Reassessment of amphetamine- and phencyclidine-induced locomotor hyperactivity as a model of psychosis-like behavior in rats.

Locomotor hyperactivity induced by psychotomimetic drugs, such as amphetamine and phencyclidine, is widely used as an animal model of psychosis-like behaviour and is commonly attributed to an interaction with dopamine release and N-methyl-D-aspartate (NMDA) receptors, respectively. However, what is often not sufficiently taken into account is that the pharmacological profile of these drugs is complex and may involve other neurotransmitter/receptor systems. Therefore, this study aimed to assess the effect of three antagonists targeting different monoamine pathways on amphetamine- and phencyclidine-induced locomotor hyperactivity. A total of 32 rats were pre-treated with antagonists affecting dopaminergic, noradrenergic and serotonergic transmission: haloperidol (0.05 mg/kg), prazosin (2 mg/kg) and ritanserin (1 mg/kg), respectively. After 30 min of spontaneous activity, rats were injected with amphetamine (0.5 mg/kg) or phencyclidine (2.5 mg/kg) and distance travelled, stereotypy and rearing recorded in photocell cages over 90 min. Pre-treatment with haloperidol or prazosin both reduced amphetamine-induced hyperactivity although pre-treatment with ritanserin had only a partial effect. None of the pre-treatments significantly altered the hyperlocomotion effects of phencyclidine. These findings suggest that noradrenergic as well as dopaminergic neurotransmission is critical for amphetamine-induced locomotor hyperactivity. Hyperlocomotion effects of phencyclidine are dependent on other factors, most likely NMDA receptor antagonism. These results help to interpret psychotomimetic drug-induced locomotor hyperactivity as an experimental model of psychosis.

Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy.

The first-line treatment for psychotic disorders remains antipsychotic drugs with receptor antagonist properties at D2-like dopamine receptors. However, long-term administration of antipsychotics can upregulate D2 receptors and produce receptor supersensitivity manifested by behavioral supersensitivity to dopamine stimulation in animals, and movement disorders and supersensitivity psychosis (SP) in patients. Antipsychotic-induced SP was first described as the emergence of psychotic symptoms with tardive dyskinesia (TD) and a fall in prolactin levels following drug discontinuation. In the era of first-generation antipsychotics, 4 clinical features characterized drug-induced SP: rapid relapse after drug discontinuation/dose reduction/switch of antipsychotics, tolerance to previously observed therapeutic effects, co-occurring TD, and psychotic exacerbation by life stressors. We review 3 recent studies on the prevalence rates of SP, and the link to treatment resistance and psychotic relapse in the era of second-generation antipsychotics (risperidone, paliperidone, perospirone, and long-acting injectable risperidone, olanzapine, quetiapine, and aripiprazole). These studies show that the prevalence rates of SP remain high in schizophrenia (30%) and higher (70%) in treatment-resistant schizophrenia. We then present neurobehavioral findings on antipsychotic-induced supersensitivity to dopamine from animal studies. Next, we propose criteria for SP, which describe psychotic symptoms and co-occurring movement disorders more precisely. Detection of mild/borderline drug-induced movement disorders permits early recognition of overblockade of D2 receptors, responsible for SP and TD. Finally, we describe 3 antipsychotic withdrawal syndromes, similar to those seen with other CNS drugs, and we propose approaches to treat, potentially prevent, or temporarily manage SP.

[MEDICAL CANNABIS].

The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea and inflammation. Current research is inspecting the use of cannabis for many diseases, including multiple sclerosis, epilepsy, dystonia, and chronic pain. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and:pain and diarrhea in Crohn's disease. Despite their therapeutic potential, cannabinoids are not free of side effects including psychosis, anxiety, paranoia, dependence and abuse. Controlled clinical studies investigating the therapeutic potential of cannabis are few and small, whereas pressure for expanding cannabis use is increasing. Currently, as long as cannabis is classified as an illicit drug and until further controlled studies are performed, the use of medical cannabis should be limited to patients who failed conventional better established treatment.

Inhibition of apomorphine-induced behavioral sensitization in rats pretreated with fluoxetine.

Despite a number of clinically useful effects, there is growing evidence that psychosis and impulse control disorders develop in patients on apomorphine therapy. Evidence suggests a critical role of serotonin-1A receptors in psychosis, drug abuse, and in the mechanism of action of the prototypical selective serotonin reuptake inhibitor fluoxetine. We investigated whether fluoxetine can prevent apomorphine-induced behavioral sensitization in a rat model of psychosis. Animals treated with fluoxetine (5 and 10 mg/kg) for 2 weeks were subsequently cotreated with apomorphine (1.0 mg/kg) for 7 days. A single injection of apomorphine increased motor activity, whereas repeated daily injections produced a progressive sensitization of motor behavior. The sensitization effects of apomorphine did not occur in fluoxetine-pretreated and subsequently cotreated animals. To further elucidate the mechanism involved in the inhibition of apomorphine sensitization in fluoxetine-treated animals, we found that apomorphine-induced motor behavior was much greater in repeated apomorphine-treated than repeated saline-treated animals. It was also greater in apomorphine and fluoxetine-cotreated animals, but not in animals pretreated and cotreated with fluoxetine. The mechanism involved in the inhibition of apomorphine sensitization in fluoxetine-pretreated animals is discussed. The findings introduce an innovative approach for extending the therapeutic use of apomorphine and classical psychostimulant drugs.

[Acute psychosis as a side effect of efavirenz therapy with metabolic anomalies: an important differential diagnosis of HIV-associated psychoses]. / Akute Psychose als Nebenwirkung der Therapie mit Efavirenz bei metabolischer Anomalie : Eine wichtige Differenzialdiagnose HIV-assoziierter Psychosen.

Among patients with human immunodeficiency virus (HIV) infections psychiatric disease poses a particular challenge for caregivers. Neuropsychiatric side effects of efavirenz have been described in up to 40% of patients showing dizziness, insomnia, unusual dreams, mood instability, personality alterations and thought disorders. In immigrants from Africa and South America these side effects may be related to elevated plasma concentrations of efavirenz due to polymorphisms of cytochrome P450 isozymes (especially G516T). Alleles for these polymorphisms are more frequent in African and South American patients. We report a case of a 52-year-old patient from Guinea who was referred to the department of neurology under the diagnosis of HIV-associated neurocognitive disorder (HAND). Since the start of combined antiretroviral therapy (cART) including efavirenz the patient had suffered severe personality alterations, acoustic and visual hallucinations and delusions which led to discrimination and reduced quality of life. Diagnostic procedures including magnetic resonance imaging (MRT) and spinal fluid analysis resulted in normal values and did not explain the disease. After switching to nevirapin instead of efavirenz the psychotic symptoms disappeared within 5 days.

Strategies to prevent the neuropsychiatric side-effects of corticosteroids: a case report and review of the literature.

PURPOSE OF REVIEW: The use of corticosteroids is increasing, and while the physical complications of their use are well known, the neuropsychiatric consequences are not. This review focuses on preventing these neuropsychiatric complications. Although there are limited data on this subject, it is a problem that clinicians face on a regular basis. RECENT FINDINGS: The incidence of neuropsychiatric complications rises rapidly once the daily dose of prednisone is greater than 40 mg. Other risk factors for neuropsychiatric symptoms are damaged blood-brain barrier and hypoalbuminemia. All patients receiving corticosteroids and their caregivers should be warned about the potential neuropsychiatric complications. Small trials have supported the use of various agents as prophylaxis. The development of neuropsychiatric symptoms secondary to corticosteroids should lead to prompt involvement of liaison psychiatry. SUMMARY: There is a lack of large randomized controlled studies to inform clinical practice. At present, lithium and olanzapine probably represent the best choices for prophylaxis. Patients with a prior history of steroid-related psychosis or mania should be considered for prophylaxis when future courses of steroids are prescribed as limited data, and our clinical experience suggests that this can reduce the future episodes of neuropsychiatric side-effects.

Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being.

BACKGROUND: Cannabis varies considerably in levels of its two major constituent cannabinoids - (delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Recently, we found evidence that those who smoked cannabis containing detectable levels of CBD had fewer psychotic-like symptoms than those whose cannabis had no CBD. The present study aimed, first, to replicate those findings and, second, to determine whether protective effects of CBD may extend to other harms of cannabis, such as memory impairment and reduced psychological well-being. METHOD: A total of 120 current cannabis smokers, 66 daily users and 54 recreational users were classified into groups according to whether analysis of their hair revealed the presence or absence of CBD and high versus low levels of THC. All were assessed on measures of psychosis-like symptoms, memory (prose recall; source memory) and depression/anxiety. RESULTS: Lower psychosis-like symptoms were found in those whose hair had CBD compared with those without. However, this was seen only in recreational users, who had higher levels of THC in their hair. Higher THC levels in hair were associated with increased depression and anxiety. Prose recall and source memory were poorer in daily users with high THC levels in hair while recognition memory was better in individuals with CBD present in hair. CONCLUSIONS: CBD attenuates the psychotic-like effects of cannabis over time in recreational users. Higher THC negatively impacts on memory and psychological well-being. These findings raise concerns for the harms stemming from use of varieties such as 'skunk' (sensimillia), which lack any CBD but currently dominate the supply of cannabis in many countries.

The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited.

BACKGROUND: Glucocorticoids are widely prescribed for a variety of diseases and are known to cause neuropsychiatric as well as somatic side effects. OBJECTIVE: This article will review the incidence, clinical characteristics, course, and treatment of neuropsychiatric effects of glucocorticoids. METHODS: We performed a literature review of the neuropsychiatric complications of glucocorticoids using the PubMed database. RESULTS: The neuropsychiatric effects of glucocorticoids involve affective, behavioral, and cognitive manifestations. Serious neuropsychiatric effects occur in about 6% of patients who receive steroids. Although the effects of glucocorticoids are unpredictable, the administered dose is the most significant risk factor for the development of neuropsychiatric symptoms. Dosage reduction typically results in clinical recovery. Although evidence from controlled trials is sparse, administration of antipsychotics or mood stabilizers may be beneficial in the prevention and treatment of neuropsychiatric effects of steroids. CONCLUSION: The neuropsychiatric effects of glucocorticoids are more diverse than the often-misleading term "steroid psychosis" suggests. This label should be limited to those patients who are truly psychotic, and specific designations applied to patients with other effects. The adverse neuropsychiatric effects of glucocorticoids remain poorly characterized in the literature (which consists largely of case reports and case series). Reliable risk factors (other than dose) that identify individuals at risk are lacking; guidelines for the prevention of neuropsychiatric effects are not evidence-based. Further controlled clinical studies are needed to elucidate the optimal management of glucocorticoid-induced neuropsychiatric symptoms.

Risky recreation: synthetic cannabinoids have dangerous effects.

Use of synthetic marijuana (also known as spice, K2, aroma, and eclipse) is often viewed by young people as harmless recreation. Until recently, the substance was freely available in U.S. convenience stores and head shops, and it is still available via the Internet. Emerging evidence shows a wide range of responses to the drug, including paranoia, aggressive behavior, anxiety, and short-term memory deficits. Synthetic cannabinoids are not currently detectable via standard toxicology tests. Recognition and management of synthetic cannabinoid use are discussed.

[A study on clinical features of patients with benzodiazepines use disorder (BZsUD), and characteristics of psychiatric treatments which may cause BZsUD].

BACKGROUND AND AIMS: The aims of present study are to clarify the clinical features of patients with benzodiazepine use disorder (BZsUD), and to examine the characteristics of psychiatric treatments which may cause BZsUD. METHODS: We conducted a medical chart and interview survey to 87 outpatients with benzodiazepine use disorder, who had consecutively visited the four hospitals, specialized in addiction problems, located in metropolitan area, during a month of December, 2011. RESULTS: Consequently, 88.5% of the patients with BZsUD reported to obtain BZs to be abused from general psychiatric clinics, and 83.9% contracted BZsUD in process of general psychiatric treatment. Among the patients who contracted BZsUD in process of psychiatric treatment, 43.8% were speculated to have the other substance-related disorders such as methamphetamine or alcohol-related disorder at start of the psychiatric treatment. Further, approximately 70% of them reported that surplus BZs were prescribed without consideration of storing drugs, and over 40% also reported that BZs were prescribed without a medical examination. CONCLUSIONS: The findings of the present study may let us to propose the following four measures to be taken for prevention of BZsUD: First, latent substance-related disorders should not be overlooked, second, short-acting and high-potency BZs should not be prescribed if possible, third, storing and abusing BZs should always be considered, and finally, BZs should be prescribed with a medical examination.

Fatty acid amide hydrolase (FAAH) inhibition reduces L-3,4-dihydroxyphenylalanine-induced hyperactivity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned non-human primate model of Parkinson's disease.

Dopaminergic therapies remain the most efficacious symptomatic treatments for Parkinson's disease (PD) but are associated with motor complications, including dyskinesia, and nonmotor complications, such as psychosis, impulse control disorders (ICD), and dopamine dysregulation syndrome (DDS). Nondopaminergic neurotransmitter systems, including the endocannabinoid system, are probably critical to the development of these complications. The role of fatty acid amide hydrolase (FAAH) in mediating l-3,4-dihydroxyphenylalanine (L-DOPA)-induced behaviors was explored in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmoset model of PD. Pharmacodynamic and locomotor effects of the selective FAAH inhibitor [3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate (URB597) were assessed via bioanalytical (liquid chromatography-tandem mass spectrometry) and behavioral observation approaches. URB597 (3, 10, 30, or 60 mg/kg p.o.) increased plasma levels of the FAAH substrates N-arachidonoyl ethanolamide (anandamide), N-oleoyl ethanolamide, and N-palmitoyl ethanolamide by 10.3 ± 0.3-, 7.8 ± 0.2-, and 1.8 ± 0.1-fold (mean of URB597 groups ± S.E.M.), respectively, compared with vehicle (all p < 0.001) 4 h after administration. Treatment with L-DOPA (20 mg/kg s.c.) alleviated parkinsonism but elicited dyskinesia, psychosis-like-behaviors and hyperactivity, a potential correlate of ICD and DDS. During the 2 to 4 h after L-DOPA, corresponding to 4 to 6 h after URB597 administration, URB597 reduced total L-DOPA-induced activity and the magnitude of hyperactivity by 32 and 52%, respectively, to levels equivalent to those seen in normal animals. Treatment with URB597 (10 mg/kg p.o.) did not modify the antiparkinsonian actions of L-DOPA or L-DOPA-induced dyskinesia and psychosis. URB597 did not alter plasma L-DOPA levels and was without behavioral effects when administered alone. Inhibition of FAAH may represent a novel approach to reducing L-DOPA-induced side effects, such as ICD and DDS, while maintaining the antiparkinsonian benefits of L-DOPA treatment.

Betaine prevents and reverses the behavioral deficits and synaptic dysfunction induced by repeated ketamine exposure in mice.

As an N-methyl-D-aspartate (NMDA) receptor inhibitor, ketamine has become a popular recreational substance and currently is used to address treatment-resistant depression. Since heavy ketamine use is associated with persisting psychosis, cognitive impairments, and neuronal damage, the safety of ketamine treatment for depression should be concerned. The nutrient supplement betaine has been shown to counteract the acute ketamine-induced psychotomimetic effects and cognitive dysfunction through modulating NMDA receptors. This study aimed to determine whether the adjunctive or subsequent betaine treatment would improve the enduring behavioral disturbances and hippocampal synaptic abnormality induced by repeated ketamine exposure. Mice received ketamine twice daily for 14 days, either combined with betaine co-treatment or subsequent betaine post-treatment for 7 days. Thereafter, three-chamber social approach test, reciprocal social interaction, novel location/object recognition test, forced swimming test, and head-twitch response induced by serotonergic hallucinogen were monitored. Data showed that the enduring behavioral abnormalities after repeated ketamine exposure, including disrupted social behaviors, recognition memory impairments, and increased depression-like and hallucinogen-induced head-twitch responses, were remarkably improved by betaine co-treatment or post-treatment. Consistently, betaine protected and reversed the reduced hippocampal synaptic activity, such as decreases in field excitatory post-synaptic potentiation (fEPSP), long-term potentiation (LTP), and PSD-95 levels, after repeated ketamine treatment. These results demonstrated that both co-treatment and post-treatment with betaine could effectively prevent and reverse the adverse behavioral manifestations and hippocampal synaptic plasticity after repeated ketamine use, suggesting that betaine can be used as a novel adjunct therapy with ketamine for treatment-resistant depression and provide benefits for ketamine use disorders.

[Unusual case of the criminal administration of ranitidine]. / Niezwykly przypadek przestepczego podania ranitydyny.

Psychoactive substances (alcohol, narcotics and drugs) are used for facilitation of various crimes, mostly sexual assaults ("rape pills", "date-rape drugs") and/or robbery. The most popular drugs used for criminal purposes are: benzodiazepines, antipsychotic, hypotensive and anesthetic agents. Sometimes, however, other types of drugs are employed. The authors present an unusual, first in the literature, attempt at the criminal use of ranitidine--a popular antisecretive drug (H2-blocker)--as a "date-rape drug". The present paper discusses problems of scientific information flow to the criminal world, easy accessibility of psychoactive agents and difficulties in medico-legal opinion and penal qualification in such cases.

Pharmacological strategies for the management of comorbid depression and schizophrenia.

Introduction: Depressive symptoms may occur in any phase of schizophrenia and can have far-reaching consequences.Areas covered: The author focuses on recent reviews and meta-analyses dealing with the prevalence, importance, etiopathogenesis, and pharmacotherapy of comorbid depression and schizophrenia. Depressive symptoms in acute episodes may improve in parallel with psychosis due to antipsychotic treatment. Therefore, the first step is to evaluate the current antipsychotic treatment of psychotic symptoms and consider changing the dosage. A second step is switching antipsychotic medications, since there are indications that some medications are slightly more effective in reducing depressive symptoms than others. For persistent depressive episodes, additional therapeutic interventions are indicated. Most guidelines recommend the administration of antidepressants as an add-on treatment with a limited evidence level. Immunotherapeutic strategies could be successful, at least in some schizophrenia patients.Expert opinion: In the near future, precision psychiatry should enable clinicians to recognize specific biotypes with unique biosignatures that will guide accurate and prompt clinical management for individual patients.

[Cannabis use in subjects at ultra high risk for psychosis]. / Usage de Cannabis chez les sujets à ultra-haut risque de psychose.

Cannabis use is widespread among people at ultra-high risk (UHR) for psychosis. The causal link as well as the temporal link between cannabis use and further occurrence of psychosis in UHR people remain inconclusive. Current science data supported an increased risk of transition to psychosis in cannabis users who are genetically predisposed to psychosis. This risk would be even greater in the presence of a family history of psychosis, in case of a strong use and an early onset use. Several models have been cited to explain the link between cannabis use and the subsequent onset of psychosis or prepsychotic states: cannabis-induced modifications of some brain structures, a dysregulation of the hypothalamic-pituitary axis and an alteration of normal neurological development via the endocannabinoid system. Cannabis represents a modifiable risk for psychosis. Current interventions aim to reduce or stop the cannabis use in order to reduce the risk of transition to psychosis.

Olfactory learning prevents MK-801-induced psychosis-like behaviour in an animal model of schizophrenia.

There is mounting evidence to support the concept that education is associated with the formation of a functional reserve in the brain, a process that appears to provide some protection against certain aspects of severe central nervous system disorders. The goal of this study was to examine whether learning prevents psychosis-like behaviour in an animal model of schizophrenia. A series of behavioural tasks were used to assess olfactory learning-induced protection against the effects of NMDA channel blocker, MK801. This blocker caused sensory-motor disturbances, spatial learning acquisition deficit, and swimming strategy alterations in pseudo-trained and naive rats, but had a considerably lesser effect on trained rats. In sharp contrast, olfactory learning provided no protection against d-amphetamine application. Our data support the notion that learning-induced protection against schizophrenic behaviour is maintained by non-NMDA-mediated enhanced activation of local connections in the relevant cortical networks.

[Neuropsychiatric adverse events in patients with chronic hepatitis C treated with pegylated or recombinant interferon-alpha]. / Neuropsychiatryczne skutki uboczne u chorych z przewleklym zapaleniem watroby typu C leczonych pegylowanym lub rekombinowanym interferonem-alfa.

UNLABELLED: The aim of the study was an assessment of the incidence and types of neuropsychiatric serious adverse events (NSAE) in patients with compensated chronic hepatitis C (CHC) treated with recombinant or pegylated interferon-alpha (IFN-alpha) plus ribavirin (RBV). METHOD: NSAE were defined as neuropsychiatric consequences of IFN-alpha+RBV therapy that resulted in discontinuation therapy or initiation of disorders requiring hospitalization or chronic neuropsychiatric treatment. A group of 273 patients (144 males and 129 females, mean age 41) without significant past psychiatric and neurological disorders was prospectively observed. Of them 89 patients were treated with recombinant IFN-alpha+RBV. Both subgroups did not differ with regard to demographic or hepatological parameters. RESULTS: Overall NSAE were present in 13 patients (4.8% of the sample): psychiatric SAE emerged in 10 patients and 3 patients suffered from neurological SAE. NSAE emerged in nine patients treated with recombinant IFN-alpha and in four patients treated with pegylated IFN-alpha (p=0.03). CONCLUSIONS: NSAE in CHC patients during IFN-alpha+RBV therapy occur rarely. However, potentially severe neuropsychiatric consequences of the treatment in some patients indicate the need for neuropsychiatric monitoring during the therapy. Treatment with pegylated IFN-alpha may be associated with less neuropsychiatric SAE than treatment with recombinant IFN-alpha in patients with compensated CHC.

Selective serotonin reuptake inhibitors, fluoxetine and paroxetine, attenuate the expression of the established behavioral sensitization induced by methamphetamine.

To obtain an insight into the development of a new pharmacotherapy that prevents the treatment-resistant relapse of psychostimulant-induced psychosis and schizophrenia, we have investigated in the mouse the effects of selective serotonin reuptake inhibitors (SSRI), fluoxetine (FLX) and paroxetine (PRX), on the established sensitization induced by methamphetamine (MAP), a model of the relapse of these psychoses, because the modifications of the brain serotonergic transmission have been reported to antagonize the sensitization phenomenon. In agreement with previous reports, repeated MAP treatment (1.0 mg/kg a day, subcutaneously (s.c.)) for 10 days induced a long-lasting enhancement of the increasing effects of a challenge dose of MAP (0.24 mg/kg, s.c.) on motor activity on day 12 or 29 of withdrawal. The daily injection of FLX (10 mg/kg, s.c.) or PRX (8 mg/kg, s.c.) from 12 to 16 days of withdrawal of repeated MAP administration markedly attenuated the ability of the MAP pretreatment to augment the motor responses to the challenge dose of the stimulant 13 days after the SSRI injection. The repeated treatment with FLX or PRX alone failed to affect the motor stimulation following the challenge of saline and MAP 13 days later. These results suggest that the intermittent and repetitive elevation of serotonergic tone may inhibit the expression of the motor sensitization induced by pretreatment with MAP. It is proposed that clinically available serotonin reuptake inhibitors could be useful for preventing the recurrence of hallucinatory-paranoid state in drug-induced psychosis and schizophrenia.

Cannabis and Neuropsychiatry, 2: The Longitudinal Risk of Psychosis as an Adverse Outcome.

Psychosis is one of the most serious among the adverse effects associated with cannabis use. The association between cannabis use and psychosis has been variously explored in a series of recent meta-analyses. The results of these meta-analyses show that persons who develop psychosis experience onset of psychosis about 2-3 years earlier if they are cannabis users; this effect is not observed with alcohol or other substance use. Higher levels of cannabis use are associated with greater risk of psychosis. Current cannabis abuse or dependence (but not past use or lower levels of current use) increases the risk of transition into psychosis in persons at ultrahigh risk of psychosis. About a third of patients with first-episode psychosis are cannabis users, and, at follow-up, about half of these users are found to continue their cannabis use. Continued cannabis use (in those who are treated after developing psychosis) is associated with higher risk of relapse into psychosis, and discontinuation of cannabis use reduces the risk of relapse to that in cannabis nonusers. Finally, persons with psychosis who continue to use cannabis have more severe positive symptoms and poorer levels of functioning. Because experimental studies in humans show that cannabinoids and cannabis can induce psychotic symptoms, it is reasonable to assume that the epidemiologic data indicate a causal effect of cannabis in anticipating, triggering, or exacerbating psychosis in vulnerable individuals and in worsening the course and outcome of the illness in those who continue to use the substance. Given the public health implications of these findings, the trend to legalize medical marijuana must be viewed with concern, and efforts are necessary to educate patients and the public about the serious mental and physical health risks associated with cannabis use and abuse.

Memory-sparing cognitive deterioration in the elderly: what is the diagnosis?

The case presented highlights the difficult differential diagnosis of memory-sparing cognitive decline in an elderly patient with previously stable bipolar illness. Many disorders can contribute to cognitive and behavioral deterioration in this population, including reversible causes, particularly delirium and psychiatric illness, and irreversible structural or progressive processes including vascular disease, dementia with Lewy bodies, normal-pressure hydrocephalus, and frontotemporal dementia.