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.

Paliperidone for the treatment of ketamine-induced psychosis: a case report.

Ketamine is an anaesthetic and analgesic drug synthesized in the 1960s from phencyclidine. The recreational use of ketamine increased among the dance culture of techno and house music, in particular in clubs, discotheques, and rave parties. The psychotropic effects of ketamine are now well known and they range from dissociation to positive, negative, and cognitive schizophrenia-like symptoms. We report a case of a chronic oral consumption of ketamine which induced agitation, behavioral abnormalities, and loss of contact with reality in a poly-drug abuser; these symptoms persisted more than two weeks after the drug consumption had stopped. Antipsychotic treatment with paliperidone led to a successful management of the psychosis, getting a complete resolution of the clinical picture. Paliperidone has proven to be very effective in the treatment of ketamine-induced disorders. Moreover, the pharmacological action and metabolism of paliperidone are poorly dependent from the activity of liver enzymes, so that it seems to be one of the best second generation antipsychotics for the treatment of smokers and alcohol abusers.

The ultimate intra-/extra-dimensional attentional set-shifting task for mice.

BACKGROUND: Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric diseases. The most widely used neuropsychological tests for the evaluation of attentional set shifting in humans are the Wisconsin Card Sorting Test and the Cambridge Neuropsychological Test Automated Battery Intra-/Extra-Dimensional set-shift task (ID/ED). These tasks have proven clinical relevance and have been successfully adapted for monkeys. However, similar tasks currently available for rodents are limited, mainly because of their manual-based testing procedures. The current limitations of rodent attentional set-shifting tasks are hampering translational advances in psychiatric medicine. METHODS: To closely mimic the Cambridge Neuropsychological Test Automated Battery ID/ED task in primates, we present the development of a novel operant-based two-chamber ID/ED "Operon" task for mice. RESULTS: We show the ability of this novel task to measure attentional set shifting in mice and the effects of genetic and pharmacologic manipulations of dopamine and glutamate. In genetically modified mice with reduced catechol-O-methyltransferase activity there was selective improvement on extradimensional shift abilities and impairment of serial reversal learning. Chronic administration of phencyclidine produced a selective impairment of extradimensional shift while producing a generalized decrease in latency to respond. CONCLUSIONS: We demonstrate that this novel ID/ED Operon task may be an effective preclinical tool for drug testing and large genetic screening relevant to the study of executive dysfunctions and cognitive symptoms of psychiatric disorders. These findings may help elucidate the biological validity of similar findings in humans.

The association between phencyclidine use and partner violence: an initial examination.

The association between phencyclidine (PCP) use and violent behavior is unclear. The current investigation evaluated the association between PCP addiction and intimate partner violence, a specific violent behavior, using the substance abuse evaluations of 109 PCP, 81 cannabis, and 97 polysubstance (alcohol and cannabis) abusing offenders. Relative to both comparison groups, PCP users were more likely to receive inpatient referrals, have a significant legal history, and have perpetrated past-year general and intimate partner violence. Data suggest that PCP use may be associated with greater violence perpetration than cannabis use alone or in conjunction with problematic alcohol use.

Increased impulsive choice for saccharin during PCP withdrawal in female monkeys: influence of menstrual cycle phase.

BACKGROUND: In previous studies with male and female rhesus monkeys, withdrawal of access to oral phencyclidine (PCP) self-administration reduced responding for food under a high fixed-ratio (FR) schedule more in males than females, and with a delay discounting (DD) task with saccharin (SACC) as the reinforcer impulsive choice for SACC increased during PCP withdrawal more in males than females. OBJECTIVES: The goal of the present study was to examine the effect of PCP (0.25 or 0.5 mg/ml) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle. MATERIALS AND METHODS: In component 1, PCP and water were available from two drinking spouts for 1.5 h sessions under concurrent FR 16 schedules. In component 2, a SACC solution was available for 45 min under a DD schedule. Monkeys had a choice of one immediate SACC delivery (0.6 ml) or six delayed SACC deliveries, and the delay was increased by 1 s after a response on the delayed lever and decreased by 1 s after a response on the immediate lever. There was then a 10-day water substitution phase, or PCP withdrawal, that occurred during the mid-follicular phase (days 7-11) or the late luteal phase (days 24-28) of the menstrual cycle. Access to PCP and concurrent water was then restored, and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases. RESULTS: PCP deliveries were higher during the luteal (vs follicular) phase. Impulsive choice was greater during the luteal (vs follicular) phase during withdrawal of the higher PCP concentration. CONCLUSIONS: PCP withdrawal was associated with elevated impulsive choice for SACC, especially in the luteal (vs follicular) phase of the menstrual cycle in female monkeys.

The forensic and legal implications of water, wet, or fry.

Embalming fluid applied to marijuana cigars or cigarettes, with or without the addition of phencyclidine (PCP), has several names, such as water, wet, illy, and fry. Individuals who commit crimes under the influence of this substance are often violent and may appear psychotic, with symptoms resembling schizophrenia or delirium. Currently, there are no case reports or case law involving the use of this substance. Wet may impair one's competency to stand trial (CST). The authors present a composite case of a man who abused wet for three years and had been sober for three months when he presented for a CST evaluation. The authors posit that individuals who use wet may raise settled (fixed) insanity or defenses of not guilty by reason of insanity in the future.

Neuropsychological effects of formaldehyde use.

This study compared five individuals who intentionally ingested formaldehyde (possibly laced with PCP) in marijuana cigarettes to a control group on measures of cognitive ability. Formaldehyde, a major component in embalming fluid, is legal to purchase and possess and has become popular due to its euphoric properties. In significant doses, the chemical is a neurotoxin. The effects of inadvertent exposure are fairly well known, but the effects of intentional ingestion have only recently been investigated. In addition, there has been little research on the effects of formaldehyde use specific to intellectual ability and cognitive intactness. The results of this study indicate intentional ingestion may cause a decline in neuropsychological intactness, as measured by performance on the Shipley Institute of Living Scale.

Chloroquine psychosis masquerading as PCP: a case report.

Chloroquine and its derivatives have been drugs of choice in the prophylaxis and treatment of malaria for over 50 years. These drugs are also frequently used in the treatment of various rheumatologic disorders. Because many Americans now travel abroad and may require chloroquine prophylaxis, as well as the fact that such medications are readily available through Internet-based supply houses, clinicians should be aware of the potential toxicity associated with the use of these agents. We present the case of an adolescent female who presented with acute, chloroquine-induced toxic psychosis resembling that induced by phencyclidine (PCP) in clinical presentation and laboratory findings. In the acute setting, the differentiation between chloroquine toxic psychosis and PCP psychosis may be difficult. Therefore, the syndrome of chloroquine-induced psychosis is reviewed and its differentiation from PCP psychosis highlighted as it relates to important aspects of this case.

Long-term effects of developmental PCP administration on sensorimotor gating in male and female rats.

RATIONALE: Acutely administered N-methyl-D-asparate (NMDA) antagonists are used to model schizophrenia, as measured by impairments in sensorimotor gating reflected in decreases in prepulse inhibition of the startle response (PPI). Aspects of acute NMDA receptor antagonism limit the applications of these models. OBJECTIVE: The aim of this paper is to determine the long-term effects of developmental phencyclidine (PCP) treatment on sensorimotor gating in both male and female rats. MATERIALS AND METHODS: Male and female Sprague Dawley rats were injected with PCP (10 mg/kg s.c.) on postnatal days (PN) 7, 9, and 11 and were tested for PPI on PN 32-34. The groups were then divided and some of the animals received a single dose of PCP (10 mg/kg s.c.) on PN 45. The animals were tested again for PPI at approximately 1, 4, and 6 weeks after the treatment. RESULTS: There were no significant effects of neonatal-only treatment. One week after the PN 45 treatment, animals that were treated as neonates and as adolescents (PCP/PCP) were significantly impaired in PPI in both sexes. Male and female PCP/PCP rats also had significant increases in acoustic startle response 4 weeks posttreatment, which subsequently declined. PPI impairments in both sexes recovered over time and the adolescent-only treated females showed significant increases (improvement) in PPI approximately 6 weeks posttreatment. CONCLUSION: These data suggest that treatment with an NMDA receptor antagonist during adolescence or early adulthood can produce a relatively long-term impairment of PPI (approximately 1 week) and that this effect is more pronounced in male animals.

When the drug of choice is a drug of confusion: embalming fluid use in inner city Hartford, CT.

This paper examines the use of a new illicit drug--embalming fluid mixtures--in Hartford, CT based on a recent assessment of drug consumption in an outreach-recruited sample of 242 not-in-treatment active drug users. Sociodemographic, drug use, and health and social problems of drug users who do and do not use embalming fluid mixture are presented, revealing some notable differences between these two groups of street drug users. Despite regular consumption, we report that embalming fluid mixture users are often uncertain about what is in this new drug, despite experiencing often powerful effects. Urine toxicology findings from a subsample of individuals who used embalming fluid mixtures in the last 48 hours, reveal the frequent presence of phencyclidine (PCP) as well as other drugs. The public health implications of this new wave of PCP use are assessed.

Drugs of abuse and the elicitation of human aggressive behavior.

The drug-violence relationship exists for several reasons, some direct (drugs pharmacologically inducing violence) and some indirect (violence occurring in order to attain drugs). Moreover, the nature of that relationship is often complex, with intoxication, neurotoxic, and withdrawal effects often being confused and/or confounded. This paper reviews the existing literature regarding the extent to which various drugs of abuse may be directly associated with heightened interpersonal violence. Alcohol is clearly the drug with the most evidence to support a direct intoxication-violence relationship. The literatures concerning benzodiazepines, opiates, psychostimulants, and phencyclidine (PCP) are idiosyncratic but suggest that personality factors may be as (or more) important than pharmacological ones. Cannabis reduces likelihood of violence during intoxication, but mounting evidence associates withdrawal with aggressivity. The literature on the relationship between steroids and aggression is largely confounded, and between 3,4-methylenedioxymethamphetamine (MDMA) and aggression insufficient to draw any reasonable conclusions. Conclusions and policy implications are briefly discussed.

Perception of nonverbal facial cues in chronic phencyclidine abusers.

The ability to interpret nonverbal facial cues was tested in 10 young white male chronic phencyclidine (PCP) abusers. When their responses were compared with those of age-matched controls, abusers were significantly more accurate in interpreting the facial cues of videotaped medical interns. Phencyclidine abusers tend to form a socially maladroit and downwardly mobile group. However, previous studies of similar maladroit populations such as heroin addicts have indicated that they are less accurate in interpretation of nonverbal facial cues. The complex action of multiple affected neurotransmitters in PCP abusers was examined. Dopamine and serotonin were thought to be the relevant transmitters.

Female PCP-using jail detainees: proneness to violence and gender differences.

Previous studies indicate that PCP users have different characteristics from other drug users and that female PCP use is more common than use among males. Furthermore, there is evidence that those who respond to PCP with violence may differ from those who do not. This study attempted to examine comprehensively the psychological, behavioral, and background factors among female jail inmates that may contribute to a PCP preference and subjects' perception of various behavioral states while using PCP. Female PCP users were further examined relative to male PCP users to differentiate them on the basis of these perceptual factors. A distinction was further made between females and males prone to PCP-induced violence and those who do not become violent with respect to the above psychological and behavioral measures. Our results showed differences between male and female PCP users that are discrepant with the assumption that men and women perceive similar drug-related experiences. In particular, female PCP using subjects reported more dysphoria and aggressiveness when not using PCP, while male subjects were more likely to report aggressive behavior and dysphoria under the influence. Overall, these results suggest that males who prefer PCP may be self-stimulating and females who prefer PCP may be attempting to self-medicate.

Behavioral response to buspirone in cocaine and phencyclidine withdrawal.

The effects of buspirone in treating cocaine and phencyclidine (PCP) withdrawal were studied. Withdrawal symptoms of these two street-drugs are thought to be due to norepinephrine, dopamine and possibly serotonin depletion. Buspirone acts by enhancing dopaminergic and noradrenergic firing as well by suppressing serotonergic activity. Thirty-two cocaine abusers and 24 PCP abusers were withdrawn over a 30-day period. Half of each group received buspirone 10 mg t.i.d. and the other half 10 mg placebo t.i.d. In the cocaine group, buspirone was significantly more effective from the fifth day onward. In the PCP group, significant improvement was seen on the thirtieth day. Delayed effectiveness in PCP is thought due to its actions at other neurotransmitter sites.

The economic context of drug and non-drug reinforcers affects acquisition and maintenance of drug-reinforced behavior and withdrawal effects.

The focus of this review is to examine the effect of non-drug alternative reinforcers on drug-reinforced behavior. An increasing number of animal laboratory as well as human clinical studies have demonstrated the effectiveness of non-drug reinforcers in reducing steady-state levels of drug self-administration. One goal of this review was to determine what behavioral economic conditions are optimal for reducing drug-reinforced behavior. Variables such as price of the drug and non-drug reinforcer have been manipulated by changing fixed-ratio (FR) value of these commodities. Income has been changed by limiting the amount of access to the commodities or by changing session length. Substitution was evaluated by determining whether decreased demand for a drug (due to increased price) was related to increased demand for a non-drug reinforcer. A second goal of this review was to investigate transition states in the drug addiction process with respect to the role of alternative non-drug reinforcers. Animal models of acquisition and withdrawal were examined to identify behavioral economic conditions under which acquisition may be prevented or withdrawal effects (and potential for relapse) may be alleviated.

Weighing up the pros and cons: help-seeking by drug misusers in Baltimore, USA.

Forty drug misusers receiving treatment in Baltimore completed questionnaires, originally administered to drug misusers in London, about their reasons for seeking help and their worries about the treatment. Seeking help was related to the experiences of addiction, loss of control over life and financial and family difficulties. The main fears were of failing treatment. These responses are similar to those obtained in the London group. There was little correlation between objective assessment and subjects' views of their problems. This study illustrates the complexities of coming for treatment and it emphasises the need for social and medical help.

Recovery of neuropsychological functions during reduction in use of phencyclidine.

A battery of 12 neuropsychological tests were administered on two occasions to 15 chronic PCP users who reduced or eliminated use of PCP over a 4-week period. A comparison sample of 15 non-PCP drug users who did not differ in age, sex, education, and ethnic composition also were tested at the two time periods. Impairment, initially higher for PCP users, decreased significantly after reduction in use of PCP. A nonsignificant increase in impairment was found for non-PCP drug users. Analysis of each variable revealed that substantial improvement occurred on the acquisition, recall, and delayed recall scores of the Randt Memory Test. Improvement also was noted for some individuals on Trails B and Digit Symbol tests.

Dual diagnosis patients in the urban psychiatric emergency room.

Substance abuse among the mentally ill has become increasingly prominent. This article describes the problems presented by dual diagnosis patients in the urban, publicly funded, psychiatric emergency room. When such patients become acutely ill, neither the public health system nor the mental health clinician is adequately prepared to provide care. The inability to effectively treat these patients has become strikingly clear in recent years. In 1986, the Psychiatric Emergency Service at San Francisco General Hospital began to overflow with patients who required overnight stays. The intoxicated substance abusers with acute psychiatric complaints were the most difficult to manage clinically and administratively. Suggestions are offered for innovative approaches to this group of public patients: dual training of clinicians, flexible treatment programs prepared to deal with the whole person, and public funding that reflects patients' needs rather than clinicians' preferences.