Enhancement of chemotherapy by prevention of tumour cell repair

Chemotherapies are cancer treatments that work by inducing lesions in the DNA of tumour cells in order to inhibit their proliferation. However, the body naturally tries to repair these lesions, and thus reduces the efficacy of chemotherapy. Blocking the mechanisms for DNA repair would help to potentiate chemotherapy by reducing the resistance of cells to treatment. A team of researchers directed by Frédéric Coin, Inserm Research Director at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) in Strasbourg (a Joint Inserm/CNRS/University of Strasbourg Research Unit), has discovered a new drug that inhibits repair: spironolactone, which seems likely to be used in the very short term as an adjuvant to chemotherapy.
Their results are published in
Chemistry & Biology.

UV rays, physical or chemical agents—the human body is constantly subject to environmental insults that cause more or less damage to our DNA. The body has therefore developed a whole system for proofreading and repair. Among these mechanisms, NER (Nucleotide Excision Repair) has been studied for several years by the researchers in a team led by Frédéric Coin and Jean-Marc Egly at IGBMC. This mechanism can thus detect a lesion, and then replace the damaged DNA fragment with an intact fragment.

Cytotoxic chemotherapy is aimed at blocking the division of malignant cells in order to prevent tumour growth. Included among the drugs used to treat many cancers such as colorectal, face and neck, testicular, bladder, ovarian and lung cancers are medications based on platinum. These drugs bind to cellular DNA, induce damage in the latter, and thus prevent its replication. Blocking DNA repair mechanisms, specifically NER activity, would help to potentiate chemotherapy by reducing the resistance of cells to the treatment.

The researchers at IGBMC therefore sought a drug that would inhibit NER activity. They thus tested over 1,200 therapeutic drugs and demonstrated the action of spironolactone, a drug already used for the treatment of hypertension, on NER activity. Specifically, the researchers showed that its action, when combined with that of platinum derivatives, caused a substantial increase in cytotoxicity for malignant colonic and ovarian cells.

Since spironolactone is already in use for other purposes, it does not require a new application for marketing authorisation, and its side-effects are already known. This result thus bodes very well for the rapid development of new chemotherapy protocols that include spironolactone.

illustration coin

© Inserm/ Frédéric Coin

Immunofluorescence labelling, 1 h after treatment, of XPC proteins (in red) and XPB proteins (in green) involved in NER activity. On the right, treatment with spironolactone induces rapid degradation of XPB, which explains its inhibition of NER.

Malaria – “Wake and kill”: a new concept for the elimination of relapse

A team of researchers coordinated by Prof Dominique Mazier (AP-HP, UPMC, Inserm Unit 1135, CNRS ERL 8255) and Dr Georges Snounou, Research Director at CNRS (UPMC, Inserm Unit 1135, CNRS ERL 8255) has succeeded in culturing the dormant hepatic stage of the malaria parasite, previously inaccessible to researchers. The initial results from this technical breakthrough have enabled the development of a new concept for the elimination of malaria relapse due to the activation of these dormant forms. It should enable the establishment of a new strategy for the management of this illness, which would involve combining a drug capable of activating the dormant parasite with one of the many drugs effective against the parasite.
These results have just been published in the journal Nature Medicine.

Present-day management of malaria

After the bite from an infected mosquito, the parasite that causes malaria reaches the liver, where it multiplies. It then propagates in the bloodstream, where its proliferation causes a potentially fatal illness. In some cases, including that of the parasite Plasmodium vivax in humans, a fraction of hepatic parasites may remain “dormant” for a year or more, hence their name, hypnozoites. These subsequently “wake,” or reactivate, over time, and give rise to a bloodstream infection. This feature is probably the source of the belief that malaria persists for life.

The hypnozoite constitutes a two-fold problem in terms of controlling/eliminating malaria—a greater number of cases needing treatment, and increased transmission. Unfortunately, primaquine, and a recently developed analogue, tafenoquine, the only drugs capable of killing hypnozoites, have adverse effects on the body that are sometimes serious. The identification of reliable alternative drugs therefore constitutes a public health emergency. Until now, the search for new anti-hypnozoite drugs has been based on observations made in humans infected with P. vivax, or in monkeys infected with a parasite related to P. vivax, Plasmodium cynomolgi.


Through a collaboration with teams from the national IDMIT Center[1] at the French Atomic Energy and Alternative Energies Commission (CEA), and those of the Biomedical Primate Research Centre(BPRC) in the Netherlands, the team led by Prof Dominique Mazier and Dr Georges Snounou first succeeded in maintaining cultures of infected hepatic cells for 40 days, i.e. nearly four times longer than is usually achieved. The team then demonstrated the persistence of dormant stages throughout the duration of culture, with some reactivating over the time, thus mimicking what happens in humans. It also tested new drugs (discovered at the Institut Pasteur in Paris), which inhibit epigenetic factors, on these hypnozoites. These drugs act by targeting histone methyltransferases, and are able to kill the blood stage of the parasite. Paradoxically, one of them activated the hypnozoites. This unexpected result led the team to formulate a new strategy, “Wake and Kill,” which involves combining a drug that activates the dormant parasite with one of the many available treatments known to be effective against the multiplying parasite.

Results provide hope for the management of malaria 

Thanks to this methodology, developed via an international and multi-institute collaboration (Inserm, CNRS, CIMI, CEA, UPMC, AP-HP, Institut Pasteur Paris), it will now be possible to screen drugs in vitro for their anti-hypnozoite effect, thus limiting the need for animals. The challenge is to adapt this technique to screening a large number of compounds. In addition, the possibility of growing hypnozoites in culture will finally allow scientists to study this enigmatic parasite stage, described 100 years after the discovery of the causative agent of malaria by Laveran in 1880.

[1] Infectious Diseases Models For Innovative Therapies

Why does the brain remember dreams?

Some people recall a dream every morning, whereas others rarely recall one. A team led by Perrine Ruby, an Inserm Research Fellow at the Lyon Neuroscience Research Center (Inserm/CNRS/Université Claude Bernard Lyon 1), has studied the brain activity of these two types of dreamers in order to understand the differences between them. In a study published in the journal Neuropsychopharmacology, the researchers show that the temporo-parietal junction, an information-processing hub in the brain, is more active in high dream recallers. Increased activity in this brain region might facilitate attention orienting toward external stimuli and promote intrasleep wakefulness, thereby facilitating the encoding of dreams in memory.

The discovery in video ( subtitles in english ) :

The reason for dreaming is still a mystery for the researchers who study the difference between “high dream recallers,” who recall dreams regularly, and “low dream recallers,” who recall dreams rarely. In January 2013 (work published in the journal Cerebral Cortex), the team led by Perrine Ruby, Inserm researcher at the Lyon Neuroscience Research Center, made the following two observations: “high dream recallers” have twice as many time of wakefulness during sleep as “low dream recallers” and their brains are more reactive to auditory stimuli during sleep and wakefulness. This increased brain reactivity may promote awakenings during the night, and may thus facilitate memorisation of dreams during brief periods of wakefulness.

In this new study, the research team sought to identify which areas of the brain differentiate high and low dream recallers. They used Positron Emission Tomography (PET) to measure the spontaneous brain activity of 41 volunteers during wakefulness and sleep. The volunteers were classified into 2 groups: 21 “high dream recallers” who recalled dreams 5.2 mornings  per week in average, and 20 “low dream recallers,” who reported 2 dreams per month in average. High dream recallers, both while awake and while asleep, showed stronger spontaneous brain activity in the medial prefrontal cortex (mPFC) and in the temporo-parietal junction (TPJ), an area of the brain involved in attention orienting toward external stimuli.


Temporo-parietal jonction (TPJ) © Perrine Ruby / Inserm

“This may explain why high dream recallers are more reactive to environmental stimuli, awaken more during sleep, and thus better encode dreams in memory than low dream recallers. Indeed the sleeping brain is not capable of memorising new information; it needs to awaken to be able to do that,”

explains Perrine Ruby, Inserm Research Fellow.

The South African neuropsychologist Mark Solms had observed in earlier studies that lesions in these two brain areas led to a cessation of dream recall.  The originality of the French team’s results is to show brain activity differences between high and low dream recallers during sleep and also during wakefulness.

“Our results suggest that high and low dream recallers differ in dream  memorization, but do not exclude that they  also differ in dream production. Indeed, it is possible that high dream recallers produce a larger amount of dreaming than low dream recallers” concludes the research team.

A French researcher attended at the 2014 AAAS meeting in Chicago

European cutting-edge research will be attended at the annual meeting of the American Association for the Advancement of Science (AAAS) in Chicago. Inserm will be represented by Karine Clément, scientific coordinator of the European project METACARDIS (Metagenomics in Cardiometabolic Diseases) at the session entitled “Inside out: the impact of gut flora on diabetes and obesity”.

Three leading European researchers on the gut microbiome will be present at the 2014 AAAS meeting, on Saturday 15 February, to share their recent findings on the relations between gut flora and obesity, diabetes, and cardio-metabolic diseases in general. Their findings are at the cutting-edge of one of the most innovative and challenging areas of biomedical research and could make a vital contribution to the fight against obesity and diabetes.

In recent years, the 1.5 kilos of bacteria that live inside our bodies, mainly in the gut, have proven their crucial importance for our healthy functioning. Beyond their more obvious role in digestion, they are also involved, for example, in the development of the immune system and the neuronal system, and in the onset of certain diseases.

The speakers:

Karine Clément – Professor, Institute of Cardiometabolism and Nutrition, and National Institute of Health and Medical Research (Inserm), France
Functional Genomics of Human Obesity Related to Cardiometabolic Diseases
Coordinator of the European project METACARDIS.

Sven Pettersson – Professor, Karolinska Institutet, Sweden
How Early Life Gut Flora May Contribute to Obesity and Diabetes Later in Life

Oluf B. Pedersen – Professor, University of Copenhagen, Denmark
Links Between Human Gut Microbiota and Metabolic Pathologies

Discussant: Jenny Leonard – Editor,, USA


About this session:
When? Saturday, 15 February 2014 – 1:00 PM to 2:30 PM
Where? Grand Ballroom C North (Hyatt Regency Chicago)


About the 2014 AAAS annual meeting in Chicago – Feb 13-17
The AAAS Annual Meeting is a widely recognized general science event. Thousands of leading scientists, engineers, educators, policymakers, and journalists gather from around the world to discuss recent developments in science and technology. The 2014 theme, Meeting Global Challenges: Discovery and Innovation, focuses on finding sustainable solutions through inclusive, international, and interdisciplinary efforts that are most useful to society and enhance economic growth.

About CommHERE
CommHERE – – aims to increase awareness of the activities and outcomes of the various health research projects funded by the European Union. The CommHERE consortium comprises nine research institutions in six European countries, ensuring close connection with active health researchers. Stay in touch with European research with

Mechanism elucidated: how smell perception influences food intake

A research team led by Giovanni Marsicano, a Inserm Research Director at Unit 862 (NeuroCentre Magendie, Bordeaux), has succeeded in elucidating how the endocannabinoid system controls food intake through its effects on the perception of smells. These results are due to appear in the journal Nature Neuroscience on 9 February 2014.

Nature-Neuro Nose_illustration

© Charlie Padgett

In animals, as in humans, hunger mechanisms are known to stimulate food intake. Hunger triggers a set of mechanisms that encourage feeding, for example by increasing sensory perceptions such as the sense of smell. The researchers have now succeeded in revealing what links hunger and increased smell perception in the brain, and the resulting urge to eat.

The researchers have discovered how this mechanism is initiated in the endocannabinoid system in mice. This system interconnects receptors located in the brain and involved in different sensations such as euphoria, anxiety, or even pain, that are also sensitive to cannabinoid substances, such as cannabis.

The researchers discovered that the CB1 cannabinoid receptors control a circuit that connects the olfactory bulb (the region in the nervous system that initially handles olfactory information, located above the nose) to the olfactory cortex (higher structures of the brain). When the sensation of hunger is felt, it triggers the activity of the cannabinoid receptors, which in turn activate the olfactory circuit, which then becomes more responsive.

It is therefore this biological mechanism that brings about the increased sensitivity to smell during hunger, explaining one of the reasons for food intake and attraction to food.

The researchers expect that the circuit involved in the olfactory system is altered in obese or anorexic patients, and that sensitivity to smell may be more or less strong compared to normal. Elucidation of the biological mechanism will allow better management of these types of pathologies.

This work was funded by ERC (European Research Council).

Autism: birth hormone may control the expression of the syndrome in animals

The scientific community agrees that autism has its origins in early life—foetal and/or postnatal. The team led by Yehezkel Ben-Ari, Inserm Emeritus Research Director at the Mediterranean Institute of Neurobiology (INMED), has made a breakthrough in the understanding of the disorder. In an article published in Science, the researchers demonstrate that chloride levels are elevated in the neurons of mice used in an animal model of autism, and remain at abnormal levels from birth. These results corroborate the success obtained with the diuretic treatment tested on autistic children by the researchers and clinicians in 2012, and suggest that administration of diuretics to mice before birth corrects the deficits in the offspring. They also show that oxytocin, the birth hormone, brings about a decrease in chloride level during birth, which controls the expression of the autistic syndrome. 

This work is due to appear in the 6 February 2014 issue of Science.

Neurons contain high levels of chloride throughout the entire embryonic phase. As a result, GABA, the main chemical messenger of the brain, excites the neurons during this phase instead of inhibiting them, in order to facilitate construction of the brain. Subsequently, a natural reduction in chloride levels allows GABA to exercise its inhibitory role and regulate the activity of the adolescent/adult brain. In many brain disorders (childhood epilepsy, cranial trauma, etc.), studies have shown abnormally high chloride levels. Having made various observations, Dr Lemonnier’s team (Brest), and Yehezkel Ben-Ari’s team at Inserm carried out a clinical trial in 2012, based on the hypothesis of high chloride levels in the neurons of patients with autism. The researchers showed that administration of a diuretic to children with autism (which reduces neuronal chloride levels) has beneficial effects[1]. The results of the trial supported this hypothesis, but because high neuronal chloride levels could not be demonstrated in children with autism, it was not possible to prove the mechanism proposed or justify the treatment.

In the present study, the researchers therefore used two animal models of autism, a genetic model, Fragile X syndrome, which is the genetic mutation most frequently associated with autism, and another, generated by injecting the spleen of pregnant mice with sodium valproate, a product known to generate abnormalities in children, including autistic spectrum disorder.

A high level of chloride in the brain

For the first time, the researchers recorded the activity of neurons at the embryonic stage and immediately after birth in order to observe modifications in chloride levels. These observations showed that neuronal chloride levels are abnormally high in both young and adult animals used in the autism model. GABA strongly excites neurons, and the researchers recorded aberrant electrical activities in the brain, which persist in adult animals.

The fall in chloride level, a particularly impressive phenomenon seen at birth in control animals, is absent in both of these animal models, and the neurons have the same chloride level before and after birth. These high levels are due to reduced activity of a chloride transporter, thus preventing transport of chloride out of the neuron. As a result, a major feature of neurons during birth is abolished in animal models of autism.

“Chloride levels during delivery are determinants of the occurrence of autism spectrum disorder,”

 explains Yehezkel Ben-Ari, an Emeritus Research Director at Inserm.

Beneficial effects of the diuretic on brain activity

The researchers administered a diuretic treatment to the mother (in both animal models) for 24 h shortly before delivery to see if this would restore brain inhibition in the offspring. They showed that the drop in chloride level was re-established in the neurons several weeks after a single treatment during birth. According to the research team, antenatal treatment restored brain activity to approximately normal levels, and corrected the “autistic” behaviour in the animals once they became adults.

“These results thus validate the working hypothesis that led us to the treatment we developed in 2012,” states the principal author of the study.

Oxytocin, the birth hormone, naturally reduces chloride levels

The role of oxytocin in reducing neuronal chloride was also studied. The researchers had previously shown in 2006[2] that this hormone, which triggers labour, also has many beneficial actions on the brains of newborns, including protective effects in the event of complications during delivery, and even analgesic properties. Oxytocin acts like the diuretic, reducing the intracellular chloride levels.

In the present study, the team tested the long-term effects of blocking the actions of the hormone before birth. A drug that blocks the signals generated by oxytocin was injected into pregnant mice. The researchers evaluated the effects of this blockage on the offspring, and showed that it reproduced the entire autism-like syndrome in them, both with respect to the electrical and behavioural aspects (identical to the two animal models of autism). As a result, the hormone’s natural actions, just like those of the diuretic, are crucial to this delicate phase, and may control the pathogenesis of autism via the cellular chloride levels.

“These data validate our treatment strategy, and suggest that oxytocin, by acting on the chloride levels during delivery modulates/controls the expression of autism spectrum disorder,”

 states Yehezkel Ben-Ari.

Taken together, these observations suggest that earliest possible treatment is essential for maximum possible prevention of the disorder.

This work raises the importance of carrying out early epidemiological studies in order to better understand the pathogenesis of the disorder, especially through analysing data on deliveries where a drop in chloride has occurred. Indeed, complicated deliveries with episodes of prolonged lack of oxygen, for example, or complications during pregnancy, such as viral infections, are often suggested as risk factors.

Finally, given the role of oxytocin in triggering labour, “although it is true that epidemiological data suggesting that scheduled caesarean deliveries may have increased the incidence of autism are controversial, it nonetheless remains that these studies should be followed up and extended in order to confirm or refute this relationship, which is still possible,” insists Yehezkel Ben-Ari, who concludes, “To treat this type of disorder, it is necessary to understand how the brain develops and how genetic mutations and environmental insults modulate brain activity in utero.

[1] See press release – Inserm press room – Un essai clinique prometteur pour diminuer la sévérité des troubles autistiques (A promising clinical trial for reducing the severity of autistic disorders) (Translational Psychiatry, 2012)

[2] Maternal Oxytocin Triggers a Transient Inhibitory Switch in GABA Signaling in the Fetal Brain During Delivery. Tyzio et al, Science 2006

Addictive behaviours in adolescents

In France, the levels of use of some psychoactive substances, especially alcohol, tobacco and cannabis, remain high among adolescents, despite progress in regulatory efforts to limit access to these products by minors, and regular prevention campaigns.

As part of preparing the Government Plan to combat drugs and addictive behaviours (2013-2017[1], the French Government’s Inter-Departmental Mission for the Fight against Drugs and Drug Addiction (MILDT) requested Inserm to prepare an overview of scientific knowledge regarding the susceptibility of adolescents (aged 10 to 18 years) to use psychoactive substances known to be consumed in significant amounts by young people (alcohol, tobacco and cannabis), as well as their susceptibility to develop other habits known to potentially cause problems (video/Internet games, gambling). The mandate from MILDT also included the analysis of strategies for effective prevention and intervention for this age bracket.

conduite addictive chez les ados


To fulfil this remit, Inserm brought together a multidisciplinary group of experts in epidemiology, public health, human and social sciences, addiction, neuroscience and communication.

Analysis by the experts of data from the major surveys of use in France[2] and from the international scientific literature of the last ten years has enabled a better evaluation of the scale of the phenomenon in young people aged 10-18 years, and has helped to identify the major products involved and trends in use patterns, risk factors, and the main effects on health and associated social harm, and finally to describe those intervention strategies that have been evaluated, with a view to making recommendations to help prevent unsafe use and to help care for the adolescents involved.

The experts observed, in particular, a change in use and patterns of consumption of some psychoactive substances, such as, for example, the tendency toward occasional binge drinking that is developing among adolescents. Furthermore, they emphasise the greater sensitivity of this population to the neurotoxic effects of alcohol and cannabis compared to adults, something that makes adolescents especially vulnerable to the consequences of using these substances.

Adolescence, a period of vulnerability

Adolescence is accompanied by many physiological and physical changes, and is also a stage of complex psychological maturation and development. The young person progressively frees himself or herself from parental dependence, and develops a high level of social interaction; s/he seeks new experiences, which often include a certain resistance to established rules. Adolescence also constitutes a phase of curiosity, risk-taking and defiance.

Initiation into using legal psychoactive substances (alcohol/tobacco), as well as some illegal substances (cannabis etc.), occurs mainly during this period: only 6.6% of 17 year old adolescents have not tried any of these products. Adolescents show highly variable expectations/motives, usually differentiated along social and gender lines. They show little sensitivity to warnings regarding long-term risks to health, as they perceive them only as very remote risks that do not really concern them.

Most of the studies emphasise that for adolescents a positive first experience of psychoactive substances may influence subsequent use, encouraging regular use and the potential development of dependence.

The adolescent brain is more vulnerable to psychoactive substances than the adult brain. It has the distinction of being in a state of transition toward the adult state. The processes of brain maturation (which continue until approximately 25 years of age) lead to a heightened degree of vulnerability in adolescents to the neurotoxic effects of psychoactive substances in general. One area of the brain, the prefrontal cortex, which allows decision making and adaptation of behaviour to the situation, is especially involved in this maturation during adolescence.

Regardless of the product under consideration, early experimentation and initial drug use increase the risks of later dependence and more subsequent harm overall.

Psychoactive substance use
[3] and associated harm

There are distinctions between unsafe drug use (endangerment), abuse or harmful use (injurious to health), and dependence. The term “addiction” generally covers dependence, but this is point is still being debated. For some authors, addiction is characterised by the persistent inability to control a behaviour, and the continuation of the latter despite the knowledge and presence of its harmful effects.

  • Alcohol

In France, alcohol is the most consumed psychoactive substance in terms of level of experimentation, occasional use, and precocity of experimentation. In 2011, 91% of boys and girls had tried alcohol by the end of adolescence. In 2010, 58% of pupils aged 11 years stated that they had already tried an alcoholic drink.

Regular alcohol use (at least 10 times a month) is evident by the end of junior secondary school: in 2010, 7% of students in the 4th year of junior secondary school (approximate age 14-15) stated that they had consumed an alcoholic drink at least 10 times in the month prior to the survey. In 2011, 15% of boys and 6% of girls aged 17 years engaged in this regular drinking; however, daily alcohol consumption was observed in fewer than 1% of 17 year olds. A reduction in the difference between boys and girls can be noted between 2008 and 2011, as well as a slight increase in regular use.

Some participants had experienced alcoholic intoxication (drunkenness) from the start of secondary school. Among 4th year students at junior secondary school, 34% stated that they had already experienced such an episode. At 17 years of age, 59% of boys and girls stated that they had already been drunk in their lives, and 53% stated that they had been on a drinking binge (namely the consumption of at least 5 standard drinks on a single occasion) in the month prior to the survey. The rates of binge drinking in the month are continuing to increase: 46% in 2005, 53% in 2011.

In 2011, although France occupied a median position in Europe as regards binge drinking among 16 year olds, it was above the mean for regular alcohol consumption.

Harm and vulnerability among adolescents

Compared with adults, alcohol use among adolescents, especially massive intoxication, has more marked neurotoxic effects on the brain, both at the structural level (the production of new neurons/neurogenesis) and the functional level, as reflected by a greater interference with cognitive function (learning/memory). It has been documented that the morphological and functional impacts are greater for girls than for boys of the same age. The deficits observed in the medium term are proportional to the quantity of alcohol consumed.

Young people are less sensitive to the “negative” effects of alcohol (drowsiness, hypothermia, lack of motor coordination, etc.), but are more receptive to effects experienced as “positive” (disinhibition, facilitation of social interaction, etc.).

  • Tobacco

In 2011, more than 2 out of 3 (68%) 17 year olds had tried tobacco.

Tobacco is the psychoactive product most used on a daily basis in adolescence: 30% of girls and 33% of boys are daily smokers at 17 years of age. According to data from 2011, daily use can be seen from the start of secondary school (8% for 3rd year students (approximate age 13-14 years) and 16% for 4th year students (14-15 years). A small increase in daily smoking was seen from 2008 to 2011.

In 2011, France was among the European countries with the highest levels of smoking among 16 year olds.

Associated harm

Apart from the high risk of dependence, tobacco has many well-known long-term consequences for health (respiratory and cardiovascular disease, cancers, etc.).

  • Cannabis

In France, cannabis is the illegal substance most used during adolescence. In 2011, 42% of 17 year old adolescents had already smoked cannabis at least once (39% of girls and 44% of boys). Boys were heavier users than girls, who tried the product at an older age.

Initial experimentation, while very rare at entry into secondary school, was observed in the final years of junior secondary school (11% of 3rd year students, 24% of 4th year students), and in nearly one in two senior secondary school students in 2011.

In 2010-2011, 2% of 4th year, 6% of 5th year, and 7% of final year secondary school students (approximately 16-18 years of age) were using cannabis regularly (at least ten times in the previous month). Of 17 year old adolescents, 5% showed a risk of problem use or even dependence in 2011: 7% of boys and 3% of girls.

France, together with Canada, the Czech Republic, Switzerland, the United States and Spain, were among the countries with the highest prevalence of cannabis use among adolescents in 2011.

Harm and vulnerability among adolescents

In the hours following cannabis use, observed cognitive impairment involves attention, reaction time, working memory, and executive function. Furthermore, there is a significant correlation between use and various “acting out” behaviours (attempted suicide, bulimia, unsafe sexual behaviours, etc.) due to lowered inhibition.

This cognitive impairment tends to disappear within a month of stopping use. In adolescents, some of this impairment may persist, including after weaning, especially if use began before the age of 15 years. Long-term cognitive impairment is observed in proportion to dose, frequency, duration of exposure and age at first use of cannabis.

Regular use of cannabis has long-term effects that may affect school results and personal relationships.

Finally, cannabis use may also precipitate psychiatric disorders (anxiety disorders, depression, symptoms of psychosis and schizophrenia) in adolescents. This risk of psychotic disorders may be influenced by certain genetic factors, age of exposure and pre-existing vulnerability to psychosis (family history).

  • Other substances and polydrug use

– Psychotropic drugs and other illegal products

In 2011, 41% of 17 year olds stated that they had taken at least one psychotropic drug in their lives. The most frequently tried psychotropic drugs are anxiolytic drugs (15%), sleep-inducing drugs (11%), and antidepressants (6%).

Experimentation with illegal products other than cannabis, such as amphetamines (including ecstasy), hallucinogenic mushrooms, LSD, cocaine or heroin appears only at the end of adolescence, in proportions from 3% for hallucinogenic mushrooms and cocaine to 0.8% for heroin. Most of this experimentation declined over the period from 2008 to 2011, especially for ecstasy.

At 17 years of age, almost no regular use of illegal substances other than cannabis was seen. Only inhaled products such as adhesives, solvents or poppers showed relatively high levels of experimentation at this age (9% said they had tried the latter).

Energy drinks and alcopops

Energy drinks are consumed alone or mixed with alcohol, such as pre-mixed drinks (alcopops), mixtures of soft drinks and strong spirits, ranging from 5 to 8% alcohol by volume. At all ages of adolescence, boys are more frequent consumers of energy drinks than girls. In France, consumption of energy drinks has gone from 20% in the 1st year of secondary school to 36% in the 5th year.

Consumption of premixed drinks remains relatively less frequent than that of other main categories of alcoholic drinks. The infatuation of young people, especially girls, with this type of drink, highly sweetened and flavoured to mask the alcohol content, has been curbed by the imposition in France of a very high tax specifically on these products.

The combination of energy drinks with alcoholic drinks has been identified as a source of risk—it increases the consequences of drinking, particularly the risk of unprotected sexual relations. Furthermore, there may be a link between consumption of energy drinks combined with alcohol and the subsequent development of alcohol dependence.

Polydrug use

At age 17, 4% of adolescents stated that they were daily tobacco smokers and regular consumers (at least 10 times per month) of alcoholic drinks, or daily smokers of tobacco and regular smokers of cannabis. Finally, 2% were regular polydrug users of tobacco, alcohol and cannabis.

Video/Internet game playing and gambling,[4] and associated harm


With regard to video/Internet games and gambling, one refers to social or recreational play or gambling (i.e. simple use), unsafe or problem play or gambling (i.e. abuse), and excessive or pathological play or gambling (i.e. dependence).

  • Video/Internet game playing

In 2011, of the 80% of 17 year olds who stated having used the Internet in the previous seven days, approximately one in four used it for 2-5 hours a day; fewer than one in five for 5-10 hours, and one in ten used it for over 10 hours a day.

Depending on the country and the measurement method used, the prevalence of problem Internet use by adolescents may vary from 2 to 12%. In France, in 2011, the initial estimations show that 3-5% of 17 year olds may be involved.

Furthermore, 5% of 17 year olds may play video games for 5 to 10 hours a day. Although the total time spent playing games is higher for boys than for girls, the time spent in front of a screen is identical, since girls are heavier users of social networking.

While video games may have positive aspects, especially regarding the development of cognitive and spatial functions, they may also lead to a loss of control and behavioural problems. Among the different types of games, MMORPG (Massive Multiplayer Online Role Playing Games), usually played by boys, have been described as particularly addictive.

Of 17 year old players (all types of video games), 26% stated that they had encountered problems at school or at work, and approximately 4% stated that they had experienced money problems in the previous year because of their playing habits.

Associated harm

Apart from the time spent, which can sometimes prove to be very long, problems of a psychic and somatic nature may occur in cases of excessive use: sleep disorders, irritability, sadness, anxiety, isolation, deterioration in academic performance, problems with parents, etc. Problem use of video games may encourage use of substances (tobacco, cannabis, alcohol, energy drinks, etc.), and increase the risk of sedentary behaviour and overweight

  • Gambling

In France as in most Western countries, gambling is illegal below the age of 18. However, according to international studies, minors do participate in gambling: 80% have already gambled in their lifetime, and 10-20% gamble weekly.

Initiation most often takes place in adolescence (even at the start of adolescence according to some authors), usually in the family circle; boys gamble more than girls, regardless of country studied or the reporting period.

In France, gambling among 17 year old adolescents was investigated for the first time in 2011: 44% had already gambled in their lifetime, and 10% had gambled that week. Of 17 year olds who had gambled in the previous week, 14% were gamblers in the moderate risk category, and 3% were excessive gamblers. Therefore, 1.7% of 17 year olds may be considered to have a moderate-risk or excessive gambling habit.

In France, gambling by adolescents mainly takes the form of scratch-cards and lottery tickets purchased from a tobacconist. The possibility of online gambling is especially attractive to young people, even minors. Nearly 14% of 17 year olds stated that they had gambled on the Internet at least once in the previous year.

Associated harm

Although the drift into addiction associated with gambling does not directly cause physical harm, it may have negative consequences (use of psychoactive substances, symptoms of depression and anxiety, suicide risk, financial loss, deterioration in academic performance, criminal activity, etc.). Studies evaluating harm from problem/pathological gambling in adolescence are still scarce, although it has been noted that the prevalence of problem/pathological gambling is higher among adolescents than adults.

Factors associated with problem use

Psychological factors (poor self-esteem, lack of self-confidence, etc.), socioeconomic, academic (disrupted schooling) and familial (intergenerational transmission of addictive behaviours) contribute to problem substance use or habits leading to addictive behaviour.

While adolescents from privileged backgrounds have higher levels of experimentation, young people from underprivileged social backgrounds or who have academic problems are at higher risk of engaging in regular excessive use of tobacco, alcohol or cannabis. Likewise, young people whose parents show addictive behaviours are at major risk of regular or excessive use: children of smokers are twice as often smokers themselves, children of excessive drinkers are twice as often regular drinkers themselves. It is the same for gambling.

Family cohesion (understanding between parents and children, parents’ knowledge of their children’s entourage and activities) reduces the risk of addictive behaviours in adolescents.

The experts also note the influence of the circle of friends and all the marketing products and advertising information produced by industries to encourage young people to buy legal addictive products (tobacco, alcohol, games in general). These advertisements and marketing tools may also limit the efficacy of prevention programmes aimed at young people.

Finally, the role of genetic factors in the risk of dependence needs to be emphasised. According to studies, a non-negligible share of the risk of developing an addiction might be attributable to genetic factors, and many candidate genes have been identified that are linked to addiction to individual substances.

Support for adolescents and prevention strategies

  • Support for adolescents

Supporting the adolescent in the community depends on early intervention and strategies for risk reduction. Early intervention involves acting as early as possible so that unsafe behaviour does not take hold; strategies for risk reduction aim to reduce harm without seeking abstinence. Support in a consultation room setting and hospital/residential treatment is aimed at reducing use or even complete weaning from use.

Free anonymous “Clinics for Young Users” (CJC in French), operating since 2004, are dedicated reception and treatment facilities for young users of psychoactive substances. These clinics offer scientifically validated care plans. “Motivational counselling,” carried out in an outpatient setting, is based on the need to highlight and support the adolescent’s motivation so that s/he can change the addictive behaviour(s). Cognitive behavioural therapy (CBT) provides young people with alternative strategies for managing situations that contribute to addictive acting out, and family therapies support parents and their environment in mentoring and supporting the young person. Their efficacy has been demonstrated in the context of CJCs in France and Europe. They have also proven to be effective in serious situations, with those under 16 years of age, and where there are substantial behavioural problems.

Other approaches exist, such as psychodynamic approaches, centred on the individual and the strengthening of the self. They serve more often as a model for understanding than as a basis for action.

In cases where outpatient care has failed, residential care, which includes long periods in hospital and aftercare, enables the holistic evaluation and follow-up of adolescents (addictions and reintegration into work or education).

  • Effective prevention strategies 

Several intervention strategies have shown beneficial effects in preventing or reducing the use of psychoactive substances. In particular, three types of interventions are usually included in programmes of validated efficacy: the development of psychosocial skills[5] in young people (management of emotions, decision-making, self-esteem) and their parents (improvement in communication, conflict management); multi-component strategies (including local players other than the school and the parents in addition to developing the skills of the young people and their parents).

There are also other types of interventions: remote support (computer or mobile telephone); media campaigns (especially for cutting down on tobacco), and legislative and regulatory actions aimed at limiting access to addictive substances.


The experts emphasise that the actions to be developed must focus primarily on alcohol and tobacco, and even cannabis, based on the levels of use and associated harm, which are greater than for other substances or for games.

Recommendations from the expert group have three main objectives:

Prevent initiation, or delay the age at which it occurs 

The expert group recommends creating awareness among the public and the different players (young people, parents, those involved in the education, education-related, and medical sectors, etc.) of the adolescents vulnerability, and of the dangers associated with early initiation. This would involve emphasising, without sensationalising, messages describing the long-term impact on health, especially the brain, of rapidly consuming large amounts of alcohol, and of using cannabis regularly during adolescence. To modify the existing motivations, expectations and representations of these products, media campaigns must be accompanied by educational and legislative measures.

To prevent initiation, the experts also emphasise the importance of developing the psychosocial skills of adolescents. This might happen as part of group activities, including those in an academic setting, and be based on the age of first use of the various substances (10-12 years for tobacco, for example).

Adolescents remain very sensitive to messages conveyed by their parents. This is why the expert group recommends regularly informing parents on the harm associated with early use, the trends in use patterns among young people, and the marketing codes that target them and are aimed at encouraging use. It is a matter of helping the parents to adopt the most appropriate attitude for the situation.

By improving the training given to those involved in education, sports or recreation, all players in contact with adolescents may be informed of addiction issues, and trained in the early detection of problems and in the interventions that may be carried out.

In order to better control tobacco and alcohol sales, the experts recommend that purchase of these products be systematically accompanied by the presentation of an official document indicating age. They emphasise respect for and strengthening of laws to regulate advertising that promotes gambling at a young age. There should also be better visibility of the content of video games through the provision and improvement of logos specifying the age classification and content.

Avoid regular use and damage to physical and social health

To avoid the development of addictive behaviour, the expert group recommends improving the detection of unsafe use and early intervention, strengthening first-line actions such as the “Clinics for Young Users,” by training staff in early intervention methods, and training some of them in treatments of proven efficacy (CBT, MDFT-type family therapy[6]). In cases where outpatient care has failed, adolescents with addictive behaviour should be offered care in specialised centres and in a residential setting.

The existence of mental distress or illness associated with excessive use or addictions requires a strengthening of the links between addiction services and paediatric/general psychiatry, especially those specialising in evaluation and early intervention in young adults, and with adolescent centres.

Finally, the expert group recommends improvement in cooperation between professionals in education, health and justice (liaison with children’s court judges and judicial protection of youth) to optimise guidance and care.

Provide national and regional coordination of the territorial players

The expert group underlines the need for local support and the development of cross-cutting public management structures for addiction at local level in order to provide regional coordination for the territorial players. An inventory of the preventive actions on a regional scale in France would facilitate knowledge and dissemination of validated prevention strategies, and enable recommendations for schools and local governments. To ensure this coordination, the experts recommend the establishment of a committee for the evaluation of prevention programmes, which are rarely evaluated at present.

Recommendations for research have also been formulated:

Multidisciplinary, clinical and fundamental research, combined with longitudinal studies, should be supported in order to follow the trajectories of use and life so as to better understand use, risk/resilience factors, and health and social effects (consequences for education, for example) of psychoactive substance use or game-playing that leads to addictive behaviours.

Human and social science research, especially on the motivations and social habits of adolescents, seems necessary for more effective interventions.

The experts emphasise the interest of developing, evaluating and validating the tools for detection and intervention strategies for young people showing addictive behaviour.
They also recommend carrying out research on methods for preventing addiction among young people (role of digital technology, for example).


[1]  Plan adopted on 19 September 2013.

[2] Since the end of the 1990s, three surveys have been conducted on the use of psychoactive products in the adolescent population: HBSC (Health Behaviour in School-aged Children), ESPAD (European School Survey Project on Alcohol and Other Drugs) and ESCAPAD (Survey on Health and Consumption on Call-up and Preparation for Defence Day), covering the entire period from 11 to 17 years of age.

[3] According to the HBSC, ESPAD and ESCAPAD surveys

[4] According to the ESCAPAD survey

[5] Ability of a person to effectively meet the demands and challenges of everyday life (WHO)

[6] Multidimensional Family Therapy