Posts Tagged ‘THC’


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.