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.

[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.

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.

Can gradual dose titration of ketamine for management of neuropathic pain prevent psychotomimetic effects in patients with advanced cancer?

BACKGROUND: Ketamine is often used to manage neuropathic pain in patients with cancer. However, it occasionally causes psychotomimetic effects such as vivid dreams, nightmares, illusions, hallucinations, and altered body image. OBJECTIVE: To examine whether gradual dose titration of ketamine for management of neuropathic pain prevents psychotomimetic effects in patients with advanced cancer. METHODS: This was a retrospective chart review. We administered ketamine when neuropathic pain in patients with advanced cancer became refractory to opioids and oral adjuvant analgesics. The starting dose of ketamine was 10 mg/d by continuous intravenous infusion. The dose was gradually increased by 10 mg/d every 4 to 6 hours to 50 mg/d or until the pain was relieved. It was subsequently increased by 25 mg/d every 12 to 24 hours until the pain was relieved. RESULTS: For this study, we enrolled 46 patients with advanced cancer. The mean age was 52.2 ± 16.9 years. The mean dose at onset of action and maximum dose of ketamine were 56 ± 58 and 272 ± 214 mg/d, respectively. The mean pain intensity (numerical rating scale) decreased significantly from 7.3 ± 2.0 to 3.5 ± 2.2 after the administration of ketamine (P < .01). The effectiveness was 69.5%. No psychotomimetic effect of less than 300 mg/d was observed during the introduction phase even though psychotropic drugs were not prescribed. Mild sedation was observed in 3 patients (7%) as the only adverse effect during the introduction phase. CONCLUSION: Gradual dose titration of ketamine for management of neuropathic pain can prevent psychotomimetic effects in patients with advanced cancer.

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.

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.

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.

Can "steroid switching" improve steroid-induced psychosis in a patient with advanced cancer?

In palliative care, steroids are often used to alleviate symptoms such as pain, fatigue, anorexia, nausea, and vomiting. Steroids occasionally induce psychiatric adverse effects. It has been reported that treatment of the steroid-induced psychiatric symptoms involves dosage reduction or discontinuation of steroid, and concomitant administration of psychotropics. There were few reports on effectiveness of treatment of steroid-induced psychiatric symptoms by switching from one steroid to the other. We experienced the case of 67-year-old man with malignant pleural mesothelioma and pulmonary emphysema who developed psychiatric symptoms after switching from oral prednisolone 10 mg/day to intravenous betamethasone 2 mg/day. He began to complain that "time repeats cycles of going and coming" and that he was "unable to distinguish between daytime and night," and his face became expressionless. He gazed at familiar healthcare professionals as if seeing them for the first time, complaining: "I feel something obscure or strange in my head." He was unable to remember events on the same or the previous day at all, and made no verbal response to questions by healthcare professionals. He did not know how to eat or use the toilet, and thus required assistance in daily life activities. He did not respond even when talked to by his family members. He continued gazing at them, sometimes saying: "Where am I now? Am I sick?" He behaved restlessly, repeating cycles of lying and sitting. The symptoms disappeared gradually after re-switching from intravenous betamethasone 2 mg/day to oral prednisolone 10mg/day. "Steroid switching" may serve as a valid alternative treatment.

Anesthesia with ketamine, propofol, and fentanyl decreases the frequency of postoperative psychosis emergence and confusion in schizophrenic patients.

STUDY OBJECTIVE: To investigate whether total IV anesthesia with ketamine, propofol, and fentanyl affects the frequency of postoperative psychosis emergence or confusion in schizophrenic patients. DESIGN: Prospective, controlled study. SETTING: Hirosaki National Hospital and Hakodate Watanabe Hospital. PATIENTS: 76 ASA physical status I and II schizophrenic patients taking chronic antipsychotic drugs and schedule for orthopedic surgery of extremities. INTERVENTIONS: In Group A (n = 38) patients, anesthesia was maintained with sevoflurane, nitrous oxide, and fentanyl. In Group B (n = 38) patients, anesthesia was maintained with ketamine, propofol, and fentanyl. MEASUREMENTS AND MAIN RESULTS: The frequency of psychosis emergence or confusion (54%) in Group A during the first 48 hours after surgery was significantly higher than the 30% figure in Group B. CONCLUSION: Ketamine, when combined with propofol and fentanyl, is an appropriate anesthetic drug for schizophrenic patients.

[Short-acting anesthesia in cosmetic surgery of the breasts]. / Kratkotraina anesteziia pri niakoi estetichni operatsii vurkhu mlechnite zhlezi.

Fourteen patients subjected to short-term cosmetic operations on the mammary glands comprise the study group. Anesthesia was performed with ketamine 0.07 mg/kg/min, applied against the background of droperidol 0.1 mg/kg or diazepam 0.2 mg/kg and spontaneous ventilation with nitrous oxide and oxygen in proportion 3:1. At the end of the ketamine anesthesia 1.0 g pyracetam was applied. There was negligible decrease in the systolic arterial pressure and decreased occurrence of psychotic reactions during the early postoperative period.