Methamphetamine-associated psychosis: Clinical presentation, biological basis, and treatment options.

INTRODUCTION: Methamphetamine associated psychosis (MAP) represents a mental disorder induced by chronic methamphetamine use in a subset of users. The prevalence of the disorder has increased in several countries in Europe and Asia where methamphetamine use has increased. MAP remains difficult to distinguish from primary psychiatric disorders, especially schizophrenia, creating complications in prescribing treatment plans to patients. DESIGN: This narrative review sought to summarize difficulties related to MAP diagnosis and highlight the need for a better treatment model. Current best practices are described and potential novel therapies and future research suggested. RESULTS: Results suggest that clear biological and clinical differences appear between patients presenting with MAP and schizophrenia and that there may exist distinct subgroups within MAP itself. MAP-specific treatment studies have been few and have focused on the use of antipsychotic medication. Antipsychotic treatment has been shown to alleviate the psychotic symptoms of MAP but produce debilitating adverse effects and fail to adequately address methamphetamine use in patients. CONCLUSIONS: Continued identification of subgroups within the heterogenous MAP population may lead to better diagnosis, treatment, and outcomes for patients. Psychosocial therapies should be explored in addressing the cooccurring substance use and psychosis in the treatment of MAP.

Antiepileptic drug-induced psychosis associated with MTHFR C677T: a case report.

BACKGROUND: Various antiepileptic drugs can potentially cause psychiatric side effects in patients with epilepsy, but the precise mechanism of these actions remains unknown. In recent years, the common polymorphism C677T in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has attracted attention for its role in the onset of psychiatric diseases. MTHFR and several vitamins (as cofactors) are crucial for remethylation of homocysteine via folate and homocysteine metabolism. We report a case of a Japanese patient who presented with reversible schizophrenia-like symptoms during antiepileptic drug therapy. CASE PRESENTATION: Our patient had frontal lobe epilepsy and had been treated with several antiepileptic drugs since the age of 13 years. He developed auditory hallucinations and multiple personalities at 17 years of age, several months after the initiation of phenytoin and phenobarbital, despite these antiepileptic drugs being used within the therapeutic ranges. Genetic analysis revealed that he was homozygous for the C677T polymorphism of MTHFR. Hyperhomocysteinemia, hypomethionemia, and multiple vitamin deficiencies, including folate, riboflavin, and pyridoxal, were identified at the age of 23 years. Vitamin supplementation and alteration of the antiepileptic drugs improved his psychotic symptoms. Multiple vitamin deficiencies with homozygous MTHFR C677T should be considered in patients presenting with schizophrenia-like symptoms during antiepileptic drug therapy. CONCLUSIONS: To the best of our knowledge, this is the first report of antiepileptic drug-induced psychosis associated with homozygous C677T and multiple vitamin deficiencies. Our findings will contribute to the elucidation of the pathogenesis of the psychiatric side effects of antiepileptic drugs and lead to improved medical management for patients with epilepsy.

The prevalence of psychotic symptoms in kratom (Mitragyna speciosa Korth.) Users in Malaysia.

BACKGROUND: Kratom is a traditional medicinal herb widely used in Malaysia and Thailand. Despite its widespread use and statements by regulatory agencies on the potential for kratom-associated psychosis, there is little data regarding the prevalence of psychotic symptoms among kratom users. This study investigated the prevalence of psychosis among kratom users, described psychotic symptomatology and severity, while examining associations between kratom use characteristics and the occurrence of psychotic symptoms. METHODS: This cross-sectional clinical survey recruited 150 regular kratom users. The Mini International Neuropsychiatric Interview (MINI) and Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) diagnostic criteria were used to evaluate psychotic symptomatology among kratom users, and the Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of psychiatric symptoms. Chi-square tests with Yate's correction were performed to determine the association between kratom use characteristics and the occurrence of psychotic symptoms among kratom users in this study. RESULTS: Six out of 150 kratom users (4%) presented with any psychotic symptoms. The psychotic symptoms reported were positive symptoms and thought alienation, with a mean BPRS score of 33 (i.e., mild severity). Variables related to kratom use (such as intake of kratom with diphenhydramine, duration of kratom use, and quantity and frequency of daily kratom use) were not associated with the occurrence of psychotic symptoms among kratom users. CONCLUSION: Although psychotic symptoms could occur among regular kratom users, they were rare and not significantly associated with kratom use characteristics. We found no evidence of elevated psychosis among regular users.

The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review.

BACKGROUND: Cannabis is increasingly available for the treatment of chronic pain, yet its efficacy remains uncertain. PURPOSE: To review the benefits of plant-based cannabis preparations for treating chronic pain in adults and the harms of cannabis use in chronic pain and general adult populations. DATA SOURCES: MEDLINE, Cochrane Database of Systematic Reviews, and several other sources from database inception to March 2017. STUDY SELECTION: Intervention trials and observational studies, published in English, involving adults using plant-based cannabis preparations that reported pain, quality of life, or adverse effect outcomes. DATA EXTRACTION: Two investigators independently abstracted study characteristics and assessed study quality, and the investigator group graded the overall strength of evidence using standard criteria. DATA SYNTHESIS: From 27 chronic pain trials, there is low-strength evidence that cannabis alleviates neuropathic pain but insufficient evidence in other pain populations. According to 11 systematic reviews and 32 primary studies, harms in general population studies include increased risk for motor vehicle accidents, psychotic symptoms, and short-term cognitive impairment. Although adverse pulmonary effects were not seen in younger populations, evidence on most other long-term physical harms, in heavy or long-term cannabis users, or in older populations is insufficient. LIMITATION: Few methodologically rigorous trials; the cannabis formulations studied may not reflect commercially available products; and limited applicability to older, chronically ill populations and patients who use cannabis heavily. CONCLUSION: Limited evidence suggests that cannabis may alleviate neuropathic pain in some patients, but insufficient evidence exists for other types of chronic pain. Among general populations, limited evidence suggests that cannabis is associated with an increased risk for adverse mental health effects. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs. (PROSPERO: CRD42016033623).

[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.

Cannabis-induced psychosis associated with high potency "wax dabs".

With mounting evidence that the risk of cannabis-induced psychosis may be related to both dose and potency of tetrahydrocannbinol (THC), increasing reports of psychosis associated with cannabinoids containing greater amounts of THC are anticipated. We report two cases of emergent psychosis after using a concentrated THC extract known as cannabis "wax," "oil," or "dabs" raising serious concerns about its psychotic liability. Although "dabbing" with cannabis wax is becoming increasingly popular in the US for both recreational and "medicinal" intentions, our cases raise serious concerns about its psychotic liability and highlight the importance of understanding this risk by physicians recommending cannabinoids for purported medicinal purposes.

Caffeine-induced psychiatric manifestations: a review.

The association between caffeine consumption and various psychiatric manifestations has long been observed. We present two cases that show the ability of caffeine to induce psychotic and manic symptoms, and we also review the extant literature on caffeine-induced psychiatric manifestations. On the basis of our own and others' findings, we suggest that caffeine may be related to not only de-novo psychotic or mood symptoms but also to aggravation of pre-existing psychotic or mood disorders. We therefore suggest that caffeine consumption among patients with mood or psychotic symptoms should be assessed carefully in clinical practice as part of routine psychiatric evaluations.

Aripiprazole for treating cannabis-induced psychotic symptoms in ultrahigh-risk individuals.

Cannabis-induced psychotic symptoms (CIPSs) have both similarities and differences with positive symptoms of schizophrenia, and it remains unclear whether CIPSs result from dopaminergic mechanisms and can be treated with antipsychotics. We report the case of a 22-year-old male patient with ultrahigh risk criteria for psychosis, who reported cannabis addiction and recurrent CIPSs. Aripiprazole 10 mg/d could totally and durably suppress CIPSs in the patient, but had no effect on the smoking level. Treating CIPSs in ultrahigh risk individuals who cannot stop or refuse stopping cannabis might fit a harm-reduction strategy by preventing transition into psychosis.

Jobelyn® pretreatment ameliorates symptoms of psychosis in experimental models.

BACKGROUND: Psychosis is a chronic neurological disorder and it remains a major medical and social problem in most African countries. Individuals with psychotic illness in this region tend to seek help from traditional medical practitioners, who prescribe herbal remedies as alternative forms of treatment for the disease. Jobelyn® (JB) is a commercial polyherbal formulation that has been acclaimed to show beneficial effects in neurological disorders. However, its usefulness in psychosis has not been scientifically validated. Thus, this study was undertaken to evaluate its effects on animal models predictive of human psychosis. METHODS: Antipsychotic activity of JB was assessed based on the inhibition of stereotyped behavior induced by amphetamine or apomorphine in mice. Amphetamine-induced hyperactivity and lethality in aggregated mice were additional tests employed to further evaluate the antipsychotic property of JB. The effect of JB on catalepsy was also assessed, using the inclined plane paradigm. RESULTS: JB (5-50 mg/kg, p.o.) significantly (p<0.05) inhibited stereotypy induced by amphetamine (10.0 mg/kg, i.p.) or apomorphine (1 mg/kg, i.p.), which suggests antipsychotic activity. Furthermore, JB (5-50 mg/kg, p.o.) reduced lethality in aggregated mice and inhibited hyperactivity induced by amphetamine, respectively. However, JB (5-50 mg/kg, p.o.) did not cause cataleptic behavior, as it failed to alter the duration of stay of the animals on the inclined plane. CONCLUSIONS: Taken together, these findings suggest that JB exhibits antipsychotic-like activity, devoid of the adverse effect of cataleptic behavior, and may offer some beneficial effects in the symptomatic relief of psychotic ailments.

The yin and yang of cannabis-induced psychosis: the actions of Δ(9)-tetrahydrocannabinol and cannabidiol in rodent models of schizophrenia.

The link between cannabis and psychosis has often been debated with polarized views on the topic. There is substantial epidemiological evidence showing that cannabis increases the risk of psychosis, whereas other research suggests that schizophrenia patients self-medicate with the substance. These conflicting accounts may at least be partially explained by the two phytocannabinoids cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC) and their opposing actions on schizophrenia-related symptoms. In the present review we will first focus on how traditional rodent models of schizophrenia have been used to improve our understanding of the propsychotic actions of THC and the antipsychotic actions of CBD. We will also review novel rodent models used to address genetic vulnerability to cannabis-induced schizophrenia and show that specific genes are being uncovered that modulate cannabinoid action (e.g. the schizophrenia susceptibility gene neuregulin 1). We will also review rodent studies that have addressed interactions between THC and CBD. These animal studies underscore great complexity with some studies showing that CBD antagonises the neurobehavioural effects of THC, while others show the opposite, that CBD potentiates the actions of THC. Various mechanisms are put forth to explain these divergent effects such as CBD antagonism at central CB1 receptors or that CBD inhibits proteins that regulate THC disposition and metabolism (e.g. the ABC transporter, P-glycoprotein).

Potential protective effects of cannabidiol on neuroanatomical alterations in cannabis users and psychosis: a critical review.

Cannabis use and the development of schizophrenic psychoses share a variety of similarities. Both start during late adolescence; go along with neuropsychological deficits, reduced activity, motivation deficits, and hallucinations suggesting impairment of similar brain structures. In cannabis heavy users diminished regional gray and white matter volume was reported. Similar alterations were observed in the large literature addressing structural abnormalities in schizophrenia. Furthermore, in cannabis using schizophrenic patients, these brain alterations were especially pronounced. Close relatives of schizophrenic patients showed greater cannabis-associated brain tissue loss than non-relatives indicating a genetically mediated particular sensitivity to brain tissue loss. Possible mechanisms for the induction of structural brain alterations are here discussed including impairments of neurogenesis, disturbance of endocannabinoids and diminished neuroplasticity. Especially direct THC effects (or via endocannabinoids) may mediate diminished glutamatergic neurotransmission usually driving neuroplasticity. Correspondingly, alterations of the kynurenic acid blocking NMDA receptors may contribute to brain structure alterations. However, different cannabis compounds may exert opposite effects on the neuroanatomical changes underlying psychosis. In particular, cannabidiol (CBD) was shown to prevent THC associated hippocampal volume loss in a small pilot study. This finding is further supported by several animal experiments supporting neuroprotective properties of CBD mainly via anti-oxidative effects, CB2 receptors or adenosine receptors. We will discuss here the mechanisms by which CBD may reduce brain volume loss, including antagonism of THC, interactions with endocannabinoids, and mechanisms that specifically underlie antipsychotic properties of CBD.

Antipsychotic property of aqueous and ethanolic extracts of Lonchocarpus cyanescens (Schumach and Thonn.) Benth. (Fabaceae) in rodents.

Lonchocarpus cyanescens (LC) is a medicinal plant commonly used in combination with other recipes in the treatment of psychotic disorders in traditional medicine. This study was designed to examine whether the aqueous and ethanolic extracts of LC possess antipsychotic property in rats. The antipsychotic effects of the extracts were assessed using the amphetamine animal model of psychosis in rats. The effect of the extracts on spontaneous motor activity was also studied in the open field test in mice. The extrapyramidal side effect of catalepsy was tested based on the ability of the extracts to alter the duration of akinesia in mice placed on a vertical wrapped string. Aqueous and ethanolic extracts of LC (25-400 mg/kg, i.p.) significantly (p < 0.05) suppressed stereotyped behaviour induced by amphetamine (10.0 mg/kg, i.p.) in rats, which suggest antipsychotic activity. The extracts (25-400 mg/kg, i.p.) further produced a significant (p < 0.05) reduction in spontaneous motor activity of the animals in the open field test. However, in contrast to chlorpromazine, a typical antipsychotic, the extracts did not induce cataleptic behaviour in the animals. Preliminary phytochemical screening showed the presence of alkaloids, anthraquinones, cardiac glycosides, cyanogenetic glycosides, flavonoids, saponins, steroids and tannins in the leaves of LC. The presence of these secondary metabolites was confirmed by thin-layer chromatography. Taken together, these findings suggest that the extracts possess phytochemically active constituents with antipsychotic property. Thus, this investigation provides evidence that may justify the ethnomedicinal applications of Lonchocarpus cyanescens as the major constituent of the recipe used for the management of psychosis in Nigeria.

['Steroid psychosis' during treatment for premature labour]. / 'Steroïdpsychose' bij behandeling van dreigende vroeggeboorte.

A 30-year-old woman, 33 weeks pregnant, without a significant psychiatric history, was admitted for treatment of premature labour. She was treated with betamethasone intramuscularly, with a total dose of 24 mg divided over 2 days, and nifedipine orally with beneficial effect on the contractions. However, within 24 h after completion of tocolytic treatment, she developed a psychosis with delusions and hallucinations necessitating readmission, first to an obstetric ward, later to a psychiatric ward. At least part of this episode may be characterized as delirium. Eventually, she was treated with haloperidol. It is argued that her psychosis was caused by the corticosteroid, since psychiatric disturbance is a well-known complication of corticosteroid therapy. To our knowledge, psychosis during pregnancy as a result of treatment with corticosteroids has not been reported previously.

Can "steroid switching" improve steroid-induced musical hallucinations in a patient with terminal cancer?

The patient was a 57-year-old woman with malignant pleural mesothelioma. She had a past history of anxiety neurosis but not had any history of otological diseases. On admission to our hospice (day 1), she complained of dyspnea and wheezing associated with the progression of her underlying disease. After we started oral betamethasone (2 mg/d), dyspnea was alleviated and the frequency of wheezing was reduced. On day 3, she began to experience musical hallucinations that were manifested in opera/piano concert music and a child's voice. The episodes of musical hallucinations occurred approximately 10 times a day and disappeared spontaneously within several minutes. She had not experienced these symptoms before. We reduced the dose of betamethasone to 1 mg/d, but the musical hallucinations continued. Then on day 11, we switched betamethasone (1 mg/d) to prednisolone (10 mg/d) and we then gradually tapered off prednisolone. The frequency of musical hallucinations decreased and she ceased to experience musical hallucinations on day 29. However, on day 40, her dyspnea was aggravated again, so we started treatment with prednisolone (5 mg/d). Dyspnea was alleviated and no musical hallucinations occurred. On Day 51, dyspnea was worsened and we switched prednisolone to betamethasone (4 mg/d), which she hoped to use. The betamethasone alleviated the dyspnea but she developed musical hallucinations that were similar to the previous episodes. The musical hallucinations disappeared spontaneously 4-5 days later without changing the betamethasone. Musical hallucinations never occurred thereafter. She later died due to the exacerbation of disease.