Depressants, also known as “downers,” are drugs that reduce central nervous system activity. Their effects, which are mainly psychoactive, calm the user down, sedate them and possibly put them to sleep. Other effects include analgesia (pain relief), hypotension (decreased blood pressure), bradycardia (reduced heart rate), muscle relaxation, anti-anxiety, and anti-convulsion. There may also be instances of cognitive and memory impairment as well as euphoria if used in higher concentrations or abused over a long period of time.
Depressants can be prescribed for a variety of clinical indications, but are also used illegally. The potential for these drugs to be abused is relatively high and withdrawal symptoms can be serious. They can create a physical dependence, affecting the body in manners which require continued use for survival. Usually these withdrawal symptoms are opposite to the effects elicited by the depressant such as agitation, sweating, muscle aches, anxiety as well as nausea, vomiting and diarrhea. Like most chronically abused drugs, tolerance will make abuse worse and the withdrawal reinforces depressant abuse. Three major types of depressants are a) opiates and opioids, b) barbiturates, and c) tranquilizers and benzodiazepines.
Opioids
Opioids (drugs that have opiate-like behavior and bind the opioid receptors) and opiates (drugs derived from opium) are a class of drugs used in a variety of indications. These clinical uses include analgesia (morphine), cough suppression (codeine), diarrhea (crude opium preparations), anesthesia (fentanyl) and detoxification (methadone). Some of these drugs are more addictive than others, especially morphine and heroin (diacetylmorphine). The effects depend on what they bind, how fast acting they are and how long their sustained effects are. For example, heroin is fast acting, producing euphoria and relaxation, while codeine is relatively slower and seems to produce only drowsiness.
There are four major classes of opioid receptors that mediate responses of opiates and opioids. They are delta, kappa, mu and nociceptin receptors, and can further be subdivided to subtypes. All are located in brain and spinal cord where they mediate effects. Natural chemicals can bind these receptors to induce analgesia, but opiates and opioids can produce greater effects in addition to analgesia. The mechanism of action by opiates and opioids is diverse. They can be full agonists (activates receptors), partial agonists (weak activating and possibly some inhibition) and antagonists (block the activation of receptor). Generally, opioids and opiates modulate or block activation of neurons by other neurotransmitters, most likely glutamate and GABA.
The most widely abused opiate is heroin. Heroin, which is a minor chemical modification of morphine, is rapidly absorbed and produces a rush. This rush is followed by an intense euphoria and sedation. Often times, this euphoria is sustained or made more intense by the co-use of cocaine, combined in the form of a “speedball.” This causes a synergistic euphoria. Frequent or chronic use of heroin as well as abuse of some other opioids/opiates (morphine, methadone) normally results in tolerance and dependence. This tolerance happens because the amount of opioid receptors, such as the mu receptors, decrease after long term use.
Withdrawal symptoms may include sweating, anxiety, insomnia, nausea and vomiting. Amazingly, unlike cocaine and amphetamines, heroin (including abused opiates/opioids) can produce a physical dependence in addition to psychological dependancy. These symptoms show up as gooseflesh, hyperthermia (high body temperature), chills and shakes. Scientists postulate that the reason for addiction and dependence is a result of central nervous system suppression. When heroin’s effects wear off, the central nervous system hyper-activates in reaction after suppression dissipates. This withdrawal and dependence, which may last up to a day after stoppage of use, induces the chronic user to seek out more drugs.
First line therapy for opiate and opioid dependancy is usually in the form of using a less potent opioid. These include methadone and buprenorphine. Though it may seem odd to use an opioid to treat dependence by a drug that is also an opioid, the thought is that the withdrawal symptoms to drugs like morphine or heroin are so intense, they foster reinstatement and abuse. In other words, the pains from stopping drug use reinforce use.
Therefore, methadone and buprenorphine, which are longer acting then heroin and morphine, stave off withdrawal. The next step is to wean the abuser off of opioids and opiates entirely because methadone and burprenorphine also have potential for dependancy. This may also include the use of nalaxone, an opioid antagonist, which blocks agonist effects. Psychotherapy is also used in combination to change the mind of the abuser as it has been reported that even after a long cessation, the user may still crave the drug.
Barbiturates
Barbiturates are derived from barbituric acid and are part of the class of drugs that induce sedation and hypnosis (or induce sleep), but have anticonvulsant, antiepileptic, and muscle relaxant properties. They are generally used for anesthesia in surgery and for insomnia (though currently, these drugs are being replaced by benzodiazepines). Some common barbiturates include phenobarbital, thiopental and mephobarbital. Their effects range from quick to long acting. Barbiturates produce their effects by binding to GABA receptors, specifically the GABAA subtype. GABA receptors are inhibitory in nature and therefore decrease or inhibit neurotransmission. Their activation leads to decreased neuroactivity.
Barbiturates are highly addictive and is a main reason for their replacement by less addictive benzodiazepines. They are abused because of their sedative and hypnotic (sleep-inducing) properties. Barbiturates are also abused due to their ability to induce amnesia (for a short period of time). Some barbiturates even stimulate euphoria and contentment along with impaired judgment, which similar to alcohol effects. It is not odd consequently to see users abuse both alcohol and barbiturates. As users frequent barbiturate use, they become increasingly dependent on these drugs. Physiologically, their bodies become more tolerant aiding chronic use. Withdrawal strongly reinforces barbiturate use. These symptoms include tremors, seizures, convulsions, anxiety, increased heart rate, muscle pain, hallucinations and confusion. If left untreated, the withdrawal of barbiturates can lead to sudden death. This is very serious and much unlike other types of abused drugs.
Treatment of barbiturate abuse is difficult and almost never done outside a detoxification facility or hospital setting. This is especially true when the effects of barbiturates wear off. Without continued use, the abuser can die from withdrawal. Therefore, chronic users are rarely taken off barbiturates immediately. Rather the dependency is treated by slowly weaning the user off of barbiturates. This is often accompanied by the addition of benzodiazepines such as diazepam to alleviate some of the withdrawal symptoms. Some users are also treated for alcohol abuse at the same time to produce effective results. In addition to pharmacotherapy, psychological intervention is needed to aid the user back to reality in terms of societal interaction and keep them from rebound.
Benzodiazepines
As aforementioned, benzodiazepines (sometimes referred as tranquilizers) were developed to replace barbiturates and their addictive potential. With that stated, they can be used in almost all clinical indications that barbiturates are prescribed for such as a sleep aid, anti-anxiety, anti-convulsant, anti-epilepsy and muscle relaxant. The well known benzodiazepines are diazepam (Valium), alprozalem (Xanax), and lorazepam (Ativan). By far, their use is almost exclusively aimed for insomnia and anti-anxiety. They are usually taken orally, but in emergency cases such as panic attacks or seizures, benzodiazepines are injected intravenously.
Similar to barbiturates, benzodiazepines bind the GABAA receptor to inhibit neurotransmission by affecting the receptors. The difference between barbiturates and benzodiazepines is that they do not bind the same site to produce this action. Though the addictive potential is less, they can still be abused for the relief they provide with respect to sleep and anxiety. Also, if taken in high enough concentrations and abused long enough, they can induce euphoria along with disorientation, sluggish movement and confusion. Mood swings and erratic behavior can happen in some chronic user. Like all abused drugs, the user can develop tolerance to benzodiazepines, and unfortunately they have similar withdrawal effects when effects wear off.
Treatment for benzodiazepine abuse is similar to barbiturates, which starts as a slow weaning off of the drugs. Users may be given flumazenil, a benzodiazepine antagonist, to aid in recovery. Flumazenil is additionally approved for benzodiazepine overdose. Psychotherapy is often needed to help the person operate in society in a normal manner, cognitively and behaviorally. Despite these effects, benzodiazepines are one of the most prescribed drugs. If prescribed for shorter amount of time, the potential for abuse is decreased. In terms of pharmacology, benzodiazepines are the better alternative to barbiturates.
