Posts Tagged ‘THC’

by Amy Schleunes

When Lilian Kloft stumbled across a 2015 study showing a connection between cannabis use and susceptibility to false memories, she found herself wondering about the legal implications of the results. The study had discovered that heavy users of cannabis were more likely than controls to form false memories—recollections of events that never occurred, for example, or warped memories of events that did—even when they were not at the moment “high.”

This kind of false remembering can pose difficulties for people gathering reliable testimony in the event of a crime, says Kloft, a PhD student in psychopharmacology and forensic psychology at Maastricht University in the Netherlands. Consequently, the growing acceptance of cannabis worldwide raises questions not only about how the drug affects memory, but also about how law enforcement officials should conduct interviews with suspects, victims, and witnesses who may be under the influence or regular users of the drug.

In order to further investigate the connection between cannabis and false memory formation, Kloft and collaborators recruited 64 volunteers for a series of experiments. Participants, who were occasional cannabis users, were given a vaporizer containing either cannabis or a hemp placebo and then told to inhale deeply and hold their breath for 10 seconds. After that, the researchers tested them in three different tasks designed to induce false memories.

In the first task, the team asked the volunteers to memorize lists of words, and then to pick out those words from test lists that also included dummy words. As expected, both the sober and the intoxicated participants falsely remembered some of the dummy words. But while the sober participants mostly falsely remembered words that were strongly associated with words on the original lists, the intoxicated participants also selected less-related and completely unrelated terms.

In the next two tasks, the researchers wanted to see if they could induce false memories by providing misinformation to the participants. Hoping to imbue these tests with more real-world relevance than a list of words, Kloft and colleagues designed two immersive virtual reality scenarios involving common crimes. In the first, the “eyewitness scenario,” participants observed a fight on a train platform, after which a virtual co-witness recounted the incident but with several errors, including falsely recalling a police dog that wasn’t part of the altercation. In the “perpetrator scenario,” participants entered a crowded bar and were instructed to commit a crime themselves—to steal a purse.

The researchers observed a range of effects associated with cannabis as the intoxicated subjects interacted in these virtual environments. Some participants laughed and talked to the virtual characters in the scenarios, Kloft reports, while others became paranoid and required assistance in stealing the purse. “One person even ran away so quickly that they ripped out the whole VR setup and it fell to the ground,” she says. When researchers interviewed the participants afterward using a combination of leading and non-leading questions, those who were intoxicated showed higher rates of false memory for both the eyewitness and perpetrator scenarios compared with controls.

To look for longer-term effects of cannabis, the experimenters called the subjects back a week later and tested them again on the word lists, this time with a few different dummy words thrown in. They also re-interviewed the subjects about the VR scenarios using a combination of old and new questions. As before, they found lower memory accuracy in the word-association test in those who had been intoxicated compared with sober participants. There were no statistically significant differences between the groups for the virtual reality scenarios, a result that Kloft says may indicate memory decay over time in all participants.

Cognitive neuropsychopharmacologist Manoj Doss, a postdoc at Johns Hopkins University who was not involved in the study, has used word association and other tasks in his own research to demonstrate that tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, increases false memories when participants attempt to retrieve information they’d previously learned. Doss says that the study by Kloft and collaborators is novel not only because it employs virtual reality, but because it shows that both the real-world scenarios and the word association task can induce false memories.

For the tests administered after one week, however, Doss notes that it’s difficult to determine if the researchers were observing actual false memories, because participants might remember both the accurate and the dummy information they encountered in the original experiment. In the follow-up test, “people might say yes to the things they’re not supposed to just because they saw them in that first test,” says Doss. He suggests that increasing the number of items tested, as well as separately analyzing the new and previously used word tests and interview questions, could reveal a higher incidence of false memories in the delayed test for the participants who took cannabis.

Giovanni Marsicano, a neuroscientist at the University of Bordeaux in France who did not participate in the research, says that the new results match up with findings he’s made in mice: animals that receive injections of THC are more likely than controls to associate unrelated stimuli—itself a sort of false memory. His work has also shown that a cannabinoid receptor known as CB1 that is highly abundant in the hippocampus and prefrontal cortex probably plays a key role in the formation of these incidental associations. One of this receptor’s main jobs is to decrease the release of neurotransmitters. Marsicano hypothesizes that when the CB1 receptor is activated, neural signaling is inhibited in such a way that the brain is less able to separate correct from incorrect information.

Roger Pertwee, a pharmacologist at the University of Aberdeen in the UK who was not involved in the research, says that the Dutch team’s results aren’t surprising given what’s known about how cannabinoids affect memory. Unlike endogenous cannabinoids, which tend to selectively activate some CB1 receptors and not others, compounds in cannabis activate all CB1 receptors at once; this indiscriminate activation may also somehow contribute to the formation of false memories, explains Pertwee, who works with GW Pharmaceuticals, a company that makes prescription medicines derived from cannabis.

In the future, Kloft says she’s interested in looking at how people regard the memories they form when high in order to find out whether they “trust” those memories. “Are they confident in them, and is there any strategy they pursue to correct for their probably impaired memory?”

Study coauthor Elizabeth Loftus, a cognitive psychologist and human memory expert at the University of California, Irvine, says that the team’s study should prompt people to think about best practices when it comes to intoxicated witnesses. “The law recognizes that there are vulnerable witnesses who need extra special care and attention when you’re interviewing them: young children, people with mental disabilities, sometimes the elderly are included in that category,” Loftus says. “Might not [people who are high] be another example of . . . vulnerable witnesses where you’ve got to be extra careful?”

https://www.the-scientist.com/notebook/cannabis-increases-propensity-for-false-memories-67473?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_source=hs_email&utm_medium=email&utm_content=87631437&_hsenc=p2ANqtz–3qIL8Nng2JbtXCj4SM5wciCtEP1dVQlCZ5bcSGcfOZ4lZ6v_Hyruet-yvSuzp2a67Xy5el2TdFX8Tpyb8oU7OBsMjdg&_hsmi=87631437

If you’re smoking weed to ease your stress during the coronavirus pandemic, experts say it’s time to think twice.

Smoking marijuana, even occasionally, can increase your risk for more severe complications from Covid-19, the disease caused by the novel coronavirus.

“What happens to your airways when you smoke cannabis is that it causes some degree of inflammation, very similar to bronchitis, very similar to the type of inflammation that cigarette smoking can cause,” said pulmonologist Dr. Albert Rizzo, chief medical officer for the American Lung Association. “Now you have some airway inflammation and you get an infection on top of it. So, yes, your chance of getting more complications is there.”

Hey wait, you might say, I’ve only just started and I’m not smoking much — so what’s the harm?
The problem, said Dr. Mitchell Glass, a pulmonologist and spokesperson for the American Lung Association, is that the last thing you want during a pandemic is to make it more difficult for a doctor to diagnose your symptoms.

“Covid-19 is a pulmonary disease,” Glass said. “Do you really want to have a confounding variable if you need to see a doctor or a healthcare worker by saying, ‘Oh, and by the way, I’m not a regular user of cannabis, but I decided to use cannabis to calm myself down.’

“You don’t want to do anything that’s going to confound the ability of healthcare workers to make a rapid, accurate assessment of what’s going on with you,” he added.

Is that cough from smoking or coronavirus?

“Chronic” marijuana smoking, defined as daily use, damages the lungs over a period of time. The end result “looks a lot like chronic bronchitis, which is of course one of the terms we use for chronic obstructive lung disease, or COPD,” Glass said.

Smokers, people with COPD and other chronic lung diseases, as well as people with moderate to severe asthma are among those at high risk for severe illness from Covid-19, including the worst-case scenario of being placed on a ventilator in order to continue breathing.

Signs of lung damage from smoking even just a few cigarettes can show up in a matter of days.

While a hit or two of marijuana doesn’t compare, there are some unique properties to a joint of weed that are definitely problematic for the lungs even if you’re a new smoker, Glass said.

Think of what happens to a cigarette when lit and left in an ashtray — it will burn quickly all the way down to the filter, with nothing left but ash.

“It’s surrounded by paper. It’s completely dried out. It is made to burn at a very high temperature,” Glass said.

Now think of how a joint burns — there’s always some weed left, the “roach,” as it is called.

“Marijuana burns at a much, much lower temperature than a commercially made cigarette,” said Glass. “Because of that, the person is inhaling a certain amount of unburnt plant material.”

That irritates the lungs in the same manner as ragweed, birch and oak pollen does for those allergic to them, he said.

“So right off the bat there are those patients who would be increasingly susceptible to having a bronchospasm or cough because they have a more sensitive airway.”

And since a dry cough is a key sign of Covid-19, any cough caused by smoking a joint of weed could easily mimic that symptom, making diagnosis more difficult.

The need for a clear head

There’s another factor as well. As we all know, weed not only calms you down, but it messes with your ability to function — and that does you no favors if you find yourself having a medical emergency during a pandemic.

“You’re reducing anxiety, but that is still a change in your thinking, a change in the way you are handling facts, how you’re grasping situations,” Glass said.

“Now there’s a healthcare worker who is gowned, gloved, possibly in a hazmat suit trying to get through to you. These are people who are trying to decide if you should be going home, coming into the emergency room, or worst case scenario, that you need to be put on a ventilator,” he continued.

“They want the person who’s agreeing and giving informed consent to be completely in control of their thought processes.”

More Americans are using weed

In 2018, more than 43 million Americans aged 12 or older reported using marijuana in the past year, according to the 2018 National Survey on Drug Use and Health (PDF).

Around four million of those are people with “marijuana use disorder, meaning that this has escalated to the point where it’s a problem in their lives,” said Jessica Hulsey, founder of the Addiction Policy Forum, which advocates on behalf of patients and families struggling with substance use disorder and addiction.

“Experts at the National Institutes of Health released some guidance for our patients and our families. saying marijuana use disorder could be a risk factor for complications from Covid-19,” Hulsey said.

“Because it attacks the lungs, the coronavirus that causes Covid-19 could be an especially serious threat to those who smoke tobacco or marijuana or who vape,” the NIH said in its announcement.

“We need to make sure that these users are aware that marijuana is in essence an underlying health condition,” Hulsey added. “They should take extra precautions by minimizing use to the extent that is possible, and even start virtual treatment and a recovery journey while everyone’s stuck at home.”

The national drug survey also found more than a third of young adults aged 18 to 25 said they used marijuana during 2018, along with more than 13% of adults aged 26 or older.

But it’s not just the young. Earlier this year, a study found use by older adults is rising sharply. In 2006, only 0.4% of people over 65 reported using marijuana products in the past year. By 2018, over 4% of those same aged seniors say they are now using, the study found.

“Marijuana use among seniors is not bouncing up and down like with other drugs. It’s a straight line up,” said study co-author Joseph Palamar, an associate professor of population health at New York University’s Grossman School of Medicine, in an interview in February.

Are even more Americans turning to weed during this time of crisis?

Simply put, no one knows. Each state handles reporting differently, Glass says, and sales estimates often combine both THC, the main psychoactive compound in marijuana that produces the “high,” and CBD, the medicinal compound that is now sold over the counter.

“I made a few phone calls and the numbers ranged quite literally from a million to 30 million. So who knows how many people are getting their hands on cannabis to relieve their anxiety during this time,” Glass said.

What to do?

If you’re not a regular smoker of marijuana, don’t start, experts say.

“Don’t confound your caregivers with trying to sort out whether your dry cough and change in behavior is due to the fact that you’re a novice with marijuana or it’s associated with Covid-19,” Glass said.

“If you do need to see a caregiver, be sure you’re very honest with them about when you last used, and how often you use,” Glass said, “so they can get a good, clear story on what the impact of inhaling marijuana is on you.”

Remember the bottom line when it comes to smoking and Covid-19, Rizzo said.

“It’s common sense that anything you inhale that has been combusted and contains particles or chemicals can inflame your airways,” he said. “So you’re already making your body fight off foreign particles before it even has to fight off the infection.”

https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html


Dr. Anjali Rajadhyaksha
Professor of Neuroscience in Pediatrics
Associate Dean of Program Development
Weill Cornell Graduate School


Dr. Francis Lee
Psychiatry/Pharmacology; Chair and Psychiatrist-in-Chief
Mortimer D. Sackler, M.D. Professor in Psychiatry, Weill Cornell Medicine


Dr. Caitlin Burgdorf

A common variation in a human gene that affects the brain’s reward processing circuit increases vulnerability to the rewarding effects of the main psychoactive ingredient of cannabis in adolescent females, but not males, according to preclinical research by Weill Cornell Medicine investigators. As adolescence represents a highly sensitive period of brain development with the highest risk for initiating cannabis use, these findings in mice have important implications for understanding the influence of genetics on cannabis dependence in humans.

The brain’s endocannabinoid system regulates activity of cannabinoids that are normally produced by the body to influence brain development and regulate mood, as well as those from external sources, such as the psychoactive ingredient THC, also known as Δ9-tetrahydrocannabinol, which is found in cannabis. An enzyme called fatty acid amide hydrolase (FAAH) breaks down a cannabinoid called anandamide that is naturally found in the brain and is most closely related to THC, helping to remove it from circulation.

In the study, published Feb. 12 in Science Advances, the investigators examined mice harboring a human gene variant that causes FAAH to degrade more easily, increasing overall anandamide levels in the brain. They discovered that the variant resulted in an overactive reward circuit in female—but not male adolescent mice—that resulted in higher preference for THC in females. Previous clinical studies linked this FAAH variant with increased risk for problem drug use, but no studies had specifically looked at the mechanistic effect on cannabis dependence.

“Our study shows that a variant in the FAAH gene, which is found in about one-third of people, increases vulnerability to THC in females and has large-scale impact on brain regions and pathways responsible for processing reward,” said lead author Dr. Caitlin Burgdorf, a recent doctoral graduate from the Weill Cornell Graduate School of Medical Sciences. “Our findings suggest that genetics can be a contributing factor for increased susceptibility to cannabis dependence in select populations.”

The team found that female mice with the FAAH variant showed an increased preference for the environment in which they’d been exposed to THC over a neutral environment when they were exposed to the substance during adolescence, and the effect persisted into adulthood. However, if female mice with this variant were exposed to THC for the first time in adulthood, there was no increased preference for THC. These findings in mice parallel observations in humans that a select population of females are more sensitive to the effects of cannabis and demonstrate a quicker progression to cannabis dependence. “Our findings suggest that we have discovered a genetic factor to potentially identify subjects at risk for cannabis dependence,” said Dr. Burgdorf.

The investigators also found that the genetic variant led to increased neuronal connections and neural activity between two regions of the brain heavily implicated in reward behavior. Next, the team reversed the overactive reward circuit in female mice and found that decreasing circuit activity dampened the rewarding effects of THC.

As substance abuse disorders often emerge during adolescence, the investigators say this study has significant implications for translating these findings to inform developmental and genetic risk factors for human cannabis dependence.

“Our study provides new insights into cannabis dependence and provides us with a circuit and molecular framework to further explore the mechanisms of cannabis dependence,” said co-senior author Dr. Anjali Rajadhyaksha, professor of neuroscience in pediatrics and associate professor of neuroscience in the Feil Family Brain and Mind Research Institute and a member of the Drukier Institute for Children’s Health at Weill Cornell Medicine.

Although genetic factors are increasingly found to be associated with risk for other types of addiction, very few studies have investigated genetic factors associated with increasing risk for cannabis dependence. “In the future, we could use the presence of this FAAH genetic variant to potentially predict if an individual is more likely to be vulnerable to cannabis dependence,” said co-senior author, Dr. Francis Lee, chair of the Department of Psychiatry at Weill Cornell Medicine and psychiatrist-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center. “We are getting one step closer to understanding exactly how neurodevelopmental and genetic factors play interrelated roles to increase susceptibility for cannabis dependence.”

Additional authors on the study were Dr. Deqiang Jing, Ruirong Yang and Chienchum Huang from the Department of Psychiatry at Weill Cornell Medicine; Drs. Teresa A. Milner and Dr. Virginia M. Pickel from the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine; Dr. Matthew N. Hill from departments of Cell Biology and Anatomy and Psychiatry at University of Calgary; and Dr. Ken Mackie from the Department of Psychological and Brain Sciences at Indiana University Bloomington.

This research was supported by the National Institute of Health (Grants T32DA039080, R01DA08259, R01HL098351, R01HL136520, R01DA042943, R01NS052819, R01DA029122), Weill Cornell’s Mowrer Memorial Graduate Student Fellowship, NewYork-Presbyterian Youth Anxiety Center, the Pritzker Neuropsychiatric Disorders Research Consortium, the DeWitt-Wallace Fund of the New York Community Trust, and The Paul Fund.

https://news.weill.cornell.edu/news/2020/02/preclinical-study-links-human-gene-variant-to-thc-reward-in-adolescent-females


An assortment of edible marijuana products. Most edibles in a recent study inaccurately described the amount of THC on their labels.

By CATHERINE SAINT LOUIS

An analysis of 75 edible marijuana products sold to patients in Seattle, San Francisco and Los Angeles found that labels on just 17 percent accurately described their levels of THC, the main psychoactive ingredient, researchers reported Tuesday.

Sixty percent of the products had less THC than their packages advertised, and 23 percent of them had more THC than claimed.

“We need a more accurate picture of what’s being offered to patients,” said Dr. Donald Abrams, the chief of hematology and oncology at San Francisco General Hospital. He was not involved in the new study, which was published in JAMA.

“What we have now in this country is an unregulated medical marijuana industry, due to conflicts between state and federal laws,” Dr. Abrams said.

After ingesting marijuana, patients experience the maximal high one to three hours later. (It is felt within minutes after smoking.) Inaccurate labels complicate the consumption of marijuana for medical purposes.

Products with too little THC, or tetrahydrocannabinol, may fail to deliver symptom relief to those with debilitating conditions like chronic pain, and those with too much may overwhelm users.

Some of Dr. Abrams’s older cancer patients have tried edibles, he said, because they do not want to smoke marijuana. But some have eaten too much THC, with unpleasant results such as severe anxiety.

In the new study, cannabis candy, drinks and baked goods from 47 brands were tested by the Werc Shop, a laboratory with outposts in California and Washington State.

The Johns Hopkins University School of Medicine paid for the study except for the cost of the testing, which was covered by the Werc Shop. The company’s chief executive, Jeffrey Raber, is a study author.

Some discrepancies were notably large: In one case, a product had just three milligrams of THC even though its label claimed 108, said Ryan Vandrey, the study’s lead author and an associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

The researchers declined to name specific manufacturers or products. “I didn’t want to get sued,” Dr. Vandrey said.

“The point is not to say, ‘Hey, X medical marijuana company, you’re bad,’ ” he added. The more serious issue is that “we don’t have the kind of quality assurance for edibles that we have for any other medicine.”

The analysis found some geographical differences: The likelihood of having edible medical marijuana with more THC than advertised was higher in Los Angeles, while the likelihood of having it with less THC than labeled was greater in Seattle.

The researchers also tested each product for cannabidiol, or CBD, a nonpsychoactive ingredient of marijuana that is being studied in purified form as a possible aid to children with intractable epilepsy.

Forty-four products had detectable levels of CBD, though only 13 disclosed CBD. Nine had less CBD than labeled; four had more.

One limitation was that just one laboratory performed the analysis, medical and lab experts cautioned. Methodologies and results vary from lab to lab.

Some variability in test results is routine in this sort of analysis, so the researchers classified labels as accurate if the THC content was within 10 percent of the claimed levels.

Still, Remy Kachadourian, a chemist who has analyzed edible marijuana, suggested that 10 percent variability was too narrow.

“Plus or minus 15 percent is acceptable, and not only in my lab, but other labs in Colorado,” said Dr. Kachadourian, a senior scientist at CMT Laboratories in Denver.

Even though 23 states and the District of Columbia have medical marijuana programs, the federal government does not recognize marijuana as medicine and considers it illegal.

“When that changes,” Dr. Abrams said, “we’ll see the industry rushing to standardize dosing, as well as laboratory testing of products.”

http://mobile.nytimes.com/2015/06/24/health/labels-for-edible-marijuana-often-err-on-potency-study-says.html?ref=health&_r=1&referrer=

Thanks to Mike Moore for bringing this to the attention of the It’s Interesting community.