A retrospective analysis of the "Neverending Trip" after administration of a potent full agonist of 5-HT2A receptor - 25I-NBOMe.

BACKGROUND: 5-HT2A receptor (e.g. 25I-NBOMe) agonists not only pose risks of acute intoxication but also long-term effects and significant adverse reactions, e.g. hallucinogen persisting perception disorder (HPPD), derealization, and depersonalization. AIMS: We evaluated the risk associated with single and repeated use of 25I-NBOMe. We aimed to identify factors that may increase the risk of HPPD, increase its severity and determine the time when the first symptoms appear. Herein, we report the first extensive evaluation of 25I-NBOMe-induced HPPD. METHOD: We assessed all reports (58) collected by The Pomeranian Pharmacovigilance Centre (PPC) from 2013 to 2020. RESULTS: The study included a total of 58 reports of adverse reactions caused by 25I-NBOMe. In the case of 15 reports (in patients aged 19-26 years), symptoms persisted many months after the discontinuation of 25I-NBOMe. The most common were: pseudohallucinations, bizarre delusions, derealizations and in some cases development or worsening of depression has been diagnosed. HPPD-like symptoms were most common in patients who took the drug regularly (i.e., several times a month). The risk of HPPD-like symptoms is higher in patients who have severe visual pseudohallucinations, severe bizarre delusions, derealization and/or depersonalization onset immediately after taking the drug. Recurrence of HPPD symptoms may be provoked by many factors, however, there is some cases there is no apparent reason. HPPD after 25I-NBOMe use can last from 2 months up to 2 years. In some patients, pharmacological treatment was necessary due to 25I-NBOMe-induced HPPD and depression. CONCLUSIONS: The study showed long-lasting effects after 25I-NBOMe administration and allowed for the determination of HPPD risk factors.

Brivaracetam: First Canadian Experience in an Intractable Epilepsy Population.

OBJECTIVE: To evaluate the effectiveness and tolerability of brivaracetam (BRV) in a refractory epilepsy population in an outpatient clinical setting. METHODS: Retrospective medical information system review and self-report questionnaire for all patients treated with BRV until the end of 2017. RESULTS: Thirty-eight patients were included, 73.7% female and mean age 36.2. The mean number of antiepileptic drugs (AEDs) for previous use was 8.9, and for current use was 2.5. Mean seizure frequency in the last 3 months was 12 per month. At 3, 6, 12, and 15 months, the 50% responder rates were 36.1%, 32%, 41.2%, and 45.5%, respectively. Patients took BRV for a median duration of 8.25 months, ranging from 7 days to 60 months. Retention rate was 75.0%, 72.0%, 59.2%, and 47.9% at 3, 6, 12, and 15 months, respectively. Overall, the main reasons for discontinuation were adverse events (AEs) (52.3%), lack of efficacy (35.3%), or both (11.8%). The rate of total AEs was 60.5% according to medical records and 85.7% according to questionnaire, including mostly tiredness, psychiatric, and memory complaints. Psychiatric side effects occurred in 31.6% according to medical records and 47.4% according to questionnaire results, which is higher than previously reported and persisted throughout the study period. CONCLUSIONS: BRV appears to be a useful and safe add-on treatment, even in a very refractory group of patients. In this real-life clinical setting, psychiatric AEs were found at a higher rate than previously published.

Measurement of psychological state changes at low dopamine transporter occupancy following a clinical dose of mazindol.

RATIONALE: The beneficial effects of psychostimulant drugs in the treatment of psychiatric disorders occur because they increase the extracellular dopamine concentration by inhibiting re-uptake of extracellular dopamine at dopamine transporters. However, the psychological effects at low dopamine transporter occupancy have not been well demonstrated. OBJECTIVES: The purpose of the study was to evaluate the psychological effects, dopamine transporter occupancy, and dopamine release induced by a single oral administration of a clinical dose of mazindol. METHODS: Ten healthy male volunteers were orally administered a placebo and a clinical dose of mazindol (1.5 mg) on separate days. The psychological effects of mazindol were assessed using a visual analogue scale to detect alterations in the state of consciousness. The amount of blockade of dopamine transporters was assessed using positron emission tomography with [18F]FE-PE2I and extracellular dopamine release was measured as the amount of change in [11C]raclopride binding. RESULTS: Following administration of a clinical dose of mazindol, the dopamine transporters were blocked by 24-25 %, and the binding potential of [11C]raclopride was reduced by 2.8-4.6 %. The differences of a score measuring derealisation and depersonalization associated with a positive basic mood were significantly correlated with the change in the [11C]raclopride binding in the limbic striatum. CONCLUSIONS: A subtle alteration in the state of consciousness was detected with a correlation to the changes in the [11C]raclopride binding, which implies that a subtle alteration in extracellular dopamine concentration in the limbic striatum by a small amount of dopamine transporter occupancy can affect the state of consciousness. TRIAL REGISTRATION HTTPS://UPLOAD.UMIN.AC.JP/CGI-OPEN-BIN/CTR_E/CTR_VIEW.CGI?RECPTNO=R000009703 : UMIN000008232.

Anomalous bodily-self experiences among recreational ketamine users.

INTRODUCTION: Out-of-body experiences present a unique paradigm to investigate cognitive and neural mechanisms of bodily-self processes and their disorders. Previous work on out-of-body experiences associated with sleep paralysis supported a model in which illusory movement experiences reflect disrupted bodily-self integration generating anomalous vestibular and motor sensations. Further disintegration and progression of the experience may then give rise to out-of-body feelings, which in turn may instigate out-of-body autoscopy. METHODS: The current study assesses the disintegration model through analyses of out-of-body experiences reports from an online survey of individuals reporting recreational ketamine use (n=128) and cross-validation in a sample of nonketamine polydrug users (n=64). Path analyses using intensity and frequency measures of anomalous experiences assess the fit of seven competing models. RESULTS: The disintegration model (illusory movement → out-of-body feelings → out-of-body autoscopy) emerged as the best fitting model overall and results support full mediation of the relation between illusory movement experiences and out-of-body autoscopy by out-of-body feelings. Moreover, lifetime measures of ketamine use predicted the frequency of illusory movement experiences. CONCLUSIONS: The results corroborate this structural model of out-of-body phenomena and encourage a framework for future studies into aetiological mechanisms of out-of-body experiences to include neurochemical systems.

Does marijuana use lead to aggression and violent behavior?

Marijuana use and violent behavior are causing widespread public concern. This article reviews theory and research on the relation between marijuana use and aggressive/violent behavior. It is evident from the inconsistent findings in the literature that the exact nature of the relation remains unclear. This article identifies several possible reasons for these contradictory findings and provides suggestions for future research. In particular, more research is needed on the different subtypes of aggressive behavior. Further research is also needed to elucidate the associations between gender, marijuana use, and violent behavior. Likewise, an important task for future research is to continue to tease apart the complex relations between gang involvement, marijuana use, and violent behavior. Longitudinal studies also warrant further investigation. Moreover, future research should control for several potentially confounding variables.

Is depersonalization disorder initiated by illicit drug use any different? A survey of 394 adults.

OBJECTIVE: Previous studies have documented that in a substantial minority of individuals with depersonalization disorder, onset is first triggered by illicit drug ingestion. The goal of this study was to systematically compare a large sample of individuals with drug-initiated (D) versus non-drug-initiated (ND) chronic depersonalization. METHOD: We conducted an internet survey of 394 adults endorsing DSM-IV-TR depersonalization and/or derealization symptoms. Sixty-four questions were utilized to inquire about demographic and clinical characteristics, illness course, substance use history, and treatment response. The Cambridge Depersonalization Scale (CDS) was administered. The study was conducted from September 2005 to January 2006. RESULTS: Compared to the ND group (n = 198), the D group (n = 196) included more male and younger individuals. The 2 most common precipitating drugs were cannabis and hallucinogens, followed by ecstasy. The majority of participants had modest use histories prior to onset and never ingested subsequently. The 2 groups endorsed similar illness course, impairment, suicidality, and limited treatment response. The D group showed significantly greater improvement over time than the ND group (P = .002), although the groups did not differ in reported psychotherapy or pharmacotherapy effectiveness. The groups did not differ in CDS total score or on the 4 subscale scores of unreality of self, perceptual alterations, unreality of surroundings, and temporal disintegration. On the numbing subscale of the CDS, the ND group scored higher (P = .009) only prior to controlling for age and gender. CONCLUSION: The study strongly supports a uniform syndrome for chronic depersonalization/derealization regardless of precipitant.

Perceptual organization in ketamine users: preliminary evidence of deficits on night of drug use but not 3 days later.

N-methyl-D-aspartate (NMDA)-receptor antagonists such as ketamine can induce transient schizophrenia-like symptoms and cognitive dysfunctions in healthy volunteers similar to those observed in patients with schizophrenia. Perceptual organization deficits have been documented in schizophrenia and are thought to be related to some symptoms associated with the illness. The current study was designed to determine whether people who repeatedly self-administer ketamine would also show deficits in perceptual organization. Using a psychophysically well-controlled measure of contour integration, we compared a group of recreational users (n = 16) to a group of poly-drug using controls (n = 16). Contour integration performance was measured on the night of drug use and 3 days later when drug free. The results showed that on the night of drug use, ketamine produced a dysfunction in contour integration however, this was not present 3 days later when drug free. Levels of dissociation were also higher in ketamine users only on the night of drug use. These preliminary data provide some support for the role of NMDA-receptor hypofunctioning in dysfunctional coordination of cognitive activity.

Effects of psilocybin on time perception and temporal control of behaviour in humans.

Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115 microg/kg), and high (250 microg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects' ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of 'depersonalization' and 'derealization' phenomena including disturbances in subjective 'time sense.' Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin's selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation.

Two cases of "cannabis acute psychosis" following the administration of oral cannabis.

BACKGROUND: Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. CASE PRESENTATIONS: We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. CONCLUSION: While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

Medication-associated depersonalization symptoms: report of transient depersonalization symptoms induced by minocycline.

Patients with depersonalization disorder experience episodes in which they have a feeling of detachment from themselves. Symptoms of depersonalization may occur in individuals who have other mental disorders, or who have various medical conditions, or who have taken certain medications. A woman developed depersonalization symptoms after initiation of minocycline therapy. Her symptoms ceased after treatment was stopped and recurred when she restarted the drug. Medications that have been associated with causing symptoms of depersonalization are presented and the postulated pathogenesis by which some of these drugs induced depersonalization symptoms is discussed. Medication-associated depersonalization symptoms typically resolve once the inducing drug has been withdrawn.

Depersonalization-derealization syndrome induced by reboxetine.

A high variety of factors have been implicated in the emergence of depersonalisation and derealisation episodes, including different drugs. A case abruptly induced by two applications of reboxetine, a selective and specific norepinephrine reuptake inhibitor, is reported occurring in a 50-year-old woman treated for a major depressive episode. The episode rapidly remitted after discontinuation of reboxetine. Previous data having indicated a role of the serotonin system in the pathophysiology of the phenomenon, a noradrenaline induced serotonin liberation of Raphe neurons is suggested as possible underlying mechanism.

A case of depersonalization-derealization syndrome during treatment with quetiapine.

A case who schizophrenia developed patient male of a 65-year-old is reported depersonalization-derealization syndrome following treatment with quetiapine, an atypical antipsychotic. The literature is reviewed for possible biological mechanisms that may account for this phenomenon.

Regional cerebral blood flow and depersonalization after tetrahydrocannabinol administration.

OBJECTIVE: The aim of this study was to examine the relationship between depersonalization induced by tetrahydrocannabinol (THC), and regional brain activation. METHOD: Cerebral blood flow (CBF) was measured by means of positron emission tomography (PET) in 59 normal right-handed volunteers before and following intravenous infusions of THC. RESULTS: After THC, CBF showed a global increase which was more marked in the right hemisphere, frontal lobes and anterior cingulate. CONCLUSION: Regression analyses showed positive correlations between the right frontal and anterior cingulate and depersonalization.