Designer Drugs: Physiological effects

Last modified: Saturday, 30. May 2009 - 3:04 pm

Many designer drugs share a steep dose-response curve, meaning its effects can triple or quadruple with only minor increases in consumption. A 150 mg dose of MDMA, for example, can produce double the effects of a 120 mg dose. As many of the designer analogs are manufactured in underground laboratories, unknowns about the concentration of active ingredients have the potential to cause life-threatening situations.
Even experienced users of ketamine can miscalculate the dosage and find themselves on the verge of slipping into unconsciousness. In non-clinical settings, this potentially life-threatening state is called a “K-hole” and may be accompanied by convulsions, vomiting, and respiratory depression. Researchers report that while most users recover within 72 hours after ketamine usage, language and some aspects of memory impairment linger. Visual flashbacks have been reported days or weeks after use. Amnesia, aggressive behavior, and paranoid or delusional thinking have been reported after high recreational ingestion of ketamine.
The central nervous system actions that result from taking even small amounts of methamphetamine, on the other hand, include extreme alertness, increased energy, decreased appetite, increased respiration, hyperthermia, and euphoria — generally the effects sought by users. But over time, side effects such as irritability, insomnia, confusion, tremors, convulsions, anxiety, paranoia, and aggressiveness begin to intrude. These symptoms are magnified by lack of sleep. Withdrawal often produces severe depression.
The impact of MDMA use on the body includes muscle tension, involuntary teeth clenching, nausea, blurred vision, rapid eye movement, faintness, and chills or sweating. Immediate side effects may include nausea, dizziness, disorientation, anxiety, and panic attacks. 2C-B, a close cousin to MDMA, has a stimulating effect on the central nervous system, usually causing a slight rise in blood pressure and a quickening of the heart rate. As a result, 2C-B could pose a danger to those suffering from diabetes, epilepsy, or cardiac problems.
Because of high demand, ecstasy pills are frequently mixed with fillers and other active substances, most commonly amphetamines (speed), caffeine, and ephedrine (a natural amphetamine-like substance). Some pills have been found to contain DXM (dextromethorphan), a dissociative psychedelic found in some cough medicine, and PMA (paramethoxyamphetamine), a highly toxic hallucinogenic stimulant.
Because 2C-B is clandestinely produced, users are unaware of the dose they are ingesting and may be overwhelmed by the drug’s effects. Users seeking MDMA-like effects do not expect or enjoy the unpleasant physical side effects on the body, including acute nausea, diarrhea, cramps, and gas. There are also several reports of allergic-type reactions causing increased mucus production concentrated in the windpipe and lungs.
2C-B is not physically addictive, as is the case with methamphetamine or GHB. However, if used very regularly, there is the possibility that psychological dependence could develop. When used at dance clubs or large indoor events, there are dangers associated with overexertion as a common reaction to drug’s stimulatory effect, thereby causing dehydration and possible collapse. Nevertheless, to date, no deaths have been attributed to this drug.
GHB temporarily inhibits the release of dopamine in the brain. This may cause increased dopamine storage, which is followed by increased dopamine release when the GHB influence wears off. This effect could account for the middle-of-the-night awakenings common with use of higher GHB doses, and the general feelings of increased well-being, alertness, and arousal the next day.
There is much debate and considerable conflicting evidence regarding the mechanism of action of PCP. It is thought to stimulate alpha-adrenergic receptors in the brain and to elevate epinephrine, norepinephrine, and serotonin levels. PCP is also thought to inhibit communication along certain central nervous system pathways. Still others think that PCP acts on opiate receptors.
The physical effects of PCP on the user can be as varied and unpredictable as the psychological reactions. At low to moderate doses, PCP produces a slight increase in breathing rate and a more pronounced rise in blood pressure and pulse rate. Respiration becomes shallow, and flushing and profuse sweating occur. Generalized numbness of the extremities and loss of muscular coordination may also occur.
Harmful side effects
Most of the pleasing physical sensations and Mental effects of drugs covered in this section come from the forced release of serotonin and dopamine in the brain. Over the medium and long term, repeated abuse has been shown to damage dopamine transporters by shriveling the nerve endings of these crucial cells.
Methamphetamine and MDMA have been shown to cause damage to dopamine transporters. Anecdotally, users of both these drugs refer to the hardships of “coming down” and the “hangover” typified by fatigue and depression that typically lasts several days.
Methamphetamine use causes a sharp spike in blood pressure, dangerously irregular heartbeats, chest pain, shortness of breath, diarrhea, nausea, and vomiting. The drug can increase body temperature to critical levels, provoking cascading failures in vital systems. Brain hemorrhage is perhaps the biggest risk associated with abuse of the drug, which, if not fatal, can cause permanent paralysis and speech loss.
Ketamine toxicity is less of a concern than the accidents caused by the suddenness and duration of the dissociative state. Sudden collapse can lead to accident or injury, and loss of consciousness coupled with vomiting can lead to a blockage of the airway that could cause the user to choke to death.
At high doses, PCP prompts a drop in blood pressure, pulse rate, and respiration. These reactions may be accompanied by nausea, vomiting, blurred vision, uncontrolled eye movement, drooling, loss of balance, an exaggerated gait, seizures, convulsions, coma, and death.
PCC, a common by-product of PCP’s illicit manufacture (sometimes accounting for 10-25% of the mixture), causes abdominal cramps, diarrhea, and in sufficient doses, coma. PCC is an unstable compound, degrading to piperidine. Contaminated batches of PCP can sometimes be recognized by a strong fishy odor. When heated, as when it is smoked and inhaled, PCC liberates hydrogen cyanide, so cyanide poisoning in PCP smokers is also a strong possibility.
Long-term health effects
Some of the popularity associated with so-called designer drugs comes from the belief that these drugs are “safe” and not addictive. Both assumptions are wrong.
Methamphetamine is highly addictive. Users trying to abstain from use may suffer withdrawal symptoms that include depression, anxiety, fatigue, paranoia, aggression, and intense drug cravings. Chronic abuse of methamphetamine produces a psychosis similar to schizophrenia and may include violent behavior, anxiety, confusion, and insomnia. Users can also exhibit psychotic behavior, including auditory hallucinations, mood disturbances, delusions, and paranoia, possibly resulting in homicidal or suicidal thoughts.
Methamphetamine can cause brain damage that results in slower motor and cognitive functioning — even in users who take the drug for less than a year — according to two studies published in the March 2001 issue of the American Journal of Psychiatry. Over time, the damage that meth use does to dopamine receptors appears to seriously reduce the overall level of dopamine in the brain. This can result in symptoms like those of Parkinson’s disease, Alzheimer’s disease, stroke, and epilepsy, characterized by shaking and difficulty with walking, movement, coordination, and memory.
GHB is also addictive. Regular, daily use of GHB can cause physical dependency with harsh withdrawal symptoms. At four to six average doses per week, people report finding that they need to increase their dose to get the same level of intoxication. Many subsequently report that they need a little GHB just to feel normal. With very heavy use (one or more doses per day), many people report very serious physical addiction. Stopping “cold turkey” results in anxiety, inability to sleep, and feeling like the heart is arrhythmic (irregular).
More people are overdosing on GHB than ecstasy. In 2000, 2,482 GHB users visited the emergency room for an overdose, compared with 1,742 ecstasy users. There also are more deaths from GHB. According to the DEA, 73 people have died from taking GHB since 1995, compared to 27 ecstasy-related deaths from 1994 to 1998.
Although not thought to incite physical dependency, MDMA should not be considered risk-free. Recent studies confirm that MDMA is neurotoxic. A report published in June 1999 by researchers at Johns Hopkins University confirmed that the forced release of serotonin damages serotonin receptors in the brain. The serotonin system plays a direct role in regulating mood, aggression, sexual activity, sleep, and sensitivity to pain. The study, conducted on primates, showed that exposure to MDMA for four days caused brain damage that was evident six to seven years later. It was the first study to demonstrate MDMA’s potential for causing permanent brain damage.
Recent studies suggest all N-methyl-D-aspartate (NMDA) antagonists cause brain damage to the portions of the brain responsible for higher cognitive functions like memory and speech. These are the areas most affected by dissociative anesthetics and include ketamine, dextromethorphan (DXM), phencyclidine (PCP or angel dust), nitrous oxide (whippets), and dizocilpine (MK-801).
The long-term impact of 2C-B use is unknown. The September 1998 Journal of Analytical Toxicology reported that very little data exist about the pharmacological properties, metabolism, and toxicity of 2C-B. The relationship between its use and disease and death are unknown.
Given the similarity of its chemical structure to MDMA and the relatedness of effects on the user, it seems reasonable to infer that 2C-B may possess similar neurotoxic qualities, but more research is needed before any such conclusions can be drawn.

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