The role of non-ordinary states of consciousness occasioned by mind-body practices in mental health illness.

BACKGROUND: Research with hallucinogens suggests that non-ordinary states of consciousness (NOSCs), particularly mystical-type experiences, predict improvements in various affective disorders and substance use disorders (SUDs). Little is known, however, about the therapeutic potential of NOSCs induced by mind-body practices such as meditation, yoga and breathwork. METHODS: We conducted a literature review in online databases (PubMed, Scopus, Google Scholar) and preprint databases (SSRN, bioRxiv) to identify studies of NOSCs induced by mind-body practices and their effects in affective disorders and SUDs. RESULTS: A wide variety of mind-body practices involving physical movement (i.e., shamanic drumming, yoga) and deliberate immersive experiences (i.e., meditation, breathwork) have been reported in the literature. Preliminary evidence, mostly from qualitative studies and open label studies, suggest that mind-body practices produce NOSCs. These experiences have also been correlated with short-term reductions in anxiety and depression, with increased motivation to change addictive behaviors, and with enhanced self-awareness and well-being. LIMITATIONS: Findings are limited by the scarcity of literature in this field. Further rigorous and methodologically sound empirical research is needed, including comparative studies of NOSCs occasioned by different methods. CONCLUSIONS: Mind-body practices may represent a promising approach for treating mental health disorders. The NOSCs induced by such practices may lead to beneficial shifts in perceptions, values, beliefs, and behaviors. Given the challenges with hallucinogen-based therapies, mind-body practices may represent a more accessible and acceptable way of eliciting potentially helpful NOSCs in clinical practice.

Ketamine-facilitated behavioral treatment for cannabis use disorder: A proof of concept study.

BACKGROUND: Sub-anesthetic ketamine infusions may benefit a range of psychiatric conditions, including alcohol and cocaine use disorders. Currently, there are no effective pharmacological treatments for cannabis use disorder. OBJECTIVES: The objective of this uncontrolled proof of concept trial was to test the feasibility, tolerability, and potential therapeutic effects of integrating ketamine infusions with a behavioral platform of motivational enhancement therapy and mindfulness-based relapse prevention in treating cannabis use disorder (CUD). METHODS: Eight cannabis-dependent individuals (four female, four male) receiving motivational enhancement therapy and mindfulness-based relapse prevention behavioral treatments completed this single-blind outpatient 6-week study. Participants received either one or two infusions of ketamine (0.71 mg/kg [infusion 1]; 1.41 mg/kg [infusion 2] for non-responders) during the study. Participants self-reported cannabis use (Timeline Follow-Back) and underwent an assessment of confidence in abstaining from using cannabis (Drug-Taking Confidence Questionnaire) at predetermined time points throughout the study. RESULTS: Ketamine infusions were well-tolerated and there were no adverse events. Frequency of cannabis use decreased significantly from baseline (B = 5.1, s.e = 0.7) to the week following the first infusion (B = 0.8, s.e = 0.412), and remained reduced at the end of the study (B = 0.5, s.e = 0.3). Participants' confidence in their ability to abstain from cannabis in potentially triggering situations increased significantly from baseline to the end of study. CONCLUSIONS: These findings suggest that combining ketamine with behavioral therapy is feasible,tolerable, and potentially helpful, in treating cannabis-dependent individuals.

Guanfacine extended-release for cannabis use disorder: a pilot feasibility trial.

Background: Currently, there are no established pharmacotherapies for cannabis use disorders (CUDs). As a long-acting alpha-2-adrenergic receptor agonist, guanfacine extended-release (G-XR) could be useful in the treatment of CUDs by mitigating withdrawal and improving behavioral control.Objectives: To evaluate the feasibility and tolerability of G-XR as a treatment for CUDs.Methods: In an eight-week open-label outpatient pilot trial, we evaluated the safety and tolerability of G-XR in 22 cannabis dependent individuals. Using 2 different titration schedules, G-XR was gradually titrated to a dose of 4 mg or the highest dose tolerated. All participants received standard medication management.Results: Retention at week eight was 41%. Average daily amount of cannabis use (in grams: F1,86 = 8.74, p = .004; in dollars: F1,86 = 16.67, p < .0001) and cannabis using days (F1,86 = 7.67, p = .007) significantly reduced over the course of study participation. There were no significant differences between the titration schedules on emergence of side effects (Fisher exact test, p = .378) or retention (Log-Rank Test X21 = 0.021, p = .886). A total of 3 participants achieved 3 weeks or greater of total abstinence.Conclusions: G-XR is a feasible treatment for CUDs, and should be evaluated further in an efficacy trial.

A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial.

OBJECTIVE: Research has suggested that subanesthetic doses of ketamine may work to improve cocaine-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of this trial was to test whether a single ketamine infusion improved treatment outcomes in cocaine-dependent adults engaged in mindfulness-based relapse prevention. METHODS: Fifty-five cocaine-dependent individuals were randomly assigned to receive a 40-minute intravenous infusion of ketamine (0.5 mg/kg) or midazolam (the control condition) during a 5-day inpatient stay, during which they also initiated a 5-week course of mindfulness-based relapse prevention. Cocaine use was assessed through self-report and urine toxicology. The primary outcomes were end-of-study abstinence and time to relapse (defined as first use or dropout). RESULTS: Overall, 48.2% of individuals in the ketamine group maintained abstinence over the last 2 weeks of the trial, compared with 10.7% in the midazolam group (intent-to-treat analysis). The ketamine group was 53% less likely (hazard ratio=0.47; 95% CI=0.24, 0.92) to relapse (dropout or use cocaine) compared with the midazolam group, and craving scores were 58.1% lower in the ketamine group throughout the trial (95% CI=18.6, 78.6); both differences were statistically significant. Infusions were well tolerated, and no participants were removed from the study as a result of adverse events. CONCLUSIONS: A single ketamine infusion improved a range of important treatment outcomes in cocaine-dependent adults engaged in mindfulness-based behavioral modification, including promoting abstinence, diminishing craving, and reducing risk of relapse. Further research is needed to replicate these promising results in a larger sample.

New Directions in Medication-Facilitated Behavioral Treatment for Substance Use Disorders.

A promising approach to addressing substance use disorders is to integrate pharmacotherapy with a behavioral treatment with which synergy is possible. In this review, we focus on recent research suggesting that this approach may be effective for cocaine and cannabis use disorders, both of which currently lack efficacious medications. We summarize potential targets of pharmacotherapy of particular relevance to combined medication-behavioral treatment and examine preliminary evidence of clinical efficacy. Common to these promising medications is a hypothesized mechanism of action predicated on reversing drug-related neural adaptations, such as high reactivity to stress or drug cues, that might undermine fruitful engagement with behavioral treatment. We also review emerging medications, such as certain glutamatergic and serotonergic agents, which may be feasibly integrated with existing treatments. We conclude with an outline of future directions for research.

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. METHODS: One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. RESULTS: There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. CONCLUSIONS: Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder.

Individual mindfulness-based psychotherapy for cannabis or cocaine dependence: a pilot feasibility trial.

BACKGROUND: Mindfulness-based approaches may be effective treatments for substance use disorders (SUDs), but they have only been investigated for SUDs in the group setting. METHODS: A novel 10-week individual mindfulness-based psychotherapy was provided weekly to participants. Tolerability and therapeutic feasibility were assessed by retention rates, incidence of adverse events or clinical worsening, and abstinence rates at the end of the protocol. RESULTS: Twenty-five patients were enrolled overall, and 19 completed (74% overall retention rate). Of the 14 cannabis dependent patients enrolled in the study, 11 completed (79%), and 8 achieved abstinence (57% by intent-to-treat analysis) at 10 weeks. Of the 11 cocaine dependent patients, 8 completed (73%), and 6 achieved abstinence (55% by ITT) at 10 weeks. Abstinence rates were substantially greater than those of historical comparison groups. CONCLUSIONS: These findings indicate that mindfulness training can be tolerably and feasibly extended to the individual psychotherapy setting for the treatment of cocaine or cannabis dependence.

A comparison of independent depression and substance-induced depression in cannabis-, cocaine-, and opioid-dependent treatment seekers.

Depressive symptoms often coexist with substance use disorders (SUDs). The DSM-IV has identified two distinct categories for depression coexisting with SUDs-independent depression and substance-induced depression. While this distinction has important therapeutic and prognostic implications, it remains difficult to make in clinical practice; the differentiation is often guided by chronological and symptom severity criteria that patients may be unable to precisely provide. Furthermore, it is unclear whether the various substances commonly abused-cannabis, cocaine, and opioids-are equally associated with the two types of depression. Predictors, associations, and other markers may be helpful in guiding the diagnostic process. We, therefore, examined the differences between cannabis-, cocaine-, and opioid-dependent individuals contending with independent depression and those contending with substance-induced depression in regard to several variables, hypothesizing that independent depression is more commonly found in females, and that it is associated with higher symptom severity and psychiatric comorbidity. Cocaine-, cannabis-, and/or opioid-dependent, treatment-seeking individuals underwent a structured clinical interview for DSM-IV-TR disorders after providing consent at our clinical research site; those with co-existing primary depression or substance-induced depression diagnoses were provided with further questionnaires and were entered into this analysis (n= 242). Pair-wise comparisons were conducted between the groups classified as independent versus substance-induced depression with 2-by-2 tables and chi-square tests for dichotomous independent variables, and t-tests for continuous variables. Binomial logistic regression was performed in order to ascertain which of the variables were significant predictors. Women were more likely than men to have independent depression (p< .005). Cannabis dependence was highly associated with independent depression (p< .001), while cocaine dependence was highly associated with substance-induced depression (p< .05). Independent depression was associated with higher Hamilton depression scale scores (16 vs. 10, p< .005), and was more highly associated with the comorbid diagnosis of posttraumatic stress disorder (p< .05). Cannabis dependence (p< .001) and female gender (p< .05) were highly significant predictors of major depression specifically. Gender, cannabis dependence, psychiatric severity, and psychiatric comorbidity have variable, statistically significant associations with independent and substance-induced depression, and may be helpful in guiding the diagnostic process.

Mindfulness impairments in individuals seeking treatment for substance use disorders.

BACKGROUND: Mindfulness training may be an effective treatment for substance use disorders (SUDs). Little research has been done, however, on baseline levels of mindfulness in the substance using population. OBJECTIVES/METHODS: We investigated mindfulness levels using the Mindful Attention Awareness Scale (MAAS) in individuals presenting for substance use treatment, and compared polydrug vs. monodrug users, as well as investigated for differences between groups based on substance used, predicting that group means would fall below the mean obtained from a large national adult sample, that the different drug groups would have comparable scores, and that the polydrug users would have a significantly lower score than do monodrug users. RESULTS: We found that the means of most drug groups were below the national mean, and that the polydrug users had a lower score on the MAAS than did monodrug users (4 vs. 3.6, p = 0.04). We were also surprised to find that opiate users had a significantly higher score (4.31) than did users of other substances (p = 0.02). CONCLUSION/SIGNIFICANCE: These results suggest that mindfulness deficits may be common in the substance using population, that there may be sub-groups in which these deficits are more pronounced, and that they may be a suitable focus of SUD treatment. These findings lend support to the ongoing development of mindfulness-based treatments for SUDs, and suggest that particular sub-groups may benefit more than others. Future research can aim at clarifying these deficits, and at elucidating their clinical relevance.

The emerging role of meditation in addressing psychiatric illness, with a focus on substance use disorders.

Over the past 30 years the practice of meditation has become increasingly popular in clinical settings. In addition to evidence-based medical uses, meditation may have psychiatric benefits. In this review, the literature on the role of meditation in addressing psychiatric issues, and specifically substance use disorders, is discussed. Each of the three meditation modalities that have been most widely studied-transcendental meditation, Buddhist meditation, and mindfulness-based meditation-is critically examined in terms of its background, techniques, mechanisms of action, and evidence-based clinical applications, with special attention given to its emerging role in the treatment of substance use disorders. The unique methodological difficulties that beset the study of meditation are also considered. A brief discussion then integrates the research that has been completed thus far, elucidates the specific ways that meditation may be helpful for substance use disorders, and suggests new avenues for research.