clozapine and Marijuana-Abuse

In recent years, there has been a growing interest in developing adequate treatments for patients with a diagnosis of schizophrenia and a comorbid substance use disorder (SUD). In the present paper we aim to critically review published reports on the use of conventional and second-generation antipsychotics in the treatment of patients with schizophrenia and comorbid SUD, to provide clinicians with a clearer view of the pharmacological treatment of this highly prevalent dual diagnosis based upon the evidence arising from the scientific literature.. A search of the relevant literature from Medline, PsycLIT and EMBASE databases, included in the Science Citation Index, and available up to November 2006 was conducted using the terms: 'schizophrenia', 'substance use disorder' and 'antipsychotics'.. While research on the use of conventional antipsychotics has remained limited, the majority of studies suggest the effectiveness of second-generation antipsychotics, particularly clozapine, for patients with schizophrenia and a comorbid substance use disorder.. In the absence of randomized controlled trials that could provide more reliable information, clinical decisions may need to rely on indirect data provided by the increasing number of case reports, open trials and retrospective studies showing a decrease in cigarette smoking, alcohol, cocaine or cannabis use and an improvement of overall psychiatric symptoms.

Topics: Alcoholism; Antipsychotic Agents; Clozapine; Cocaine-Related Disorders; Combined Modality Therapy; Comorbidity; Cross-Sectional Studies; Diagnosis, Dual (Psychiatry); Humans; Marijuana Abuse; Schizophrenia; Smoking Cessation; Substance-Related Disorders

Cannabis use disorders (CUDs) are highly comorbid in patients with schizophrenia and associated with poor outcome. Clozapine has been put forward as the first choice antipsychotic in this patient group. However, little is known about the mechanisms underlying the assumed superiority of clozapine.. A total of 38 patients with DSM-IV schizophrenia (30 with and 8 without a DSM-IV CUD) and 20 healthy comparison subjects were included between April 2009 and June 2012. Patients were randomized to antipsychotic treatment with clozapine or risperidone. At baseline and after 4weeks of medication, brain response to cannabis-related, positive and neutral images was measured using functional MRI. Neural correlates of cue reactivity were assessed in the following regions of interest: amygdala, ventral striatum, insula, thalamus, orbitofrontal cortex and anterior cingulate cortex. Subjective craving was assessed using self-report questionnaires (OCDUS and MCQ).. At baseline, patients with a comorbid CUD showed higher subjective craving and greater activation in response to cannabis-related images compared to patients without a CUD and healthy controls in most regions of interest. Clozapine treated patients reported a greater reduction in craving (F(1,28)=6.0, p=0.04) and showed a larger decrease in amygdala activation during cannabis-related images compared to risperidone treated patients (T=3.94, pFWE=0.006). In addition, significant correlations were found between subjective craving and thalamus and insula activation during cannabis-related images.. These findings provide evidence that clozapine is superior to risperidone in decreasing subjective craving and cue reactivity for cannabis-related images probably due to a differential effect on dopaminergic neurotransmission.. 'Nederlands trial register' (http://www.trialregister.nl), nr NTR1761, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1761.

Topics: Antipsychotic Agents; Brain; Brain Mapping; Clozapine; Comorbidity; Craving; Cues; Humans; Magnetic Resonance Imaging; Male; Marijuana Abuse; Medication Adherence; Risperidone; Schizophrenia; Treatment Outcome; Visual Perception; Young Adult

Cannabis use disorders (CUDs) are highly comorbid in patients with schizophrenia and are associated with poor outcome. Clozapine has been put forward as the first choice antipsychotic in this comorbid group. However, little is known about the mechanisms underlying the assumed superiority of clozapine. We compared the effects of clozapine and risperidone on attentional bias, subjective craving and associated regional brain activity in patients with schizophrenia and CUD. Overall, 36 patients with schizophrenia and 19 healthy controls were included. Patients were randomised to antipsychotic treatment with clozapine or risperidone. At baseline and after 4 weeks of medication use, regional brain responses were measured during a classical Stroop and a cannabis word Stroop using functional magnetic resonance imaging. Clozapine-treated CUD patients showed a larger reduction in craving and in activation of the insula during the cannabis word Stroop, while risperidone-treated patients showed a larger decrease in activation of the right anterior cingulate cortex during the classical Stroop. A significant association was found between decreases in subjective craving and decreases in insula activation during the cannabis word Stroop. These findings strongly suggest that clozapine may be a better treatment choice in patients with schizophrenia and CUD than risperidone.

Topics: Adolescent; Adult; Antipsychotic Agents; Attentional Bias; Brain Mapping; Clozapine; Craving; Humans; Magnetic Resonance Imaging; Male; Marijuana Abuse; Netherlands; Predictive Value of Tests; Risperidone; Schizophrenia; Schizophrenic Psychology; Stroop Test; Time Factors; Treatment Outcome; Young Adult

Topics: Adolescent; Antipsychotic Agents; Catatonia; Clozapine; Delusions; Feeding and Eating Disorders of Childhood; Haiti; Humans; Male; Marijuana Abuse; Olanzapine; Schizophrenia; Weight Loss

Despite high rates of marijuana abuse in schizophrenia, the physiological interactions between tetrahydrocannabinol (THC) and antipsychotic medications are poorly understood. A well-characterized feature of schizophrenia is poor gating of the P50 auditory-evoked potential. This feature has been translationally modeled by the DBA/2 mouse, which exhibits poor suppression of the P20-N40 AEP, the rodent analog of the human P50. Previous work has demonstrated that this deficit is reversed by the antipsychotic clozapine. It is unknown, however, if this effect is altered by THC administration. Using a conditioning-testing paradigm with paired auditory stimuli, the effects of clozapine and dronabinol (a pharmaceutical THC formulation) on inhibitory P20-N40 AEP processing were assessed from in vivo hippocampal CA3 recordings in anesthetized DBA/2 mice. The effects of clozapine (0.33 mg/kg) and dronabinol (10 mg/kg) were assessed alone and in combination (0.33, 1 or 1.83 mg/kg clozapine with 10mg/kg dronabinol). Improved P20-N40 AEP gating was observed after acute administration of 0.33 mg/kg clozapine. Co-injection of 0.33 mg/kg clozapine and 10 mg/kg THC, however, did not improve gating relative to baseline. This effect was overcome by higher doses of clozapine (1 and 1.83 mg/kg), as these doses improved gating relative to baseline in the presence of 10 mg/kg THC. 10 mg/kg THC alone did not affect gating. In conclusion, THC does not prevent improvement of P20-N40 gating by clozapine.

Topics: Acoustic Stimulation; Animals; Antipsychotic Agents; CA3 Region, Hippocampal; Clozapine; Conditioning, Psychological; Dose-Response Relationship, Drug; Dronabinol; Drug Interactions; Evoked Potentials, Auditory; Humans; Male; Marijuana Abuse; Mice; Mice, Inbred DBA; Models, Animal; Psychotropic Drugs; Schizophrenia; Sensory Gating

Treatment guidelines suggest antipsychotic monotherapy in the treatment of psychosis. 20-40% of patients take combination therapy in clinical practice due to inadequate treatment response to monotherapy. First-generation antipsychotic monotherapy was ineffective in case of our patient who had severe psychotic symptoms. Switching to a second generation antipsychotic had partial therapeutic effect, the severe psychotic condition was persistent. For this reason the therapy was changed to olanzapine-clozapine combination. Due to this combination the patient's psychotic symptoms disappeared. He was able to maintain the relationship with psychiatrist. During this therapy we observed good compliance, no more drug abuse and no relapse.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Marijuana Abuse; Medication Adherence; Olanzapine; Psychotic Disorders; Treatment Outcome

Substance abuse and psychotic disorders have a high rate of comorbidity. Both disorders are associated with changes in the dopaminergic transmission in the mesocorticolimbic pathways of the brain. Since antipsychotic medications interact with the dopamine receptors in these pathways, these medications could affect craving for substances. In the current study, the effect of clozapine (n = 27, mean dosage 350 mg), risperidone (n = 54, mean dosage 3.46 mg) and olanzapine (n = 60, mean dosage 13.78 mg) on subjective craving for cannabis was compared in 123 patients with cannabis dependence and psychotic disorder. Patients treated with risperidone reported significantly more craving compared with patients treated with clozapine (Z = -3.19, p = .001) or olanzapine (Z = -2.24, p = .025). No significant differences in craving between clozapine and olanzapine were found. These results are in concordance with findings in the literature on this subject and could be explained by differences in three dopamine mediated mechanisms of these compounds: 1) occupancy rate of dopamine D(2) receptors, 2) dissociation rate of dopamine D(2) receptors, 3) D(1)/D(2) occupancy ratio. Risperidone and clozapine show a maximal difference in D(2) receptor occupancy rate, dissociation rate and D(1)/D(2) ratio. Olanzapine is intermediate between risperidone and clozapine in these characteristics.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cannabis; Clozapine; Cohort Studies; Dopamine; Female; Humans; Longitudinal Studies; Male; Marijuana Abuse; Olanzapine; Receptors, Dopamine D1; Receptors, Dopamine D2; Risperidone; Schizophrenia

Marijuana (cannabis) is the most commonly abused drug by adolescents and young adults and also by people with schizophrenia or other psychotic disorders. An increasing number of studies suggest that regular cannabis users can show psychotic episodes similar to schizophrenic disorders but it still unclear if cannabis induced psychotic disorder is a distinct entity requiring special therapy or regular cannabis use consequently leads to schizophrenia. Therefore, we retrospectively compared psychotic patients with and without cannabis use by clinical profile. Clinical data of 85 patients with schizophrenia spectrum disorder were analyzed retrospectively. Cannabis use was not reported by 43 persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least 1 year (Cnbs1 subgroup). Clinical data were collected from electronic medical documentation of patients concerning anamnesis, family history, socio-demographic condition, symptoms and psychiatric state, acute and long-term therapies. Men were over-represented in the cannabis abuser group while mean age was lower among them compared to the Cnbs0 subgroup. Prevalence of suicidal attempts was increased in men without cannabis use. Patients without cannabis use spent more time in hospital and smoking was more frequent among them. Positive and negative symptoms and family history did not differ significantly between the two subgroups. Dosage, intensity and length of pharmacotherapy was different between the two subgroups. These results revealed that certain clinical aspects were different in case of cannabis-related schizophrenia spectrum disorder compared to schizophrenia.

Topics: Adolescent; Adult; Aggression; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Hallucinations; Haloperidol; Humans; Hungary; Male; Marijuana Abuse; Olanzapine; Paranoid Disorders; Piperazines; Psychomotor Performance; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Schizophrenia; Schizophrenic Psychology