Translational Psychiatry volume 8, Article number: 89 (2018) 

Abstract 

There is a strong association between cannabis use and schizophrenia but the underlying cellular links are poorly understood. Neurons derived from human-induced pluripotent stem cells (hiPSCs) offer a platform for investigating both baseline and dynamic changes in human neural cells. Here, we exposed neurons derived from hiPSCs to Δ9-tetrahydrocannabinol (THC), and identified diagnosis-specific differences not detectable in vehicle-controls. RNA transcriptomic analyses revealed that THC administration, either by acute or chronic exposure, dampened the neuronal transcriptional response following potassium chloride (KCl)-induced neuronal depolarization. THC-treated neurons displayed significant synaptic, mitochondrial, and glutamate signaling alterations that may underlie their failure to activate appropriately; this blunted response resembles effects previously observed in schizophrenia hiPSC- derived neurons. Furthermore, we show a significant alteration in THC-related genes associated with autism and intellectual disability, suggesting shared molecular pathways perturbed in neuropsychiatric disorders that are exacerbated by THC. 

In summary, we found significant associations of THC- related pathways to autism and intellectual disability. Furthermore, we have used a dynamic, human-relevant system to demonstrate a phenotypic link between THC treatment and schizophrenia. We hypothesize that THC exposure, by impacting many of the same synaptic and epigenetic pathways already associated with psychiatric disorders, may serve as an additive risk to existing genetic/ epigenetic risk factors.  

For complete paper

There is a strong association between cannabis use and schizophrenia but the underlying cellular links are poorly understood. Neurons derived from human-induced pluripotent stem cells (hiPSCs) offer a platform for investigating both baseline and dynamic changes in human neural cells. Here, we exposed neurons derived from hiPSCs to Δ9-tetrahydrocannabinol (THC), and identified diagnosis-specific differences not detectable in vehicle-controls. RNA transcriptomic analyses revealed that THC administration, either by acute or chronic exposure, dampened the neuronal transcriptional response following potassium chloride (KCl)-induced neuronal depolarization. THC-treated neurons displayed significant synaptic, mitochondrial, and glutamate signaling alterations that may underlie their failure to activate appropriately; this blunted response resembles effects previously observed in schizophrenia hiPSC- derived neurons. Furthermore, we show a significant alteration in THC-related genes associated with autism and intellectual disability, suggesting shared molecular pathways perturbed in neuropsychiatric disorders that are exacerbated by THC.

Full Article  (cited 26/6/18)

All Young Cannabis Users Face Psychosis Risk  (Medscape and JAMA Psychiatry)  June 15, 2018

Cannabis use directly increases the risk for psychosis in teens, new research shows. A large prospective study of teens shows that "in adolescents, cannabis use is harmful" with respect to psychosis risk, study author Patricia J. Conrod, PhD, professor of psychiatry, University of Montreal, Canada, told Medscape Medical News.

The study included 3720 adolescents from the Co-Venture cohort, which represents 76% of all grade 7 students attending 31 secondary schools in the greater Montreal area.

Cannabis use, in any given year, predicted an increase in psychosis symptoms a year later, said Conrod. This type of analysis is more reliable than biological measures, such as blood tests, said Conrod. "Biological measures aren't sensitive enough to the infrequent and low level of use that we tend to see in young adolescents," she said.

The effect was observed for the entire cohort. This finding, said Conrod, means that all young cannabis users face psychosis risk, not just those with a family history of schizophrenia or a biological factor that increases their susceptibility to the effects of cannabis.

"The whole population is prone to have this risk," she said.

In light of these results, Conrod called for increased access by high school students to evidence-based cannabis prevention programs.

The study was published online June 6 in JAMA Psychiatry.

For complete article

Abstract

BACKGROUND:

Half of U.S. states have legalized medical cannabis (marijuana), some allow recreational use. The economic and public health effects of these policies are still being evaluated. We hypothesized that cannabis legalization was associated with an increase in the proportion of motor vehicle crash fatalities involving cannabis-positive drivers, and that cannabis use is associated with high-risk behavior and poor insurance status.

CONCLUSIONS:

Since legalization of cannabis, THC-positivity among MVC fatalities has tripled state-wide, and THC-positivity among patients presenting to the highest-level trauma center has doubled. THC-positive patients are less likely to use protective devices and more likely to rely on publically funded medical insurance. These findings have implications nationally and underscore the need for further research and policy development to address the public health effects and the costs of cannabis-related trauma.

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Abstract

Background: Depression is one of the most consistent risk factors implicated in both the course of escalating substance use behaviors and in the development of substance dependence symptoms, including those associated with marijuana use. In the present study, we evaluate if depression is associated with marijuana use disorder symptoms across the continuum of marijuana use frequency.

Methods: Data were drawn from six annual surveys of the National Survey of Drug Use and Health to include adults who reported using marijuana at least once in the past 30 days (N =28,557).

Results: After statistical control for sociodemographic characteristics and substance use behaviors including marijuana use, alcohol use, smoking, and use of illicit substances other than marijuana, depression was positively and significantly associated with each of the marijuana use disorder symptoms as well as the symptom total score. Adult marijuana users with depression were consistently more likely to experience marijuana use disorder symptoms and a larger number of symptoms, with the magnitude and direction of the relationship generally consistent across all levels of marijuana use frequency from 1 day used in the past month to daily marijuana use.

Conclusions: Depression is a consistent risk factor for marijuana use disorder symptoms over and above exposure to marijuana suggesting that depressed individuals may represent an important subgroup in need of targeted substance use intervention.

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