Researchers have detected significant levels of metals in the blood and urine among marijuana users, concluding that marijuana may be an important and under-recognised source of lead and cadmium exposure. This is among the first studies to report biomarker metal levels among marijuana users and most likely the largest study to date, that links self-reported marijuana use to internal measures of metal exposure, rather than just looking at metal levels in the cannabis plant. The results are published online in the journal Environmental Health Perspectives.
Measurements reported by participants for exclusive marijuana use compared to nonmarijuana-tobacco had significantly higher lead levels in blood (1.27ug/dL) and urine (1.21ug/g creatinine).
“Because the cannabis plant is a known scavenger of metals, we had hypothesised that individuals who use marijuana will have higher metal biomarker levels compared to those who do not use,” said first author Katelyn McGraw, postdoctoral researcher. “Our results therefore indicate marijuana is a source of cadmium and lead exposure.”
The researchers, from Columbia University Mailman School of Public Health, combined data from the National Health and Nutrition Examination Survey for the years 2005-2018, a biannual programme of studies designed to assess the health and nutritional status of adults and children in the U.S.
McGraw and colleagues classified the 7254 survey participants by use: non-marijuana/non-tobacco, exclusive marijuana, exclusive tobacco, and dual marijuana and tobacco use. Five metals were measured in the blood and 16 in urine.
The researchers used four NHANES variables to define exclusive marijuana and tobacco use: current cigarette smoking, serum cotinine levels, self-reported ever marijuana use, and recent marijuana use. Exclusive tobacco use was defined as individuals who either answered yes to ‘do you now smoke cigarettes, or if individuals had a serum cotinine level >10ng/mL.
The study found higher levels of cadmium (Cd) and lead (Pb) in blood and urine among participants reporting exclusive marijuana use compared to non-smokers. Cd and Pb levels were also higher in exclusive marijuana users who reported using marijuana within the last week. Cd biomarker levels were higher in those who smoked only marijuana than , either because of differences in frequency of use or differences in Cd levels in the tobacco and cannabis plants themselves. However, blood and urinary Pb levels among exclusive marijuana users and exclusive tobacco users were similar. Dual marijuana and tobacco users also had higher levels of Cd and Pb compared with non-smokers.
These observations marijuana use is an important and underrecognised source of Cd and Pb exposure independent of tobacco use, the researchers concluded.
Marijuana is the third most commonly used drug in the world behind tobacco and alcohol. As of 2022, 21 states and Washington D.C., covering more than 50 percent of the U.S. population, have legalised recreational use of marijuana; and medical marijuana is legal in 38 states and Washington D.C. However, because marijuana is still illegal at the federal level, regulation of contaminants in all cannabis-containing products remains piecemeal and there has been no guidance from federal regulatory agencies like the FDA or EPA. As of 2019, 48.2 million people, or 18% of Americans, report using marijuana at least once in the last year.
While 28 states regulate inorganic arsenic, cadmium, lead, and total mercury concentrations in marijuana products, regulation limits vary by metal and by state.
“Going forward, research on cannabis use and cannabis contaminants, particularly metals, should be conducted to address public health concerns related to the growing number of cannabis users,” said Tiffany R. Sanchez, PhD, assistant professor of environmental health sciences at Columbia Public Health, and senior author.
I walked into a store in Cape Town and I bought a gram of cannabis for R100. With GroundUp’s money. I had my editor’s consent.
The store was small, dimly lit, and lined with a variety of cannabis products in glass jars.
On the table was a stack of medical forms used by a doctor to prescribe cannabis to people for health reasons.
I did not have a doctor’s note. So I complimented the salesman on his luscious black curls. I think it worked because he became very chatty. Let’s call him Bob.
We discussed how the store works and the current laws. He said they’re working in a “grey area”.
There are two ways the store sells cannabis to people, Bob explained.
Method one: the membership system. Bob said that members pay a monthly fee and receive a certain amount of cannabis over a month. He says this gets around the legal problem, which is, he says, that “buying and selling” are not allowed. With the membership system, Bob said, you’re not doing either.
Method two: the medical method. The store uses section 21 of the Medicines Act to facilitate medical sales.
Bob said he was keen for the store to use the medical route for customers during the day and to run a club in the evenings where members come and smoke in a chilled environment.
I explained to Bob that I get quite anxious when I smoke. I can hear myself think with an echo of my thoughts swirling in my brain. (Boring truth be told, I haven’t smoked cannabis in years, and I didn’t smoke what I bought either. I won’t reveal who did.) Bob recommended a specific cannabis for me.
I asked him if he could recommend a doctor so I could get a prescription. Laughing, he said that he was a doctor. I think he was only half-joking, because it seemed like we then used method two: the medical route. He took out a scale and some bright green cannabis. He weighed it, and sold me 1 gram of OG Kush for R100.
Nope, that’s not how the law works
Was Ashraf’s transaction legal? No, according to a lawyer with expertise in the cannabis industry whom we spoke to.
First, the lawyer explained, cannabis can only be produced in a facility licensed by the South African Health Products Regulatory Authority (SAHPRA). It’s unlikely that the store obtained its cannabis from such a licensed facility. In fact there is a view that even weighing out a small amount of weed from a bag obtained from a licensed cultivator, and then packaging it, is manufacturing.
Second, if Section 21 of the Medicines Act is to be used, the sale of the cannabis can only take place after the doctor has prescribed it and SAHPRA has authorised the sale of weed to that particular patient. (Ashraf didn’t even give Bob his name.)
Even if these two conditions are met, no sale of cannabis to a patient can take place outside of a retail or community pharmacy.
There’s nothing unique about Ashraf’s experience. Dozens of stores across the country are selling cannabis using the same approach. We got the impression that in Durban there isn’t even a pretence of trying to be legal as there is in some of the Cape Town and Johannesburg stores. Our experience in Durban is that you can pretty much walk into stores and simply buy cannabis over the counter without any fuss.
How it got this way
South Africa’s cannabis sector is in limbo five years after the Constitutional Court ruled that cultivation and possession of the plant for private use is legal.
In 1997, Gareth Prince, a practising Rastafarian, applied to the Law Society of the Cape of Good Hope to be admitted as an attorney. The Society rejected his application because he had two criminal convictions for possession of cannabis and he continued to smoke cannabis. Prince argued that the use of cannabis was part of his religion, and that the Law Society’s decision violated his right to religious freedom.
Prince took the decision to court in 1998. But the High Court, Supreme Court of Appeal and Constitutional Court ruled in favour of the Law Society. The Constitutional Court’s 2002 decision was close: five versus four.
After the Constitutional Court’s judgment, Prince and two cannabis activists – Jeremy Acton and Jonathan Ruben – approached the courts again. Instead of focussing solely on religious freedom, their applications challenged provisions of the Drugs Act and Medicines Act that criminalised the use of cannabis on the basis that these provisions violated the right to privacy in section 14 of the Constitution. As these challenges were related, the High Court consolidated the cases.
In 2017, the Western Cape High Court declared the provisions in the Drugs Act and Medicines Act that criminalise private adult use of cannabis unconstitutional. This decision was upheld by the Constitutional Court in 2018. This judgment has become known as Prince 3. But the Constitutional Court did not confirm the High Court order that decriminalised the dealing of cannabis. Parliament was given 24 months to deal with the offending legislation.
In the event that Parliament didn’t fix things within the two-year deadline, the court ruled that its reading-in remedy (which permits the narrow exception for personal use) would become permanent, at least until Parliament amended the law.
Five years later, the slow pace of drafting legislation following the Prince 3 judgment has resulted in a proliferation of businesses using “grey areas” in the wording.
“People are looking for gaps, so these so-called dispensaries are stepping into the market claiming to sell something legal,” explained Andy Gray, chair of the Cannabis Working Group at SAHPRA and a pharmacy lecturer at the University of KwaZulu Natal (UKZN).
Substances that you can ingest are scheduled by SAHPRA from 0 to 8. A schedule 0 substance has very few controls; anyone can sell it without any licence required. At the other end of the scale, a schedule 8 substance is very strictly controlled, it may have some medicinal benefits but also has extremely high potential for abuse. Medical practitioners have to get special permission from SAHRPA for use and prescription of any of these substances.
After the Constitutional Court ruling, SAHPRA lowered the schedules of some of the substances found in cannabis. Low doses of Cannabidiol (CBD), a component of cannabis that isn’t psychoactive, were lowered to schedule 0 in complementary medicine products. But it is unclear if CBD in products such as drinks and gummies, with their varying dosages, manufacturing processes and contents – found in nearly every major shopping outlet – qualify as “complementary medicines”.
Tetrahydrocannabinol (THC), the key psychoactive component of cannabis, was lowered from schedule 7 to schedule 6. But schedule 6 substances are still highly restricted: According to SAHPRA these are medical substances that have “a moderate to high potential for abuse” which necessitates strict control and management of supply, including restrictions on repeat prescriptions and a supply limit of 30 days’ worth.
Danmari Duguid is head of the cannabis department at Schindlers Attorneys who represented Julian Stobbs and Myrtle Clarke, intervening parties in the 2018 Constitutional Court case, Prince 3. She says that the only way you can legally buy cannabis containing THC is through the medical route. This is done using section 21 of the Medicines Act.
Why section 21 of the Medicines Act is important
In a nutshell, this clause is a way for people with particular needs to legally obtain medicines that have not been registered by SAHPRA, but contain scheduled substances. For example, patients with serious cases of lung or skin cancer use Section 21 authorisation to access a medication called nivolumab (branded as Opdivo). SAHPRA has registered a lung and skin cancer medicine called pembrolizumab (branded as Keytruda) but this may not work with every patient.
In the 2000s, the Treatment Action Campaign (TAC) famously imported a generic version of a drug called fluconazole to treat an illness that particularly affects people with advanced HIV disease. A patented version of the medicine was available in the country but it was extremely expensive. The much more affordable version of the medicine that the TAC imported was not registered in South Africa, so the then Medicines Control Council allowed a doctor working with the TAC to import the medicine for patients using section 21 of the Medicines Act.
But section 21 authorisations are far from a straightforward legal route to using cannabis as explained above.
Hardly any of the cannabis retailers that claim to use the section 21 process are adhering to what’s legally required. It is in theory possible but in practice very hard for small cannabis retailers to do so.
Also, the Cannabis for Private Purposes Bill, currently before Parliament, does not provide for a recreational or adult market.
Gray told GroundUp that he fears people who want to buy and sell recreational cannabis in private will continue to abuse the medical route.
This happened in California in the United States, where the state legalised cannabis through the medicinal route and this led to extensive abuse of the process by patients, doctors and retailers.
The most direct way to combat this abuse is through the introduction of an adult use market, said Gray. This would mean cannabis products would be highly regulated and taxed, similar to alcohol and tobacco. This model could include the “legacy” or “peasant cultivators” who grow cannabis in rural parts of the country, and cannot meet the strict conditions for growing medical grade cannabis, said Gray.
Duguid agrees that the adult use model would work best for the legalisation of recreational cannabis sale and use in the future.
“At the moment you are allowed to brew beer for your own consumption, similar to how you are now allowed to grow cannabis for your own consumption after the 2018 judgement; but the moment you want to retail the product you should need a licence like you do to sell alcohol. This would ensure you meet certain safety standards,” said Duguid.
The Department of Agriculture and Land Reform and the Presidency recently hosted the Phakisa Action Lab in June 2023, which brought together 130 representatives of government and business, religious leaders and legal experts to discuss the legalisation of cannabis and hemp.
The final report from Phakisa emphasised that the government is taking a “science-based and human rights approach” approach to creating and regulating an adult use market, but that the “supply and trade of cannabis to consumers remains illegal”.
The report suggests adding a clause to the Cannabis for Private Purposes Bill which would remove cannabis from the Drugs Act “subject to parliamentary process and approval”.
The report highlights that adult use legalisation must include “the existing historical cultivation of cannabis by indigenous communities and black rural farmers”.
But it does not provide a timeline for doing this.
Recreational drug use may be a factor in a significant proportion of admissions to cardiac intensive care, with various substances detected in 1 in 10 such patients, suggest the findings of a multicentre French study published online in the journal Heart.
Drug use was also associated with significantly poorer outcomes, with users nearly 9 times as likely to die or require emergency intervention as other heart patients while in hospital, and 12 times as likely to do so if they used more than one drug.
Recreational drug use is a known risk factor for cardiovascular incidents, such as a heart attack or abnormal heart rhythm (atrial fibrillation), explain the researchers. An estimated 275 million people around the globe indulged in this activity in 2022, a 22% increase on the figure for 2010, they add.
But it’s not clear how common recreational drug use is among patients admitted to hospital with heart problems, or to what extent this affects the likely course of their condition.
To try and find out, the researchers analysed the urine samples of all patients admitted to cardiac intensive care in 39 French hospitals during one fortnight in April 2021, with a view to detecting recreational drug use.
During this period, 1904 patients were admitted, 1499 of whom provided a urine sample – average age 63, 70% male. Of these, 161 (11%) tested positive for various recreational drugs, but only just over half (57%) of whom admitted to using.
Prevalence was even higher among the under-40s, 1 in 3 (33%) of whom tested positive for recreational drugs.
The most frequently detected substance was cannabis (9%), followed by opioids (2%), cocaine (just under 2%), amphetamines (nearly 1%), and MDMA or ecstasy (just over 0.5%).
Compared with other non-using heart patients, users were more likely to die or to require emergency intervention for events such as cardiac arrest or acute circulatory failure (haemodynamic shock) while in hospital: 3% vs 13% – especially if they had been admitted for heart failure or a particular type of heart attack (STEMI).
After adjusting for other underlying conditions, such as HIV, diabetes, and high blood pressure, users were nearly 9 times as likely to die or require emergency treatment.
While cannabis, cocaine, and ecstasy were each independently associated with these incidents, and single drug use was detected in nearly 3 out of 4 patients (72%), several drugs were detected in more than 1 in 4 (28%) users: these patients were at even greater risk, being 12 times as likely to die or require emergency treatment.
This is an observational study, so can’t establish that recreational drug use resulted in admission to cardiac intensive care. The researchers also acknowledge that the study was only conducted over 1 fortnight in April, so the findings might not be applicable to other months of the year or the longer term.
And they caution: “Although the strong association between the use of recreational drugs and the occurrence of [major adverse events] suggests an important prognostic role, the limited number of events requires caution in the clinical interpretation of these findings.”
But recreational drugs can increase blood pressure, heart rate, temperature, and consequently the heart’s need for oxygen, they explain.
And they conclude: “While the current guidelines recommend only a declarative survey to investigate recreational drug use, these findings suggest the potential value of urine screening in selected patients with acute cardiovascular events to improve risk stratification in [cardiac intensive care].”
In a linked editorial, doctors from London’s St Bartholomew’s Hospital and Queen Mary’s University of London reiterate that the study wasn’t designed to uncover a causal relationship. Larger studies would be needed to try and establish that.
But the study findings prompt two obvious questions, they suggest: “(1) Should patients admitted to intensive cardiac care units be screened for recreational drug use: and (2) What, if any, interventions might be implemented following a positive patient test result?”
Knowing that a patient had used recreational drugs might shed light on the cause of their condition and inform how it’s managed, they suggest. It might have other benefits too.
“A positive test result would provide an opportunity for counselling about the adverse medical, psychological, and social effects of drugs, and for the implementation of interventions aimed at the cessation of drug use,” they write.
But quite apart from the cost, screening raises issues of patient confidentiality and the potential for discrimination in how targeted screening might be applied, they say.
And they conclude: “There is a considerable way to go, however, before screening for recreational drug use can be recommended.”
Children prescribed a stimulant to manage symptoms of attention deficit hyperactivity disorder (ADHD) do not have more substance use or substance use disorder (SUD) as adolescents or young adults, according to a new study appearing in JAMA Psychiatry.
The study’s findings may provide some reassurance to parents and clinicians who may be hesitant to prescribe ADHD stimulant medications out of fear that this may result in future substance abuse.
“Stimulants are the first-line treatment recommended for most individuals with ADHD – the drug class is an evidence-based treatment with few side effects,” said Brooke Molina, PhD, professor of psychiatry, psychology and paediatrics at University of Pittsburgh. “Because stimulant medications are classified by the Drug Enforcement Administration as schedule two substances with the potential for misuse, many people fear that harmful substance use could result.”
Marked by chronic patterns of inattention, hyperactivity or impulsivity, ADHD is a chronic condition that must be monitored throughout an individual’s life.
Molina and her colleagues assessed patients with ADHD over a 16-year period from childhood through adolescence to early adulthood to see if there was any association between stimulant treatment and subsequent substance use. The study accounting for dozens of demographic, clinical and psychosocial factors that may predispose an individual to treatment and substance use to address the relationship between childhood use of prescription stimulants and later SUD.
“Our study not only accounted for age, but also used a statistical method that adjusted over time for the many characteristics that may distinguish treated from non-treated individuals,” said study co-author Traci Kennedy, PhD, assistant professor of psychiatry at Pitt. “Considering these factors allowed us to more accurately test the relationship between stimulants and substance use.”
While other studies have sought to uncover and define a possible connection between prescription stimulant use for ADHD and SUD, the association between the two has remained controversial. Some studies suggested a protective effect of prescription stimulant use on the risk of having SUD later in life, while others failed to find an association.
After accounting for a number of factors, the researchers found no evidence that prescription stimulant treatment in childhood provided protection against developing a SUD for adolescents or young adults with ADHD. Nor did they find an association between stimulant use during childhood and increased substance misuse in the future
While some study participants self-reported an increase over time in heavy drinking, marijuana use, daily cigarette smoking and using other substances, an association with age was also found for stimulant treatment, with older participants being less likely to continue taking medication. When these trends were paired with rigorous statistical analysis, results provided no evidence that prolonged stimulant use is associated with reduced or increased risk for SUD.
“We hope the results of this study will help educate providers and patients,” Molina said. “By understanding that stimulant medication initially prescribed in childhood is not linked to harmful levels of substance use, I anticipate that parents’ and patients’ fears will be alleviated.”
Pitt researchers plan to study individuals who were first diagnosed with ADHD and treated with stimulants in adulthood. The study aims to learn if there are differences in the characteristics and outcomes of these adults compared to people who were diagnosed and first treated with stimulants in childhood.
The rate at which women eliminate alcohol from their bloodstream is largely predicted by their lean body mass, although age plays a role, too, scientists found in a new study published in the journal Alcohol Clinical and Experimental Research. Since women with obesity also have more lean body mass, older women with obesity clear alcohol from their systems 52% faster than younger women of healthy weights, the study found.
“We believe the strong relationship we found between participants’ lean body mass and their alcohol elimination rate is due to the association that exists between lean body mass and lean liver tissue – the part of the liver responsible for metabolising alcohol,” said research group leader M. Yanina Pepino, a professor of food science and human nutrition at the University of Illinois Urbana-Champaign.
To explore links between body composition and alcohol elimination rates, the team conducted a secondary analysis of data from a study performed at and another at Indiana University, Indianapolis. Both projects used similar methods to estimate the rate at which alcohol is broken down in the body.
The combined sample from the studies used in the analysis included 143 women who ranged in age from 21 to 64 and represented a wide range of body mass indices – from healthy weights to severe obesity. Among these were 19 women who had undergone different types of bariatric surgery. Lean body mass is total body weight minus fat.
In a subsample of 102 of these women, the researchers had measured the proportions of lean and fat tissue in their bodies and calculated their body mass indices. Based on their BMI, those in the subsample were divided into three groups: normal weight (BMI of 18.5–24.9), overweight BMI (25–29.9) and obese (BMI 30+).
As the researchers expected, women with higher BMI had not only more fat mass than women of healthy weights, they also had more lean mass. On average, the group with obesity had 52.3 kg of lean mass, compared with 47.5 kg for the normal weight group.
The two studies both used an alcohol clamp technique, where participants received an intravenous infusion of alcohol at a rate controlled by a computer-assisted system. The system calculated personalised infusion rates based upon each participant’s age, height, weight and gender and was programmed so they would reach a target blood alcohol concentration of .06% within 15 minutes and maintain that level for about two hours
Using a breathalyser, breath samples were collected at regular intervals throughout the experiments to estimate participants’ blood alcohol concentration and provide feedback to the system.
“We found that having a higher fat-free body mass was associated with a faster alcohol elimination rate, particularly in women in the oldest subgroups,” said Neda Seyedsadjadi, a postdoctoral fellow at the university and the first author of the study.
“The average alcohol elimination rates were 6 grams per hour for the healthy weight group, 7 grams for the overweight group, and 9 grams for the group with obesity,” she said. “To put this in perspective, one standard drink is 14 grams of pure alcohol, which is found in 12 ounces of beer, 5 ounces of table wine or 1.5 ounces shot of distilled spirits.”
The interaction between participants’ age and lean body mass accounted for 72% of the variance in the time required to eliminate the alcohol from their system, the team found.
Pepino, who also holds an appointment as a health innovation professor at Carle Illinois College of Medicine, has conducted several studies on alcohol response in bariatric surgery patients.
The findings also shed light on alcohol metabolism and body composition in women who have undergone weight loss surgery. Researchers have long known that bariatric surgery alters women’s response to alcohol but were uncertain if it affected how quickly they cleared alcohol from their systems.
Some prior studies found that these patients metabolised alcohol more slowly after they had weight loss surgery. The new study’s findings indicate that these participants’ slower alcohol elimination rates can be explained by surgery-induced reductions in their lean body mass. Weight loss surgery itself had no independent effects on patients’ alcohol elimination rates, the team found.
With growing legalisation and recreational use of cannabis comes a change in attitudes. Research has shown that dispensaries often recommend cannabis for the easing of pregnancy symptoms, especially morning sickness.
Growing evidence links cannabinoid consumption during pregnancy with poor child outcomes, though the exact effects on the developing foetus remain unclear. In a study published in Frontiers in Pediatrics, researchers in the US have now examined how timing of cannabis exposure during pregnancy impacts foetal development.
“We show that even when marijuana use occurred only in the first trimester of pregnancy, birth weight was significant reduced, by more than 150g on average,” said senior author Dr Beth Bailey, professor and director of population health research at Central Michigan University. “If that use continued into the second trimester, newborn head circumference was significantly decreased as well.”
Continued exposure results in largest deficiencies
“These findings are important as newborn size is one of the strongest predictors of later child health and development,” added study first author Dr Phoebe Dodge.
Recent work, including the research by Dodge et al., has shown significant effects of cannabis use on newborn size. “Size deficits were largest among newborns exposed to marijuana throughout gestation,” Bailey explained. The babies born after continued in-utero exposure were nearly 200g lighter, and their head circumference was nearly 1cm less than that of babies who had not been exposed. Pregnancy cannabis use did not significantly predict newborn length in this study.
The effects the scientists observed have also shed light on patterns of use. Their study showed that occasional use, such as for first trimester morning sickness, may reduce fetal growth in the same way as continued use throughout pregnancy. The same is true for other use in early stages, including cases when someone uses cannabis not knowing they are pregnant.
Quitting before pregnancy is best recommendation
The authors pointed out that in their study they did not have information about how much or how often participants used cannabis. Their results were based on whether people did or did not use it at certain times in pregnancy. Therefore, the study could not establish if there was a connection between heavy use and more pronounced outcomes in newborn growth.
More studies are needed to determine whether timing or amount of use is most important when it comes to effects on newborn size, they wrote.
“The best recommendation is that women should be advised to quit marijuana use prior to becoming pregnant,” Dodge said. However, quitting as soon as possible after getting pregnant is the second-best option to avoid long term adverse health and developmental outcomes. “There are some benefits of quitting among those who begin pregnancy using marijuana,” she continued.
In a study published in the journal PNAS, detailed brain imaging data from 20 healthy volunteers revealed how the potent psychedelic compound, DMT (dimethyltryptamine), alters brain function. During the immersive DMT experience, there was increased connectivity across the brain, with more communication between different areas and systems. The changes to brain activity were most prominent in areas linked with ‘higher level’ functions, such as imagination.
DMT is a potent psychedelic found naturally in certain plants and animals, and unlike classic psychedelics, such as LSD or psilocybin, DMT’s has shorter-lasting effects on the brain, measured in minutes, rather than hours. It occurs in trace amounts in the human body and is the major psychoactive compound in ayahuasca.
The study is the first to track brain activity before, during and after the DMT experience in such detail.
Dr Chris Timmerman, from the Centre for Psychedelic Research at Imperial College London, and first author on the study, said: “This work is exciting as it provides the most advanced human neuroimaging view of the psychedelic state to-date.
“One increasingly popular view is that much of brain function is concerned with modelling or predicting its environment. Humans have unusually big brains and model an unusually large amount of the world. For example, like with optical illusions, when we’re looking at something, some of what we’re actually seeing is our brain filling in the blanks based on what we already know. What we have seen with DMT is that activity in highly evolved areas and systems of the brain that encode especially high-level models becomes highly dysregulated under the drug, and this relates to the intense drug ‘trip’.”
DMT can produce intense and immersive altered states of consciousness, with the experience characterised by vivid and bizarre visions, a sense of ‘visiting’ alternative realities or dimensions, and similarities with near death experiences. But exactly how the compound alters brain function to account for such effects has been unclear.
In the latest study, 20 healthy volunteers were given an injection of the drug while researchers from Imperial’s Centre for Psychedelic Research captured detailed imagery of their brains, enabling the team to study how activity changes before, during and after the trip.
Volunteers intravenously received a high dose of DMT (20mg), while simultaneously undergoing functional magnetic resonance imaging (fMRI) of their brain and electroencephalography (EEG). The total psychedelic experience lasted about 20 minutes, and at regular intervals, volunteers provided a rating of the subjective intensity of their experience (on a 1 to 10 scale).
The fMRI scans found changes to activity within and between brain regions in volunteers under the influence of DMT. Effects included increased connectivity across the brain, with more communication between different areas and systems. These phenomena, termed ‘network disintegration and desegregation’ and increased ‘global functional connectivity’, align with previous studies with other psychedelics. The changes to activity were most prominent in brain areas linked with ‘higher level’, human-specific functions, such as imagination.
The researchers highlight that while their study is not the first to image the brain under the influence of psychedelics or the first to show the signatures of brain activity linked to psychedelics, it is the first to combine imaging techniques to study the brain during a highly immersive psychedelic experience. They explain the work provides further evidence of how DMT, and psychedelics more generally, exert their effects by disrupting high level brain systems.
Prof Robin Carhart-Harris, founder of the Centre for Psychedelic Research at Imperial College London, and senior author on the paper (now working at the University of California, San Francisco), commented: “Motivated by, and building on our previous research with psychedelics, the present work combined two complementary methods for imaging the brain imaging. fMRI allowed us to see the whole of the brain, including its deepest structures, and EEG helped us view the brain’s fine-grained rhythmic activity.
“Our results revealed that when a volunteer was on DMT there was a marked dysregulation of some of the brain rhythms that would ordinarily be dominant. The brain switched in its mode of functioning to something altogether more anarchic. It will be fascinating to follow-up on these insights in the years to come. Psychedelics are proving to be extremely powerful scientific tools for furthering our understanding of how brain activity relates to conscious experience.”
The Imperial team is now exploring how to prolong the peak of the psychedelic experience through continuous infusion with DMT, and some are also advising on a commercially run trial to assess DMT for patients with depression.
Analysis of US poison centre data has shown that suspected suicidal cannabis exposures have increased 17% annually, over a period of 12 years. According to the study published in the journal JAMA Network Open, more than 92%, involved other substances in addition to cannabis, and the data cannot show a direct causal link between cannabis and suicide attempts.
Still, the findings are cause for concern, the researchers said, especially since the increase was more pronounced among children and women during and after the pandemic.
“This study adds to already ample evidence that cannabis use, particularly by younger people, has significant implications for mental health,” said study co-author Tracy Klein, a WSU associate professor of nursing. “We don’t have evidence that cannabis alone was the primary driver of a suicide attempt, but we do know that cannabis can worsen certain mental health conditions and increase impulsivity.”
The researchers found 18,698 cases of intentional, suspected suicide cannabis exposures reported to U.S. poison centers from 2009 to 2021. Of these cases, 9.6% resulted in death or major outcomes such as permeant disability. The researchers noted that while more of these exposures involved younger people, severe consequences occurred more often among people 65 and older.
U.S. poison centers take calls 24-hours a day from households and healthcare facilities to provide toxicology expertise in suspected poisoning cases. They also investigate the causes, often following up with patients and doctors to determine if patients took substances intentionally or not.
It is well known that accidental cannabis poisonings have been increasing since many states legalized cannabis. Some policies can help prevent these unintentional cases, Klein said, such as packaging guidelines so edible cannabis products are not mistaken for candy.
Intentional cannabis poisonings, on the other hand, have not been well studied, which is one of the reasons the researchers undertook this analysis, and their findings point to the need for more mental health services.
“We have a significant shortage of mental health and primary care providers in the United States,” Klein said. “We know that mental health needs not only changed but became even more acute during the COVID-19 emergency. Cannabis is one part of that.”
Other research has shown that cannabis use is associated with depression and anxiety in youth and that it may interfere with brain development as well. Recent studies have also suggested a link between suicidal ideation and cannabis use in young people. Given this evidence, it is especially important to limit youth access to cannabis, said Janessa Graves, first author and a WSU nursing associate professor.
“Children and adolescents shouldn’t be able to purchase or access cannabis,” Graves said. “We also need to educate kids and parents around the risks of cannabis. I think many people just aren’t aware the impacts cannabis can have on brain development, and on behavioural and mental health, especially in adolescents and young adults.”
Researchers have found that a simple injection of hormone called fibroblast growth factor 21 (FGF21) protects mice against ethanol-induced loss of balance and righting reflex, effectively sobering them up.
“We’ve discovered that the liver is not only involved in metabolising alcohol but that it also sends a hormonal signal to the brain to protect against the harmful effects of intoxication, including both loss of consciousness and coordination,” says co-senior study author Steven Kliewer of the University of Texas Southwestern Medical Center, regarding the study results published in the journal Cell Metabolism.
“We’ve further shown that by increasing FGF21 concentrations even higher by injection, we can dramatically accelerate recovery from intoxication. FGF21 does this by activating a very specific part of the brain that controls alertness,” says Kliewer.
The consumption of ethanol produced by the natural fermentation of simple sugars in ripening fruits and nectars can cause intoxication, impairing mobility and judgement. Animals that consume fructose and other simple sugars have evolved liver enzymes to break down ethanol.
FGF21 is a hormone that is induced in the liver by a variety of metabolic stresses, including starvation, protein deficiency, simple sugars, and ethanol. In humans, ethanol is by far the most potent inducer of FGF21 described to date. Previous studies showed that FGF21 suppresses ethanol preference, induces water drinking to prevent dehydration, and protects against alcohol-induced liver injury.
In the new study, Kliewer and co-senior study author David Mangelsdorf of the University of Texas Southwestern Medical Center show that FGF21 plays a broader role in defending against the harmful consequences of ethanol exposure than previously thought. In mice, FGF21 stimulated arousal from intoxication without changing the breakdown of ethanol. Mice lacking FGF21 took longer than their littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduced the time needed for mice to recover from ethanol-induced unconsciousness and lack of muscle coordination.
Surprisingly, FGF21 did not counteract sedation caused by ketamine, diazepam, or pentobarbital, indicating specificity for ethanol. FGF21 mediated its anti-intoxicant effects by directly activating noradrenergic neurons in the locus coeruleus region in the brain, which regulates arousal and alertness. Taken together, the results suggest that the FGF21 liver-brain pathway evolved to protect against ethanol-induced intoxication. According to the authors, this pathway may modulate a variety of cognitive and emotional functions to enhance survival under stressful conditions.
Whether activation of the noradrenergic system contributes to FGF21’s other effects is yet to be determined. Although both FGF21 and noradrenergic nervous system activity are induced by ethanol in humans, additional studies will also be required to determine whether FGF21’s anti-intoxicant activity translates to humans.
“Our studies reveal that the brain is the major site of action for FGF21’s effects,” Mangelsdorf says. “We are now exploring in greater depth the neuronal pathways by which FGF21 exerts its sobering effect.”
The decriminalisation of cannabis for private use does not include the workplace, a Johannesburg Labour Court judge has ruled.
Judge Connie Prinsloo, in a recent ruling, said submissions by the National Union of Metalworkers of South Africa (NUMSA) that the Constitutional Court had ruled that cannabis was no longer a “drug” but just a “plant or a herb” were wrong.
She said the Concourt “Prince” judgment in 2018 did not offer any protection to employees against disciplinary action should they contravene company policies or disciplinary codes.
She said the apex court had not said cannabis was no longer a drug, as the union had argued, but had merely allowed for its personal consumption, in private, by adults.
The case before Judge Prinsloo was a review of the dismissal of two PFG Building Glass employees in October 2020 who had tested positive for cannabis while on duty. The National Bargaining Council for the Chemical Industry had found their dismissal to be fair. The union said it was unfair since cannabis was not a drug according to the Constitutional Court.
The company, through its witnesses, presented evidence that being under the influence of alcohol or drugs within the workplace was an offence for which dismissal was the prescribed sanction for the first offence.
This was because the company took workplace safety very seriously and it had a moral and legal duty to ensure that the working environment was safe.
On site, there was gas, large forklifts, extremely hot processes and dangerous chemicals used to make heavy glass which could potentially cut or crush someone.
The company followed the Occupational Health and Safety Act and had a zero-tolerance policy towards alcohol and drugs.
Referring to evidence at the bargaining council, Judge Prinsloo said it had been suggested by the employees that the company was “sticking to the old stigmatisation” of cannabis, whereas the Constitutional Court, in the Prince judgment, had said it was “just a plant … a herb” and could be legally possessed and used.
Company representatives, however, said it was still recognised as a drug and an employee was not permitted to be on site under the influence of alcohol or drugs.
One of the dismissed employees, Mr Nhlabathi, testified that he had used cannabis three days before he reported to work on the day he tested positive. He said he had been employed since 2016 and had “been smoking dagga and doing his job properly”. He disputed that the alcohol and drug policy related to cannabis but only to “alcohol and substances”.
His colleague, Mr Mthimkhulu, also relied on the Constitutional Court judgment that “dagga was a herb and not a substance”. Both claimed they were not aware that they could be fired for testing positive for cannabis.
Judge Prinsloo said the arbitrator had accepted that the company had a zero tolerance policy and that it treated cannabis as a drug because it was a “mind altering substance”.
The arbitrator had said the Prince judgment did not overrule the provisions of the Occupational Safety Act.
Judge Prinsloo said it was evident that the union and the employees had confused issues relating to the decriminalisation of the use of cannabis in private and the rights of employers to take disciplinary action against an employee who contravened a disciplinary code.
The Prince judgment declared specific provisions of the Drugs and Trafficking Act to be inconsistent with the right to privacy and therefore invalid to the extent that they made the use or possession of cannabis in private, by an adult person, a criminal offence.
The Constitutional Court had held, however, that it was common cause that cannabis was a harmful drug.
“The court did not interfere with the definition of a drug, nor did it declare dagga to be a plant or a herb,” Judge Prinsloo said.
“The applicant’s understanding of the judgment was either very limited or totally wrong,” she said.
The company was entitled to set its own standards of conduct and dismissal was an appropriate sanction, she said, dismissing the review.
