From the Journals

Synthetic cannabinoid use linked to multiple risk factors

Synthetic cannabinoids are made in a lab to have marijuanalike properties, but often have more short-term medical and behavioral toxicities. We at the University of Florida McKnight Brain Institute in Gainesville have studied bath salts and synthetics in the laboratory, but there have been few human studies. The current studies by Clayton et al. and Ninnemann et al., following shortly after the American Academy of Pediatrics warning about the effects of cannabis smoking in adolescents (Pediatrics. 2017 10.1542/peds.2016-4069), are a grim reminder that adolescence is a period of extreme vulnerability to drugs of abuse. Synthetic cannabinoids, as addiction specialists will attest, produce some signs and symptoms of cannabis intoxication, but often with more acute problems, with greater intensity, and of longer duration. In the current two studies, it is clear that the reported consequences of synthetic cannabinoids are greater in terms of risk behaviors and depression than in marijuana smokers.

Dr. Mark S. Gold

Dr. Mark S. Gold

Cannabis or synthetic cannabis smoking causes psychiatric problems, but more problems and risk behaviors are seen in synthetic marijuana users, like those reported in these studies. Our work suggests that synthetic use might interact with brain receptors and systems in a way more like concussion, causing subtle neurotoxicities. Synthetic cannabinoids have received considerable attention in the media because of their ability to produce acute neurologic syndromes, bizarre behaviors, and prolonged psychiatric distress. The current studies reinforce the clinical experience of addiction and psychiatric professionals, and the notion that drugs of abuse should be considered extremely dangerous until proven safe.

Mark S. Gold, MD, is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. He also is chairman of the scientific advisory boards for RiverMend Health, Atlanta.


 

FROM PEDIATRICS

An estimated 1 in 10 high school students uses synthetic cannabinoids, which are linked to multiple other risk behaviors, and use is more likely among students with depressive symptoms, marijuana use, and alcohol use, investigators in two studies reported.

Fake marijuana Courtesy DEA
More serious effects have included “seizures, permanent cardiovascular damage, renal damage, stroke, psychosis, paranoia, aggression, anxiety attacks, dependence, and death (through suicide, adverse reaction, or overdose),” reported Heather B. Clayton, PhD, and her associates at the Centers for Disease Control and Prevention.

“Overall, we observed that ever use of synthetic cannabinoids was associated with the majority of health risk behaviors included in our study and that those associations tended to be more pronounced for ever use of synthetic cannabinoids than for ever use of marijuana only, particularly for substance use behaviors and sexual risk behaviors,” they wrote (Pediatrics. 2017 March 13. doi: 10.1542/peds.2016-2675).

Dr. Clayton’s team analyzed data from 15,624 students in grades 9-12 from the cross-sectional 2015 Youth Risk Behavior Survey, including all 50 states and Washington. The questions asked about use of marijuana, synthetic cannabinoids, or both. The question about synthetic cannabinoids included reference to street names of the drug, such as K2, Spice, fake weed, King Kong, Yucatan Fire, Skunk, or Moon Rocks. Another three dozen questions asked about risk behaviors related to substance use, violence and injury, mental health, and sexual health.

The results revealed that 29% of students had ever used only marijuana and 9% had ever used synthetic cannabinoids. Most of the students, 61%, had never used either. Although 23% of marijuana users had used synthetic cannabinoids, nearly all (98%) of the cannabinoids users had used marijuana.

Compared with those who had used only marijuana, adolescents who had ever used synthetic cannabinoids were considerably more likely to engage in substance use (adjusted prevalence ratio [aPR] = 4.85 for current alcohol use; aPR =151.90 for ever use of heroin) or sexual risk behaviors (had sexual intercourse with four or more persons during their life; aPR = 6.20). They also were more than twice as likely to have tried marijuana before age 13 years (aPR = 2.35) and were more likely to have used marijuana at least once in the past month (aPR = 1.36) and to have used marijuana 20 or more times in the past month (aPR = 1.88).

“Youth may progress from marijuana use only to the use of synthetic cannabinoids for a variety of reasons, such as ease of access, perception of safety, and ability to be undetected by many drug tests,” Dr. Clayton and her associates wrote.

The second study found similar associations between marijuana use and later use of synthetic cannabinoids. Andrew L. Ninnemann of the University of Missouri–Columbia, and his associates collected data twice over a 12-month period from 964 high school students at seven public schools in Southeast Texas (Pediatrics. 2017 March 13. doi: 10.1542/peds.2016-3009), to examine the relationship of synthetic cannabinoid use with anxiety, depression, impulsivity, and marijuana use.

The first assessment occurred in spring of 2011 and the second in spring of 2012. Most respondents (response rate, 62%) were sophomores (73%) or juniors (24%), with only 1% each of freshmen and seniors; 1% reported “other.” The sample included 31% African American students, 29% white students, 28% Hispanic students, and 12% of other ethnicities.

Males were more likely than females to use synthetic cannabinoids, and African American students were less likely to use them than teens of other ethnicities. Depression at baseline predicted use of synthetic cannabinoids a year later (adjusted odds ratio [aOR] = 1.42, P = .04), as did alcohol use (aOR = 1.85, P = .02), marijuana use (aOR = 2.47, P less than .001), and synthetic cannabinoid use at baseline (aOR = 2.36, P less than .001).

Students also were more likely to use marijuana at follow-up if they had used alcohol (aOR = 1.96, P less than .001) or marijuana (aOR = 4.52, P less than .001) at baseline. However, neither demographic variables nor anxiety, impulsivity, synthetic cannabinoid use, or other drug use significantly predicted marijuana use 1 year later.

Mr. Ninnemann’s study also found a slightly higher prevalence of synthetic cannabinoid use at baseline than the Clayton study did, with 13% of the Texas sample reporting use.

“The substantial risks associated with even a single episode of synthetic cannabinoid use emphasize the critical importance of identifying and targeting potential risk factors,” Mr. Ninnemann and his coauthors wrote. “Our findings indicate that prevention and intervention efforts may benefit from targeting depressive symptoms and alcohol and marijuana use to potentially reduce adolescent use of synthetic cannabinoids.”

Dr. Clayton and her colleagues mentioned a past study finding that 50% of elementary schools, 33% of middle schools, and 13% of high schools do not require instruction on alcohol or other drug use prevention. The U.S. trend of cannabis legalization also introduces uncertainty, the investigators noted.

“It is unclear what impact the legalization of marijuana will have on the use of synthetic cannabinoids,” Dr. Clayton’s team wrote. The evidence is contradictory on the likelihood of teens trying marijuana in these environments, but “there is a concern that if marijuana use increases, the use of synthetic marijuana may also increase,” they noted.

The Clayton study did not have external funding. The Ninnemann study received funding from the National Science Foundation, the National Institute of Child Health and Human Development, and the National Institute of Justice. The authors of both studies reported that they had no disclosures.

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