyle choices, might affect male fertility.

In a new study, a team of investigators from the Harvard T. H. Chan School of Public Health in Boston, MA, has focused on the effects that smoking marijuana has on markers of male fertility.

The researchers’ findings, which they report in a study paper that features in the journal Human Reproduction, ran counter to the hypothesis that they established at the beginning of the study.

“[The] unexpected findings highlight how little we know about the reproductive health effects of marijuana and, in fact, of the health effects of marijuana in general,” notes study author Jorge Chavarro.

“Our results need to be interpreted with caution, and they highlight the need to further study the health effects of marijuana use,” he emphasizes.
Higher sperm concentration among users

To begin with, the research team speculated that men who either smoked or had smoked marijuana would have poor sperm quality. However, that is not the conclusion that this study reached.

In their research, the investigators recruited 662 men who attended the Fertility Clinic at Massachusetts General Hospital in Boston between 2000 and 2017. The average participant was 36 years old, white, and had a college degree.

To assess sperm quality, the researchers collected and analyzed 1,143 semen samples from the study participants. They also took blood samples from 317 of the men. The team used the blood samples to test for reproductive hormones.

Additionally, the researchers asked the men to fill in questionnaires asking them about their use of marijuana, including whether they had ever smoked more than two joints and whether they still used marijuana.

The team found that 365 (or 55 percent) of the participants had smoked marijuana at some point in their lives. Of these people, 44 percent no longer used this substance, while 11 percent self-identified as current smokers.

In looking at the semen samples, the researchers noticed that men who had used marijuana had higher average sperm concentrations than nonsmokers.

More specifically, marijuana users had an average sperm concentration of 62.7 million sperm per milliliter of ejaculate, whereas their peers who had never smoked marijuana had 45.4 million sperm per milliliter of ejaculate.

The investigators also observed that among marijuana smokers, only 5 percent had sperm concentrations below 15 million sperm per milliliter of ejaculate — the threshold for “normal” sperm concentration levels — while 12 percent of never-smokers had sperm concentrations below this level.

Scientists have identified several cannabinoid compounds that could potentially treat colorectal cancer.

A team at Pennsylvania State University College of Medicine in Hershey, United States (U.S.), tested hundreds of cannabinoids on various types of hum
an colorectal cancer cells in the laboratory.

Of these, 10 synthetic cannabinoids showed the ability to stop cancer cell growth. The well-known cannabis compounds tetrahydrocannabinol (THC) and cannabidiol (CBD) showed negligible ability to do the same.

The researchers see their findings as a starting point for further studies to better understand the anticancer effects that they observed, and to evaluate the compounds’ potential for drug development.

They report their results in a paper that features in the journal Cannabis and Cannabinoid Research.

Senior study author Prof. Kent E. Vrana, who is chair of the Department of Pharmacology, said: “Now that we’ve identified the compounds that we think have this activity. We can take these compounds and start trying to alter them to make them more potent against cancer cells.”

“And then, eventually, we can explore the potential for using these compounds to develop drugs for treating cancer.”

Another finding reported in the study indicates that marijuana smokers who used the substance more frequently also tended to have higher blood testosterone levels.

Still, the researchers warn that their results may not apply to the general male population since the study focused specifically on men seeking treatment at a fertility clinic.

Even though they were unexpected, the authors suggest that their findings do make logical sense in the context of marijuana’s effect on the human endocannabinoid system, which responds to the active compounds present in this substance.

“Our findings were contrary to what we initially hypothesized. However, they are consistent with two different interpretations, the first being that low levels of marijuana use could benefit sperm production because of its effect on the endocannabinoid system, which is known to play a role in fertility, but those benefits are lost with higher levels of marijuana consumption.”

“An equally plausible interpretation is that our findings could reflect the fact that men with higher testosterone levels are more likely to engage in risk-seeking behaviors, including smoking marijuana,” Nassan added.

Also, using a leading-edge technique, researchers defined the cell types in both newborn and adult human testes and identified biomarkers for spermatogonial stem cells, opening a path for new strategies to treat male infertility.

The production of sperm — otherwise known as spermatogenesis — generates more than 1,000 sperm per second in normal males. This productivity comes, in part, from a special cell type called the spermatogonial stem cell. The staying power of this stem cell has allowed many celebrities, including Robert DeNiro and Pablo Picasso, to father children after the age of 65.

Yet spermatogonial stem cells have not been well studied in humans, and attempts to grow them in the lab for clinical purposes have had limited success. In a study published February 5, 2019 in Cell Reports, researchers at University of California San Diego School of Medicine used a technique called single-cell Ribo Nucleic Acid (RNA)/genetic material sequencing to develop a clearer picture of human spermatogonial stem cells and how sperm are formed. They also developed tools to better isolate these stem cells.

This advance, the researchers write, opens the possibility that spermatogonial stem cell transplants could be developed to treat male infertility, an issue that affects more than 100 million men worldwide.

“Single-cell RNA sequencing determines the activity of hundreds of genes in the genomes of single cells,” said senior author Miles Wilkinson, PhD, professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at UC San Diego School of Medicine. “Because each cell type has a different combination of active genes, this technique allows new cell types to be identified. Applying this approach to the testis, we uncovered many different stages of sperm precursor cells in human testes.”

In adult human testes, the researchers identified several cell subtypes that likely include spermatogonial stem cells. They also found cells with the characteristics of spermatogonial stem cells in human newborns.

“Given that spermatogonial stem cells are not necessary for generating sperm until puberty, this finding in newborns raises the possibility that these cells perform as-of-yet unknown functions in infants and young children,” Wilkinson said.

Their study also identified many unique molecules — biomarkers — that define spermatogonial stem cells. These biomarkers, which they detected with specific antibodies, allowed the researchers to efficiently capture human spermatogonial stem cells.

Wilkinson’s team also identified the genes active in other cells that support spermatogonial stem cells. The finding may help researchers develop protein cocktails that drive spermatogonial stem cell proliferation in the laboratory, and allow them to scale up enough of the cells for clinical applications.

“This was a proof-of-principal for future clinical studies to use spermatogonial stem cell therapy as a means to treat men suffering from infertility, including cancer patients rendered infertile by chemotherapy,” said Wilkinson.

Meanwhile, according to a new study, chronic pain top reason for medical marijuana use.

The study did not measure whether marijuana actually helped with chronic pain, but the top reported reason for use is aligned with marijuana research.

Chronic pain is the most common reason people give when they enroll in state-approved medical marijuana programmes.

That’s followed by stiffness from multiple sclerosis and chemotherapy-related nausea, according to an analysis of 15 states published Monday in the journal Health Affairs.

The study didn’t measure whether marijuana actually helped anyone with their problems, but the patients’ reasons match up with what’s known about the science of marijuana and its chemical components.

“The majority of patients for whom we have data are using cannabis for reasons where the science is the strongest,” said lead author Kevin Boehnke of the University of Michigan.

Meanwhile, a study suggests that men who live on main roads are more likely to have difficulty getting an erection due to exposure to pollution.

Toxic fumes reduced blood flow to the genitals, tests on rats showed, putting them at risk of developing erectile dysfunction.

Men may also find they get tired quicker during sex, as the fumes can reduce lung capacity, researchers claim.

The study comes amid an array of evidence showing a growing association between polluted air and diseases, as well as fertility.

The study, at Guangzhou University in China, compared the sexual performance of rats in four different groups, The Sun reports.

The first group inhaled pollutants for two hours of the day for three months, the second for four hours, and the third for six hours.

The fourth group did not breathe polluted air, the study, published in the Journal of Sexual Medicine, revealed.

A ‘significant reduction’ in erectile function was seen in the groups of rats that had inhaled polluted air for four and six hours.

Dr. Shankun Zhao, who was involved in the study, said: “For the first time our study revealed the effect of vehicle exhaust on penile erection.

“Our results raise concerns about the potential role played by long-term exposure to gasoline vehicle exhaust in the development of erectile dysfunction.”

Previous studies have linked pollution to an increased risk of breast cancer, mouth cancer, autism in children and heart disease.

Scientists at The Chinese University, Hong Kong found men living in areas with high levels of air pollution were found to have distorted sperm.

Experts analysed exposure to sooty particles which are particularly linked to emissions of old diesel cars.

These particles – called PM2.5 – are so fine that they are breathed into the lungs and enter the blood stream.

The study, published in the BMJ journal Occupational and Environmental Medicine in November 2017, warned ambient air pollution “may serve as a risk factor of male reproductive health.”

Cannabinoids is a term that scientists use to refer to a large group of compounds that mostly exert their effect through cannabinoid receptors.

A receptor is a signal-receiving protein that sits on or inside cells and can alter cell behavior when it binds to a molecule that matches its affinity.

There are three main categories of cannabinoids. Phytocannabinoids are those that occur naturally in the cannabis, or marijuana, plant; endocannabinoids are those that arise within the body; while synthetic cannabinoids are those that scientists create in the laboratory.

Research on the medical uses of cannabinoids has tended to focus on the treatment of pain and conditions such as anxiety and depression.

However, more recently, scientists have shown growing interest in the potential anticancer effects of cannabinoids.

For the recent study, the researchers chose to investigate synthetic cannabinoids. From a “library of 370 molecules,” they identified 10 synthetic cannabinoids that “inhibited cell viability” in seven types of colorectal cancer cells that came from human tumors.

Prof. Vrana explains that cancer can arise in cells in several different ways. “Each of the seven cells we tested,” he says, “had a different cause or mutation that led to the cancer, even though they were all colon cells.”

To screen the library of candidates, he and his team first cultured the cancer cells for eight hours and then treated them with one of the compounds for another 48 hours.

If a compound showed signs of being able to reduce viability in one type of colorectal cancer cell, the researchers then tested it on the six other types.

After further tests and analyses, they whittled the number down to 10 compounds.

“Here, we demonstrated that 10 synthetic compounds are highly efficacious and moderately potent for reducing the viability of seven [colorectal cancer] cell lines,” note the authors.

For the sake of comparison, they also ran tests on the two well-known phytocannabinoids THC and CBD. However, these showed a negligible ability to limit colorectal cancer cell viability.

The 10 compounds belong to three different classes of synthetic cannabinoid. The classes have many similarities, but they also have some small differences.

Prof. Vrana says there is a need for further research to understand better how the compounds work, and how to make them more potent and effective against colorectal cancer.

“We know how one of them works,” Prof. Vrana notes,” “which is by inhibiting the division of cells in general.”

“We also found that the most potent and effective compounds don’t seem to work through traditional marijuana receptors, although we’re not sure of the exact mechanism yet.”


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