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.

Generation Z: Adolescent Xenobiotic Abuse in the 21st Century.

NMDA receptor antagonists include the prescription medication ketamine, the illicit xenobiotics PCP, MXE, and other novel PCP analogs, and the OTC medication DXM. The NMDA receptor antagonist most commonly abused by adolescents in the United States is DXM. These xenobiotics cause dissociative effects by non-competitively inhibiting the action of glutamate at the NMDA receptor. Additionally, these agents modulate the actions of monoamine neurotransmitters, agonize opioid receptors, and inhibit nitric oxide synthase. Patients typically present with sympathomimetic and neuropsychiatric clinical manifestations after abuse of NMDA receptor antagonists. Treatment is generally symptomatic and supportive. Interventions include benzodiazepines, propofol, fluids, antiemetics, aggressive cooling, and respiratory support.

Phencyclidine Intoxication Case Series Study.

BACKGROUND: Phencyclidine (PCP) is a synthetic compound derived from piperidine and used as an anesthetic and hallucinogenic. Little has been recently published regarding the clinical presentation of PCP intoxication. PCP use as a recreational drug is resurging. OBJECTIVE: Our objective was to describe clinical findings in patients presenting to the emergency department (ED) under the influence of PCP. METHODS: This was a case series study conducted at a tertiary care center with an annual census of 100,000 patients/year. Emergency physicians, residents, physician assistants, and research assistants identified patients with possible PCP intoxication. Self-reported PCP use, report by bystanders or Emergency Medical Services (EMS) staff, was used in this process. A structured data collection form was completed, documenting both clinical and behavioral events observed by the treating team during the ED visit. RESULTS: We collected data on 219 patients; 184 were analyzed; two patients were excluded secondary to incomplete data. The mean age of patients was 32.5 years (±7 years) with 65.2 % being males. PCP use was self-reported by 60.3 % of patients. Of the 184 patients, 153 (83.1 %) received a urine drug screen (UDS); 152 (98.7 %) were positive for PCP. On arrival, 78.3 % of patients were awake and alert, and 51.6 % were oriented to self, time/date, and place. Mean physiological parameters were the following: heart rate 101.1 bpm (±24.3), RR 18.9 bpm (±3.4), BP 146.3 (±19.4)/86.3 (±14.0) mmHg, 36.9° C (±0.5), and pulse oximetry 98.2 % (±1.9). Clinical findings were the following: retrograde amnesia in 46 (25 %), horizontal nystagmus in 118 (64.1 %), vertical nystagmus in 90 (48.9 %), hypertension in 87 (47.3 %), and agitation in 71 (38.6 %). Concomitant use of at least one other substance was reported by 99 (53.8 %) patients. The mean length of stay in the ED for all subjects was 261.1 (±172.8) minutes. Final disposition for 152 (82.6 %) patients was to home. Of the 184 patients, 14 (7.6 %) required admission; 12 were referred to Crisis Response Center. CONCLUSION: Patients with PCP intoxication tended to be young males. The prevalent clinical signs and symptoms were the following: retrograde amnesia, nystagmus, hypertension, and psychomotor agitation. Co-use of other substances was the norm. Most patients presenting to the ED with PCP intoxication do well and can be discharged home after a period of observation.

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 evolving high: new designer drugs of abuse.

Over the past decade, emerging drugs of abuse and synthetic derivatives of more traditional agents have flooded the market. While Europe was the first to experience a surge in the use of drugs such as synthetic cathinones and cannabinoids, poison centers throughout the United States have seen a dramatic rise in calls related to these new designer drugs of abuse. In the majority of cases, care is largely supportive but significant medical and traumatic complications may occur. Providers must be aware of the ever-changing trends in abuse, so that they may optimally care for poisoned patients.

Vaccines against drugs of abuse: a viable treatment option?

Drug addiction is a chronically relapsing brain disorder. There is an urgent need for new treatment options for this disease because the relapse rate among drug abusers seeking treatment is quite high. During the past decade, many groups have explored the feasibility of using vaccines directed against drugs of abuse as a means of eliminating illicit drug use as well as drug overdose and neurotoxicity. Vaccines work by inducing drug-specific antibodies in the bloodstream that bind to the drug of abuse and prevent its entry into the brain. The majority of work in this area has been conducted with vaccines and antibodies directed against cocaine and nicotine. On the basis of preclinical work, vaccines for cocaine and nicotine are now in clinical trials because they can offer long-term protection with minimal treatment compliance. In addition, vaccines and antibodies for phencyclidine, methamphetamine and heroin abuse are currently under development. An underlying theme in this research is the need for high concentrations of circulating drug-specific antibodies to reduce drug-seeking and drug-taking behaviour when the drug is repeatedly available, especially in high doses. Although vaccines against drugs of abuse may become a viable treatment option, there are several drawbacks that need to be considered. These include: a lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice;a lack of an effect on drug craving that predisposes an addict to relapse; and tremendous individual variability in antibody formation. Forced or coerced vaccination is not likely to work from a scientific perspective, and also carries serious legal and ethical concerns. All things considered, vaccination against a drug of abuse is likely to work best with individuals who are highly motivated to quit using drugs altogether and as part of a comprehensive treatment programme. As such, the medical treatment of drug abuse will not be radically different from treatment of other chronic diseases.

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.

Inpatient treatment of PCP abusers and users.

Screening of 155 consecutive admissions to a voluntary, 4-6 week substance abuse inpatient rehabilitation program revealed a 13% prevalence of PCP abuse (defined by DSM-III criteria) and a 23% prevalence of nonabusive PCP use. The 20 PCP abusers were significantly younger (31.6 vs 40.2 years) and had more prior arrests (2.0 vs 0.8) than the 36 nonabusive users, but did not differ in other sociodemographic characteristics. The age range of patients was older than previously reported in the literature, with three PCP abusers (15%) and 15 users (42%) 40 years of age or older. A majority of both abusers (80%) and users (97%) also abused other drugs, including alcohol (57%), opiates (29%), marijuana (29%), and stimulants (18%). The mean length of stay for PCP abusers was 27 days, with 11 completing inpatient treatment. Urine samples were collected upon admission from all patients and assayed for PCP by gas chromatography with N-P detection (sensitivity = 0.1 ng/mL). Patients with initial positive PCP results had follow-up urines collected at least weekly until the PCP assay was negative or they left the treatment program. Twenty-seven percent of patients had PCP detected in admission urine samples, one-third of whom initially denied PCP use. Six patients still had PCP detected after 4 weeks of hospitalization, without evidence of PCP reuse. These findings suggest that PCP abuse and use are common among unselected patients seeking substance abuse inpatient treatment and that they are not confined to the adolescent/young adult age group.

PCP: a dangerous drug.

PCP is again becoming a popular drug of abuse in the United States, particularly among the young. A variety of medical, psychiatric and pathologic effects make PCP both appealing and profoundly dangerous to naive and chronic drug users. Pharmacologic intervention is helpful in PCP-induced acute intoxication and psychosis. Effective long-term treatment is available in addiction programs.

Modification of phencyclidine intoxification and biodisposition by charcoal and other treatments.

Studies were conducted to determine whether single or combination treatments of charcoal, paraffin, cholestyramine, and/or ammonium chloride (NH4Cl), would alter the rotarod-measured motor dysfunction induced by 10 to 90 mg/kg of phencyclidine (PCP). Additionally, the effect of NH4Cl/charcoal treatment of the biodisposition of 50 mg/kg PCP was evaluated in order to assess whether amelioration of behavioral effects could be correlated to alterations in brain levels, plasma levels, and/or the renal clearance of PCP and metabolites. NH4Cl/charcoal treatment proved more effective at reducing intoxication than either treatment singly, though effectiveness was reduced by larger doses of PCP. NH4Cl/charcoal treatment reduced intoxification by 40, 16, and 21% at PCP doses of 10, 25, and 50 mg/kg. However, the reduction in motor dysfunction observed at 25 and 50 mg/kg PCP was greater than the sum of the individual treatments. In contrast, the effect of combined NH4Cl and charcoal treatment on the biodisposition of 50 mg/kg PCP is not synergistic, but appears instead to be due simply to the additive effects of the individual treatments. Thus the amelioration of PCP intoxication cannot be fully explained by alterations in PCP biodisposition.

Management of PCP intoxication.

Phencyclidine has a wide range of deleterious effects. Drug users may not even know that they have taken PCP since it is so easily disguised. Physicians should look for decreased reality testing, erythema, dry skin and other manifestations. The varied signs and symptoms of acute intoxication can be dealt with quickly and effectively. Management strategies include acidification of the urine and diuresis, as well as more specific antidotes, depending on the neurotransmitter system most affected.