In general, these agents depress the central nervous system. The most common effects of their use, other that the euphoria and mood-altering effects, are sedation, muscle relaxation, drowsiness and, potentially, coma.
Mechanistically, CNS depressants may act as agonists at receptors whose normal function is to suppress neural activity (endorphins, GABA) or they may act directly on the nerve to suppress its activity.
The MAJOR depressants include:
Sedative/Hypnotics -- This class includes the barbiturates (phenobarbitone, butalbital, et c.) and benzodiazepines (diazepam, Valium®). They are used primarily in the treatment of nervousness, anxiety, and insomnia.
Alcohol -- This drug, while having medical uses, is most often encountered as a recreational drug.
Anti-histaminics -- These drugs are used primarily to treat colds and allergic rhinitis. They act by block histamine at its receptor. The abuse potential for this class of drugs is low. They are, however, sometimes used in speedballing (combining with CNS stimulants) or in the manufacture of certain street drugs.
OTC/Look-Alikes -- Many anti-histaminics are (or were) formulated to resemble the major depressants (Quaalude®, Valium®) in attempts to either fool prospective buyers or use a placebo effect to replace those more addicting substances.
Opium is the milky fluid that is derived from Papaver somniferum, the poppy plant. It is a mixture of all the constituents including the primary alkaloids morphine, codeine, and thebaine. Opium itself may be used medicinally and abused either by oral ingestion, injection, or smoking. While opium has been used for more than a thousand years, modern abuse became a problem with the use of morphine and laudanum (an opium-containing medicine) during the American Civil and Crimean Wars. More common is the use and abuse of the individual opium alkaloids. The naturally occurring alkaloids are called opiates while synthetic (man-made) derivatives are called opioids. All the drugs that are classified as opiates/opioids possess, in varying degrees, the same actions, effects, and abuse potential.
Other semi-synthetic and synthetic opioids that are used and abused in today's society include hydrocodone (Vicodin®), hydromorphone (Dilaudid®), Oxycodone (Percodan®, Tylox®), meperidine (Demerol®), pentazocine (Talwin®), fentanyl (Sublimaze®), and propoxyphene (Darvon®). These agents are used as analgesics or to help induce anæsthesia before surgery.
The action of these drugs is their ability to block pain receptors mediated by a compound made in the body called substance P (the both decrease its release and block its action directly). They also will decrease the ability of pain nerves to transmit the feeling of pain to the brain (they inhibit the activity of that nerve). This feeling of "no pain" is one of the reasons for their abuse. Additionally, the cause the release of dopamine in the brain which in turn activates the pleasure reward centre of the brain. This is another aspect of their abuse potential. The sensation of pleasure is so strong that many heroin users describe the rush as a very intense orgasmic feeling.
In addition to these affects, the opiates/opioids have other effects on the body. These include sedation, drowsiness, sleep, slurred speech, and a prolonged time to react to stimuli. They may also stimulate that part of the brain that causing vomiting (this area is called the chemoreceptor trigger zone) -- apomorphine is used to induce vomiting in veterinary medicine when dogs have been poisoned. The drugs also inhibit the coughing centre of the brain and cause constipation in the gastrointestinal system (they are used for these purpose in medicine -- to treat cough and diarrhœa). They also inhibit the center of the brain that controls cardiac function and respiratory function (these effects are often the cause of death in opiate/opioid overdose -- the patient stops breathing and the heart may stop pumping). They also cause the pupils of the eye to constrict. These pinpoint pupils are unresponsive to light (which would normally cause the pupils to dilate or enlarge). This action is used to help physicians determine if an overdose is due to morphine or a similar drug. (NOTE that cocaine and amphetamine cause the opposite effect -- pupil dilation.)
There are street-manufactured designer drugs that have similar actions as the opiates/opioids. These are often fentanyl derivatives that are much more potent that heroin (thus increasing the risk of overdose). MPPP is one such derivative of meperidine that if manufactured improperly may contain impurities that cause symptoms similar to Parkinson's disease.
As with the stimulants, opiates/opioids may be combined with other drugs. Popular combinations include codeine with glutethimide (a sedative hypnotic) and pentazocine with an anti-histamine (such as diphenhydramine or Benadryl®, commonly called T's and Blues). These combinations are reported to take two drugs that alone produce less euphoria/rush than stronger drugs and combine them to achieve a rush more like that seen with heroin.
The concerns of combining drugs and careless drug use (dirty needles, source, method of manufacture) are the same as those for the stimulants, namely dilution or adulteration with toxic chemicals, infection, hepatitis, et c. The social concerns are also similar with the abuse of these substance being correlated with increased crime activity, financial and family problems, et c.
Treatment approaches to opiate/opioid abuse are specific for the situation. In cases of overt toxicity (overdose), the patient is given naloxone or a similar drug that acts as an antagonist to block the effects of the opiate/opioid. Using heroin as an example, administration of this drug will completely counteract the effects of the heroin. In cases of severe overdose this can be a life-saving intervention, allowing the patient to breath. There are, however, two concerns with its use. Firstly, the blocking effects of the drug often wear off before the heroin has cleared the body. Consequently, the heroin may once again depress respiration to cause death. Patients must be monitored closely to prevent this from happening. Secondly, it will produce immediate withdrawal symptoms which may have to be treated by the physician. In cases where the individual wishes to stop using the drug, there are treatments that allow gradual withdrawal of the heroin (or similar drugs). One such treatment is the continuous administration of naloxone, which will block the effects of the heroine, hence no rush or positive re-inforcement from its use. A second drug that blocks the addictive properties of heroin (and other drugs of abuse) is clonidine. It is used in a similar manner as naloxone. Another treatment involves the administration of a drug with much weaker euphoric or positive re-inforcement effects, but it does have enough activity to prevent the unpleasant withdrawal symptoms. Methadone (Dolophine®) is the drug commonly used in this respect (hence the term methadone clinic). A methadone derivative that is also used for its sustained action (it last for up to 72 hours) is l-alpha-acetyl methadol. In any of these latter treatments, there must be some desire of the individual to really kick the habit.
Drugs that belong to this class may produce either sedation (a calming effect) or hypnosis (they induce sleep) and are used medically for these effects. Other legitimate uses for these drugs is to decrease neuroses, the treatment of anxiety, insomnia, epilepsy, and to produce mild tranquilisation and muscle relaxation.
They produce respiratory depression, similar to the opioids/opiates, but do not possess the other actions of heroin. The lethal actions of the drug are through this ability to stop respiration. Some classes (the barbiturates) produce more respiratory depression than others (the benzodiazepines).
The general effects of sedative hypnotics include anxiolytic (anti-anxiety), disinhibitory, sedative, hypnotic, and anaesthetic actions. Overdoses may cause respiratory depression, coma and death. Additionally there are some effects that are specific to the class.
Barbiturates also provide some feeling of pleasure (though not as great as that seen with the stimulants or the opiates/opioids. Another aspect of the effects of barbiturates is the fact that the mood of the user may predicate the response of drug use. For example, if the person is in an aggressive, combative, or argumentative mood, then the drug will make the person more aggressive, combative, or argumentative (an extension of the disinhibition). If the person is extremely tired when the drug is taken, they may simply sleep. If the person is feeling jovial, then their mood will be further elevated, et c. Tolerance develops to the actions of barbiturates and cross tolerance within the chemical class does occur. The tolerance is two-fold, being both pharmacokinetic and pharmacodynamic in nature (refer to the classifications of tolerance discussed previously).
The benzodiazepines are very similar to the barbiturates in their effects. The major difference in the two classes of drugs is that barbiturates are more toxic (the respiratory depression occurs at lower doses) than the benzodiazepines. Therefore, it is much harder to overdose on diazepam than on phenobarbital (another reason for the preference for benzodiazepines as abused substances). Tolerance and cross tolerance also occurs with the benzodiazepine class of drugs.
Withdrawal from either class of drugs are presented as symptoms of anxiety, agitation, anorexia (decreased appetite), nausea, vomiting, increased heart rate, sweating, cramps, and tremors. One aspect of withdrawal common for these agents that is not seen as much with the stimulants is the period of time it takes to develop and go through withdrawal. Many of these drugs produce their effect for a long period of time (up to days in some cases). Typically, the longer acting the drug, the longer it takes for withdrawal to develop and the longer it takes to go through withdrawal. Also, typically the longer the withdrawal, the less severe it is. (NOTE that this same principle applies to the development of tolerance -- the longer acting the drug, the longer it takes to develop tolerance).
Some of the sedative hypnotics are no longer available for legitimate use. Methaqualone was taken off the market for the high abuse that was occurring with it. It is now available on the street from either street manufacturers or it is smuggled from outside the country. Many times the street form of methaqualone may not even contain the real drug, but may be PCP, diazepam, or even Benadryl®.
GHB has never been officially marketed in this country for medical use. It is sporadically abused but gaining in popularity. One aspect of GHB that makes it popular is its ability to cause exotic or bizarre dreaming episodes.
The skeletal muscle relaxants methocarbamol (Robaxin®) and carisoprodol (Soma®) are widely prescribed for chronic back pain and spasm. Their abuse is widespread among those people who take them initially for muscle spasm. Tolerance does develop which accounts, at least in part, to their over use. Their effects are similar to the sedative hypnotics.
Summary -- In many cases, the abuse of these downers begins with legitimate prescriptions for real medical problems. Through the development of tolerance and the desirable effects of the drug (disinhibition and mood elevation for all of the above drugs and pleasure with the barbiturates), they become misused and abused, with the person often resorting to illegal transactions to obtain the drug.