Provider Perspectives of Battlefield Acupuncture: Advantages, Disadvantages and Its Potential Role in Reducing Opioid Use for Pain.

OBJECTIVES: Nonpharmacological options to treat pain are in demand, in part to address the opioid crisis. One such option is acupuncture. Battlefield acupuncture (BFA) is an auricular needling protocol currently used to treat pain in the Veterans Health Administration. We aimed to identify the advantages and disadvantages of BFA from providers' perspectives. METHODS: We rely on an inductive qualitative approach to explore provider perceptions through thematic analysis of semistructured interviews with 43 BFA providers across the nation. RESULTS: We identified the following themes. Disadvantages included: (1) clinical guidelines are insufficient; (2) patients often request multiple BFA visits from providers; (3) BFA can be uncomfortable; (4) BFA may not be an effective treatment option unless it can be provided "on demand"; and (5) BFA can promote euphoria, which can have deleterious consequences for patient self-care. Perceived advantages included: (1) BFA can simultaneously effectively control pain while reducing opioid use; (2) BFA may alleviate the pain that has been unsuccessfully treated by conventional methods; (3) BFA gives providers a treatment option to offer patients with substance use disorder; (4) BFA helps build a trusting patient-provider relationship; (5) BFA can create the opportunity for hope. CONCLUSIONS: Providers perceive BFA to have many benefits, both clinical and relational, including ways in which it may have utility in addressing the current opioid crisis. BFA is easy to deliver and has potential clinical and relational utility. Efforts to better understand effectiveness are warranted.

Characterisation and outcome of neuropsychiatric symptoms in patients with anti-NMDAR encephalitis.

BACKGROUND: Encephalitis due to anti-N-methyl-D-aspartate receptor antibodies (ANMDARE) is the most frequent immune-mediated encephalitis. It is distinguished by the subacute onset of neuropsychiatric symptoms. OBJECTIVE: To evaluate the characteristic neuropsychiatric symptoms and their outcome in patients diagnosed with ANMDARE. METHODS: This was a prospective, longitudinal study in patients with a diagnostic suspicion of ANMDARE that presented to the National Institute of Neurology from March 2018 to February 2019. A comparative analysis of two groups (positive N-methyl-D-aspartate receptor [NMDAR] vs. negative NMDAR antibodies in cerebrospinal fluid [CSF]) was done on admission and at discharge. Neuropsychiatric systematic assessments included the Neuropsychiatric Inventory Questionnaire, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method Severity, the Montreal Cognitive Assessment, and the Overt Agitation Severity Scale. RESULTS: 24 individuals were analysed: 14 had positive NMDAR antibodies, and 10 had negative NMDAR antibodies in CSF. On admission, agitation/aggression, euphoria/exaltation, and disinhibition were more common in patients with positive antibodies. Excited catatonia and delirium were diagnosed more frequently in patients with positive antibodies. At discharge, there was an important decrease in neuropsychiatric symptoms, but substantial cognitive impairment remained. The mean hospitalisation length was 41.71 (SD 39.33) days for patients with definitive ANMDARE (p 0.259). CONCLUSIONS: Neuropsychiatric symptoms profile in ANMDARE was associated with the early onset of euphoria/exaltation and disinhibition, accompanied by marked psychomotor agitation. When ANMDARE was suspected, the presence of excited-type catatonia and delirium showed a tendency to predict definitive ANMDARE. At discharged, most patients recovered from catatonia, delirium, and psychosis, but marked cognitive symptoms, anxiety, and depression persisted at discharge.

Abuse Potential of Pregabalin: A Systematic Review.

BACKGROUND: Several case reports and epidemiological studies have raised concern about the abuse potential of pregabalin, the use of which has increased substantially over the last decade. Pregabalin is, in some cases, used for recreational purposes and it has incurred attention among drug abusers for causing euphoric and dissociative effects when taken in doses exceeding normal therapeutic dosages or used by alternative routes of administration, such as nasal insufflation or venous injection. The magnitude of the abuse potential and the mechanism behind it are not fully known. OBJECTIVE: The aim of this study was to present a systematic review of the data concerning the abuse potential of pregabalin. METHODS: We performed a systematic literature search and reviewed the preclinical, clinical and epidemiological data on the abuse potential of pregabalin. RESULTS: We included preclinical (n = 17), clinical (n = 19) and epidemiological (n = 13) studies addressing the abuse potential of pregabalin. We also reviewed case reports (n = 9) concerning abuse of pregabalin. The preclinical studies indicated that pregabalin possesses modulatory effects on the GABA and glutamate systems, leaving room for an abuse potential. Further, clinical studies reported euphoria as a frequent side effect in patients treated with pregabalin. The majority of case reports concerning abuse of pregabalin involved patients with a history of substance abuse and, similarly, epidemiological studies found evidence of abuse, especially among opiate abusers. CONCLUSIONS: Overall, the available literature suggests an important clinical abuse potential of pregabalin and prescribers should pay attention to signs of abuse, especially in patients with a history of substance abuse.

Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy.

BACKGROUND: Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use. OBJECTIVES: To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer. SEARCH METHODS: We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy. DATA COLLECTION AND ANALYSIS: At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI). MAIN RESULTS: We included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I(2) = 0% in both analyses).People had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I(2) = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I(2) = 0%).People reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence). Comparison with other anti-emetics There was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I(2) = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I(2) = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I(2) = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross-over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I(2) = 0%).People had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I(2) = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.People had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I(2) = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I(2) = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I(2) = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I(2) = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I(2) = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.People reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I(2) = 51%; low quality evidence).In comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.Two trials with 141 participants compared an anti-emetic drug alone with a cannabinoid added to the anti-emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events. Quality of the evidence The trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti-emetic treatment regimens. Furthermore, the quality of evidence arising from meta-analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results. AUTHORS' CONCLUSIONS: Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.

Empirical support for a multi-dimensional model of sensations experienced by youth during their initial smoking episodes.

AIMS: To examine the dimensionality of sensations experienced during initial tobacco smoking. DESIGN: Cross-sectional survey. SETTING: Thirteen secondary schools located in British Columbia, Canada. PARTICIPANTS: Data from 1187 adolescents who responded 'yes' to the question: 'Have you ever tried cigarette smoking, even one or two puffs?'. MEASUREMENTS: Participants answered questions about their demographic characteristics, tobacco smoking history and sensations experienced during their initial smoking episodes. FINDINGS: The sensations appear to represent the following three separate but modestly correlated dimensions: a pleasant dimension defined by feeling good and relaxed; an unpleasant dimension defined by coughing, feeling sick and nervous; and a 'buzz' dimension defined by feeling high and dizzy. The three factors made statistically significant contributions to the prediction of transition to regular smoking (defined as having smoked at least 100 cigarettes in one's life-time) after adjusting for age, sex and age at first puff. CONCLUSIONS: The results suggest that three relatively distinct physiological systems appear to explain the relationship between initial smoking sensations and probability of becoming a regular smoker. Researchers examining sensations experienced during initial tobacco smoking episodes should consider using a three-dimensional profile of symptoms composed of pleasant, unpleasant and buzz dimensions.

Psychobiology of drug-induced religious experience: from the brain "locus of religion" to cognitive unbinding.

The recent interest in the psychopharmacological underpinnings of religious experiences has led to both the laboratory characterizations of drug-induced mystical events and psychobiological models of religious experiences rooted in evolution and fitness. Our examination of this literature suggests that these theories may be congruent only within more modern religious and cultural settings and are not generalizable to all historical beliefs, as would be expected from an evolutionarily conserved biological mechanism. The strong influence of culture on the subjective effects of drugs as well as religious thoughts argues against the concept of a common pathway in the brain uniquely responsible for these experiences. Rather, the role of personal beliefs, expectations and experiences may interject bias into the interpretation of psychoactive drug action as a reflection of biologically based religious thought. Thus, psychobiological research proposing specific brain mechanisms should consider anthropological and historical data to address alternative explanations to the "fitness" of religious thought. A psychobiological model of the religious experience based on the concept of cognitive unbinding seems to accommodate these data better than that of a specific brain locus of religion.

The neuropsychiatry of multiple sclerosis: focus on disorders of mood, affect and behaviour.

Neuropsychiatric symptoms are common in multiple sclerosis (MS). They include two broad categories of disturbances: abnormalities in cognition, and abnormalities of mood, affect and behaviour. The present review deals with the epidemiology, clinical features, etiology and treatment of disturbances included in the second category, i.e., major depression, fatigue and sleep disorders, bipolar disorder, euphoria, pathological laughing and crying, anxiety, psychosis and personality changes. Major depression is one of the most common neuropsychiatric disorders in MS with an approximate 50% lifetime prevalence rate. Early recognition and management of depression in MS is of major importance because it is a key predictor of morbidity, mortality, quality of life, possibly physical outcome and disease exacerbations, adherence to immunomodulatory treatments and suicide risk in MS patients, as well as of the caregiver's distress and quality of life. The etiopathogenesis of neuropsychiatric disorders in MS has been incompletely investigated. It is postulated that a complex interplay of biological, disease-related, behavioural and psychosocial factors contribute to the pathophysiology of most of them. Management of neuropsychiatric symptoms in MS is often effective, although commonly based on evidence provided by case studies and uncontrolled trials. A comprehensive biopsychosocial neuropsychiatric approach is essential for the optimal care of patients with MS.

Pattern of use and subjective effects of Salvia divinorum among recreational users.

BACKGROUND: Salvia divinorum is a member of the Lamiaceae family and contains the psychotropic diterpene and kappa-opioid receptor agonist salvinorin-A. Originally a shamanic inebriant used by the Mexican Mazatec Indians, the plant and its preparations are becoming increasingly popular among non-traditional users. METHODS: Demographic data and information on pattern of use and subjective effects were obtained by means of self-report questionnaires from a sample of 32 recreational users of salvia and other psychedelics. RESULTS: Involvement with salvia appeared to be a recent phenomenon. Smoking the extract was the preferred form of administration. Subjective effects were described as intense but short-lived, appearing in less than 1 min and lasting 15 min or less. They included psychedelic-like changes in visual perception, mood and somatic sensations, and importantly, a highly modified perception of external reality and the self, leading to a decreased ability to interact with oneself or with one's surroundings. CONCLUSIONS: Although some aspects of the subjective effects reported were similar to high doses of classical psychedelics with serotonin-2A receptor agonist activity, the intense derealization and impairment reported appear to be a characteristic of salvia. The observed simultaneous high scores on the LSD and PCAG subscales of the Addiction Research Center Inventory (ARCI) have been previously reported for other kappa-opioid agonists, and support kappa receptor activation as the probable pharmacologic mechanism underlying the modified state of awareness induced by salvia.

Increased frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant.

RATIONALE: Ayahuasca is a South American psychoactive plant tea which contains the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and monoamine-oxidase inhibitors that render DMT orally active. Previous investigations with ayahuasca have highlighted a psychotropic effect profile characterized by enhanced introspective attention, with individuals reporting altered somatic perceptions and intense emotional modifications, frequently accompanied by visual imagery. Despite recent advances in the study of ayahuasca pharmacology, the neural correlates of acute ayahuasca intoxication remain largely unknown. OBJECTIVES: To investigate the effects of ayahuasca administration on regional cerebral blood flow. METHODS: Fifteen male volunteers with prior experience in the use of psychedelics received a single oral dose of encapsulated freeze-dried ayahuasca equivalent to 1.0 mg DMT/kg body weight and a placebo in a randomized double-blind clinical trial. Regional cerebral blood flow was measured 100-110 min after drug administration by means of single photon emission tomography (SPECT). RESULTS: Ayahuasca administration led to significant activation of frontal and paralimbic brain regions. Increased blood perfusion was observed bilaterally in the anterior insula, with greater intensity in the right hemisphere, and in the anterior cingulate/frontomedial cortex of the right hemisphere, areas previously implicated in somatic awareness, subjective feeling states, and emotional arousal. Additional increases were observed in the left amygdala/parahippocampal gyrus, a structure also involved in emotional arousal. CONCLUSIONS: The present results suggest that ayahuasca interacts with neural systems that are central to interoception and emotional processing and point to a modulatory role of serotonergic neurotransmission in these processes.

Acute mania and hemichorea.

A 61-year-old man suddenly became euphoric and talkative. Later the same day, he developed hemichoreic movements of the left limbs. The patient fulfilled the DSM-IV criteria for a manic episode by abnormally and persistently elevated mood, decreased need for sleep, high distractibility, pressured speech, increased goal-directed activity, and hypersexuality. The mood changes persisted for several weeks. Magnetic resonance imaging of the brain showed a right thalamic infarction. The co-occurrence of hemichorea and mania caused by focal thalamic lesion is very rare. It may be explained by dysfunction in basal ganglia thalamocortical circuitry.

Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria.

To test the effect of selegiline, a specific monoamine oxidase B (MAO-B) inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine in experienced users, eight cocaine-dependent (CD) subjects were evaluated using a within-subjects design. Each subject participated in two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans (baseline scan followed 24 h later by a second scan obtained in conjunction with a 40-mg cocaine infusion) performed before and after a 1-week period of daily treatment with 10 mg selegiline administered orally. The hippocampus and amygdala were evaluated because of their hypothesized involvement in the addiction process, and the thalamus was evaluated as a comparison region. Following 7 days of selegiline treatment, the magnitude of the subjective euphoria ("high") produced by cocaine infusion was reduced by 40% (cocaine by selegiline interaction F = 7.15, df = 1.21, p = .014). Selegiline treatment also altered glucose utilization (normalized against whole brain counts) in the two limbic regions, but not the thalamus. In the amygdala, the effects of cocaine differed, depending upon whether or not patients were being treated with selegiline (cocaine by selegiline interaction F = 4.67, df = 1,19.8, p = .043). A different effect was observed in the hippocampus, where selegiline treatment decreased metabolic activity irrespective of whether cocaine was given (main effect F = 7.70, df = 1.20, p = .012). The concomitant changes in both the subjective experience of the "high" and normalized amygdala glucose utilization after selegiline treatment, suggest that a relationship exists between cocaine-induced euphoria and limbic metabolism. The data suggest that selegiline may be a useful adjunct in the treatment of cocaine dependence.

Site of opioid action in the human brain: mu and kappa agonists' subjective and cerebral blood flow effects.

OBJECTIVE: Humans experience the subjective effects of mu and kappa opioid agonists differently: mu agonists produce mainly euphoria, while kappa agonists are more likely to produce dysphoria. This study tested the hypothesis that these subjective effects would be associated with anatomically distinct changes in regional cerebral blood flow (CBF) relative to baseline as assessed with single photon emission computed tomography (SPECT). METHOD: Nine nondependent opioid abusers participated in the study. In the first phase of the study, the participants were acclimated to effects of the study drugs. In the second phase they underwent repeat challenges with the study drugs followed by an assessment of CBF with use of the SPECT tracer [99mTc]HMPAO. Medications tested were the prototypic mu agonist hydromorphone, the mixed agonist/antagonist butorphanol (which has a kappa agonist component of activity), and saline placebo. RESULTS: Subjective effects of the drugs were distinctly different. Hydromorphone produced increased ratings of "good effects," while butorphanol led to more "bad effects." Hydromorphone significantly increased regional CBF in the anterior cingulate cortex, both amygdalae, and the thalamus--all structures belonging to the limbic system. Butorphanol caused a less distinct picture of regional CBF increases, mainly in the area of both temporal lobes. CONCLUSIONS: This study demonstrates that opioids with different subjective effects also produce statistically significant patterns of change in regional CBF from baseline, and the regions of statistical significance appear in different brain regions. In addition, these results demonstrate the applicability of SPECT functional neuroimaging in the study of medications with potential abuse liability.

Persistent recurrence of hypomania and prosopoaffective agnosia in a patient with right thalamic infarct.

The authors report a 63-year-old man with a history of brief isolated manic episodes who became persistently hypomanic after a small right thalamic infarct. Detailed behavioral and neuropsychologic assessment were performed 18 months after the stroke and revealed a prosopoaffective agnosia as the foremost cognitive disorder, i.e., an impairment in the identification of emotional facial expressions with preserved discrimination of facial identity. Difficulties in reasoning on humorous material and other signs of mild right hemisphere dysfunction were present, but other perceptual, frontal and abstract-reasoning cognitive functions were unimpaired. Prosopoaffective agnosia has not been reported previously in thalamic lesions or in primary or secondary mania. The authors discuss the hypothetical relationships between a right hemisphere deficit in processing emotions and relapsing of the patient's hypomanic behavior.

Burns with inhalation injury and petrol aspiration in adolescents seeking euphoria through hydrocarbon inhalation.

We have recently managed four adolescent boys severely injured while aspirating petrol to achieve euphoria. This is a practice that occurs sporadically in this group in which alcohol and drugs are more difficult to procure by reason of their age and fiscal resources. The injuries sustained included extensive burns all with associated severe inhalation injury secondary to smoke and products of combustion, complicated by hydrocarbon pneumonitis.

Neuroendocrine and psychological effects of restricted environmental stimulation technique in a flotation tank.

The restricted environmental stimulation technique or REST is a method of relaxation where the level of environmental sensory inputs is kept very low. A particular REST technique called tank flotation, or flotation REST, consists of 1 h sessions in a tank containing water with a high salt content and maintained at 35.5 degrees C. In this protocol, five normal subjects were studied before and during 2 h after a 60 min flotation REST session and a control session of 60 min in a supine position on a bed. Cortisol, thyreostimulating hormone (TSH), thyroxine (T4), prolactin, melatonin, luteinizing hormone (LH), growth hormone (GH), beta-endorphin, vasopressin (ADH), gamma-aminobutyric acid (GABA) and homovanillic acid (HVA) were measured in plasma. HVA, 5-hydroxy-indoleacetic acid (5-HIAA) and vanylmandelic acid (VMA) were measured in urine. There were no changes in hormones concentrations that could be attributed to flotation REST. The urinary excretion of VMA was lower after the flotation REST session. The psychological consequences of flotation REST were more easily demonstrated than the neuroendocrine changes that are assumed to reflect the state of relaxation. Flotation REST increased subjective levels of sedation and euphoria. The possible mechanisms by which flotation REST induces relaxation are discussed.