[Cocaine addiction: current data for the clinician]. / Addiction à la cocaïne : données actuelles pour le clinicien.

Cocaine remains the second most commonly used illicit drug worldwide after cannabis. Observed levels of cocaine use among countries considerably vary. An increased cocaine use is recorded in the general European population. Cocaine addiction is a worldwide public health problem, which has somatic, psychiatric, socio-economic and judicial complications. It is a multifactorial disorder variable in its clinical manifestations and heritable. Compared to the general population, there is a high prevalence of somatic and psychiatric disorders among cocaine-dependent patients. There are predictable dose-related effects of pharmacological action of cocaine and effects which are uncommon, unrelated to dose and occur randomly in this population. The number of patients entering drug treatment for primary cocaine use has been increasing in Europe for several years. However, there is no specific pharmacotherapy with established efficacy for the treatment of cocaine addiction, nor is any medication approved by regulatory authorities for such treatment. Recent controlled clinical studies and laboratory studies have highlighted some very promising medications. The perfect therapeutic platform for abstinence initiation and relapse prevention of cocaine addiction is a combination of pharmacological treatments and behavioral treatments. Targeting somatic and psychiatric comorbidity is another way to use pharmacological treatments in addictions.

[Tobacco use and illicit substance use disorders: what should we have to do?]. / Consommation de tabac et trouble lié à l'usage de substances illicites: que devrions-nous faire ?

UNLABELLED: Tobacco use is a commonplace phenomenon in our society. Its use is responsible for more death and disease than any other noninfectious cause. More deaths are caused each year by tobacco use than by all deaths from HIV, illegal drug use, alcohol use, motor vehicle injuries, suicides, and murders combined. Tobacco remains responsible for greater morbidity than alcohol and all other drugs combined. Tobacco dependence is highly prevalent among drug-dependent patients. Substance abuse patients smoke more and are more vulnerable to the effects of smoking than general populations. Traditional substance abuse therapeutic programs too frequently focus only on treatment of alcohol or other drugs rather than including treatment for tobacco dependence. Currently, there are no official medical recommendations for the treatment of tobacco addiction in illicit polysubstance users. METHODS: A comprehensive literature search from a range of electronic databases (PubMed, Embase, PsycInfo, Google Scholar) was conducted for the period from 1988 to September 2012, using the following keywords alone or in combination: tobacco, nicotine, cocaine, cannabis, amphetamines, opiates, substance abuse, substance dependence, addiction, treatment. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. RESULTS: Our literature review will focus on epidemiological, neurobiological, clinical interactions between tobacco, alcohol and other illicit drugs. It will also focus on therapeutic programs in this dual addictive disorder. The aim of this literature review is to make proposals for the treatment of tobacco addiction in polysubstance users entering in specific therapeutic programs.

[Gamma-hydroxybutyric acid (GHB): more than a date rape drug, a potentially addictive drug]. / Acide gamma-hydroxy-butyrique (GHB): plus qu'un agent de soumission chimique, une véritable source d'addiction.

According to available information, GHB and its precursors--gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD)--are used especially in a nightlife scene characterized by the search for amplified sensations through the combination of electronic music, marathon dancing, and substance abuse. Evidence indicates that GHB/GHL is used particularly in some subpopulations and in places, such as in gay nightclubs. Commonly known as Gorliquid ecstasy, it was misused in the 1980s for its bodybuilding effects and in the 1990s as a recreational drug at music venues. In the same period, media coverage of the use of GHB in sexual assault (often referred to as date rape) brought the drug into the spotlight. GHB/GHL addiction is a recognized clinical entity evidenced by severe withdrawal symptoms when the drug is abruptly discontinued after regular or chronic use. There is evidence that negative health and social consequences may occur in recreational and chronic users. Nonfatal overdoses and deaths related to GHB have been reported. These undesirable effects and especially the deaths appear to have prompted campaigns to limit the use of GHB. Clinicians must also be aware of GBL, which is being sold and used as a substitute for GHB.

[Complications of cocaine addiction]. / L'addiction à la cocaïne: de nombreuses conséquences.

Addiction is a chronic relapsing disorder characterized by repetitive and compulsive drug-seeking behavior and drug abuse despite negative health or social consequences. Cocaine addiction is a significant worldwide public health problem, which has somatic, psychological, psychiatric, socio-economic and judicial complications. Some of the most frequent complications are cardiovascular effects (acute coronary syndrome, cardiac arrhythmias, increased blood pressure); respiratory effects (fibrosis, interstitial pneumonitis, pulmonary hypertension, alveolar haemorrhage, asthma exacerbation; emphysema), neurological effects (strokes, aneurysms, seizures, headaches); risk for contracting HIV/AIDS, hepatitis B and C, sexual transmitted disease and otolaryngologic effects. Other complications are not discussed here. The vast majority of studies indicate that there are cognitive deficits induced by cocaine addiction. Attention, visual and working memories, executive functioning are affected in cocaine users. Psychiatric complications found in clinical practice are major depressive disorders, cocaine-induced paranoia, cocaine-induced compulsive foraging and panic attacks.

[Cocaine and crack addiction: a growing public health problem]. / Addiction a la cocaïne et au "crack": un problème de santé publique qui s'aggrave.

Cocaine addiction is an important public health problem worldwide, and use of this drug is growing in France. Cocaine produces its psychoactive and addictive effects primarily by acting on the brain's reward system--a set of interconnected regions that regulate pleasure and motivation. An initial short-term effect due to a build-up of the neurochemical dopamine gives rise to euphoria and to a desire to take the drug again. Cocaine's many longer-term effects include addiction, persistent craving and a high risk of relapse. Dysregulation of brain reward pathways is associated with a drastic escalation of drug-seeking behaviors and intake. Cocaine addiction is rapidly progressive and can have severe medical, psychiatric and psychosocial consequences. There are no proven pharmacotherapies for cocaine addiction. However, cocaine addiction being due to a pharmacologically induced reduction in the neuroplasticity of brain circuits mediating normal reward learning, novel pharmacotherapies directly targeting the biological pathology of addiction should be feasible. Progress in the neurobiology of cocaine dependence has enabled researchers to identify medications that might help patients initiate abstinence and avoid relapse. Several such medications, and a vaccine, have given encouraging results in controlled clinical trials with cocaine-dependent patients. Major behavioral therapies have also proven to be effective on cocaine addiction. Treatment approaches combining medication and behavioral intervention are likely to produce the best results.

[Neuroimaging and cocaine: mapping dependence?]. / Neuro-imagerie et cocaïne: une cartographie de la dépendance ?

Two principal techniques are used in functional neuroimaging: positron-emission tomography (PET) and functional magnetic resonance imaging (fMRI). FMRI is noninvasive and non-irradiating; it has good temporal and spatial resolution, but it is not at all specific. PET has a lower spatial and temporal resolution but better sensitivity and high specificity. Functional neuroimaging studies in individuals who are and are not cocaine-dependent have confirmed the blockage of cerebral dopamine transporters by acute cocaine intake and the mechanism of down-regulation in chronic consumers. This blockage is expressed by depletion of dopaminergic D2 postsynaptic receptors and low levels of dopamine release. Variations in the protocols and in the results of neuroimaging studies of craving make their interpretation difficult, although several cerebral structures do appear to be particularly involved. Neuroimaging has no recognized clinical indications in the field of dependence or more generally in psychiatry, but it is an essential research tool.

[Current pharmacotherapies and immunotherapy in cocaine addiction]. / Pharmacothérapies actuelles et immunothérapie dans l'addiction à la cocaïne.

Cocaine is more and more used and abused in France. Cocaine dependence is quite serious and is associated with numerous adverse health consequences. No effective pharmacotherapy for cocaine dependence is yet available. Recent advances in neurobiology, brain imaging and some clinical trials suggest that certain medications that modulate GABAergic, dopaminergic, and glutamatergic systems, as well as immunotherapy, show promise in the treatment of cocaine addiction. Recent controlled clinical studies have tested some of these drugs, which act on the various neurobiological circuits modified by cocaine exposure and clinically improve patients' symptoms. Pharmacological agents such as modafinil, GABAergic agents (baclofen, topiramate, tiagabin, and vigabatrin), disulfiram, aripiprazole, N-acetylcysteine and cocaine vaccine seem very promising in the treatment of cocaine dependence. However, this must be confirmed in larger patient populations.

New treatments for cocaine dependence: a focused review.

Cocaine, already a significant drug problem in North and South America, has become a more prominent part of the European drug scene. Cocaine dependence has major somatic, psychological, psychiatric, socio-economic, and legal implications. No specific effective pharmacological treatment exists for cocaine dependence. Recent advances in neurobiology have identified various neuronal mechanisms implicated in cocaine addiction and suggested several promising pharmacological approaches. Data were obtained from Medline, EMBASE, and PsycINFO searches of English-language articles published between 1985 and June 2007 using the key words: cocaine, addiction, cocaine dependence, clinical trials, pharmacotherapy(ies) singly and in combination. Large well-controlled studies with appropriate statistical methods were preferred. Pharmacological agents such as GABA agents (topiramate, tiagabine, baclofen and vigabatrin) and agonist replacement agents (modafinil, disulfiram, methylphenidate) seem to be the most promising in treatment of cocaine dependence. The results from trials of first- and second-generation neuroleptics are largely negative. Aripiprazole, a partial dopaminergic agonist that may modulate the serotonergic system, shows some promise. Preliminary results of human studies with anti-cocaine vaccine, N-acetylcysteine, and ondansetron, are promising, as are several compounds in preclinical development. While no medication has received regulatory approval for the treatment of cocaine dependence, several medications marketed for other indications have shown efficacy in clinical trials. An anti-cocaine vaccine and several compounds in preclinical development have also shown promise. Findings from early clinical trials must be confirmed in larger, less selective patient populations.

Interest for delivery of cocaethylene in a sustained release emulsion vs saline evaluated on behavioral sensitization in naive and cocaine-sensitized mice.

RATIONALE: Repeated administration of psychostimulant elicits behavioral sensitization, characterized by an augmented locomotor response to a subsequent challenge injection. This sensitization is paralleled by neural adaptations. Evidences suggest that the rate at which drugs of abuse are delivered to the brain play a key role in this plasticity. Cocaethylene is a pharmacologically active homolog of cocaine, known to have a pharmacokinetic profile different to that of cocaine. OBJECTIVES: Utilizing locomotor sensitization, we evaluated the consequences of the administration of cocaethylene in a rapid- and slow-onset formulation, in naïve and cocaine-sensitized mice. MATERIALS AND METHODS: We investigated the development of sensitization after repeated administration of cocaine and cocaethylene and the effects of cocaethylene in animals previously exposed to cocaine. Cocaethylene was dissolved in two vehicles (saline and emulsion). RESULTS: As observed with cocaine, chronic cocaethylene treatment in saline induced a behavioral sensitization, while in a sustained release emulsion, no behavioral sensitization was observed. Moreover, the expression of the sensitized behavior observed in cocaine-treated mice was reduced or totally abolished after cocaethylene administration in saline and emulsion, respectively. Interestingly, administration of cocaine in mice chronically treated with cocaethylene in saline induced an increase in locomotor activity as compared to control animals. In contrast, no difference was observed after the administration of cocaine in animals chronically treated with cocaethylene in emulsion or control group. CONCLUSIONS: Cocaethylene in a sustained release emulsion blocked locomotor sensitization. These results suggest that cocaethylene, in a specific galenic preparation, such as gum, may be an efficacious harm-reduction alternative to cocaine users.

Economic and social effects of high-dose buprenorphine substitution therapy. Six-month results.

The purpose of this study was to analyze the impact of high-dose buprenorphine substitution therapy in opiate-dependent patients in terms of use of psychoactive substances, associated risks, social integration, and the social cost generated by the use of these substances. This was a longitudinal quantitative survey carried out in 1083 patients who were evaluated at three times: at the beginning of substitution therapy (D0), at 6 months and then at 12 months follow up (M6, M12). Data were collected with an anonymous self-administered questionnaire, completed in the presence of an investigating physician. Results demonstrated that patients treated with high-dose buprenorphine for 6 months, consumed fewer psychoactive drugs (heroin, cocaine, benzodiazepines) and had fewer associated risks. Additionally, several criteria involved in social integration showed improvement; morbidity and mortality decreased after the first 6 months of substitution therapy. These improvements were followed by a reduction in the social cost of drug use generated by the group of patients considered. These initial results require confirmation in the final analysis of the study taking into account the 12-month follow up.