Does cannabis use substitute for opioids? A preliminary exploratory survey in opioid maintenance patients.

Various studies showed that people with substance use disorder use cannabis to reduce withdrawal or dose of their main drug. Using a questionnaire about their cannabis use, 118 participants in an opioid maintenance treatment (OMT) in Germany were examined regarding this strategy. 60% reported to use cannabis. Of those, 72% were using cannabis in the suggested way. Cannabis was used to substitute for, e.g., heroin (44.8%) and benzodiazepines (16.4%). We also asked for an estimation of how good cannabis was able to substitute for several substances (in German school grades (1 till 6)); heroin average grade: 2.6 ± 1.49. Besides that we asked about the idea of cannabis as "self-medication", e.g., to reduce pain (47%) and about negative consequences from cannabis use. Our results suggest to consider the use of cannabis by patients in OMT rather as a harm reduction strategy to reduce the intake of more dangerous drugs.

Stress-Induced Sensitization of Insula Activation Predicts Alcohol Craving and Alcohol Use in Alcohol Use Disorder.

BACKGROUND: Stress and alcohol cues trigger alcohol consumption and relapse in alcohol use disorder. However, the neurobiological processes underlying their interaction are not well understood. Thus, we conducted a randomized, controlled neuroimaging study to investigate the effects of psychosocial stress on neural cue reactivity and addictive behaviors. METHODS: Neural alcohol cue reactivity was assessed in 91 individuals with alcohol use disorder using a validated functional magnetic resonance imaging (fMRI) task. Activation patterns were measured twice, at baseline and during a second fMRI session, prior to which participants were assigned to psychosocial stress (experimental condition) or a matched control condition or physical exercise (control conditions). Together with fMRI data, alcohol craving and cortisol levels were assessed, and alcohol use data were collected during a 12-month follow-up. Analyses tested the effects of psychosocial stress on neural cue reactivity and associations with cortisol levels, craving, and alcohol use. RESULTS: Compared with both control conditions, psychosocial stress elicited higher alcohol cue-induced activation in the left anterior insula (familywise error-corrected p < .05) and a stress- and cue-specific dynamic increase in insula activation over time (F22,968 = 2.143, p = .007), which was predicted by higher cortisol levels during the experimental intervention (r = 0.310, false discovery rate-corrected p = .016). Cue-induced insula activation was positively correlated with alcohol craving during fMRI (r = 0.262, false discovery rate-corrected p = .032) and alcohol use during follow-up (r = 0.218, false discovery rate-corrected p = .046). CONCLUSIONS: Results indicate a stress-induced sensitization of cue-induced activation in the left insula as a neurobiological correlate of the effects of psychosocial stress on alcohol craving and alcohol use in alcohol use disorder, which likely reflects changes in salience attribution and goal-directed behavior.

A History of Childhood Maltreatment Has Substance- and Sex-Specific Effects on Craving During Treatment for Substance Use Disorders.

Rationale: Childhood maltreatment (CM) leads to detrimental mental health outcomes, such as substance use disorders (SUD). This study examined prevalence and severity of all five types of CM with respect to specific substances and sex in treatment-seeking individuals with SUD. The influences of type of CM and symptoms of depressiveness, anxiety, and perceived stress on substance craving at admission as well as craving reduction during SUD treatment were examined. Methods: N = 546 patients in treatment for SUD and N = 109 individuals in opioid maintenance treatment filled out questionnaires regarding CM (Childhood Trauma Questionnaire) and psychopathologies. Substance craving was assessed throughout treatment using the Mannheim Craving Scale. Group differences in CM, type of substance and sex were examined. General linear models were applied to examine influences on substance craving. Results: Higher prevalence and severity of all five subtypes of CM were observed in individuals with SUD compared to the general population. Women were more severely affected by emotional and sexual abuse than men. Patients with cannabis use disorder reported more severe experiences of emotional abuse compared to all other substances. Craving at admission to treatment was influenced by emotional abuse, however, symptoms of depressiveness, anxiety, and perceived stress contributed to craving at admission or craving reduction during treatment. Conclusion: CM relates to SUD and should be incorporated in prevention and treatment of SUD. Underlying mechanisms of the association might relate to impairments in processing and regulation of stress, emotions, and interpersonal relations following a history of CM.

Exploring Influences on Theory of Mind Impairment in Opioid Dependent Patients.

Theory of mind (ToM) is an aspect of social cognition impaired in different addictive disorders, including opioid addiction. This study aimed at replicating ToM deficits in opioid dependent patients undergoing opioid maintenance treatment (OMT) and exploring the influence of substance use related variables, executive functions and childhood maltreatment on ToM in opioid dependent patients. 66 opioid dependent patients were tested using the Movie for Assessment of Social Cognition (MASC) and compared with the data of healthy controls. Furthermore, the opioid dependent patients underwent testing for executive functions and filled in the Childhood Trauma Questionnaire (CTQ). Performance on the MASC was significantly poorer in the opioid dependence group than in the control group, even when recent additional drug use and psychiatric comorbidities were controlled for. No correlations were found between ToM and substance use related factors. Aspects of ToM performance in opioid dependent patients correlated significantly with different EF domains. ToM correlated significantly with the CTQ scales for physical maltreatment. The results confirm impaired ToM in opioid dependent patients and highlight executive functions and childhood maltreatment as influential factors. The lack of associations between ToM and substance use related variables and the association with childhood maltreatment suggest that ToM impairments might be a risk factor predating substance abuse.

Impaired working memory performance in opioid-dependent patients is related to reduced insula gray matter volume: a voxel-based morphometric study.

Opioid-dependent patients frequently show deficits in multiple cognitive domains that might impact on their everyday life performance and interfere with therapeutic efforts. To date, the neurobiological underpinnings of those deficits remain to be determined. We investigated working memory performance and gray matter volume (GMV) differences in 17 patients on opioid maintenance treatment (OMT) and 17 healthy individuals using magnetic resonance imaging and voxel-based morphometry. In addition, we explored associations between substance intake, gray matter volume, and working memory task performance. Patients on OMT committed more errors during the working memory task than healthy individuals and showed smaller insula and putamen GMV. The duration of heroin use prior to OMT was associated with working memory performance and insula GMV in patients. Neither the substitution agent (methadone and buprenorphine) nor concurrent abuse of illegal substances during the 3 months prior to the experiment was significantly associated with GMV. Results indicate that impaired working memory performance and structural deficits in the insula of opioid-dependent patients are related to the duration of heroin use. This suggests that early inclusion into OMT or abstinence-oriented therapies that shorten the period of heroin abuse may limit the impairments to GMV and cognitive performance of opioid-dependent individuals.

Therapeutic Drug Monitoring of Naltrexone and 6ß-Naltrexol During Anti-craving Treatment in Alcohol Dependence: Reference Ranges.

AIMS: Aim of this study was to associate concentration of naltrexone and its major active metabolite 6ß-naltrexol in blood with therapeutic outcome during treatment with naltrexone in subjects with alcohol dependence. Treatment with the µ-opiate receptor antagonist naltrexone has been shown to reduce craving for alcohol and alcohol intake in patients suffering from alcohol dependence. SHORT SUMMARY: This article shows the use of therapeutic drug monitoring in alcohol dependent patients, who are treated with naltrexone. The plasma concentrations of naltrexone and 6ß-naltrexol showed high inter-individual variability. They were predictive for treatment response, as they correlated significantly with the reduction of alcohol craving. METHODS: Naltrexone and 6ß-naltrexol were analysed by high performance liquid chromatography with column switching and spectrophotometric detection. Alcohol craving was assessed with the Obsessive-Compulsive Drinking Scale (OCDS). RESULTS AND CONCLUSIONS: The study included 43 patients who were treated with naltrexone with a dose of 50 mg/day. Blood was taken for drug analysis 8 h after the last dose of the day at Week 4, 8 and 12. The plasma concentrations of naltrexone and 6ß-naltrexol showed high inter-individual variability. They were predictive for treatment response, as they correlated significantly with the reduction of alcohol craving. Defining patients with OCDS reduction of 70% or higher as responders, the mean±SD concentration of naltrexone plus naltrexol was 22 ± 13 ng/ml compared to 15 ± 8 ng/ml in patients with score reductions of 1-69%. Further analyses indicated that concentrations of 17-50 ng/ml at 8 h and 7-20 ng/ml at 24 h after drug intake were required for treatment response. CONCLUSIONS: Since plasma concentration of naltrexone plus 6ß-naltrexol was found to be predictive for reduction of alcohol craving, it is concluded that therapeutic drug monitoring has the potential to enhance naltrexone's moderate therapeutic efficiency in patients with alcohol dependence.