Depressant

Depressants, also known as central nervous system depressants, or colloquially known as "downers", are a class of psychoactive drugs characterised by decreasing neurotransmission levels, decreasing the electrical activity of brain cells, or reducing arousal or stimulation in various areas of the brain. Commonly used depressants include alcohol, opioids, and benzodiazepines. Some specific depressants influence mood, either positively (e.g., opioids) or negatively (e.g., alcohol), but depressants often have no clear impact on mood (e.g., most anticonvulsants). In contrast, stimulants, or "uppers", increase mental alertness, making stimulants the opposite drug class from depressants. Antidepressants are defined by their effect on mood, not on general brain activity, so they form an orthogonal category of drugs.

Depressants are closely related to sedatives as a category of drugs. The terms may sometimes be used interchangeably or may be used in somewhat different contexts. Nearly all commonly used depressants are addictive, and use of them carries the risk of death from respiratory depression, especially in opioids.

Depressants are used throughout the world as prescription medicines and illicit substances. Alcohol is a depressant. When depressants are used, effects often include ataxia, anxiolysis, pain relief, sedation or somnolence, cognitive or memory impairment, as well as, in some instances, euphoria, dissociation, muscle relaxation, lowered blood pressure or heart rate, respiratory depression, and anticonvulsant effects. Depressants sometimes also act to produce anesthesia. Other depressants can include drugs like benzodiazepines (e.g., alprazolam) and a number of opioids. Gabapentinoids like gabapentin and pregabalin are depressants and have anticonvulsant and anxiolytic effects. Most anticonvulsants, like lamotrigine and phenytoin, are depressants. Carbamates, such as meprobamate, are depressants that are similar to barbiturates. Anesthetics are generally depressants; examples include ketamine and propofol.

Depressants exert their effects through a number of different pharmacological mechanisms, the most prominent of which include facilitation of GABA and inhibition of glutamatergic or monoaminergic activity. Other examples are chemicals that modify the electrical signaling inside the body, such as bromides and channel blockers.

Indications

Depressants are used medicinally to relieve the following symptoms and disorders:

• Anxiety disorders such as:
• Generalized anxiety disorder
• Social anxiety disorder
• Panic attacks
• Insomnia
• Seizures
• Convulsions
• Depression
• Pain

Types

right|thumb|[[Distilled (concentrated) alcoholic beverages, sometimes called "spirit" or "hard liquor", are roughly eight times more alcoholic than beer.]]

Alcohol

An alcoholic beverage is a drink that contains alcohol (known formally as ethanol), an anesthetic that has been used as a psychoactive drug for several millennia. Ethanol is the oldest recreational drug still used by humans. Ethanol can cause alcohol intoxication when consumed. Alcoholic beverages are divided into three general classes for taxation and regulation of production: beers, wines, and spirits (distilled beverages). They are legally consumed in most countries. 100 countries have laws regulating their production, sale, and consumption.

The most common way to measure intoxication for legal or medical purposes is through blood alcohol content (also called blood alcohol concentration or blood alcohol level). It is usually expressed as a percentage of alcohol in the blood in units of mass of alcohol per volume of blood, or mass of alcohol per mass of blood, depending on the country. For instance, in North America, a blood alcohol content of 0.10 g/dL means that there are 0.10 g of alcohol for every dL of blood (i.e., mass per volume is used there).

Barbiturates

Barbiturates were once common treatments for insomnia, anxiety, and seizures, although their use has waned in recent decades. Barbiturates are sometimes used recreationally; they cause dependence and severe withdrawal, and they have a high risk of fatal overdose due to respiratory depression. By the late 1950s, concerns over the mounting social costs associated with barbiturates prompted a concerted effort to find alternative medications. Most people still using barbiturates do so for the prevention of seizures or, in mild form, for relief from the symptoms of migraines. One barbiturate that remains in use for seizure disorders is phenobarbital.

Benzodiazepines

A benzodiazepine is a drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first such drug, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955 and made available in 1960 by Hoffmann–La Roche, which has also marketed the benzodiazepine diazepam (Valium) since 1963.

thumb|Xanax ([[alprazolam) 2 mg tri-score tablets, a classical benzodiazepine sedative]]

Benzodiazepines enhance the effect of the neurotransmitter gamma-Aminobutyric acid (GABA) at the GABA_A receptor, resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties. High doses of shorter-acting benzodiazepines induce anterograde amnesia, which may be helpful for surgical and procedural anesthesia to reduce patient recall. Midazolam is often used in anesthesiology. These properties make benzodiazepines useful in treating anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal, and as a premedication for medical or dental procedures. Benzodiazepines are categorized as either short-, intermediate-, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia; longer-acting benzodiazepines are recommended for the treatment of anxiety.

In general, benzodiazepines are safe and effective in the short term, although cognitive impairments and paradoxical effects such as aggression or behavioral disinhibition occasionally occur. A minority of patients react to benzodiazepines with paradoxical agitation. Long-term use is controversial due to adverse psychological and cognitive effects, decreasing effectiveness, dependence, and benzodiazepine withdrawal syndrome, following withdrawal after long-term use. The elderly are at an increased risk of experiencing both short- and long-term adverse effects.

There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major teratogens, uncertainty remains as to whether they cause cleft palate in a small number of babies and whether neurobehavioral effects occur as a result of prenatal exposure; they are known to cause withdrawal symptoms in the newborn. Benzodiazepines can be overdosed and cause dangerous deep unconsciousness. However, they are much less toxic than their predecessors, barbiturates, and death rarely results when a benzodiazepine is the only drug taken; however, when combined with other central nervous system depressants such as alcohol and opioids, the potential for toxicity and fatal overdose increases. Benzodiazepines are commonly misused and taken in combination with other addictive drugs. In addition, all benzodiazepines are listed in the Beers List.

Cannabis

Cannabis is considered either in its own category or as a mild psychedelic. The chemical compound tetrahydrocannabinol (THC), which is found in cannabis, has many depressant effects, such as muscle relaxation, sedation, decreased alertness, and drowsiness. Contrarily, activation of the CB₁ receptor by cannabinoids causes an inhibition of GABA, which is atypical to most other depressants.

Carbamates

Carbamates are a class of depressants, or tranquilizers, that are synthesized from urea. Carbamates have anxiolytic, muscle relaxant, hypnotic, and analgesic effects. They have other uses, like muscle tremors, agitation, and alcohol withdrawal. Their muscle relaxant effects are useful for strains, sprains, and muscle injuries combined with rest, physical therapy, and other measures.

thumb|upright|[[Carisoprodol tablets]]

Side effects of carbamates include drowsiness, dizziness, headache, diarrhea, nausea, flatulence, liver failure, poor coordination, nystagmus, abuse, weakness, nervousness, euphoria, overstimulation, and dependence. Uncommon but potentially severe adverse reactions include hypersensitivity reactions such as Stevens–Johnson syndrome, embryo-fetal toxicity, stupor, and coma. It is not recommended to use most carbamates, like carisoprodol, for a long time, as physical and psychological dependence do occur.

Meprobamate was launched in 1955. It became the first psychotropic drug in America, gaining fame in Hollywood for its seemingly miraculous effects. It has since been marketed under 100 trade names, including Amepromat, Quivet, and Zirpon. Carisoprodol, which metabolizes into meprobamate and is still used mainly for its muscle relaxant effects, can potentially be abused. Its mechanism of action is very similar to that of barbiturates, alcohol, methaqualone, and benzodiazepines. Carisoprodol allosterically modulates and directly activates the human α1β2γ2 GABAAR (GABA_A) in the central nervous system, similar to barbiturates. This causes chloride channels to open, allowing chloride to flood into the neuron. This slows down communication between neurons and the nervous system. Unlike benzodiazepines, which increase the frequency of the chloride channel opening, carisoprodol increases the duration of channel opening when GABA is bound. GABA is the main inhibitory neurotransmitter in the nervous system, which causes its depressant effects.

Carbamates are fatal in overdose, which is why many have been replaced with benzodiazepines. Symptoms are similar to a barbiturate overdose and typically include confusion, poor coordination, decreased levels of consciousness, and a decreased effort to breathe (respiratory depression). An overdose is more likely to be fatal when mixed with another depressant that suppresses breathing.

Physical and psychological dependence does happen with long-term use of carbamates, particularly carisoprodol. Carisoprodol is only used in the short term for muscle pain, particularly back pain. Discontinuation after long-term use could be very intense and even possibly fatal. Withdrawal can resemble barbiturate, alcohol, or benzodiazepine withdrawal, as they all have a similar mechanism of action. Discontinuation symptoms include confusion, disorientation, delirium, hallucinations (auditory and visual), insomnia, decreased appetite, anxiety, agitation, pressured speech, tremor, tachycardia, and seizures, which could be fatal.

Carbamates gained widespread use in the 1950s, alongside barbiturates. While their use has waned due to concerns over overdose and dependence potential, newer derivatives of carbamates continue to be developed. Among these is Felbamate, an anticonvulsant that was approved in 1993 and is commonly used. It is a GABA_A positive allosteric modulator and blocks the NR2B subunit of the NMDA receptor. Other carbamates block sodium channels. Phenprobamate was used as an anxiolytic and is still sometimes used in Europe for general anesthesia and for treating muscle cramps and spasticity. Methocarbamol is a drug that is commonly known as Robaxin and is over-the-counter in some countries. It is a carbamate with muscle relaxant effects. Tetrabamate is a controversial drug that is a combination of febarbamate, difebarbamate, and phenobarbital. It is marketed in Europe and has been largely, but not completely, discontinued. On 4 April 1997, after over 30 years of use due to reports of hepatitis and acute liver failure, the use of the drug was restricted. Carisoprodol, known as "Soma", is still used for its muscle relaxant effects. It is also very commonly abused. It is a Schedule IV substance in the United States.

Approved:

• Carisoprodol/Meprobamate/Tybamate (Soma/Miltown, Solacen) (muscle relaxant, anxiolytic)
• Difebarbamate (Atrium, Sevrium)
• Emylcamate (Striatran) (anxiolytic and muscle relaxant)
• Ethinamate (Valamin, Valmid) (sedative–hypnotic)
• Febarbamate/Phenobamate (Solium, Tymium) (anxiolytic and sedative)
• Felbamate (Felbatol) (anticonvulsant)
• Hexapropymate (Merinax) (sedative–hypnotic)
• Mebutamate (Capla, Dormate) (anxiolytic, sedative, antihypertensive)
• Phenprobamate (Gamaquil, Isotonil) (muscle relaxant, sedative, anxiolytic, anticonvulsant, anesthesic)
• Procymate (Equipax) (sedative, anxiolytic)
• Styramate (Sinaxamol) (muscle relaxant, anticonvulsant)
• Tetrabamate (febarbamate, difebarbamate, phenobarbital) (Atrium, G Tril, Sevrium) (for anxiety, alcohol withdrawal, muscle tremors, agitation, and depression)

Not approved:

• Carisbamate (anticonvulsant)
• Clocental (hypnotic)
• Cyclarbamate (muscle relaxant and tranquilizer)
• Lorbamate (muscle relaxant and tranquilizer)
• Nisobamate (tranquilizer)
• Pentabamate (tranquilizer)

Gabapentinoids

Gabapentinoids are a unique and relatively novel class of depressants that selectively bind to the auxiliary α₂δ subunit (CACNA2D1 and CACNA2D2) site of certain VDCCs and thereby act as inhibitors of α₂δ subunit-containing voltage-gated calcium channels. α₂δ is nicknamed the "gabapentin receptor". At physiologic or resting membrane potential, VDCCs are normally closed. They are activated (opened) at depolarized membrane potentials, which is the source of the "voltage-gated" epithet. Gabapentinoids bind to the α1 and α2 sites of the α₂δ subunit family. Gabapentin is the prototypical gabapentinoid. The α₂δ is found on L-type calcium channels, N-type calcium channels, P/Q-type calcium channels, and R-type calcium channels throughout the central and peripheral nervous systems. α₂δ is located on presynaptic neurons and affects calcium channel trafficking and kinetics, initiates extracellular signaling cascades and gene expression, and promotes excitatory synaptogenesis through thrombospondin 1. Gabapentinoids are not direct channel blockers; rather, they disrupt the regulatory function of α₂δ and its interactions with other proteins. Most of the effects of gabapentinoids are mediated by the high-voltage activated N and P/Q-type calcium channels. P/Q-type calcium channels are mainly found in the cerebellum (Purkinje neurons), which may be responsible for the ataxic adverse effect of gabapentinoids, while N-type calcium channels are located throughout the central and peripheral nervous systems. N-type calcium channels are mainly responsible for the analgesic effects of gabapentinoids. Ziconotide, a non-gabapentinoid ω-conotoxin peptide, binds to the N-type calcium channels and has analgesic effects 1000 times stronger than morphine. Gabapentinoids are selective for the α₂δ site but non-selective when they bind to the calcium channel complex. They act on the α₂δ site to lower the release of many excitatory and pro-nociceptive neurochemicals, including glutamate, substance P, calcitonin gene-related peptide (CGRP), and more.

Gabapentinoids are absorbed from the intestines mainly by the large neutral amino acid transporter 1 (LAT1, SLC7A5) and the excitatory amino acid transporter 3 (EAAT3). They are one of the few drugs that use these amino acid transporters. Gabapentinoids are structurally similar to the branched-chain amino acids L-leucine and L-isoleucine, both of which also bind to the α₂δ site. Branched-chain amino acids like l-leucine, l-isoleucine, and l-valine have many functions in the central nervous system. They modify large neutral amino acid (LNAA) transport at the blood–brain barrier and reduce the synthesis of neurotransmitters derived from aromatic amino acids, notably serotonin from tryptophan and catecholamines from tyrosine and phenylalanine. This may be relevant to the pharmacology of gabapentinoids.

Gabapentin was designed by researchers at Parke-Davis to be an analogue of the neurotransmitter GABA that could more easily cross the blood–brain barrier and was first described in 1975 by Satzinger and Hartenstein. Gabapentin was first approved for epilepsy, mainly as an add-on treatment for partial seizures. Gabapentinoids are GABA analogues, but they do not bind to the GABA receptors, convert into GABA or another GABA receptor agonist in vivo, or directly modulate GABA transport or metabolism. Phenibut and baclofen, two structurally related compounds, are exceptions, as they mainly act on the GABA B receptor. Gabapentin, but not pregabalin, has been found to activate voltage-gated potassium channels (KCNQ), which might potentiate its depressant qualities. Despite this, gabapentinoids mimic GABA activity by inhibiting neurotransmission. Gabapentinoids prevent delivery of the calcium channels to the cell membrane and disrupt interactions of α₂δ with NMDA receptors, AMPA receptors, neurexins, and thrombospondins. Some calcium channel blockers of the dihydropyridine class are used for hypertension to weakly block α₂δ.

Gabapentinoids have anxiolytic, anticonvulsant, antiallodynic, antinociceptive, and possibly muscle relaxant properties. Pregabalin and gabapentin are used in epilepsy, mainly partial seizures (focal). Gabapentinoids are not effective for generalized seizures. They are also used for postherpetic neuralgia, neuropathic pain associated with diabetic neuropathy, fibromyalgia, generalized anxiety disorder, and restless legs syndrome. Pregabalin and gabapentin have many off-label uses, including insomnia, alcohol and opioid withdrawal, smoking cessation, social anxiety disorder, bipolar disorder, attention deficit hyperactivity disorder, chronic pain, hot flashes, tinnitus, migraines, and more. Baclofen is primarily used for the treatment of spastic movement disorders, especially in instances of spinal cord injury, cerebral palsy, and multiple sclerosis. Phenibut is used in Russia, Ukraine, Belarus, and Latvia to treat anxiety and improve sleep, as in the treatment of insomnia. It is also used for various other indications, including the treatment of asthenia, depression, alcoholism, alcohol withdrawal syndrome, post-traumatic stress disorder, stuttering, tics, vestibular disorders, Ménière's disease, dizziness, and the prevention of motion sickness and anxiety before or after surgical procedures or painful diagnostic tests. The FDA placed a black box warning on Neurontin (gabapentin) and Lyrica (pregabalin) for serious breathing problems. Mixing gabapentinoids with opioids, benzodiazepines, barbiturates, GHB, alcohol, or any other depressant is potentially deadly.

Common side effects of gabapentinoids include drowsiness, dizziness, weakness, increased appetite, urinary retention, shortness of breath, involuntary eye movements (nystagmus), memory issues, uncontrollable jerking motions, auditory hallucinations, erectile dysfunction, and myoclonic seizures.

An overdose of gabapentinoids usually consists of severe drowsiness, severe ataxia, blurred vision, slurred speech, severe uncontrollable jerking motions, and anxiety. Like most anticonvulsants, pregabalin and gabapentin have an increased risk of suicidal thoughts and behaviors. Gabapentinoids, like all calcium channel blockers, are known to cause angioedema. Taking them with an ACE inhibitor can increase the toxic effects of gabapentinoids. They may also enhance the fluid-retaining effect of certain anti-diabetic agents (thiazolidinediones). It is not known if they cause gingival enlargement like other calcium channel blockers. Gabapentinoids are excreted by the kidney, mostly in their original form. Gabapentinoids can build up in the body when someone has renal failure. This usually presents itself as myoclonus and an altered mental state. It is unclear if it is safe to use gabapentinoids during pregnancy, with some studies showing potential harm.

Physical or physiological dependence does occur during the long-term use of gabapentinoids. Following abrupt or rapid discontinuation of pregabalin and gabapentin, people report withdrawal symptoms like insomnia, headache, nausea, diarrhea, flu-like symptoms, anxiety, depression, pain, hyperhidrosis, seizures, psychomotor agitation, confusion, disorientation, and gastrointestinal complaints. Acute withdrawal from baclofen and phenibut may also cause auditory and visual hallucinations, as well as acute psychosis. Baclofen withdrawal can be more intense if it is administered intrathecally or for long periods of time. If baclofen or phenibut is used for long periods of time, it can resemble intense benzodiazepine, GHB, or alcohol withdrawal. To minimize withdrawal symptoms, baclofen or phenibut should be tapered down slowly. Abrupt withdrawal from phenibut or baclofen could possibly be life-threatening because of its mechanism of action. Abrupt withdrawal can cause rebound seizures and severe agitation.

• Phenylalanine
• NP-118809
• Gababutin
• Ziconotide (approved for pain)
• Ethanol
• Dextrothyroxine (agonist of α2δ instead of inhibiting it)
• Ethioninie
• Suloctidil
• Terodiline
• Bepridil

Gamma-hydroxybutyric acid

Gamma-hydroxybutyric acid, or "GHB", is a GABA analogue that is a naturally occurring neurotransmitter and depressant drug. It is also naturally found in small amounts in some alcoholic beverages alongside ethanol. GHB is the prototypical substance among a couple of GHB receptor modulators.

GHB has been used as a general anesthetic and as a treatment for cataplexy, narcolepsy, and alcoholism. The sodium salt of GHB, sodium oxybate, is commonly used for narcolepsy, sudden muscle weakness, and excessive daytime sleepiness. It is sold under the brand name Xyrem. an excitatory receptor that releases dopamine and glutamate, giving GHB stimulant effects, the opposite of a depressant. But in large doses, GHB activates the GABA_B receptor, an inhibitory receptor in the central nervous system, which overpowers the excitatory effects, thus causing central nervous system depression. Some antipsychotics are agonists of the GHB receptor.

GHB can usually be found in either sodium, potassium, magnesium, or calcium salts. Xywav is a medication that is a mixture of all GHB salts and is used to treat the same conditions as Xyrem. Both Xywav and Xyrem are Schedule III and have a black box warning for central nervous system depressant effects (hypoventilation and bradycardia) and for their very high potential for abuse. Death from a GHB overdose is usually caused by respiratory depression, seizures, or coma.

GHB is used illegally as an intoxicant, an aphrodisiac, and an athletic-performance enhancer. It has also been reportedly used as a date-rape drug. This caused it to be a Schedule I substance in the United States, Canada, and other countries. Xyrem, which is GHB in its sodium form, is Schedule III in the United States, Canada, and other countries. The GHB receptor is an excitatory G protein-coupled receptor (GPCR). the mechanism is currently not known but it is believed to be due to interactions with the GABA_B receptor.

Physical dependence develops quickly and is highly addictive. It shares some similarities, when suddenly discontinued, with the withdrawal symptoms of gabapentinoids phenibut and baclofen due to the activation of the GABA_B receptor. It features a typical depressant withdrawal syndrome that mimics alcohol withdrawal. Symptoms include delirium, tremor, anxiety, tachycardia, insomnia, hypertension, confusion, sweating, severe agitation which may require restraint, auditory and visual hallucinations, and possibly death from tonic-clonic seizures.

Baclofen and phenibut are very effective for withdrawal and are preferred by patients over benzodiazepines for treatment of withdrawal. They are structurally related to benzodiazepines. They positively modulate the benzodiazepine site of the GABA_A receptor, the chief inhibitory receptor of the central nervous system, just like benzodiazepines, but at a molecular level, they are structurally unrelated.

Nonbenzodiazepines bind to the benzodiazepine site on the GABA_A receptor to keep the chloride channel open. This causes chloride in the intercellular area to flood into the neuron. Since chloride has a negative charge, it causes the neuron to rest and cease firing. This results in a relaxing and depressant effect on the central nervous system.

Common nonbenzodiazepines like zolpidem and zopiclone are extremely effective for insomnia, but carry many risks and side effects. Sleeping pills, including zopiclone, have been associated with an increased risk of death.

Nonbenzodiazepines should not be discontinued abruptly if taken for more than a few weeks

due to the risk of rebound withdrawal effects and acute withdrawal reactions, which may resemble those seen during benzodiazepine withdrawal. Treatment usually entails gradually reducing the dosage over a period of weeks or several months, depending on the individual, dosage, and length of time the drug has been taken. If this approach fails, a crossover to a benzodiazepine equivalent dose of a long-acting benzodiazepine (such as chlordiazepoxide or, more preferably, diazepam) can be tried, followed by a gradual reduction in dosage. In extreme cases and, in particular, where severe addiction and/or abuse are manifested, inpatient detoxification may be required, with flumazenil as a possible detoxification tool.

Opioids

Opioids are substances that act on opioid receptors to reduce pain. Medically, they are primarily used for pain relief, including anesthesia. Opioids also cause euphoria and are highly abused.

There are three principal classes of opioid receptors: μ, κ, δ (mu, kappa, and delta), although up to seventeen have been reported, and include the ε, ι, λ, and ζ (epsilon, iota, lambda, and zeta) receptors. Conversely, σ (sigma) receptors are no longer considered to be opioid receptors because their activation is not reversed by the opioid inverse-agonist naloxone. The nociception opioid peptide receptor (NOP) (ORL1) is an opioid receptor that is involved in pain responses, anxiety, movement, reward, hunger, memory, and much more. It plays a major role in the development of tolerance to μ-opioid receptor agonists.

When pain occurs, a signal gets sent from the site of possible injury. This signal goes up the spinal cord into the brain, where it is perceived as a negative emotion known as nociception. In the central nervous system, the spine is connected to the brain by a structure called the brain stem. The brain stem is the first part of the brain that develops in a mammal out of the neural crest. It is also the oldest part of the brain and controls many automatic functions such as consciousness, breathing, heart rate, digestion, and many more. Opioid receptors are specialized pain-blocking receptors. They bind a wide range of hormones, peptides, and much more. Although they are found everywhere in the central nervous system, they are highly concentrated in the brain stem. Depending on the receptor, activation has the ability to stop pain from making its way to the brain and being perceived as pain. Hence, opioids do not actually "stop" pain; they stop awareness of pain. Pain and the ability to modify it based on an organism's environment is an evolutionary advantage, and it has been shown that it can help an organism escape and survive certain situations where they may otherwise be immobilized due to pain and injury. The midbrain nuclei of the brain stem, with structures like the periaqueductal gray, reticular formation, and rostromedial tegmental nucleus, are responsible for the majority of the physical and psychological effects of endogenous and exogenous opioids.

The μ-opioid receptor is responsible for the analgesic, euphoric, and adverse effects of opioids. The μ-opioid receptor is a G protein-coupled receptor. When the μ-opioid receptor is activated, it causes pain relief, euphoria, constipation, constricted pupils, itching, and nausea. The μ-opioid is located in the gastrointestinal tract, which controls peristalsis. This causes constipation, which can be extremely problematic and distressing. Activation of this receptor also causes relaxation of voluntary and involuntary muscles, which can cause side effects like trouble urinating and swallowing. The μ-opioid receptor can also reduce androgens, thus decreasing libido and sexual function. The receptor is also known to cause "musical anhedonia".

The μ-opioid receptor has many endogenous ligands, including endorphin.