To treat or not to treat? High-potency benzodiazepine use in a case of comorbid hallucinogen persisting perception disorder and alcohol use disorder.

Hallucinogen persisting perception disorder (HPPD) is characterized by visual disturbances that resemble psychedelic intoxication and linger after use has ceased. The most common substances precipitating HPPD, lysergic acid diethylamide (LSD) and psilocybin, are posited to do so via damage to serotonergic neurons involved in vision. Mr. N is a 37-year-old with a history of alcohol, cannabis, LSD, cocaine, and nicotine use disorders who described visual distortions that resolved when he drank heavily or received benzodiazepines for withdrawal. He did not appear psychotic. Over 20 years after his last LSD use, he continued to experience illusions of halos around objects, moving walls, and figures appearing cartoonish. He understood that his perceptual disturbances were not reality based. During hospitalization for suicidal ideation, laboratory tests, head computed tomography (CT), and electroencephalogram (EEG) studies offered no explanation for his visual disturbances other than HPPD. The visual distortions remitted with scheduled clonazepam treatment, although chemical dependency treatment programs were hesitant to accept him while on a benzodiazepine. This case emphasizes the importance of diagnostic clarification when patients present with perceptual disturbances that do not fit typical psychotic presentations. Our discussion will distinguish misperceptions from hallucinations and review the pathophysiology of HPPD. Last, we will discuss management strategies for patients with co-occurring HPPD and substance use disorders. It is necessary to discern the correct cause of visual disturbances in order to provide proper treatment. The risks and benefits of long-term benzodiazepine use must be weighed when deciding whether to prescribe them for patients with comorbid HPPD and alcohol use disorder. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Hallucinogen persisting perceptual disorder: a scoping review covering frequency, risk factors, prevention, and treatment.

INTRODUCTION: Hallucinogen persisting perception disorder (HPPD) affects a subset of persons who use hallucinogens and is defined as the repeated experience of hallucinations and other perceptual disturbances as a result of prior intoxications. As select hallucinogens are under development for the treatment of selectmental disorders, there is a need to better characterize this disorder. AREAS COVERED: A scoping review of the literature on HPPD was completed from inception to July 2021. Topics covered in the review herein include treatments for HPPD, prevalence or incidence data on HPPD among different classes of hallucinogens, risk factors for HPPD, and data pertaining to the pathophysiology of HPPD. EXPERT OPINION: Hallucinogen persisting perception disorder appears to be an uncommon yet serious event associated with prior hallucinogen exposure. The renewed interest in psychedelics as potential treatment options for select mental disorders, especially agents with hallucinogenic potential, provides the impetus to characterize HPPD in its frequency, risk and protective factors, key characteristics, as well as other clinical and treatment-related factors.

Visual snow syndrome: A clinical and phenotypical description of 1,100 cases.

OBJECTIVE: To validate the current criteria of visual snow and to describe its common phenotype using a substantial clinical database. METHODS: We performed a web-based survey of patients with self-assessed visual snow (n = 1,104), with either the complete visual snow syndrome (n = 1,061) or visual snow without the syndrome (n = 43). We also describe a population of patients (n = 70) with possible hallucinogen persisting perception disorder who presented clinically with visual snow syndrome. RESULTS: The visual snow population had an average age of 29 years and had no sex prevalence. The disorder usually started in early life, and ≈40% of patients had symptoms for as long as they could remember. The most commonly experienced static was black and white. Floaters, afterimages, and photophobia were the most reported additional visual symptoms. A latent class analysis showed that visual snow does not present with specific clinical endophenotypes. Severity can be classified by the amount of visual symptoms experienced. Migraine and tinnitus had a very high prevalence and were independently associated with a more severe presentation of the syndrome. CONCLUSIONS: Clinical characteristics of visual snow did not differ from the previous cohort in the literature, supporting validity of the current criteria. Visual snow likely represents a clinical continuum, with different degrees of severity. On the severe end of the spectrum, it is more likely to present with its common comorbid conditions, migraine and tinnitus. Visual snow does not depend on the effect of psychotropic substances on the brain.

A randomised controlled trial of vaporised Δ9-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects.

Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are both psychoactive, but only THC is considered intoxicating. There is significant interest in potential therapeutic properties of these cannabinoids and of CBD in particular. Some research has suggested that CBD may ameliorate adverse effects of THC, but this may be dose dependent as other evidence suggests possible potentiating effects of THC by low doses of CBD. We conducted a randomised placebo controlled trial to examine the acute effects of these compounds alone and in combination when administered by vaporisation to frequent and infrequent cannabis users. Participants (n = 36; 31 male) completed 5 drug conditions spaced one week apart, with the following planned contrasts: placebo vs CBD alone (400 mg); THC alone (8 mg) vs THC combined with low (4 mg) or high (400 mg) doses of CBD. Objective (blind observer ratings) and subjective (self-rated) measures of intoxication were the primary outcomes, with additional indices of intoxication examined. CBD showed some intoxicating properties relative to placebo. Low doses of CBD when combined with THC enhanced, while high doses of CBD reduced the intoxicating effects of THC. The enhancement of intoxication by low-dose CBD was particularly prominent in infrequent cannabis users and was consistent across objective and subjective measures. Most effects were significant at p < .0001. These findings are important to consider in terms of recommended proportions of THC and CBD in cannabis plant matter whether used medicinally or recreationally and have implications for novice or less experienced cannabis users.Trial registration: ISRCTN Registry Identifier: ISRCTN24109245.

Color vision impairments in schizophrenia and the role of antipsychotic medication type.

Schizophrenia patients (SCZ) demonstrate deficits in many domains of mental functioning, including visual perception. An issue that has been relatively unexplored, in terms of explaining variation in visual function in SCZ, however, is medication use. The present study explored potential medication effects on color vision in SCZ, a process that is strongly linked to dopaminergic function in the retina. SCZ patients who had clear-cut either typical (n = 29) or atypical (n = 29) monotherapy, without any other concurrent medication, and a group of age- and gender-matched healthy controls participated in the study. Color vision was assessed by the Cambridge Colour Test, using the Trivector and Ellipse subtests. The results demonstrated impaired color perception in patients with schizophrenia, especially in those receiving typical antipsychotics, but these deficits were subtle and not generalized to all parameters. Our findings are consistent with the known neurophysiology of the retina and visual pathways, and with the effects of dopamine blocking medications, but the results should be carefully interpreted.

Synesthetic hallucinations induced by psychedelic drugs in a congenitally blind man.

This case report offers rare insights into crossmodal responses to psychedelic drug use in a congenitally blind (CB) individual as a form of synthetic synesthesia. BP's personal experience provides us with a unique report on the psychological and sensory alterations induced by hallucinogenic drugs, including an account of the absence of visual hallucinations, and a compelling look at the relationship between LSD induced synesthesia and crossmodal correspondences. The hallucinatory experiences reported by BP are of particular interest in light of the observation that rates of psychosis within the CB population are extremely low. The phenomenology of the induced hallucinations suggests that experiences acquired through other means, might not give rise to "visual" experiences in the phenomenological sense, but instead gives rise to novel experiences in the other functioning senses.

Risk prediction and impaired tactile sensory perception among cancer patients during chemotherapy.

OBJECTIVES: to estimate the prevalence of impaired tactile sensory perception, identify risk factors, and establish a risk prediction model among adult patients receiving antineoplastic chemotherapy. METHOD: historical cohort study based on information obtained from the medical files of 127 patients cared for in the cancer unit of a private hospital in a city in Minas Gerais, Brazil. Data were analyzed using descriptive and bivariate statistics, with survival and multivariate analysis by Cox regression. RESULTS: 57% of the 127 patients included in the study developed impaired tactile sensory perception. The independent variables that caused significant impact, together with time elapsed from the beginning of treatment up to the onset of the condition, were: bone, hepatic and regional lymph node metastases; alcoholism; palliative chemotherapy; and discomfort in lower limbs. CONCLUSION: impaired tactile sensory perception was common among adult patients during chemotherapy, indicating the need to implement interventions designed for early identification and treatment of this condition.

A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD.

Hallucinogen persisting perception disorder (HPPD) is rarely encountered in clinical settings. It is described as a re-experiencing of some perceptual distortions induced while intoxicated and suggested to subsequently cause functional impairment or anxiety. Two forms exist: Type 1, which are brief "flashbacks," and Type 2 claimed to be chronic, waxing, and waning over months to years. A review of HPPD is presented. In addition, data from a comprehensive survey of 20 subjects reporting Type-2 HPPD-like symptoms are presented and evaluated. Dissociative Symptoms are consistently associated with HPPD. Results of the survey suggest that HPPD is in most cases due to a subtle over-activation of predominantly neural visual pathways that worsens anxiety after ingestion of arousal-altering drugs, including non-hallucinogenic substances. Individual or family histories of anxiety and pre-drug use complaints of tinnitus, eye floaters, and concentration problems may predict vulnerability for HPPD. Future research should take a broader outlook as many perceptual symptoms reported were not first experienced while intoxicated and are partially associated with pre-existing psychiatric comorbidity.

Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: Analysis of the Clinician Administered Dissociative State Scale.

INTRODUCTION: Ketamine has rapid-acting antidepressant effects. Frequently, ketamine administration also causes acute psychoactive effects - in trials, these effects are commonly measured using the Clinician Administered Dissociative State Scale (CADSS). However, the CADSS was not designed for this specific purpose, having been validated in other clinical contexts, and anecdotally does not appear to fully capture ketamine's acute psychoactive effects. METHODS: Data were obtained from 110 individuals with mood disorders (predominantly major depressive disorder) who underwent intravenous ketamine infusion. An exploratory factor analysis (EFA) was performed on the CADSS, along with assessment of internal consistency. Qualitative methods were used to conduct in-depth interviews with a subset of these participants to identify key features of the acute ketamine experience, including aspects that may not be captured by the CADSS. RESULTS: The mean total score of the CADSS was low at 7.7 (SD 9.2). Analysis of internal consistency showed a Cronbach's alpha of 0.74. Five CADSS items had low correlations with the total score. EFA lead to a one-factor solution containing 16 items. Five of the six highest loading items involved perceptual disturbances, either of time or sensation. Qualitative analyses of 10 patient narratives revealed two phenomena not captured on the CADSS: disinhibition and a sense of peace. LIMITATIONS: This study was by limited by the absence of other ratings of the participants' experience. CONCLUSION: Findings suggest that the CADSS partially captures the acute effects of ketamine administration. Further research may seek to validate a revised version of the CADSS that more accurately measures these effects.

Risk prediction and impaired tactile sensory perception among cancer patients during chemotherapy / Predição de risco e incidência de percepção sensorial tátil alterada em pacientes oncológicos durante quimioterapia / Predicción de riesgo e incidencia de percepción sensorial táctil alterada en pacientes oncológicos durante quimioterapia

ABSTRACT Objectives: to estimate the prevalence of impaired tactile sensory perception, identify risk factors, and establish a risk prediction model among adult patients receiving antineoplastic chemotherapy. Method: historical cohort study based on information obtained from the medical files of 127 patients cared for in the cancer unit of a private hospital in a city in Minas Gerais, Brazil. Data were analyzed using descriptive and bivariate statistics, with survival and multivariate analysis by Cox regression. Results: 57% of the 127 patients included in the study developed impaired tactile sensory perception. The independent variables that caused significant impact, together with time elapsed from the beginning of treatment up to the onset of the condition, were: bone, hepatic and regional lymph node metastases; alcoholism; palliative chemotherapy; and discomfort in lower limbs. Conclusion: impaired tactile sensory perception was common among adult patients during chemotherapy, indicating the need to implement interventions designed for early identification and treatment of this condition.

RESUMO Objetivos: Estimar a prevalência de percepção sensorial tátil alterada, identificar os fatores de risco e estabelecer modelo de predição de risco para seu desenvolvimento, em pacientes adultos, submetidos à quimioterapia antineoplásica. Método: Coorte histórica realizada a partir de informações obtidas em prontuários de 127 pacientes atendidos em uma unidade oncológica de um hospital privado de um município de Minas Gerais, Brasil. Os dados foram analisados por estatística descritiva, bivariada, com análise de sobrevida e multivariada por regressão de Cox. Resultados: Dos 127 pacientes analisados 57% desenvolveu percepção sensorial tátil alterada. As variáveis independentes que impactaram, de forma significativa e conjunta, com o tempo para ocorrência do desfecho foram: metástases óssea, hepática e de linfonodo regional, alcoolismo, quimioterapia paliativa e desconforto nos membros inferiores. Conclusão: A percepção sensorial tátil alterada foi um achado comum em pacientes adultos durante o tratamento quimioterápico, apontando para a necessidade da implementação de intervenções que visem identificar precocemente e prevenir ou tratar o problema.

RESUMEN Objetivos: estimar la prevalencia de percepción sensorial táctil alterada, identificar los factores de riesgo y establecer un modelo de predicción de riesgo para su desarrollo, en pacientes adultos sometidos a quimioterapia antineoplásica. Método: estudio de cohorte histórica, realizado a partir de informaciones obtenidas de fichas médicas de 127 pacientes atendidos en unidad oncológica de un hospital privado, en municipio de Minas Gerais, Brasil. Los datos fueron analizados con estadística descriptiva, bivariada, con análisis de sobrevivencia y multivariado con la regresión de Cox. Resultados: de los 127 pacientes analizados, 57% desarrollaron percepción sensorial táctil alterada. Las variables independientes que causaron impacto de forma significativa, y conjuntamente con el tiempo para ocurrencia del resultado, fueron: metástasis ósea, hepática y de linfoma regional; alcoholismo; quimioterapia paliativa; e, incomodidad en los miembros inferiores. Conclusión: la percepción sensorial táctil alterada fue un hallazgo común en pacientes adultos durante el tratamiento quimioterápico, lo que apunta para la necesidad de la implementación de intervenciones que objetiven identificar precozmente y prevenir o tratar el problema.

A placebo-controlled investigation of synaesthesia-like experiences under LSD.

The induction of synaesthesia in non-synaesthetes has the potential to illuminate the mechanisms that contribute to the development of this condition and the shaping of its phenomenology. Previous research suggests that lysergic acid diethylamide (LSD) reliably induces synaesthesia-like experiences in non-synaesthetes. However, these studies suffer from a number of methodological limitations including lack of a placebo control and the absence of rigorous measures used to test established criteria for genuine synaesthesia. Here we report a pilot study that aimed to circumvent these limitations. We conducted a within-groups placebo-controlled investigation of the impact of LSD on colour experiences in response to standardized graphemes and sounds and the consistency and specificity of grapheme- and sound-colour associations. Participants reported more spontaneous synaesthesia-like experiences under LSD, relative to placebo, but did not differ across conditions in colour experiences in response to inducers, consistency of stimulus-colour associations, or in inducer specificity. Further analyses suggest that individual differences in a number of these effects were associated with the propensity to experience states of absorption in one's daily life. Although preliminary, the present study suggests that LSD-induced synaesthesia-like experiences do not exhibit consistency or inducer-specificity and thus do not meet two widely established criteria for genuine synaesthesia.

Hallucinogen Persisting Perception Disorder and Risk of Suicide.

A 30-year-old male patient developed a hallucinogen persisting perception disorder (HPPD) after smoking cannabis laced with phencyclidine (PCP) or lysergic acid diethylamide (LSD) 10 years prior to hospital admission. Clinically, he reported seeing vivid, saturated colors and caricature-like objects. The patient described perceiving objects or people in motion as moving faster than normal. He reported living in a dream-like state and feeling numb and detached from other people and his surroundings. Upon pharmacotherapy initiation, facility transfer, and subsequent discharge from an acute psychiatry unit, he ultimately committed suicide. Although hallucinogen abuse is common in the United States, this case suggests that HPPD maybe significantly underdiagnosed and undertreated. In some cases, this oversight may perpetuate years of unnecessary patient suffering and can ultimately lead to severe depression and suicide.

Salvia divinorum: An overview of the usage, misuse, and addiction processes.

Salvia divinorum, a sage plant with leaves that can produce a psychoactive high, has been used for hundreds of years for its psycho-mimetic effects in religious rituals in South America. Salvia has now become popular mainly with adolescents and young adults for the short-lived relatively pleasant experiences many consider a "legal high" and its ready availability through Internet purchases. The main (psycho)active compound in salvia is Salvinorin A, a potent κ-opioid agonist and although the short and long-term effects have not been examined in sufficient detail, it is widely believed to have low addictive potential and low toxicity. Recent findings, however, seem to suggest that Salvinorin A can precipitate psychiatric symptoms and negatively affect cognition. Its ready availability and increasingly widespread use requires clinicians to have knowledge and awareness of its effects.

Synthetic Cannabinoid Abuse in Adolescents: A Case Series.

BACKGROUND: Synthetic cannabinoids, referred to as "Bonzai" in Turkey, are relatively new recreational drugs of abuse. Although the use of synthetic cannabinoids has been dramatically increasing in young populations in many countries, their adverse effects are not well known. OBJECTIVES: To report on the clinical features and social history of pediatric patients with a diagnosis of synthetic cannabinoid intoxication and to highlight the dangers of these drugs to public health. METHODS: We retrospectively reviewed 16 cases presenting to our Emergency Department (ED) with synthetic cannabinoid intoxication in the last 10 months. Usage characteristics and the psychoactive, physical, and metabolic effects of synthetic cannabinoids were analyzed. RESULTS: The mean age of the 16 patients with a diagnosis of synthetic cannabinoid intoxication was 15.4 ± 1.7 years (15 males, 1 female). The most common physical symptoms were eye redness, nausea/vomiting, sweating, and altered mental status; the main psychoactive findings were agitation, anxiety, hallucinations, and perceptual changes. We observed hypotension and bradycardia in 8 (50%) and 5 (31.3%) of the patients, respectively. Although most patients were discharged from the ED, 25% were transferred to an intensive care unit. They all had reduced school attendance and performance. The rates of cigarette smoking and alcohol drinking were also significantly higher. CONCLUSION: Synthetic cannabinoids are unsafe and potentially harmful drugs of abuse; they may even cause life-threatening effects. It is important for pediatricians to be familiar with the signs and symptoms of consumption of synthetic cannabinoid products. Education of parents, teachers, and adolescents about the potential health risks of using these products is essential.

Trastorno perceptivo persistente por alucinógenos: a propósito de un caso / Hallucinogen persisting perception disorder: a case report

Se presenta el caso de un varón de 26 años que experimenta clínica compatible con trastorno perceptivo persistente por alucinógenos tras la ingesta de una feniletilamina, la 4-bromo-2,5-dimetoxifeniletilamina, conocida también como Nexus, Bromo, Erox, Venus o Afro. El consumo de esta sustancia ha ido adquiriendo popularidad en España en el contexto de fiestas rave y como droga de club (AU)

We are presenting a case-report of a 26 years old man who experienced symptoms compatible with hallucinogen persisting perception disorder after the ingestion of a phenylethylamine, the 4-bromo-2,5-dimethoxyphenethylamine, also known as Nexus, Bromo, Erox, Venus or Afro. The use of this substance has gained popularity in Spain in the context of rave parties and as club drug (AU)

Developmental exposure to manganese induces lasting motor and cognitive impairment in rats.

Exposure to high manganese (Mn) levels may damage the basal ganglia, leading to a syndrome analogous to Parkinson's disease, with motor and cognitive impairments. The molecular mechanisms underlying Mn neurotoxicity, particularly during development, still deserve further investigation. Herein, we addressed whether early-life Mn exposure affects motor coordination and cognitive function in adulthood and potential underlying mechanisms. Male Wistar rats were exposed intraperitoneally to saline (control) or MnCl2 (5, 10 or 20 mg/kg/day) from post-natal day (PND) 8-12. Behavioral tests were performed on PND 60-65 and biochemical analysis in the striatum and hippocampus were performed on PND14 or PND70. Rats exposed to Mn (10 and 20 mg/kg) performed significantly worse on the rotarod test than controls indicating motor coordination and balance impairments. The object and social recognition tasks were used to evaluate short-term memory. Rats exposed to the highest Mn dose failed to recognize a familiar object when replaced by a novel object as well as to recognize a familiar juvenile rat after a short period of time. However, Mn did not alter olfactory discrimination ability. In addition, Mn-treated rats displayed decreased levels of non-protein thiols (e.g. glutathione) and increased levels of glial fibrillary acidic protein (GFAP) in the striatum. Moreover, Mn significantly increased hippocampal glutathione peroxidase (GPx) activity. These findings demonstrate that acute low-level exposure to Mn during a critical neurodevelopmental period causes cognitive and motor dysfunctions that last into adulthood, that are accompanied by alterations in antioxidant defense system in both the hippocampus and striatum.

The time-dependent and persistent effects of amphetamine treatment upon recovery from hemispatial neglect in rats.

Neglect is a neuropsychological disorder characterized by the failure to report or respond to stimuli presented to the side of the body opposite a brain lesion and occurs in approximately 40% of right hemisphere strokes. The need for effective therapies to treat neglect in humans has led to the development of a rodent model. Unilateral destruction of medial agranular cortex (AGm), which is part of a cortical network for directed attention, produces severe multimodal neglect with deficits similar to those seen in humans. Amphetamines have previously been investigated for inducing plasticity and recovery of function following brain damage. Amphetamine treatment has been shown to produce recovery from visual, frontal, and sensorimotor cortex damage in animals and this recovery may be the result of axonal growth originating from the opposite, unlesioned hemisphere. The purpose of this study was to investigate whether amphetamine treatment would induce recovery from neglect produced by unilateral AGm destruction, the time frame in which amphetamine must be administered in order to be effective, and the permanence of recovery following treatment. The results indicated that subjects injected with 2mg/kg of d-amphetamine on days 0, 2, and 5 recovered in significantly fewer days than saline-treated controls, even when administration was delayed by 2 and 7 days. Additionally, these studies indicated that recovery persisted for at least 60 days suggesting that recovery is likely to be long term.

Improvement in Visual Fields After Treatment of Intracranial Meningioma With Bevacizumab.

High-grade (World Health Organization [WHO] Grade II and III) meningiomas constitute a minority of all meningioma cases but are associated with significant morbidity and mortality, due to more aggressive tumor behavior and a tendency to recur despite standard therapy with resection and radiotherapy. They display a higher degree of vascularity than WHO Grade I meningiomas and produce angiogenic and growth factors, including vascular endothelial growth factor (VEGF). Bevacizumab, a humanized monoclonal antibody against VEGF-A, has been used in the treatment of recurrent or progressive meningiomas resistant to standard therapy. We report a patient with a recurrent left frontotemporal meningioma and associated-vision loss who experienced substantial visual field recovery after 3 cycles of bevacizumab. In addition, we provide a review of the literature regarding the efficacy of bevacizumab in the treatment of recurrent meningiomas.