Combined cannabis/methaqualone withdrawal treated with psychotropic analgesic nitrous oxide.

This article reports the first single-blind study using psychotropic analgesic nitrous oxide (PAN) for treating acute withdrawal states following the abuse of methaqualone combined and smoked with cannabis. Smoked methaqualone combined with cannabis is called "white pipe" (WP). South Africa is the only country in the world where WP is a major form of substance abuse. This article demonstrates in 101 consecutively treated patients given placebo (100% oxygen) followed by PAN that this therapy produced a measurable therapeutic effect (more than 50% improvement) in 87 patients. This study confirms that WP is a form of substance abuse confined mainly to young adult male subjects.

Patología orgánica por drogas de síntesis / Organic pathology caused by synthesis drugs

El término drogas de síntesis hace referencia a un grupo heterogéneo de sustancias muy dispares en su composición química y/o en los efectos que producen, pudiendo tratarse tanto de sustancias estimulantes como anestésicas, con un amplio espectro o variabilidad de efectos psicoactivos. La percepción de estas sustancias como drogas seguras e inocuas ha hecho que hayan alcanzado gran auge entre los jóvenes en los últimos años para su utilización con fines recreativos pero su consumo puede dar lugar a gran número de complicaciones tanto orgánicas como psiquiátricas. Las dosis tóxicas se encuentran en el rango de las usadas como recreacionales. El mayor riesgo de estas drogas viene dado por el desconocimiento sobre las sustancias que se están consumiendo, las dosis que se administran y la variabilidad en la respuesta individual. A estos riesgos hay que añadir la elevada frecuencia de policonsumo entre ellas mismas y con otras drogas, básicamente tabaco, alcohol, cannabis, cocaína y alucinógenos. Otros factores que pueden intervenir en los daños generados pueden venir condicionados por el entorno de consumo (locales cerrados, elevada temperatura …) y las características particulares del consumidor. A esto se suma el incremento de riesgo de accidentes de tráfico relacionados con alteraciones en la concentración y en la percepción (principalmente visual) bajo sus efectos. Actualmente está demostrada la capacidad de este grupo de sustancias para producir neurotoxicidad y aunque no contamos con datos definitivos para establecer su carácter irreversible, la experimentación con animales de laboratorio cada vez muestra más evidencias en esta dirección

The term of synthesis drugs makes reference to a heterogeneous group of substances with important differences in their chemical composition and/or in the effects they produce, and they may be either stimulant or anaesthetic substances, with a great spectrum or variability in their psychoactive effects. The perception of these drugs as safe and harmless has make that they were able to reach an important peak between the young population in the last years for their utilisation with recreational aims but their use can lead to a high number of psychiatric and organic complications. The toxic dose is in the rage of the used as recreational. The worst risk of these drugs is due to the ignorance of the substances that are being taken, the dose given and the variability of the individual response to them. It has to be added to these risks, the high frequency of consumption among them and with other drugs, mainly tobacco, alcohol, cannabis, cocaine and hallucinogens. Other factors that may cause an influence in the damage caused are the surround of consume (closed locals, high temperature…) and the particular characteristics of the consumer. To all this it has to be added the increased risk of traffic accidents related with changes in concentration and perception (visual mainly) under their effects. At this moment, it is demonstrated the capacity of this group of substances to produce neurotoxicity and, although we don’t have definitive data to establish their irreversible nature, the experimentation with laboratory animals is showing more and more evidence in this direction

Toxicología de las drogas de síntesis / Synthetic illicit drugs toxicology

Las drogas de síntesis o 'drogas de diseño' son sustancias psicoactivas de uso recreacional que se fabrican en laboratorios clandestinos. La producción, variedad y número de consumidores de estas drogas aumentan cada año en toda Europa, y con ellos los problemas sanitarios derivados de su uso. Estos problemas comprenden tanto sus efectos secundarios o la intoxicación aguda como sus aún no del todo conocidas repercusiones orgánicas a largo plazo, así como la toxicidad de las sustancias de corte, la de los productos residuales originados en la fabricación de la propia droga y su uso combinado con el de otras drogas. Dentro de la denominación de drogas de síntesis se diferencian principalmente cuatro grupos de sustancias muy diferentes: los derivados anfetamínicos, los opioides sintéticos, las arilhexilaminas y los derivados de la metacualona. Esta revisión aporta una descripción sistemática de dichos compuestos y de su efectos físicos y psíquicos. (AU)

The South African Community Epidemiology Network on Drug Use (SACENDU) project, phases 1-8--cannabis and Mandrax.

OBJECTIVE: To provide community-level public health surveillance information on cannabis and Mandrax (methaqualone) use and associated health and social consequences. DESIGN: A descriptive, epidemiological study of cannabis and Mandrax supply and demand indicators based on data gathered from multiple sources, including specialist treatment centres, trauma units, police records, and quantitative and qualitative studies of school students, sex workers, persons attending rave clubs, and arrestees. Networks were established at five sentinel sites to facilitate the collection, interpretation, and dissemination of data. RESULTS: Supply and demand indicators point to the widespread use of cannabis and Mandrax and significant increases in white pipe-related health and social problems. There has been an increase in the demand for treatment related to cannabis/Mandrax use, a high proportion of patients in trauma units who test positive for cannabis and/or Mandrax, and a high proportion of cannabis and Mandrax-positive arrestees. Although the use of cannabis is predominantly a male phenomenon and is widespread among young people, it occurs in all sectors of South African society. Mandrax users tend to be young, male, and coloured. CONCLUSIONS: Cannabis and Mandrax use has a number of implications for health and social policy, including the need to develop protocols for the identification and management of cannabis/Mandrax-positive trauma patients and arrestees. The study points to the need for further monitoring of cannabis and Mandrax use and the negative consequences associated with their use.

Oral cytology in cannabis smokers.

The effects of cannabis/methaqualone/tobacco smoking on the epithelial cells of the tongue, buccal mucosa and floor of the mouth were examined. Oral mucosal smears for detection of cellular changes were taken from 4 sites in 16 patients. The tongue blade scraping technique was used. The sites sampled included the buccal mucosa (left and right sides), the posterior dorsum of the tongue and the anterior floor of the mouth. Tobacco smoking and non-smoking controls were also examined. The only significant difference between cannabis users and controls was the greater prevalence of bacterial cells in the smears taken from cannabis users. However, there were also greater numbers of degenerate and atypical squamous cells in cannabis smokers than in cigarette-smoking and non-smoking controls. Epithelial cells in smears taken from cannabis users and tobacco-smoking controls also showed koilocytic changes, which were not seen in smears taken from non-smoking controls. Koilocytosis is indicative of human papilloma virus infection, although no apparent lesions were seen in the patients from whom smears had been taken. It would appear that there is a greater tendency towards damaged and immature surface epithelial cells in cannabis smokers.

A survey of reported synthesis of methaqualone and some positional and structural isomers.

Methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone) is the illicit synthetic drug of choice amongst South African drug users. Historically police and forensic investigation has proven that all methaqualone seized by the South African Police Service originates from illicit manufacturing sites both inside, and outside South Africa's borders. From a drug enforcement, and forensic point of view it is, thus, of utmost importance that the various synthetic routes available to the illicit "chemist" are fully documented and understood. This is a prerequisite for effective illicit laboratory investigation, as well as chemical and precursor monitoring. This paper gives a brief introduction to the current status with regard to methaqualone use and production in South Africa, as well as an extensive review of the synthesis of methaqualone and selected isomers reported since 1946. A table summarizing synthetic routes reported in 32 reference sources is provided.

The effects of chronic treatment and withdrawal of CNS depressants on aggressive behavior.

Young adult CD-1 male mice were housed in individual cages throughout the study. Groups of 10 to 20 mice were given gradually increasing doses of delta-9-tetrahydrocannabinol (THC) at 6.25 to 25 mg/kg i.p., trifluoperazine (TFP) at 6 to 12 mg/kg p.o., phenobarbital sodium (PS) at 20 to 35 mg/kg p.o., morphine sulfate (MS) at 5 to 20 mg/kg i.p., methaqualone (MQ) 10 to 20 mg/kg p.o. or chlordiazepoxide (CDP) 10 to 25 mg/kg p.o. over four to six weeks to develop tolerance of these drugs. Following the development of tolerance, the drugs were withdrawn. On the fourth day of withdrawal, a young (3-4 weeks old) male mouse was introduced into the cage. When the intensity of the attack was measured by the percentage of animals that killed the intruder within four hours. The results indicated 0 to 4 percent in the controls, 50-54 percent for THC, 50 percent for TFP, 42 percent for PS and 57 percent for MS. In contrast, no killing behavior was exhibited by these mice after treatment with MQ or CDP. These data suggest that enhanced aggressive behavior, elicited by withdrawal from certain psychotropic drugs, may be measured by the killing (muricidal) behavior of isolated mice.

Sex differences in physical dependence on methaqualone in the rat.

The establishment of, and sex differences in, physical dependence on methaqualone (MQ) in rats were studied by the drug-admixed food (DAF) method. Female and male rats were treated with MQ-admixed food on the same schedule of gradually increasing doses (0.5 and 1 to 6 mg of methaqualone/g of food). Only female rats showed hypothermia from MQ at 1 and 2 mg/g and motor incoordination from MQ at 4 and 6 mg/g of food. Moreover, after MQ withdrawal, severe withdrawal signs, including convulsions and death, were observed in female rats, but not in male rats. We also instituted a different schedule of graded increases in dose (1 and 2 to 10 and 12 mg/g of food) to develop physical dependence on MQ in male rats. Under this schedule male rats exhibited a hypothermia and severe motor incoordination from MQ 6 and 8 mg/g of food condition. After MQ withdrawal, various severe signs of MQ withdrawal occurred, including tremor, convulsions and death. These results demonstrate that severe physical dependence on MQ in both sexes can be established using the DAF method, and that there are marked sex differences in the physical dependence on MQ.

Cross-physical dependence of several drugs in methaqualone-dependent rats.

We investigated the characteristics of physical dependence on methaqualone. Rats were made physically dependent on methaqualone by the use of the drug-admixed food (DAF) method for 33 days. Pentobarbital, barbital, ethanol and diazepam were cross-administered against methaqualone to evaluate the degree of suppression of methaqualone withdrawal signs as an index for the cross-physical dependence liability of these drugs to methaqualone. To evaluate the cross-physical dependence liability, we used AUC of body weight loss and withdrawal scores between the first cross-administration (9 hr after the withdrawal) and 27 hr after the withdrawal. AUC of weight loss was significantly suppressed by the four test drugs as compared to each control. Withdrawal scores were also significantly inhibited by the cross-administration of barbital, ethanol and diazepam. Considering that the rats given barbital or ethanol fell asleep after the cross-administration, diazepam seems to cause the strongest suppression of methaqualone withdrawal signs among the four test drugs. Thus, physical dependence on methaqualone may be similar by nature to that on benzodiazepines rather than barbiturates and alcohol.

Methaqualone.

Methaqualone is considered a sedative hypnotic drug with a pattern of pharmacological effects similar to those of barbiturates such as pentobarbital. It does have chemical similarities to the barbiturates but was, in fact, synthesized as part of an Indian program looking for antimalarial drugs (Brown and Goenechea, 1973). Methaqualone was selected for the focus of this study five years ago, because of its popularity as a euphoriant among casual recreational drug users in the Boston area. Methaqualone, instead of a barbiturate hypnotic, was therefore used to test our proposed methodology for the assessment of the abuse liability of sedative drugs. As one reviews the history of the clinical use and illicit abuse of methaqualone, it appears particularly unfortunate that a study of this sort was neither completed nor available to our Food and Drug Administration (FDA) and Drug Enforcement Agency (DEA) in 1965. It was at this time that the drug was approved for prescription use and placed in Schedule V, a schedule which essentially places no restrictions on the clinical use of a prescription drug (Falco, 1976). This paper will both review the development of methaqualone and present an experimental methodology for assessing its abuse liability under seminaturalistic conditions.

Methaqualone withdrawal syndrome with photoparoxysmal responses and high-amplitude visual evoked potentials.

Methaqualone is a sedative hypnotic that is often abused. Tolerance and habituation may develop, and the withdrawal syndrome may include seizures. In the patient studied, methaqualone withdrawal was manifested by myoclonic and tonic-clonic seizures, an EEG photoparoxysmal response (PPR), and a high-amplitude visual evoked potential (VEP) to pattern-reversal stimuli. The EEG and VEP returned to normal after resolution of the withdrawal state. Substance withdrawal should be considered in the differential diagnosis of PPR or of an unusually high-amplitude VEP in a person with no previous history of epilepsy. Disappearance of these phenomena may be a useful indicator of the end of the withdrawal state.

Substance-induced organic mental disorders. A clinical and conceptual approach.

Drug abuse is a prevalent problem in society and often occurs as abuse of multiple substances. The authors present a model for understanding the clinical symptomatology and course of substance-induced organic mental disorders and present a hypothesis that explains how various factors might interact to produce the disorder. A clinical case is used to illustrate the use of this approach and suggestions are made for the diagnosis and treatment of these disorders.

Fixed drug eruption due to methaqualone.

We report three cases of fixed drug eruption due to methaqualone. Eruptions from methaqualone have been rarely reported since the drug's introduction in 1963. Our discovery of these three cases during a two-year period suggests that dermatologic reactions from methaqualone may be much more common than has been appreciated. This may be related to the reluctance of the patient to admit to the use or abuse of methaqualone, and physicians' lack of recognition of the widespread abuse of this drug and its possible cutaneous complications.

Pigmented lesions of the tongue in heroin addicts--fixed drug eruption.

Pigmentation of the tongue is an uncommon finding. We describe a case in which it was due to a fixed drug eruption following the inhalation of heroin pyrolysate and methaqualone vapours.

Occurrence of barbiturate, benzodiazepine, meprobamate, methaqualone and phenothiazine in car occupants killed in traffic accidents in the south of Sweden.

An investigation of the following psychoactive drugs: barbiturate, benzodiazepine, meprobamate, methaqualone and phenothiazine, was performed on all automobile occupants killed in accidents in southern Sweden during 1977 and 1978. Of 122 drivers and 55 passengers analysed, low concentrations of these drugs were found in nine drivers and in five passengers. Thus, 7.3% of the drivers were driving under the influence of drugs and, of these, two drivers (1.6% of all analysed drivers) were also inebriated. Twenty-three per cent of the drivers were inebriated only. According to the circumstances in the accidents and the number of drivers whose analyses proved positive, drug influence seldom seems to be the cause of fatal traffic accidents.

Retinal hemorrhage caused by overdose of methaqualone (Quaalude).

A 23-year-old man who had taken an overdose of methaqualone (Quaalude) developed purpura and intraretinal and preretinal (sublaminar) hemorrhages. Methaqualone-induced thrombocytopenia may have been the mechanism of these hemorrhagic complications.