Potential benefit of lamotrigine in managing ketamine use disorder.

Ketamine is an anesthetic derivative of phencyclidine (PCP; 'Angel dust') with dissociative, analgesic and psychedelic properties. Ketamine has become a popular recreational drug of abuse in many parts of the world in recent years. The preclinical studies demonstrate the reinforcing effects of ketamine and long-term ketamine abuse induces a delayed and persistent upregulation of dopamine system. In humans, there have been concerns about its liability to development of addiction. The dilemma of mental professionals in managing the treatment-seeking ketamine abusers comes from a lack of effective pharmacotherapy. Limiting evidence showed that lamotrigine, which inhibits glutamate release, is effective to reduce cocaine craving. We propose that lamotrigine might be beneficial for managing ketamine use disorder clinically. We also reported one case of ketamine use disorder who experienced a great reduction in craving and ketamine use after taking lamotrigine. Although the mechanisms underlying neuroadaptation and reward related to ketamine are not entirely clear, future clinical trials are needed to advance our understanding of the benefit yielded by lamotrigine to treat ketamine use disorder.

Phencyclidine analog use in Sweden--intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project.

BACKGROUND: 3-Methoxy-phencyclidine (3-MeO-PCP) and 4-methoxy-phencyclidine (4-MeO-PCP) are analogs of and drug substitutes for the dissociative substance PCP ("Angel dust"), a recreational drug that was most popular in the 1970s. In Sweden, use of methoxylated PCP analogs was noted starting in mid-2013, according to statistics from the Poisons Information Centre. The objective of this case series was to present clinical and bioanalytical data from analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP within the STRIDA project. STUDY DESIGN: Observational case series of consecutive patients with self-reported or suspected exposure to new psychoactive substances (NPS) and who require hospital care. PATIENTS AND METHODS: Blood and urine samples were collected from intoxicated patients presenting at emergency departments (ED) or intensive care units (ICU) all over Sweden. NPS analysis was performed by multicomponent liquid chromatographic-tandem mass spectrometric (LC-MS/MS) and LC-high-resolution MS (LC-HRMS) methods. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records. RESULTS: The Poisons Information Centre registered its first call related to methoxylated PCP analogs in July 2013, while analytically confirmed cases first appeared in October 2013. From July 2013 to March 2015, 1243 cases of suspected NPS intoxication originating from ED or ICU were enrolled in the STRIDA project. During the 21-month period, 56 (4.5%) patients tested positive for 3-MeO-PCP and 11 (0.9%) for 4-MeO-PCP; 8 of these cases involved both substances. The 59 patients were aged 14-55 (median: 26) years and 51 (86%) were men. Co-exposure to other NPSs and/or classical drugs of abuse was common with only 7 cases (12%) indicated to be 3-MeO-PCP single-substance intoxications; prominent clinical signs seen in the latter cases were hypertension (systolic blood pressure ≥ 140 mmHg; 7 cases), tachycardia (≥ 100/min; 5 cases), and altered mental status (4 cases) including confusion, disorientation, dissociation, and/or hallucinations. Mixed-drug users displayed not only the same clinical features, but also more sympathomimetic effects including agitation (38%) and dilated pupils (33%). Patients testing positive for 3-/4-MeO-PCP were typically under medical care for 1-2 days (85%), and 37% of all cases were graded as severe intoxications (Poisoning Severity Score 3). Besides standard supportive therapy, 49% of the patients were treated with benzodiazepines and/or propofol. CONCLUSION: Laboratory analysis constitutes an important basis for the assessment of NPS hazard and availability. The adverse effects noted in cases of acute intoxications involving 3- and/or 4-MeO-PCP resembled those of other dissociatives such as PCP, ketamine, and methoxetamine. However, similar to intoxications involving other NPS, poly-substance use was found to be common.

PCP: from pharmacology to modelling schizophrenia.

Phencyclidine has attracted the attention of neuroscientists for many years because of its ability to produce, in humans, a range of symptoms remarkably similar to those of patients suffering from schizophrenia. The main action of phencyclidine is as a non-competitive antagonist of the NMDA class of glutamate receptor. In the past few years, dramatic advances have been made in our understanding of the neuroanatomical and pathological basis of schizophrenia. In turn, these have allowed assessment of the ability of phencyclidine to produce equivalent changes in the rodent CNS. It has now become clear that chronic intermittent low doses of phencyclidine produce a pattern of metabolic and neurochemical changes in the rodent brain that mirror those observed in the brains of schizophrenic patients with impressive precision. This should be of enormous benefit in the search for new anti-psychotic drugs with improved efficacy against the full range of schizophrenic symptoms.

El modelo de la fenciclidina en la esquizofrenia / The phencyclidine model of schizophrenia

La fenciclidina (PCP) produce psicosis muy similares a la esquizofrenia. Mientras las psicosis inducidas por anfetamina presentan sólo síntomas positivos como delirio y alucinaciones, las psicosis inducidas por PCP presentan tanto síntomas positivos como negativos (aplanamiento afectivo, retardo psicomotor, empobrecimiento del discurso). De este modo las psicosis anfetamínicas se ajustan a un modelo schneideriano y las psicosis por PCP a un modelo bleuleriano de esquizofrenia. La PCP se une selectivamente a un sitio de unión específico, el receptor a aminoácidos excitatorios N-metil-D-aspaertato (NMDA). Estos hallazgos sugieren que una disfunción de la neurotransmisión mediada por el receptor NMDA puede contribuir a la etiopatogenia de la esquizofrenia

Phencyclidine (PCP) abuse. A close-up look at a growing problem.

PCP or "angel dust" is a dissociative anesthetic agent with notoriety as an abuse substance. Numerous members of many subcultures are frequent users of this drug. It is well known in California's psychedelia, along the East Coast, and in the middle- and working-class suburbs of the Midwest. It is important that practitioners become acquainted with the drug and its effects. Persons intoxicated with PCP have murdered their own children and have even jumped out of high-rise apartment buildings. States of florid psychosis lasting for days can follow a brief encounter with PCP. Inadvertent administration of narcotics and barbiturates to patients with acute PCP intoxication can lead to a crisis that could prove to be fatal.

Clinical implications of behavioral pharmacology research on phencyclidine.

This discussion has highlighted only some of the areas of behavioral pharmacology research with PCP, focusing largely on studies in our laboratories. Some of the areas touched upon lightly have been much more extensively investigated (e.g., PCP-like properties of psychotomimetic opioids). Some areas, such as the search for a PCP antagonist, have been studied with relatively little success so far. Two other areas, among many that are worthy of mention, are the extensive series of studies of the effects of PCP on complex learning procedures, starting with the studies by Moerschbaecher and Thompson (1980a, Moerschbaecher and Thompson 1980b), and an elegant series of studies on the determinants of oral PCP self-administration, beginning with the study by Carroll and Meisch (1980). Much progress has been made on the clinical implications of behavioral research with PCP, and we are in a much better position to respond effectively to this public health problem than we were when it emerged, only a little over 10 years ago. The impetus behind PCP research has come from two directions--from the emergence of PCP as a drug of abuse with the pressing practical questions raised by this epidemic, and from the potential that PCP research has for a fuller understanding of the brain and behavior. Although this discussion has focused on the former, progress toward the latter goal has been equally, if not more, substantial, and may have long-term health implications far beyond those presented by problems of PCP abuse.

[Phencyclidine (PCP): a psychotomimetic drug. Case report and review of literature]. / Phencyclidin (PCP): eine psychotomimetische Droge. Falldarstellung und Literaturübersicht.

A previously healthy 33-year-old patient developed a schizophrenia-like psychosis of 5 weeks' duration after inhalation of hashish contaminated with phencyclidine (PCP). The literature is reviewed and the epidemiology, clinical features, therapy and neuropharmacology of phencyclidine intoxication are discussed.

Acute effects of phencyclidine (PCP) on chronic and recreational users.

Snowball sampling techniques were used to generate a sample of 200 phencyclidine users from an area with a 10-year history of extensive PCP use. Three types of users were studied: heavy chronic, light chronic, and recreational users. The extent of PCP use varied from less than twice a month for a period of 6 months to daily use for several consecutive years. Each subject participated in a structured interview which lasted an average of 11/2 h. Subjects were asked about the acute effects of PCP, and about their moods before, during, and after using PCP. Scales based on previous research were used to measure the acute effects and moods. Results showed that heavy chronic users were more likely than recreational users to feel energized by PCP, and to experience negative ideations (thoughts about suicide and death). When age was controlled for, heavy chronic users were also more likely to experience violent effects. Analysis of moods over time showed some similar patterns between heavy chronic and recreational users, as well as some striking differences. Overall, heavy chronic users reported greater mood elevations while high on PCP, and a more dramatic drop in mood after the high wore off, than recreational users. Analysis of the results by user types clarified some of the confusion about contradictory descriptions of the effects of PCP, and point to the need to continue distinguishing between user types.