Tag: cannabis

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Potential Risk Biomarkers Found for Schizophrenia from Cannabis Use

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A new study, recently published in the journal Scientific Reports, has analysed and compared the fatty acids in the blood of individuals with schizophrenia, of those with cannabis use disorder and of those with both diagnoses, with the aim of shedding light on new biomarkers and improving the understanding of the biological relationship between the two disorders. The study also offers a powerful tool for identifying new biomarkers.

Cannabis is one of the most widely used substances in the world, with some 228 million users between the ages of 15 and 64. The risk of developing schizophrenia increases significantly with cannabis use, especially when it starts at a young age. What is more, it is estimated that approximately 10% of cannabis users will develop cannabis use disorder during their lifetime. Curiously, almost a third of individuals diagnosed with schizophrenia also meet the criteria for cannabis use disorder; and cannabis use disorder affects up to 42% of people with schizophrenia.

In this bid to shed light on the biological mechanisms that determine why some individuals develop schizophrenia while others only experience cannabis use disorder, despite similar levels of exposure to cannabis, the UPV/EHU’s Neuropsychopharmacology group has managed to detect “potential biomarkers in the blood that could help predict the risk some people have of developing a psychiatric disorder such as schizophrenia if they use cannabis”, explained Leyre Urigüen, coordinator of the study.

So, the research group compared the fatty acid content in the blood of samples taken from “a group of individuals with schizophrenia who did not use cannabis, a group who used cannabis and have developed a cannabis use disorder, a group with a dual pathology of schizophrenia with cannabis abuse, and a control group of individuals with neither a psychiatric disorder nor drug use”, explained Dr Urigüen. In the study they wanted to shed light on what happens “with people who use cannabis and develop schizophrenia; how do they differ from those who use cannabis and never develop a psychiatric disorder?” she added.

“We found considerable differences between these groups of individuals. By comparing the quantities of certain metabolites (fatty acids), we were able to perfectly differentiate between the three patient populations,” stressed the UPV/EHU researcher. “This indicates that there is an altered or different metabolism between these three groups.” In this study the Neuropsychopharmacology research group at the UPV/EHU detected “that some fatty acids differentiate between the cannabis-using group and the groups with schizophrenia and dual-diagnosis patients. These molecules could potentially be biomarkers”, said Urigüen.

Paving the way forward

The researcher is very hopeful about this finding: “I think it is important to be capable of finding blood biomarkers that can help predict the risk of developing a psychiatric disorder, such as schizophrenia due to cannabis use, and this study has proven to be the start of this way forward. Now this has to be disproved by studies with a larger cohort of people than the one we have analysed.”

In this respect, the researcher stressed that another of the strengths of the study is “the fine-tuning of plasma lipidomics in patients; in other words, the complete study of fatty acids (lipids). We are proposing a way of working that can be replicated by other groups, and that way, headway can be made in the specification of these metabolites”. This approach has been developed by the IBeA research group under the direction of the UPV/EHU professor Nestor Etxebarria. Both groups are working side by side on “various approaches to the study in which they are trying to find answers to these and many other questions”.

Source: University of the Basque Country

Categories : New Compounds and Treatments Pain ManagementTags :

Side-effect Free Cannabinoid Offers Hope for Pain Relief

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Researchers at WashU Medicine and Stanford University developed a compound that relieves pain in mice but doesn’t affect the brain, thereby avoiding mind-altering side effects and abuse potential. The custom-designed molecule, derived from cannabis, may provide an alternative to opioids for treating chronic pain. The compound is illustrated here in cyan, nestled within a protein (green and purple) involved in sensing pain. Credit: Tasnia Tarana

In the quest to develop a safe, effective alternative to opioids, researchers have developed a compound that mimics a natural molecule found in the cannabis plant, harnessing its pain-relieving properties without causing addiction or mind-altering side effects in mice.

While more studies are needed, the compound shows promise as a nonaddictive pain reliever. The study, from Washington University School of Medicine in St. Louis and Stanford University, appears in Nature.

“There is an urgent need to develop nonaddictive treatments for chronic pain, and that’s been a major focus of my lab for the past 15 years,” said the study’s senior author Susruta Majumdar, PhD, a professor of anaesthesiology at WashU Medicine. “The custom-designed compound we created attaches to pain-reducing receptors in the body but by design, it can’t reach the brain. This means the compound avoids psychoactive side effects such as mood changes and isn’t addictive because it doesn’t act on the brain’s reward centre.”

Opioids dull the sensation of pain in the brain and hijack the brain’s reward system, triggering the release of dopamine and feelings of pleasure, which make the drugs so addictive. Despite widespread public health warnings and media attention focused on the dangers of opioid addiction, numerous overdose deaths still occur. In 2022, some 82 000 deaths in the U.S. were linked to opioids.

“For millennia, people have turned to marijuana as a treatment for pain,” explained co-corresponding author Robert W. Gereau, PhD, professor of anaesthesiology and director of the WashU Medicine Pain Center. “Clinical trials also have evaluated whether cannabis provides long-term pain relief. But inevitably the psychoactive side effects of cannabis have been problematic, preventing cannabis from being considered as a viable treatment option for pain. However, we were able to overcome that issue.”

The mind-altering properties of marijuana stem from natural molecules found in the cannabis plant referred to as cannabinoid molecules. They bind to a receptor, called cannabinoid receptor one (CB1), on the surface of brain cells and on pain-sensing nerve cells throughout the body.

Working with collaborators at Stanford University, co-first author Vipin Rangari, PhD, a WashU Medicine postdoctoral research associate in Majumdar’s laboratory, designed a cannabinoid molecule with a positive charge, preventing it from crossing the blood-brain barrier into the brain while allowing the molecule to engage CB1 receptors elsewhere in the body. By modifying the molecule such that it only binds to pain-sensing nerve cells outside of the brain, the researchers achieved pain relief without mind-altering side effects.

They tested the modified synthetic cannabinoid compound in mouse models of nerve-injury pain and migraine headaches, measuring hypersensitivity to touch as a proxy for pain. Applying a normally non-painful stimulus allows researchers to indirectly assess pain in mice. In both mouse models, injections of the modified compound eliminated touch hypersensitivity.

For many pain relievers, particularly opioids, tolerance to the medications over time can limit their long-term effectiveness and require higher doses of medication to achieve the same level of pain relief. In this study, the modified compound offered prolonged pain relief – the animals showed no signs of developing tolerance despite twice-daily treatments with the compound over the course of nine days. This is a promising sign that the molecule could be used as a nonaddictive drug for relief of chronic pain, which requires continued treatment over time.

Eliminating the compound’s tolerance resulted from the bespoke design of the compound. The Stanford collaborators performed sophisticated computational modeling that revealed a hidden pocket on the CB1 receptor that could serve as an additional binding site. The hidden pocket, confirmed by structural models, leads to reduced cellular activity related to developing tolerance compared to the conventional binding site, but it had been considered inaccessible to cannabinoids. The researchers found that the pocket opens for short periods of time, allowing the modified cannabinoid compound to bind, thus minimizing tolerance.

Designing molecules that relieve pain with minimal side effects is challenging to accomplish, said Majumdar. The researchers plan to further develop the compound into an oral drug that could be evaluated in clinical trials.

Source: WashU Medicine

Categories : Obstetrics & GynaecologyTags :

Pregnant Women Over 4 Times as Likely to Use Cannabis if it is Legal

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US scientists conducting a nationwide study found that pregnant women living in states where cannabis is legally available are far more likely to use the substance, prompting a call for pregnant women to be screened for the drug.

Published in The American Journal of Drug and Alcohol Abuse, the findings show that pregnant women were around 4.6 times more likely to report using cannabis in states where it is legal for medical and recreational purposes, compared to where only CBD oil is allowed.

A large proportion of women reported using the drug for medical purposes, which is in keeping with “a growing body of evidence” that suggests in order to alleviate pregnancy symptoms cannabis is being used as a substitute for medical drugs in legalised areas.

“Therefore it is increasingly important to evaluate the risk-benefit profile of cannabis as compared to other medical treatments to understand any potential therapeutic indications for cannabis use in pregnancy,” says lead author Kathak Vachhani.

The team is calling for prenatal and primary care providers to screen and counsel patients regarding cannabis use in pregnancy, particularly in states where it is legal, for the potential effects on foetal development.

They also state public messaging “around the risks” of cannabis in pregnancy is “particularly relevant now,” as many states have recently implemented cannabis laws and established cannabis markets.

The legalisation of cannabis products has increased exponentially in the last decade in the United States. The legalisation has been piecemeal, as some states allow CBD oil, or marijuana for medical or recreational purposes. Use of these products has risen among all demographics.

Among the least studied are pregnant women. Because cannabis has been known to be used to treat some symptoms associated with pregnancy—notably nausea and vomiting.

Here, the team used data from the Behavioral Risk Factor Surveillance System compiled by the Centers for Disease Control and Prevention (CDC) between 2017 to 2020 to analyse the consumption of cannabis by 1,992 pregnant women.

While previous studies have examined the use of cannabis by pregnant women in restricted geographic areas and under particular legislative parameters, this study used a broader dataset to compare use across legalisation frameworks in 27 states.

Self-reported use was found to be “significantly higher” in pregnant women residing in states that allow medical and adult use, compared to those residing in states with restricted use.

“The unweighted dataset consisted of 426 CBD-only, 1114 medical, and 394 reactional group respondents,” the authors wrote claim. Weights were applied to each datapoint to obtain the population they represented. Of this weighted data, 2.4% from CBD-only regions reported cannabis use, while 7.1% from medical regions and 6.9% from adult-use regions reported the same. Respondents from the medical and recreational areas were 4.5 and 4.7 times more likely to use cannabis than those in CBD-only areas.

Most respondents who reported cannabis use smoked it partially or mostly for recreational purposes. “Mode of intake and reason for consumption did not differ between state groups,” the authors observe.

But what impact is this having on the mother or the foetus?

Previous studies have shown that medical cannabis usage during pregnancy can be effective for nausea and vomiting. Medical cannabis may be suitable to treat pregnancy-specific conditions which, if untreated, could be more harmful to the foetus than cannabis.

However, safe usage depends on having a comprehensive understanding of the benefits and risks of cannabis when weighed against the risks of untreated or refractory conditions such as hyperemesis gravidarum.

Therefore, more research is needed, states Vachhani, who is also from the University of Toronto Temerty Faculty of Medicine.

“Cannabis is a complex substance and its use is further complicated by factors such as the form of intake and frequency of use.

“From the mother’s health standpoint, our current understanding is rudimentary regarding the complex interplay between use (whether CBD or THC-based) and long-term health outcomes for the mother.

“There is currently no accepted therapeutic indication or safe amount of cannabis that may be consumed during pregnancy.

“Although further studies may lead to an accepted therapeutic indication, based on the current consensus the positive association between cannabis use and legalisation found in our study warrants further inquiry.”

The analysis carried out here was limited by a relatively small sample size, a lack of information regarding timing of use in pregnancy, lack of information about the chemical composition of cannabis consumed, and the potential for self-reporting biases.

Source: Taylor & Francis

Categories : Cardiovascular Disease Substance UseTags :

Marijuana and other Substances Linked to Atrial Fibrillation

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A new longitudinal study of more than 23 million people in the US concludes that some commonly used and abused drugs pose previously unidentified risks for the development of atrial fibrillation (AF). The results appeared in the European Heart Journal.

The researchers analysed data from diagnostic codes from every hospital admission, emergency room visit and medical procedure in California for the years 2005 through 2015, identifying nearly one million people without preexisting AF, but who later developed AF during these years.

They found 132 834 patients used cannabis, 98 271 used methamphetamine, 48 700 used cocaine, and 10 032 used opiates. In the study, the researchers found that marijuana users had a 35% increased likelihood of later developing AF.

“Despite exhibiting a weaker association with incident AF than the other substances, cannabis use still exhibited an association of similar or greater magnitude to risk factors like dyslipidaemia, diabetes mellitus, and chronic kidney disease. Furthermore, those with cannabis use exhibited similar relative risk of incident AF as those with traditional tobacco use,” the study authors reported.

“To my knowledge, this is the first study to look at marijuana use as a predictor of future atrial fibrillation risk,” said principal investigator Gregory Marcus, MD, MAS, a UCSF professor of Medicine with the Division of Cardiology.

AF is an abnormally disordered pumping rhythm arising from electrical disturbances in the atria. In severe cases of faulty atrial pumping, clots may form in the atria, and then break off into the bloodstream and cause deadly strokes. AF-related strokes cause more than 150 000 US deaths each year.

Unlike cocaine or methamphetamine use, both stimulants previously known to sometimes lead to sudden cardiac death due to profound disruptions in the orderly electrical signalling and pumping within ventricles there is no demonstrated mechanism whereby marijuana use causes heart arrhythmias.

Source: University of California San Francisco

Categories : AddictionTags :

Teens Have Triple the Risk of Developing Cannabis Addiction

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Adolescents have more than three times the risk of developing a cannabis addiction than adults, although they may only have the same risk of other mental health problems related to the drug, according to a new study published in the Journal of Psychopharmacology.

The study, led by King’s College London and University College London, found that adolescent cannabis users had the same odds for higher levels of subclinical depression or anxiety than adults cannabis users, nor were they more vulnerable than adult users to cannabis’s associations with psychotic-like symptoms.

These findings build on a separate study by the same team that found adolescents were not more vulnerable to associations between chronic cannabis use and cognitive impairment.

Lead author Dr Will Lawn said: “There is a lot of concern about how the developing teenage brain might be more vulnerable to the long-term effects of cannabis, but we did not find evidence to support this general claim.

“Cannabis addiction is a real issue that teenagers should be aware of, as they appear to be much more vulnerable to it than adults.

“On the other hand, the impact that cannabis use has during adolescence on cognitive performance or on depression and anxiety may be weaker than hypothesised.

“But we also replicated previous work that if someone becomes addicted to cannabis, that may increase the severity of subclinical mental health symptoms. Given adolescents are also at a greater risk of experiencing difficulties with mental health than adults, they should be proactively discouraged from regular cannabis use.”

The findings in both papers come from the CannTeen study, which is comparing the effects of regular cannabis use among adolescents and adults, while also comparing to age-matched controls (non-users of cannabis), a completely novel design.

The study involved 274 participants, including 76 adolescents (aged 16–17) who used cannabis one to seven days per week, alongside similar numbers of adult (aged 26–29) users, and teenage and adult control (comparison) participants, who all reported their cannabis use over the last 12 weeks and responded to mental health questionnaires. The cannabis users in the study, on average, used it four times per week. The adolescent and adult users were also carefully matched on gender, ethnicity, and type and strength of cannabis.

The researchers found that adolescent cannabis users were three and a half times as likely to develop severe ‘cannabis use disorder’ (ie addiction) than adult users, a finding which is in line with previous studies. Cannabis use disorder is defined by symptoms such as cravings; cannabis use contributing to failures in school or work; heightened tolerance; withdrawal; interpersonal problems caused by or exacerbated by cannabis use; or intending to cut back without success. Oof the teenage cannabis users studied, 50% had six or more cannabis use disorder symptoms, qualifying as severe cannabis use disorder.

Among people of any age, previous studies have found that roughly 9–22% of people who try the drug develop cannabis use disorder, and that risk is higher for people who tried it at a younger age, a finding which has now been robustly replicated.

The researchers say that adolescents might be more vulnerable to cannabis addiction because of factors such as increased disruption to relationships with parents and teachers, a hyper-plastic (malleable) brain and developing endocannabinoid system (the part of the nervous system that THC in cannabis acts upon), and an evolving sense of identity and shifting social life.

Adolescent users had greater odds than adult users or adolescent non-users of developing psychotic-like symptoms, but analysis showed that this is because all adolescents, and all cannabis users, are more likely to newly develop psychotic-like symptoms, rather than a different effect of cannabis for teenagers than adults. Thus, there was no interaction between cannabis use and being an adolescent. The researchers say this fits in with prior evidence that cannabis use may increase the likelihood of developing a psychotic disorder such as schizophrenia, but they warn their study did not investigate the risk of clinical psychosis or schizophrenia.

The researchers found that neither teenage nor adult cannabis users were more likely to develop depressive or anxiety symptoms than non-users. Only the adolescents that have severe cannabis use disorder had worse mental health symptoms, but the researchers caution that the small sample size for this group limits their confidence in this finding.

The separate study found that cannabis users were no more likely to have impaired working memory or impulsivity. Cannabis users were more likely to have poor verbal memory (remembering things said to you); this effect was the same in adults and teenagers, so again there was no adolescent vulnerability. However, the researchers caution that cannabis use could impact school performance during a key developmental stage of life.

The researchers caution that these findings were cross-sectional (only looking at one time point), and that longitudinal analyses of how their participants changed over time are ongoing.

Senior author Professor Val Curran (UCL Clinical Psychopharmacology Unit, UCL Psychology & Language Sciences) said: “Our findings suggest that schools should be teaching pupils more about the risk of addiction to cannabis, which has been neglected in drugs education. Becoming addicted to cannabis is a serious problem in itself, but it can also increase the likelihood of other mental health problems. Teenagers should therefore be informed of their greater risk of addiction.”

Source: King’s College London

Categories : Hospitals Substance UseTags :

Greater Hospitalisation or ED Visit Risk for Cannabis Users

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Compared to non-users, cannabis users have 22% higher rates in emergency department (ED) visits and hospitalisations, according to new research findings. The study, published in BMJ Open Respiratory Research revealed that serious physical injury and respiratory-reasons were the two leading causes of ED visits and hospitalisations among cannabis users.

The findings suggest an association between cannabis use and negative health events, which the researchers say should underline the need to educate and remind the public of the harmful impacts of cannabis on health.

“Our research demonstrates that cannabis use in the general population is associated with heightened risk of clinically serious negative outcomes, specifically, needing to present to the ED or be admitted to hospital,” said Dr Nicholas Vozoris, lead author, a respirologist at St. Michael’s and an associate scientist at the hospital’s Li Ka Shing Knowledge Institute.

“Unlike tobacco, there is some uncertainty or controversy regarding the adverse health impacts of cannabis. Some individuals may perceive that cannabis has some health benefits and is otherwise benign. Our research highlights to those using – or considering to use – cannabis, that this behaviour is associated with important negative health events.”

To compare health outcomes among cannabis users and individuals who don’t use cannabis, researchers used data collected in a survey of individuals who self-reported cannabis use and linked it with health administrative data for Ontario residents.

Using propensity score matching, researchers compared the health outcomes of nearly 4800 individuals who reported any cannabis use in the preceding 12 months with the health outcomes of over 10 000 individuals never-users, or having used cannabis only once and more than 12 months ago. Researchers incorporated 31 different variables while matching study participants to minimise an unfair comparison, including demographics, multiple physical and mental health diseases, and tobacco, alcohol and illicit drug use.

The study’s main aim was to see if there was a link between cannabis use and respiratory-related hospitalisation or ED visits. No significant associations were found between cannabis use and respiratory-related ED visits, hospitalisations, or death from any cause. However, they did find that overall visits to the ED or hospitalisations for any reason was significantly higher among cannabis users.

In addition to having greater odds of ED visits or hospitalisation, the findings show that one of every 25 cannabis users will go to the emergency department (ED) or be admitted to hospital within a year of using cannabis.

Among the reasons for ED visits or hospitalisations of cannabis users, acute trauma was the most common, with 15% of cannabis users who got medical attention receiving it for this reason, and 14% receiving care for respiratory reasons.

“The results of our research support that health care professionals and government should discourage recreational cannabis consumption in the general population,” noted Dr Vozoris.

Source: EurekAlert!

Categories : Substance UseTags :

Researchers Uncover ‘Copycat’ Cannabis Edibles

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NYU School of Global Public Health researchers have found that some cannabis edibles have a striking resemblance to popular snack foods such as Doritos, and may be easily confused for them, especially by young children, finds a new study published in Drug and Alcohol Dependence.

These “copycat” edibles also have levels of the psychoactive ingredient tetrahydrocannabinol or THC that far exceed the limits set by cannabis regulations in US states.

“At first glance, most of the packages look almost exactly like familiar snacks. If these copycat cannabis products are not stored safely, there is the potential for accidental ingestion by children or adults,” said Associate Professor Danielle Ompad, lead author of the study.

Edibles are a popular and growing segment of the cannabis market. In states where cannabis use is legal, more than half (56%) of cannabis users consume edibles.

Some edibles that use similar branding and imagery to mimic popular snack foods have been highlighted by the media. These copycat cannabis products are a public health concern given that people – including children – could mistake them for snacks and accidentally consume them. From 2017 to 2019, US Poison Control Centers handled nearly 2000 cases of young children ages 0 to 9 consuming edibles.

To gain a deeper understanding of copycat edibles, the researchers collected hundreds of photos of cannabis products and analysed their packaging, including branding, names, imagery, and THC content. Looking at the photos for 267 edibles, they found that 8% (22 photos) closely resembled 13 different snack products.

Twelve of the products were candies or sweet snacks (fruit chews, fruit snacks, rice and marshmallow treats, and gummies) and one was a salty snack (chips). Eight of the 13 packages used the exact brand or product name of the original product; the remaining five used names that were similar (for instance, “Stoner Patch Dummies” instead of “Sour Patch Kids”). Seven of the packages used the same cartoon or brand character as the original product.

Most US states that have legalised cannabis limit the amount of THC in edibles, generally 5–10mg of THC per dose and 100mg per package. According to the packaging information, these edibles contained an average of 459mg of THC with a range of 300 to 600 mg per package, far exceeding the maximum limits.

“While each package is likely intended to include multiple doses, few packages indicate the serving size or number of servings,” said Dr Ompad. “Moreover, if we’re considering 10mg a standard dose, these products could contain an alarming 30 to 60 doses per package.”

The findings highlight the risk that these copycat products could be attractive to children, given the colourful packaging and use of familiar branding and characters.

“Policies to prevent cannabis packaging from appealing to children haven’t stopped copycat products from entering the market — nor have food brands taking legal action against cannabis companies for copyright infringement,” said Dr Ompad. “People who purchase edibles that look like snack foods should store them separately from regular snacks and out of reach of children.”

Source: New York University

Categories : Substance UseTags :

Long-term Marijuana Use Could Impact Male Fertility

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Chronic use of marijuana could greatly impact male fertility and reproductive outcomes, according to a new study appearing in Fertility & Sterility. This is the first study to assess the impacts of typical substance use on testicular function via a mode of delivery, and dosage.

Robust research in animal models has shown that cannabis negatively impacts male fertility. Researchers monitored the reproductive systems of healthy male nonhuman primates following exposure to THC, the main psychoactive ingredient in marijuana.

The nonhuman primates in the study received a THC edible once daily over the course of seven months. Their THC dose was based on published medical marijuana acclimation recommendations for humans, and was increased every 70 days in alignment with the animals’ sperm development cycle. Dose adjustments were made until it reached the equivalent of a heavy medical marijuana dose in humans. Semen samples were collected at baseline before initiation of THC, and again at the end of each THC dosing timepoint.

The study found that THC use was linked to significant adverse impacts to the animals’ reproductive hormones, including decreased levels of testosterone and severe testicular shrinkage. “Specifically, we observed a greater than 50% decrease in testicular size,” said senior author Jamie Lo, MD, MCR. “Unfortunately, these effects appeared to worsen as the THC dose was increased, suggesting a possible dose-dependent effect.”

These results align with Dr Lo’s previous studies indicating similar THC-associated impacts to female reproductive hormones and the menstrual cycle.

“These early findings are concerning from a clinical standpoint,” said study lead author Jason Hedges, MD, PhD. “Even moderate doses could have a profound impact on fertility outcomes. While family planning may not be top of mind for those in their late teens and early 20s, the longer-term effects of THC on male reproductive health are not well-defined; it is possible that THC could cause lasting impacts that may alter family planning later in life.”

The researchers will continue to explore the relationship between THC and reproductive health in both male and female nonhuman primates, examining longer term THC exposure impacts, including changes to sperm count and motility, and whether discontinuing use of THC products could reverse adverse effects.

Source: Ohio Health & Science University

Categories : Medical Research & TechnologyTags :

Cannabis Use Risks Harmful Drug–Drug Interactions

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Using cannabis alongside other drugs may come with a significant risk of harmful drug-drug interactions, according to a pair of new studies in the journal Drug Metabolism and Disposition.

The researchers examined cannabinoids and their major metabolites found in the blood of cannabis users and found that they interfere with two families of enzymes that help metabolise a wide range of prescription drugs. Because of this, the drugs’ effectiveness might decrease or their negative effects might increase with too much building up in the body, causing unintended side effects such as toxicity or accidental overdose.

The authors note that despite the early stage of this research, it is important to be careful when using cannabis with other prescription drugs.

“Physicians need to be aware of the possibility of toxicity or lack of response when patients are using cannabinoids,” said Professor Philip Lazarus, senior author on the papers. “It’s one thing if you’re young and healthy and smoke cannabis once in a while, but for older people who are using medications, taking CBD or medicinal marijuana may negatively impact their treatment.”

One study focused on a family of enzymes known as cytochrome P450s (CYPs), whereas the other looked at UDP-glucuronosyltransferases (UGTs), another enzyme family. Together, these two enzyme families help metabolise and eliminate more than 70% of the most commonly used drugs from the body.

While some previous research focused on potential drug interactions caused by cannabinoids, this new research provides the first known comprehensive look at the interaction between three of the most abundant cannabinoids (tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN)) and their metabolites and all of the major CYP enzymes. This is also the first known research that looked for interactions between these cannabinoids and UGT enzymes, specifically.

“Cannabinoids stay in your body only for about 30 minutes before they are rapidly broken down,” said first author Shamema Nasrin. “The metabolites that result from that process stay in your body for much longer – up to 14 days – and at higher concentrations than cannabinoids and have been overlooked in previous studies, which is why we thought we should focus on those as well.”

Using human kidney cells, they found that cannabinoids and the major THC metabolites strongly inhibited several CYP enzymes. One key discovery was that one of the most abundant THC metabolites, called THC-COO-Gluc seems to play a major role in inhibiting several key enzymes in the liver. Looking at the UGT enzyme family, the researchers found that all three cannabinoids, but especially CBD, inhibited two of the primary UGT enzymes present in the liver. CBD was also found to block three enzymes that account for about 95 percent of kidney UGT metabolism, which helps clear toxins and certain drugs from the body.

“If you have a kidney disease or you are taking one or more drugs that are metabolised primarily through the kidney and you’re also smoking marijuana, you could be inhibiting normal kidney function, and it may have long-term effects for you,” Prof Lazarus said.

Nasrin added that these interactions between CBD and UGT enzymes could be inhibiting kidney function in patients with acute kidney disease or kidney cancer, who may be using CBD to treat pain or to try to reduce the side effects from anti-cancer drugs.

“Taking CBD or marijuana might help your pain but could be making the other drug you’re taking more toxic, and that increase in toxicity may mean that you can’t continue taking that drug,” Nasrin said. “So, there could be serious ramifications for anti-cancer drugs, and that’s only one example of the many drugs that could potentially be affected by the cannabinoid-enzyme interactions we’re seeing.”

Source: Washington State University

Categories : Obstetrics & Gynaecology Substance UseTags :

Cannabis Use in Pregnancy Predisposes Children to Stress and Anxiety

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Women who use cannabis during pregnancy, such as for stress and anxiety relief, may inadvertently predispose their children to stress susceptibility and anxiety, according to a study published in PNAS.

As cannabis continues to be legalised worldwide, many people mistakenly believe that cannabis use is without significant health risks. In line with this softening public opinion, cannabis has emerged as one of the most consumed recreational drugs of abuse during pregnancy, however the impact of maternal cannabis use on foetal and childhood development is unclear.

“We know that cannabinoid signaling plays a role in modulating stress, which is why some people use cannabis to reduce anxiety and relax,” said first author Professor Yoko Nomura at CUNY Graduate Center and Queens College. “But our study shows that in utero exposure to cannabis has the opposite effect on children, causing them to have increased levels of anxiety, aggression, and hyperactivity compared to other children who were not exposed to cannabis during pregnancy.”

Researchers examined placental gene expression and early childhood behaviour and physiology in a long-term study of 322 mother-child pairs who were drawn from an ongoing New York City-based study of stress in pregnancy started in 2009. When the children were approximately six years old, hormone levels were measured via their hair samples, electrocardiogram recordings were used to measure heart function during a stress-inducing condition, and behavioural and emotional functioning was assessed based on surveys administered to the parents.

The children of mothers who used cannabis during pregnancy showed higher anxiety, aggression, hyperactivity, and levels of the stress hormone cortisol, compared to children of non-cannabis users. Maternal cannabis use was also associated with a reduction in the high-frequency component of heart rate variability, which normally reflects increased stress sensitivity. In addition, RNA sequencing of placental tissue collected at birth in a subset of participants revealed that there was an association between maternal cannabis use and lower expression of immune-activating genes, including pro-inflammatory cytokines. The cannabis-related suppression of several placental immune-gene networks predicted higher anxiety in the children.

“Pregnant women are being bombarded with misinformation that cannabis is of no risk, while the reality is that cannabis is more potent today than it was even a few years ago. Our findings indicate that using it during pregnancy can have long-term impact on children,” said senior author Yasmin Hurd, PhD. “The study results underscore the need for nonbiased education and outreach to the public and particular vulnerable populations of pregnant women regarding the potential impact of cannabis use. Disseminating this data and accurate information is essential to improving the health of women and their children.”

Source: The Mount Sinai Hospital