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Chapter: Modern Medical Toxicology: Substance Abuse: Substances of Dependence and Abuse

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Designer Drugs - Substances of Dependence and Abuse

Designer Drugs - Substances of Dependence and Abuse
Designer drugs are congeners of active compounds that have been modified from legitimate pharmaceutical agents, and are used for recreational purposes.

Designer Drugs

Designer drugs are congeners of active compounds that have been modified from legitimate pharmaceutical agents, and are used for recreational purposes. Apart from amphetamines, there are several other groups of designer drugs (Table 34.14) which have been discussed in detail elsewhere.



Designer drugs are usually stronger and cheaper than the parent compound, and can be easily synthesised in clandestine laboratories. The term “designer drug” does not include new forms or new dosing routes of old drugs (e.g. cocaine used in freebase form, i.e. “crack”). It also does not include legal drugs which are abused (e.g. ephedrine, caffeine, phenylpro-panolamine, etc.).


Since 1983 it has become increasingly popular among adolescents and college students as a recreational drug to be used during “rave parties” which are extended dance parties often lasting all night long (Fig 34.16). The other designer amphetamines quickly followed and are mostly available as gelatin capsules or loose powder for ingestion. They have made their way into India in the late 1990s, and are quite openly abused by college students from affluent families

Uses

·             Methylenedioxymethamphetamine (MDMA) was used in the early years following its synthesis, by psychologists to enhance psychotherapy. Today, there are no legal uses for any of the designer amphetamines.

·              A herbal stimulant (‘S-5 tablets’) marketed in the Netherlands was found to contain para-methylthioamphetamine (p -MTA or 4-methylthioamphetamine {4-MTA}). It appears to be a potent selective serotonin releaser without serotonin neurotoxic effects. Efforts are on to make 4-MTA a controlled substance in the United Kingdom under the Misuse of Drugs Act. The street name for these tablets containing 100 mg of 4-MTA is “flatliners”.

Mode of Action

·              While designer amphetamines share a number of properties with the original amphetamines, unlike the latter, they are potent releasers of serotonin. Chronic administration can result in permanent damage to serotonergic neurons. There is strong evidence to suggest that MDMA use can result in alterations and potential damage to serotonin neurons. Studies have also indicated that the effects of MDMA on 5-HT neurons in the human cortex may be reversible in individuals who stop using MDMA, but the effects of MDMA on memory function may be long-lasting.

Clinical Features

·             Designer amphetamines are abused by teenagers and young adults for inducing euphoria, facilitating inti-macy and verbosity, and heightening sexuality. Users of MDMA report that it “expands consciousness” without making them lose control. Sometimes these drugs are labelled “entactogens” for their alleged ability to increase sensitivity to touch, or “empathicogens”, for their alleged ability to create empathy, especially before sexual encounters. MDMA is considered an “entheogen” which means “to become divine from within”. Entheogen refers to a state of shamanic or ecstatic possession induced by ingestion of mind-altering drugs.

·              Candyflipping” refers to the intentional combination of ecstasy with LSD. Another method of use is called “stacking” in which 3 or more tablets of MDMA are taken at once; or MDMA is mixed with alcohol, cannabis or some other drug (ketamine, GHB, cocaine, etc.) in order to modify the “high”. Stacking can increase the risk of overdose, since MDMA, acting as a stimulant, can mask the sedative effects of alcohol or any other drug. There is current vogue for combining ecstasy with sildenafil to enhance sexual pleasure (“sexstasy”).

·              Acute toxicity results in nausea, anorexia, anxiety,mydriasis, hyperthermia, muscle rigidity, trismus, sinus tachycardia, sweating, tachypnoea, cardiac arrhythmias, cardiac arrest, metabolic acidosis, rhabdomyolysis, myoglobinuria, acute renal failure, and disseminated intra-vascular coagulation. The following have been reported: convulsions, cerebral infarcts, hallucinations, paranoia, chest pain, hyperkalaemia, and fulminant hepatic failure.

·              Effects are seen 30 to 45 seconds after ingestion (on an empty stomach) in the form of a ‘rush’, which lasts 15 to 30 minutes. This is followed by a sense of clarity and joy. A booster dose may be taken at this point, to prolong these feelings. About ½ hour to 3 hours after the initial ingestion, a “plateau” phase occurs in which repetitive or trance-like movements become extremely pleasurable. The “coming down” phase occurs 3 to 6 hours after the initial ingestion, and can lead to negative feelings or emotions (depression, anxiety). Symptoms may persist for several days.

·              Hallucinations are common, and may be auditory or visual in nature. Users often describe seeing trails of lights. Flashbacks have been reported in several MDMA users. Acute panic attacks and panic disorder following use of MDMA have also been reported.

·              Hyperthermia is common in severe cases, and can contribute to death. It is similar in mechanism to malig-nant hyperthermia, which is biochemically caused by a rise of calcium ions in the myoplasm.

·              Hypertension and tachycardia are also common, while hypotension and cardiovascular collapse can occur in severe poisoning.

·              Cardiac arrhythmias are common in patients with severe toxicity following MDMA overdose.

·              Chest pain can occur with ecstasy use combined with physical exertion. Myocardial infarction has been reported. Spontaneous pneumomediastinum occurred in another case following the ingestion of three ecstasy tablets. He also recovered, and was discharged without sequelae.

·              Pulmonary oedema and ARDS may occur in severe intoxications.

·              Convulsions are common in severe toxicity.

·              Coma may develop in severe cases.

·              Intracranial haemorrhages have been reported with the use of these drugs, as in the case of regular amphetamines and cocaine.

·              Acute renal failure has been reported in patients who develop rhabdomyolysis and/or disseminated intravascular coagulation associated with MDA, MDEA or MDMA.

·              Metabolic (lactic) acidosis may occur in severe cases. Hyperkalaemia and dehydration have been reported. Hypo-natraemia associated with SIADH has also been reported.

·              Prolonged INR/PT and PTT, thrombocytopenia, anaemia and elevated fibrin degradation products have been observed in severe poisonings. A few cases of aplastic anaemia associated with MDMA use have been reported.

·              Muscle spasms, jaw clenching, tremors, and hyperre-flexia are common. Idiopathic temporomandibular joint syndrome (TMJ) has been reported in some patients, partly due to the secondary effects of bruxism and trismus observed following acute exposure.

·            Rhabdomyolysis is a common complication in patients who develop hyperthermia, seizures, coma, or muscular hyperactivity.

·            Eye pain, blurred vision and diffuse, punctate epithelial erosions of the cornea have been reported in patients who ingested MDMA and remained awake for long periods of time.

·            Chronic use results in anorexia, weight loss, exhaustion,jaundice, irritability, flashbacks, paranoia, depression, or psychosis. However, since frequent use diminishes the pleasurable effects of these drugs, users often take them only at intervals of 2 to 3 weeks, and then gradually lose interest and stop intake altogether over a period of time.* There appear to be no reports of individuals who take excessive doses of these drugs frequently over an extended period of time.

·            There are indications that chronic use of MDMA may cause mild-to-moderate subclinical impairment in cognitive func-tion, which may be related to deficits in serotonin (5-HT) function. Chronic paranoid psychosis has been reported in several cases of individuals chronically abusing MDMA.

·            Parkinsonian symptoms occurred in some patients following regular ingestion of MDMA over a prolonged period.

·            Hepatitis has been reported with chronic abuse.

·            Ecstasy has been associated with cardiovascular and musculoskeletal malformations in babies exposed in utero.

Treatment

·              Treatment measures are essentially the same as for all ampheta-mine poisonings.

Forensic Issues

·              Amphetamines are the most widely used illicit drugs (second only to cannabis) in the United Kingdom, Australia, and many parts of Europe. Significant abuse also occurs in the USA. After the introduction of amphetamines into clinical use in the early 1930s, they were available as prescription drugs for various indications (obesity, narcolepsy, attention deficit disorder, psychotherapy), and even sold over the counter in the form of nasal inhalers till the early 1970s. Since then their pharmaceutical use has been greatly curtailed, though many of these drugs are still available (under restriction) in Western countries. They are virtually banned in India.

·              Today, designer amphetamines are a rage among adolescent party-goers, and are used extensively in the course of “rave parties”. This fad has now gripped several metropolitan Indian cities where tablets of Ecstasy** (Fig 34.17) are available freely among elite circles (each tablet costing Rs.300 to 500). Much of this popularity has to do with the copious amount of informa-tion existing on these drugs on the Internet, and the fact that unlike certain other drugs like heroin and cannabis, designer drugs are considered “hep” and “cool”. Also, unlike many other hard drugs, designer drugs can be easily consumed (ingested) without the messiness of nasal insufflations, smoking, or injection. 


        Although MDMA is classified as a Schedule I drug, it is estimated by the US media that every year, hundreds of thousands of doses are used illegally. It is most commonly used by youngsters as they “roll” at underground rave parties that can last for many hours.

 

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