Addictions are cerebral disorders defined by dependence on a substance or activity, with harmful consequences. Scientists are attempting to clarify the mechanisms involved in the occurrence, maintenance, and relapse of addictions. They are also attempting to identify individual, social and environmental vulnerability factors, for better prevention and management.

  • Between the ages of 15 & 25 is when a person is most likely to become addicted
  • Alcool & cannabis : the earlier in life the consumption, the higher the risk of addiction
  • 32% of dependent consumers, tobacco is considered the most addictive
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Report drawn up in collaboration with Bertrand Nalpas, Inserm Research Director  and Addiction Project Coordinator

Loupe comprendre Understanding addictions

The most widespread addictions involve tobacco (nicotine) and alcohol. These are followed by cannabis then, a long way behind, opioids (heroin, morphine), cocaine, amphetamines, and synthetic derivatives. Addictions related to activities (rather than substances) also exist, such as gambling, video games, sex, and even compulsive buying.

Pictogramme bustes de personnes Substances with varying addictive properties frequently tried during adolescence

Addictions may occur at any time of life, but are more likely to occur between the ages of 15 and 25 years. At-risk behavior among adolescents and young adults facilitates the first experiences, and early drug use exposes individuals to an increased risk of subsequent addiction. Overall, men are more frequently affected by addictions than women.

Some substances appear to more addictive than others, owing to the proportion of addicts among users. Tobacco is said to be the most addictive substance (32% of users are addicted), followed by heroin (23%), cocaine (17%), and alcohol (15%). Addiction develops at different rates, depending on the substances. Addiction to tobacco, heroin, and cocaine may develop within a few weeks, whereas alcohol addiction is much slower.

Tobacco 32%, heroin 23%, cocaine 17%, alcohol 15%, stimulants other than cocaine (amphetamine, etc.) 11%, cannabis 9%, psychotropic medications and analgesics 9%, hallucinogenic substances 5%, poppers glue and solvents... 4%
Part des usagers développant une dépendance à la substance qu'ils consomment.
Valeurs fournies par JC Anthony et coll., Experimental and Clinical Psychopharmacology,1994; 2: 244-268 - © Inserm/Koulikoff, Frédérique

For video games, online games are reputed to be the most addictive, particularly multiplayer games. The addictive potential of gambling has not been evaluated.

The vicious cycle of gambling

Pathological gamblers are predominantly males, in their forties, and often with families. They play games of chance (roulette, slot machines) or games involving a combination of chance and strategy (betting on sports, poker, black jack). The starting point for this disorder is always an initial win which generates an extremely positive emotion and urges them to play again to relive that "magic" moment. Then playing and wining soon become a way of feeling good. However, repeated losses incite gamblers to keep trying their chances, with the hope of "making up their losses", increasing their bets as their losses increase. Their reasoning becomes warped and goes against the laws of probability with which gamblers are generally familiar. Several years generally elapse between starting to gamble and developing an established addiction.

The percentage of "pathological" gamblers in the general population is estimated at 1%.

Bloc notes Diagnosis based on strict standards

Diagnosis of addiction (or dependence) is based on clearly defined criteria, established by international authorities on mental health, and stated in the Diagnostic and Statistical manual of Mental disorders (DSM), fifth edition dated 2013. These criteria include loss of self-control, use interfering with school or professional activities, or even continued use despite awareness of the problems that it causes.

An individual is considered to suffer from an addiction when they present, or presented in the past 12 months, at least two of the following eleven criteria:

  • Overwhelming urgent need to use the substance or to gamble (craving)
  • Loss of control in terms of the amount and time spent taking the substance or gambling
  • Large amount of time spent seeking out substances or gambling
  • Increased tolerance to the addictive substance
  • Presence of withdrawal syndrome, i.e. a collection of symptoms caused by suddenly stopping use or gambling
  • Inability to fulfill important obligations
  • Use despite a physical risk
  • Personal or social problems
  • Desire or persistent efforts to reduce the doses or the activity
  • Limiting activities to spend more time on substance use or gambling/gaming
  • Continued use despite physical or psychological harm

The addiction is qualified as mild if 2 to 3 criteria are met, moderate for 4 to 5 criteria, and severe for 6 or more criteria.

DSM experts only list dependence on substances and gambling as addictions. Intensive video gaming, smartphone use, excessive sexual or professional activity are not currently perceived as genuine addictions due to the lack of convincing scientific data.

Pictogramme panneau attention Harmful consequences

When left untreated, addictions may have severe or, indeed, tragic consequences. These may be directly related to excessive substance use (overdose, alcoholic coma) or caused by long-term side effects (numerous types of cancer associated with alcohol and tobacco use, neurological and psychiatric disorders in regular drug users, HIV infection, etc.).

Driving under the influence of psychoactive substance increases the risk of a fatal accident

A study coordinated by the Observatoire français des drogues et des toxicomanies estimates that driving under the influence of alcohol gives rise to an 8.5-fold risk of causing a fatal accident. If the driver has also taken cannabis, this risk increases 15-fold.

Repeated drug use also contributes to psychological and cognitive disorders (difficulty concentrating, talking or memorizing information, for example) which may have a bearing on school or professional results, or even cause young people to drop out of the school system and lead to marginalization. Ultimately, severe, untreated addiction often leads to isolation, social exclusion, and impoverishment.

Other longer term consequences are still unclear, particularly those due to the effects of alcohol and cannabis on the brain when used during adolescence. During this period (up to the age of 20-25 years), the brain is still maturing and appears to be more vulnerable to toxic effects. Furthermore, it has been observed that the earlier substance use occurs, the greater the risk of developing an addiction in the long term.

"Binge drinking" : quand le cerveau trinque – documentaire – 3 min 42 – extrait de la série Questions de société (2011)

Rouages Complex mechanisms

Addiction develops based on at least three mechanisms:

  • an increased urge to use the substance (desire for pleasure),
  • a negative emotional state (desire for relief),
  • reduced self-control (use spirals out of control).

Addiction mainly starts with the pleasure generated by the addictive substance. This sensation is due to electrochemical changes in the brain in response to substance use. The release of dopamine, the "pleasure" and "reward" molecule, is also observed in the nucleus accumbens. The increase in dopamine concentration is the result of changes in the synaptic transmissions in the different cerebral areas, as the substance used may interfere with neurotransmitters or their receptors.

Reward circuit for addiction
The reward circuit plays a central role in the installation and maintenance of addiction. © Inserm, F. Koulikoff, Fotolia

This is combined with other mechanisms, notably serotonin release, or even the activation of endorphin receptors, endogenous molecules involved in pain relief and the sense of well-being. In the event of regular substance use, repeated stimulation of these receptors gives rise to a decrease in natural endorphin production. Pleasure is then only achieved by taking the external substance, which leads to increased tolerance to the substance and withdrawal upon stopping use.

Plaisir et addiction – Interview – 4 min – vidéo extraite de la série POM bio à croquer (2013)

Cerveau atteint Long-term brain remodeling

Addiction is consolidated by other mechanisms. The body gradually becomes insensitive to the substance and its effects, and the user has to increase the doses to achieve the same level of pleasure. Repeated drug use modifies cerebral networks and disrupts pleasure-seeking in the long term. The dopaminergic network races out of control and gives rise to an incessant need for pleasure. Other cerebral adjustments ultimately create negative effects in dependent individuals (dysphoria, anxiety, irritability). This negative emotional state, with unpleasant withdrawal sensations, is then said to become the main reason for substance use (craving relief), beyond pleasure-seeking (craving reward).

Furthermore, addictive substances modify synaptic plasticity, i.e., the ability of the neurons to reorganize themselves to incorporate new data. This appears to modify the memory of the experience, making it even more pleasant than it was, and persistent over time, encouraging them to repeat the experience.

Lastly, stimuli repeatedly associated with substance use (conditioning), such as an identical place or time of day, may ultimately activate dopamine release even before using the substance. Hence, this is how psychological dependence can develop, for instance, the need for a cigarette when having a coffee. This phenomenon may explain how environmental signals (advertising, bars, smell of alcohol) can trigger relapse even after a long period of abstinence.

Buste attention Individual and environmental risks in terms of addiction

The occurrence of addiction is based three components: the individual, product and environment.

Each individual is more or less vulnerable to addiction, and some of this vulnerability is genetic in origin. This is said to be based on varied combinations of changes affecting numerous genes, each change being ineffective on its own. Some of these genes play a role in the dopaminergic system. Hence, the A1 allele of the DRD2 dopamine receptor gene appears to constitute, at least in certain individuals, a risk factor for addiction via "seeking experiences" in the broad sense and impulsive or compulsive behavior.

These genetic variations also partly explain the variability of the effects of a drug experienced by different individuals. Pleasant sensations and positive effects on psychological function (disinhibition, forgetting problems, improved performance, etc.) are incentives to repeating the experience. High spontaneous tolerance with moderate positive effects also contributes to the development of addiction.

In terms of behavior, individuals showing signs of anxiety, or with an introverted nature, or even predisposed to depression, in whom psychotropic agents (particularly alcohol) improve psychological function, are at increased risk of addiction. This is also the case for individuals eager for intense sensations.

MRI examination of the brain in addicts evidences hypoactivation of the frontal cortical regions and hyperactivation of the regions involved in motivation, memory, conditioning and emotions. However, it has not been clearly determined whether this functional deregulation is a predisposition which precedes the development of addiction, or if it simply results from long-term substance use.

Environmental factors are also involved, particularly in terms of substance availability. For example, the main risk factor for tobacco addiction is the fact of growing up in a family of smokers, which facilitates access to tobacco. Likewise, addiction to cannabis is strongly associated with having friends who used the substance in adolescence.

Consuming alcohol from the start of adolescence increases the risk of becoming dependent

Lastly, the age at which substance use began is also a contributing factor. Early initiation gives rise to increased vulnerability. Alcohol use beginning in early adolescence leads to a ten-fold risk of alcohol dependence in adulthood, compared to later introduction to alcohol use, around the age of 20.

Prévention Management: withdrawal and support

Management of addiction requires a multidisciplinary approach: this is usually based on a combination of drug treatment, individual and/or collective psychological management, and social support. There is no magical "formula". Management is often long term and interspersed with relapses. Success mainly depends on the patient's motivation to withdraw, along with a sustainable improvement in their living conditions and self-esteem: finding a job, doing activities, having interests, finding a role and contributing to society. Discussion groups (Alcoholics Anonymous, Alcool-Assistance, Croix Bleue, Vie libre, Narcotics Anonymous, etc.) play a key role in achieving these goals. These provide major support, during and after withdrawal, thanks to the experience shared by individuals having been in similar situations.

Furthermore, recent data have evidenced new developments in the management of several addictions:

  • For alcohol withdrawal, nalmefene, marketed since the summer of 2014, is a molecule indicated for the reduction of alcohol consumption. This medicinal product is part of a new "harm reduction" policy, a strategy which aims to reduce alcohol consumption without nonetheless stopping it completely. This policy is intended for non-dependent users, or those with "mild" addiction. Baclofen has a similar use. It is still being evaluated via two studies in France (results expected in 2015), but has received a recommendation for temporary use (RTU) from the health authorities. It is indicated both to help maintain abstinence after withdrawal in alcohol-dependent patients, and for major reduction of alcohol consumption to low level use.
     
  • As regards cannabis withdrawal, multidimensional family therapy, involving parents and siblings, offers good results for cannabis withdrawal among young people who are adrift.
     
  • As regards tobacco withdrawal, electronic cigarettes appear to be at least equally effective as nicotine patches.

Pictogramme microscope Challenges facing research

Research in the field of addictions concerns different substances and addictive activities, with several dimensions: neurobiological mechanisms, individual susceptibility, and even therapeutic approaches.

Scientists are attempting to clarify numerous aspects: Why, for a given product, do some people become addicted and others not? Why is addiction so difficult to reverse? What are the long-term consequences of psychoactive substance use on the adolescent brain?

A number of teams are studying the epigenetic modifications, which occur in response to the addictive substance, environment (stress, psychological trauma, etc.) or those which are inherited. These changes modulate the level of expression of these genes and may contribute to the development of addiction.

Other teams are testing innovative therapeutic approaches, such as deep brain stimulation. A team in Marseille is using electrodes to stimulate neurons in the subthalamic nucleus involved in reward, and to evaluate the effects on addiction.

A number of medicinal products are also being studied, particularly for alcohol withdrawal. This is the case for gamma-hydroxybutyric acid, already used in some countries in the prevention of withdrawal syndrome and to maintain abstinence in alcohol-dependent individuals.

Protection naturelle contre le cannabis – communiqué de presse vidéo – 2 min 37 – vidéo extraite de la série Histoire de recherche (2015)