Methoxetamine, abbreviated as MXE, is a

dissociative Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...

hallucinogen Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized ...

that has been sold as a

designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Des ...

. It differs from many dissociatives such as

ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...

and

phencyclidine Phencyclidine or phenylcyclohexyl piperidine (PCP), also known as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptio ...

(PCP) that were developed as

pharmaceutical drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

s for use as

general anesthetic General anaesthetics (or anesthetics, see spelling differences) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma ...

s in that it was designed specifically for recreational use. It is a rare example of a drug being so widely controlled without having an existing medical use. MXE is an

arylcyclohexylamine Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs. History Phencyclidine (PCP) is believed to be the first arylcyclohexylamine with recogniz ...

. It acts mainly as an

NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...

, similarly to other arylcyclohexylamines like ketamine and PCP.

Recreational use

Effects

MXE is reported to have a similar effect to ketamine. It was often believed to possess

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

properties due to its structural similarity to 3-HO-PCP, but this assumption is not supported by data, which shows insignificant affinity for the

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical � ...

by the compound. Recreational use of MXE has been associated with hospitalizations from high and/or combined consumption in the US and UK. Acute reversible

cerebellar The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...

toxicity has been documented in three cases of hospital admission due to MXE overdose, lasting for between one and four days after exposure. MXE was designed in part in an attempt to avoid the urotoxicity associated with ketamine abuse; it was thought the compound's increased

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

and reduced dose would limit the accumulation of urotoxic

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s in the

bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...

. Like ketamine, MXE has been found to produce bladder

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

and

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

after high dose, chronic administration in mice, although the dosages used were quite large. Reports of urotoxicity in humans have yet to appear in the medical literature.

Pharmacology

Pharmacodynamics

MXE acts mainly as a selective and high-

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Partn ...

, specifically of the

dizocilpine Dizocilpine (INN), also known as MK-801, is a pore blocker of the ''N''-Methyl-D-aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is ...

(MK-801) site (K_i = 257 nM). It produces

-like effects. In addition to antagonism of the NMDA receptor, MXE has been found to act as a

serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the action of the serotonin transporter (SERT). This in turn leads to increase ...

(K_i = 479 nM; IC₅₀ = 2,400 nM). Conversely, it shows little or no effect on the

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transm ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

(K_i and IC₅₀ > 10,000 nM). Nonetheless, MXE has been found to activate

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate d ...

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...

, including in the

mesolimbic reward pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The ventral ...

. This is a characteristic that it shares with other NMDA receptor antagonists, including ketamine, PCP, and

(MK-801). Animal studies suggest MXE may have rapidly-acting

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

effects similar to those of ketamine. A study that assessed binding of MXE at 56 sites including

neurotransmitter receptor A neurotransmitter receptor (also known as a neuroreceptor) is a membrane receptor protein that is activated by a neurotransmitter. Chemicals on the outside of the cell, such as a neurotransmitter, can bump into the cell's membrane, in which the ...

s and transporters found that MXE had K_i values of >10,000 nM for all sites except the dizocilpine site of the NMDA receptor and the

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...

(SERT).

Pharmacokinetics

MXE has a longer

duration of action Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for ...

than that of ketamine.

Chemistry

MXE is an

and a

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. F ...

eticyclidine Eticyclidine (PCE, CI-400) is a dissociative anesthetic drug with hallucinogenic effects. It is similar in effects to phencyclidine but is slightly more potent. PCE was developed by Parke-Davis in the 1970s and evaluated for anesthetic potential ...

(PCE). It can also be thought of as the β-Keto-derivative of 3-methoxyeticyclidine (3-MeO-PCE), or the N-ethyl homologue of

methoxmetamine Methoxmetamine (also known as 3-MeO-2'-Oxo-PCM, MXM and MMXE) is a dissociative anesthetic of the arylcyclohexylamine class that is closely related to methoxetamine and methoxyketamine, and has been sold online as a designer drug A designer drug ...

(MXM) and methoxpropamine (MXPr). It is closely related structurally to

, and more distantly to PCP. MXE hydrochloride is soluble in ethanol up to 10 mg/ml at 25 °C.

Detection in body fluids

A forensic standard of MXE is available, and the compound has been posted on the Forendex website of potential drugs of abuse.

History

The qualitative effects of MXE were first described online in May 2010 and the compound became commercially available on a small scale in September 2010. By November the use and sale of the MXE had increased enough for it to be formally identified by the

European Monitoring Centre for Drugs and Drug Addiction The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is an agency of the European Union located in Lisbon, Portugal, and established in 1993. In June 2022, the Council of the European Union approved a reform of the organization w ...

. By July 2011, the EMCDDA had identified 58 websites selling the compound at a cost of 145–195 euros for 10 grams.

Society and culture

Media coverage

Mixmag ''Mixmag'' is a British electronic dance and clubbing magazine published in London. Launched in 1983 as a print magazine, it has branched into dance events, including festivals and club nights. History The first issue of ''Mixmag'' was prin ...

'' reported in January 2012, that people in the dance music and clubbing community have given MXE the slang name ' roflcoptr'. ''

Vice A vice is a practice, behaviour, or habit generally considered immoral, sinful, criminal, rude, taboo, depraved, degrading, deviant or perverted in the associated society. In more minor usage, vice can refer to a fault, a negative character tra ...

'' commented that it was likely that the phrase will only be used by "the same politicians, parents and journalists" who called

mephedrone Mephedrone, also known as , , and , is a synthetic stimulant drug of the amphetamine and cathinone classes. Slang names include drone, , White Magic, meow meow, bubble, ''txomin'' and yurrpt. It is chemically similar to the cathinone compounds ...

'meow meow'. After being called mexxy in UK Home Office press releases, the media adopted the name. A literature review was published in March 2012 which looked at scientific literature and information on the web. It concluded that "the online availability of information on novel psychoactive drugs, such as MXE, may constitute a pressing public health challenge. Better international collaboration levels and novel forms of intervention are necessary to tackle this fast-growing phenomenon."

Legal status

Brazil

MXE became classified as a narcotic in

Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...

in February 2014.

Canada

As of January 2010 MXE is a controlled substance in Canada.

China

As of October 2015 MXE is a controlled substance in China.

European Union

On 16 June 2014, the

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...

proposed that MXE be banned across the

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...

, subjecting those in violation to criminal sanctions. This is following the procedure for risk-assessment and control of new

psychoactive substances A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. T ...

set up by the council: Decision 2005/387/JHA.

Israel

MXE became classified as an illegal narcotic in

Israel Israel (; he, יִשְׂרָאֵל, ; ar, إِسْرَائِيل, ), officially the State of Israel ( he, מְדִינַת יִשְׂרָאֵל, label=none, translit=Medīnat Yīsrāʾēl; ), is a country in Western Asia. It is situated ...

in May 2012.

Japan

MXE became a

controlled substance A controlled substance is generally a drug or chemical whose manufacture, possession and use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law. Some treaties, notably the Single C ...

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...

from 1 July 2012, by amendment to the Pharmaceutical Affairs Law.

Poland

MXE is a

(group II-P) making it illegal to produce, sell or possess in The Republic of

Poland Poland, officially the Republic of Poland, is a country in Central Europe. It is divided into 16 administrative provinces called voivodeships, covering an area of . Poland has a population of over 38 million and is the fifth-most populous ...

as of 1 July 2015.

Russia

MXE has been a

Russia Russia (, , ), or the Russian Federation, is a List of transcontinental countries, transcontinental country spanning Eastern Europe and North Asia, Northern Asia. It is the List of countries and dependencies by area, largest country in the ...

since October 2011.

Sweden

MXE became classified as a

narcotic The term narcotic (, from ancient Greek ναρκῶ ''narkō'', "to make numb") originally referred medically to any psychoactive compound with numbing or paralyzing properties. In the United States, it has since become associated with opiates ...

Sweden Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic country located on ...

in late February 2012.

Switzerland

MXE has been illegal in

Switzerland ). Swiss law does not designate a ''capital'' as such, but the federal parliament and government are installed in Bern, while other federal institutions, such as the federal courts, are in other cities (Bellinzona, Lausanne, Luzern, Neuchâtel ...

since December 2011.

United Kingdom

Prior to March 2012, MXE was not controlled by the UK's Misuse of Drugs Act. In March 2012, the Home Office referred MXE to the

Advisory Council on the Misuse of Drugs The Advisory Council on the Misuse of Drugs (ACMD) is a British statutory advisory non-departmental public body, which was established under the Misuse of Drugs Act 1971. Mandate Its terms of reference, according to the Act, are as follows: '' ...

for possible temporary controlling under the powers given in the

Police Reform and Social Responsibility Act 2011 The Police Reform and Social Responsibility Act 2011 (c. 13) is an Act of the Parliament of the United Kingdom. It transfers the control of police forces from police authorities to elected Police and Crime Commissioners. The first police commis ...

. The ACMD gave their advice on 23 March, with the chair commenting that "the evidence shows that the use of methoxetamine can cause harm to users and the ACMD advises that it should be subject to a temporary class drug order." In April 2012, MXE was placed under

temporary class drug A temporary class drug is a relatively new status for controlled drugs, which has been adopted in some jurisdictions, notably New Zealand and the United Kingdom, to attempt to bring newly synthesised designer drugs under legal control. The controll ...

control, which prohibited it's import and sale for 12 months. :Theresa May commented in her reply to the ACMD that "the next step in this process is for the ACMD to undertake a full assessment of MXE for consideration for its permanent control under the 1971 Act." She goes on to say that she hopes the ACMD will do this as a part of the review of ketamine, "including its analogues" and that this review will be completed "within the 12 months from the making of the current order". :On 18 October 2012 the ACMD released
report
about MXE, saying that the "harms of methoxetamine are commensurate with Class B of the Misuse of Drugs Act (1971)", despite the fact that the act does not classify drugs based on harm. The report went on to suggest that all analogues of MXE should also become class B drugs and suggested a catch-all clause covering both existing and unresearched arylcyclohexamines. :MXE ceased to be covered by the temporary prohibition on 26 February 2013, when it became classified as a Class B drug.

United Nations

MXE is one of a few substances which has been controlled under the UN 1971 Convention on Psychotropic Substances since its inception. It was made a schedule II drug in November of 2016.

United States

On June 6, 2022, the U.S.

Drug Enforcement Administration The Drug Enforcement Administration (DEA; ) is a Federal law enforcement in the United States, United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within th ...

published a final rule placing MXE in Schedule I of the

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...

. :;Alabama :MXE is a Schedule I

in the state of

Alabama (We dare defend our rights) , anthem = "Alabama (state song), Alabama" , image_map = Alabama in United States.svg , seat = Montgomery, Alabama, Montgomery , LargestCity = Huntsville, Alabama, Huntsville , LargestCounty = Baldwin County, Al ...

making it illegal to buy, sell, or possess in Alabama. :;Florida :MXE is a Schedule I

in the state of

Florida Florida is a state located in the Southeastern region of the United States. Florida is bordered to the west by the Gulf of Mexico, to the northwest by Alabama, to the north by Georgia, to the east by the Bahamas and Atlantic Ocean, and to ...

making it illegal to buy, sell, or possess in Florida. :;Utah :MXE is a

in the state of

Utah Utah ( , ) is a state in the Mountain West subregion of the Western United States. Utah is a landlocked U.S. state bordered to its east by Colorado, to its northeast by Wyoming, to its north by Idaho, to its south by Arizona, and to it ...

making it illegal to buy, sell, or possess in Utah.Utah Code 58-37-4.2. Listed controlled substances.

References

External links

Erowid.org – Methoxetamine Information
{{Monoamine reuptake inhibitors Arylcyclohexylamines Designer drugs Dissociative drugs Euphoriants Ketones NMDA receptor antagonists Phenol ethers Serotonin reuptake inhibitors