Category: Substance Use

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

Many Youths with Substance Use Disorder Also Have Autism Traits

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One in five teens and young adults seeking treatment for substance use may have traits characteristic of a previously unrecognised autism spectrum disorder (ASD), according to a study by researchers at Massachusetts General Hospital (MGH).

The study, published in The American Journal on Addictions, found that among patients with an average age of 18.7 years being treated in an outpatient substance use disorder (SUD) clinic, 20% had elevated scores on the Social Responsiveness Scale-2 (SRS-2), a parent- or teacher-reported measure that has been shown to reliably identify the presence and severity of social impairment among individuals along the autism spectrum, and to distinguish autism from other disorders.

Lead author James McKowen, PhD, said this is the first study examining the prevalence of autistic traits among young people with SUD.

“Usually studies of substance use disorder in autism are done in those with an autism diagnosis already,” he said. “We have looked at this question from the other side, asking how many people with substance use disorder have autism.”

The researchers asked parents of 69 youths reporting for the first time to a specialty outpatient psychiatric SUD clinic to fill out the SRS-2 form. The form is designed to measure an individual’s social awareness, cognition, communication and motivation, and restricted interests and repetitive behaviours.

Though few differences were found between those with elevated autistic trait scores and those with lower, non-autistic scores in terms of demographic or psychiatric factors, adolescents with higher SRS-2 scores had a nearly eightfold higher likelihood of stimulant use disorder, and a fivefold higher risk for opioid use disorder.

According to the researchers, the findings highlight the importance of assessing patients in a SUD treatment setting for autistic traits.

“For clinicians, the big takeaway point from this study is that we need to get better at screening and certainly training in the presence of autism spectrum disorder,” said Dr McKown. Clinicians treat the SUD “but don’t have specialty developmental training, particularly for issues around autism.”

The researchers are developing a free clinical therapy protocol that can help clinicians better address the issues of autistic traits in patients with SUD.

Source: Massachusetts General Hospital

A Brain ‘Breathalyser’ for THC Intoxication

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Scientists have developed a noninvasive brain imaging procedure to identify individuals whose performance has been impaired by THC, the psychoactive ingredient of cannabis. As reported in Neuropsychopharmacology, the technique uses functional near-infrared spectroscopy (fNIRS) to measure brain activation patterns linked to THC intoxication. The technology could have a great impact on road and workplace safety. 

The increasing legalisation of cannabis has driven the need for a portable brain imaging procedure that can distinguish between THC-caused impairment and mild intoxication. “Our research represents a novel direction for impairment testing in the field,” explained lead author Jodi Gilman, PhD. “Our goal was to determine if cannabis impairment could be detected from activity of the brain on an individual level. This is a critical issue because a ‘breathalyser’ type of approach will not work for detecting cannabis impairment, which makes it very difficult to objectively assess impairment from THC during a traffic stop.”

In previous studies, THC has been shown to impair cognitive and psychomotor performance essential to safe driving, a factor thought to at least double the risk of fatal motor vehicle accidents. However, concentration of THC in the body does not correspond well to functional impairment. Regular cannabis users often can have high levels of THC in the body and not be impaired. Metabolites of THC can remain in the bloodstream for weeks after the last cannabis use, well beyond the period of intoxication. Thus, there is a need for a different method to determine impairment from cannabis intoxication.

In the study, 169 cannabis users underwent fNIRS brain imaging before and after receiving either oral THC or a placebo. Participants who reported intoxication after being given oral THC showed an increased oxygenated haemoglobin concentration (HbO) – a type of neural activity signature from the prefrontal cortex region of the brain – compared to those who reported low or no intoxication.

“Identification of acute impairment from THC intoxication through portable brain imaging could be a vital tool in the hands of police officers in the field,” said senior author and principal investigator A. Eden Evins, MD, MPH, founding director of the Center for Addiction Medicine. “The accuracy of this method was confirmed by the fact impairment determined by machine learning models using only information from fNIRS matched self-report and clinical assessment of impairment 76% of the time.”

The study suggested the feasibility of inexpensive, lightweight, battery-powered fNIRS devices that could be incorporated into a headband or cap, and thus require minimal set-up time.

“Companies are developing breathalyser devices that only measure exposure to cannabis but not impairment from cannabis,” said Dr Gilman. “We need a method that won’t penalise medical marijuana users or others with insufficient amounts of cannabis in their system to impair their performance. While it requires further study, we believe brain-based testing could provide an objective, practical and much needed solution.”

Source: Massachusetts General Hospital

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

Uni Students’ Prescription Drugs Misuse Happens in the Week

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Prescription drug misuse by university students happens more often during the week and when they are at home by themselves,  according to a recent study published in the journal Drug and Alcohol Dependence.

In the longitudinal study, university students at a large US university were surveyed, and asked about their prescription drug use and whether they used the medications not as intended by the doctor, such as changing the allowed dosage and frequency of when the medication was taken, or using someone else’s prescription medication.

Southern Methodist University associate professor Chrystyna D. Kouros said the study she co-authored revealed potential differences in the way university students misuse prescription drugs when compared to studies of how they use other substances. “Whereas other studies have shown that alcohol use, and to some extent marijuana use, is most likely to occur in social situations with peers and on the weekends, we found that the context of prescription drug misuse appears to be different,” Kouros said. “In our study, college students were more likely to endorse misusing prescription medication in moments when they were alone and at home. They were also more likely to misuse prescription medications during the week versus the weekend, and earlier in the day instead of the evening.”

The study focused on four classes of prescription drugs: pain relievers, stimulants, sedatives and tranquilisers. Researchers used a technique called ecological momentary assessment (EMA) to query the participating 297 students to record their behaviour in daily life. EMA involves repeated sampling of subjects’ current behaviours and experiences in real time, in their natural environments. Students were prompted by an iPod Touch four times a day to answer a brief survey. Students could also make a report if they were about to misuse a prescription.

The study suggests there might be different motivating factors underlying misuse of prescription drugs compared to other substances, Prof Kouros said.

“Current college-based prevention and intervention programs, thus, may need to be tailored or revised to also capture prescription drug misuse,” she added.

Source: Southern Methodist University

Studies Find Females More Susceptible To Addiction

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Several new studies focusing on sex differences in pain and addiction suggest that females could be more susceptible to drug addiction and addiction-like behaviours than males. Researchers also investigated how sleep deprivation affected the likelihood of relapse, partly driven by hormone differences in females and males. The studies will be presented at the American Physiological Society’s seventh conference on New Trends in Sex and Gender Medicine from 19 to 22 October.

This study used a rat model to investigate the connection between opioid abstinence and persistent sleep loss and its impact on the body’s central stress response system. Researchers specifically found persistent sleep disruption may cause or perpetuate abnormalities in their hypothalamic-pituitary adrenal axis. These abnormalities increase the risk of vulnerability to relapse during oxycodone abstinence in some individuals. Scientists are now working to identify susceptibility factors that play a role in boosting the risk of relapse. Adequate sleep may be critical for successful recovery from opioid addiction.

Researchers conducting this study explored how the opioid epidemic in the US continues and evolved during the ongoing COVID pandemic. Women have made up the majority of those prescribed opioids for pain treatment. Prescribed opioids for pain management became the primary conduit to abuse and addiction for women, and the researchers found that mitigations in opioid prescriptions have been followed by increases in the use of other substances, such as heroin and fentanyl, in both men and women. While the rate of opioid use and overdose is higher in men, women have a higher rate of overdose death. Understanding how opioid use and addiction differ in their effect on men and women is key to ending the epidemic.

A rat model was also used to evaluate sex differences in vulnerability to addiction. Their results indicate activation of a specific subset of receptors for oestrogens enhances established cocaine-seeking behaviors in female rats. In male rats, the preference for cocaine under the same circumstances was reduced, involving the area of the brain linked to compulsive behaviours. Females show a greater response than males to stimulants such as amphetamine and cocaine in part due to the gonadal hormone oestradiol, which is one of the three forms of oestrogen. The hope is these results will lead to a better understanding of the mechanisms of addiction-related behaviors and the development of sex-specific treatments for addiction.

Source: American Physiological Society

Paediatricians Can Help Adolescents Quit Vaping

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Even though e-cigarette- or vaping-associated lung injury (EVALI) were “a drop in the bucket” compared with COVID, vaping remains a significant health risk for teens, reported Anne Griffiths, MD, of the Children’s Hospital of Minnesota, during her presentation entitled “Updates on Youth Vaping” at the American Academy of Pediatrics virtual meeting

According to the 2021 National Youth Tobacco Survey, 11.3% (1.72 million) of high school students (ages 16 to 18) and 2.8% (320 000) of middle school students (ages 12 to 15)  reported using e-cigarettes in the past 30 days.
As more than half of youths who tried to stop vaping, there is an opportunity fo paediatricians to intervene, Dr Griffiths said.

Middle school students often start with zero-nicotine, flavour-only products before “they move on to a nicotine-based product and ultimately a THC-based product,” Griffiths noted. Of the middle and high school students who vape, 85% use flavoured products, with sweet and fruity flavours favoured.
Notably, disposable e-cigarettes are now more popular than refillable pods and cartridges this year, with 53.7% of all vaping students reporting use of these products. This comes down to messaging not to reuse vaping products during COVID, Dr Griffiths said.

However, vaping could be a risk factor for COVID, being diagnosed five times more often in vaping adolescents, according to a study in the Journal of Adolescent Health.

E-cigarette flavouring can suppress innate immune function, as demonstrated by studies. Others have shown that e-cigarette vapour may increase ACE2 expression in the lungs, which the receptor that enables entry of SARS-CoV-2 into host cells.

Adolescents presenting with EVALI or COVID (or both) can be differentiated Dr Griffiths said. The patient’s reaction to steroid treatment can be diagnostic: “Unlike SARS-CoV-2 where the [patient’s] improvement might be subtle [with a] gradual response to steroids, in EVALI, one day on high-dose steroids and they feel like a million bucks in comparison.”

In addition, EVALI may present with leukocytosis and high erythrocyte sedimentation rates and C-reactive protein levels, while COVID patients are more likely to have lymphopenia.

Dr Griffiths that in spite of the risks of vaping, “there’s an entire culture surrounding [kids] that can glamorise vaping life.”

Vaping companies reach out to children using methods such as YouTube vape championships, in which competitors perform various smoke tricks. In addition, vaping companies provide scholarships to students, often requiring them to write an essay on the benefits of vaping.

Source: MedPage Today

Medicinal Plant Extract Could Quell Opioid Epidemic

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In a bid to tackle the global opioid crisis, researchers have found that a Chinese medicinal plant extract can prevent morphine tolerance and dependence while also reversing opiate addiction. The researchers published their results in Pharmaceuticals.

For over two decades, opioid analgesic overprescription has driven a wave of misuse and consequent drive overdose deaths around the world, with the number of drug overdose deaths tripling in the US from 1997 to 2017. The COVID pandemic has only worsened the opioid epidemic. Fortunately, the documented effects of YHS, the extract of the plant Corydalis yanhusuo, could help curb the opioid epidemic.

“It is critical that we decrease the use and abuse of opiates,” said Olivier Civelli, PhD, professor of pharmaceutical sciences at the UCI School of Pharmacy & Pharmaceutical Sciences and corresponding author. “To help achieve this goal, we are proposing the use of this therapeutic plant. When used in animals, the Corydalis extract prevents pain and the negative effects of opiate use. The next step would be to test it with humans.”

The overprescription of opioid analgesics stemmed from treatment of chronic pain requiring repeated opioid administrations. This ultimately leads to tolerance, physical dependence, and addiction.

One possible solution involves a co-medication that maintains the analgesic benefits of opioids while preventing their adverse liabilities. The study showed that YHS, when co-administered with morphine, inhibits morphine tolerance, dependence and addiction. 

In Chinese traditional medicine, YHS has been used as an analgesic for centuries. It is considered safe and readily available for purchase.
“Opiate tolerance is of utmost importance to opiate users,” ProfvCivelli said. “They need to constantly increase the need of opiates to reach the same analgesic response. This is what leads to opiate overdose. YHS prevents opiate tolerance, so there is less need to increase opiate consumption.”

Source: University of California, Irvine

People With Substance Use Disorder at Higher Risk for COVID

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A recent study showed that people with substance use disorders (SUDs) face higher risks for developing COVID and for experiencing serious problems associated with the infection. The study, published in World Psychiatry, examined these risks in fully vaccinated individuals with SUDs.

The study included 579 372 people in the US, of whom 30 183 had a diagnosis of SUD and 549 189 without such a diagnosis) who were fully vaccinated between December 2020 and August 2021 and had not contracted COVID before their vaccinations.

The risk for breakthrough COVID infection in vaccinated people with SUDs ranged from 6.8% for tobacco use disorder to 7.8% for cannabis use disorder, all significantly higher than the 3.6% in the vaccinated non-SUD population. After controlling for demographics (age, gender, ethnicity) and vaccine types (Pfizer, Moderna, Johnson & Johnson), patients with SUDs – with the exception of those with tobacco use disorder – still had higher risks for breakthrough COVID-19 compared with matched individuals without SUDs, with the highest risks for those with cocaine use disorder and cannabis use disorder. 

The higher risk for people with SUDs was found to be largely due to their higher prevalence of comorbidities and adverse socioeconomic determinants of health (such as problems related to education, employment, and housing). However, those with cannabis use disorder, who were younger and had less comorbidities, still had a higher risk for breakthrough infection even matching for these. This could indicate that other variables, such as behavioural factors or adverse effects of cannabis on pulmonary and immune function, could explain some of their higher risk for breakthrough infection.

“In our study, the overall risk of COVID infection among vaccinated SUD patients was low, highlighting the effectiveness and the need for full vaccination in this population,” the authors wrote. “However, our findings document that this group remains a vulnerable one even after vaccination, confirming the importance for vaccinated patients with SUD to continue to take protective preventive measures against the infection.”

Source: Wiley

Prenatal CBD and THC Stunts Prozac Responsiveness in Offspring

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Scientists have found that significant amounts of THC and CBD, the two main components of cannabis enter the embryonic brain of mice in utero and impair the mice’s ability as adults to respond to fluoxetine (Prozac).

The study suggests that when the developing brain is exposed to THC or CBD, normal interactions between endocannabinoid and serotonin signaling may be diminished as exposed individuals become adults.

“Hemp-derived CBD is a legal substance in the US, and we are in a time of increasing state-level legalisation of cannabis. Therefore, use of cannabis components have increased across most levels of society, including among pregnant women. The study marks the beginning of an effort to understand the effects of THC and CBD on the endogenous cannabinoid system (ECS) in the developing brain and body,” explained Hui-Chen Lu, director of the Linda and Jack Gill Center and professor in the Department of Psychological and Brain Sciences in the IU Bloomington College of Arts and Sciences.

Researchers studied four groups of pregnant mice. Some received daily moderate doses of either THC, CBD, or a combination of equal parts THC and CBD; a control group had placebo injections throughout pregnancy. Using mass spectrometry, IU psychological and brain sciences professor Heather Bradshaw tested embryos and found that CBD and THC both could cross the placenta and reach the embryonic brain.

“The surprising part is that maternal exposure to CBD alone — a drug that is often considered as safe and harmless and is a popular ‘natural’ therapy for morning sickness — resulted in a lasting impact on adult mice offspring,” Lu said. “Both prenatal THC and CBD exposure impaired the adult’s ability to respond to fluoxetine. The results suggest taking a cautious approach to using CBD during pregnancy.”

There is however some evidence for CBD’s effectiveness in treating chronic pain and anxiety, though currently the only FDA-approved indication for CBD is the treatment of severe seizure disorders.

“We still know very little about the effects of CBD on the developing brain,” Prof Lu said.

The new paper is one of the first studies to see the potential negative impact of CBD on the developing brain and later behaviours. However observational studies in the 1980s saw increased anxiety and depression in offspring of mothers who used the lower-strength cannabis available at the time. Since women may take cannabis products for nausea and vomiting, this has relevance for public health awareness.

Study co-author Ken Mackie, Gill Chair of Neuroscience at IU Bloomington, said researchers know that prenatal cannabis exposure may increase the risk for anxiety and depression, so it is important to evaluate the response to a class of drug used to treat anxiety and depression.

Though normal mouse behaviours were seen in many tests, one test — to determine their response to stress — had a strongly atypical result. In all groups, the mice responded normally to a stressful situation. As expected, fluoxetine increased stress resilience in mice whose mothers had received the placebo. However, the drug was ineffective in mice whose mothers had received THC, CBD or their combination.

Fluoxetine works by increasing the amount of serotonin available at brain synapses, an effect known to require the endocannabinoid system. This internal system of receptors, enzymes and molecules both mediates the effects of cannabis and plays a role in regulating various bodily systems, such as appetite, mood, stress and chronic pain.

To test if maternal exposure to THC and/or CBD impaired endocannabinoid signaling in the adult offspring, the researchers tested whether boosting the ECS with a drug would restore fluoxetine’s effectiveness. They found that the ECS boosting restored normal fluoxetine responses in mice that had received THC or CBD while their brains were developing.

Source: Indiana University

Journal reference: de Sousa Maciel, I., et al. (2021) Perinatal CBD or THC Exposure Results in Lasting Resistance to Fluoxetine in the Forced Swim Test: Reversal by Fatty Acid Amide Hydrolase Inhibition. Cannabis and Cannabinoid Research.