Designer Drug Exposé: Dissociatives
Dissociatives are a bizarre group of substances that make you feel "outside" your own body. There are thousands of newly discovered substances that produce this effect.
The dissociative experience is bizarre, blissful, and, under the right conditions, deeply therapeutic.
The problem is that long-term or irresponsible use of dissociatives has the complete opposite effect — often causing users to lose touch with themselves and their behavior.
Some of these substances can even result in serious cognitive damage. For example, the synthetic dissociative drug MK-801 (Dizocilpine) has been found to cause a unique form of brain damage known as Olney’s Lesions.
What is a Dissociative Drug?
Dissociative drugs are substances that decouple one’s first-person experience from reality. They dismantle the idea of “self” and alter one’s perception of time and space.
The effects of these substances vary by dose and substance… In lower doses, users feel like they’re sitting outside their body as a detached observer; in higher doses, all remnants of our shared reality fade away.
Dissociative drugs have conflicting and paradoxical effects — they’re stimulating and sedating, neuroprotective and neurotoxic, and have both addictive and anti-addictive qualities. The effect of these drugs largely comes down to the dose and frequency in which they are used.
The vast majority of dissociative drugs work by blocking the NMDA (N-methyl-D-aspartate) receptors in the brain. These receptors are intimately involved with functions like learning, memory, and pain and are involved in the regulation of neuroplasticity (the brain's ability to reorganize itself by forming new neural connections). Blocking these receptors appears to interrupt communication between different parts of the brain, resulting in a distinct separation of one’s conscious experience from the physical body.
Newer research also points to the sigma-1 and sigma-2 receptors — which were discovered in 1982 but poorly understood until very recently. Interaction with these receptors is thought to play a role in the dissociative and antidepressant effects of dissociative drugs like ketamine.
Now, let’s explore the main categories of dissociative drugs, their effects, history, legal status, and how the designer drug boom has led to the creation of hundreds of new dissociative substances.
Please note: This list is far from comprehensive — the dissociative drug class is already mindbogglingly large, and the potential for new functional combinations is staggering.
Arylcylohexylamines
The arylcyclohexylamine family is a massive group of dissociative stimulants. New substances are discovered in this group all the time, and there are thousands of “theoretical” drugs that have yet to be created and tested.
All arylcyclohexylamines are synthetic — none of them appear in nature.
Members of this family fall somewhere on the scale between psychostimulants (similar to amphetamines) and dissociative psychedelics. The most ubiquitous members are PCP (phencyclidine), ketamine, and MXE (methoxetamine).
Most of these compounds were only invented in the last 20 years — with the exceptions of PCP (1956) and ketamine (1962).
Today, ketamine reigns king of this class. It’s listed as a Schedule III substance and continues to be used for its approved application as a surgical anesthetic — as well as numerous off-label uses, including treatment for depression, PTSD, and chronic pain.
Within the arylcyclohexylamines, we can subdivide them into 2 main groups: ketamine analogs (includes a ketone group) and PCP analogs (no ketone group):
Ketamine Analogs
Ketamine is the most widely used arylcyclohexylamine in medical practice today. It’s regarded as a sort of wonder drug in the psychedelic medicine sphere. It's proven itself inexplicably useful for treating depression in patients who otherwise haven’t responded to treatment.
There are even telehealth clinics that administer ketamine from the comfort of your own home.
Ketamine also remains popular in the recreational space, where it’s used as an alternative to alcohol at raves and music festivals. In lower doses, ketamine has an alcohol-like effect, making users feel relaxed, disinhibited, and social.
Higher doses quickly evolve into something else entirely.
Moderate to high doses produce feelings of separation and detachment from reality; users often need to sit or lie down and may experience hallucinations.
Very high doses, like those used during anesthesia or IV ketamine therapy, cause users to feel as though they're falling into an endless void where nothing and nobody exists, including themselves. This “euphoric nothingness state” involves a profound dissolution of one's sense of self and a complete detachment from reality, rendering them unable to interact with or perceive the world around them.
Ketamine’s popularity has fuelled a lot of research into similar analogs — many were created for the sole purpose of avoiding regulations on this popular (and lucrative) substance.
Ketamine analogs include 2-BrDCK (2-bromodeschloroketamine), DCK (deschloroketamine), 2-FDCK (2-fluorodeschloroketamine), FXE (fluoroketamine), HXE (hydroxetamine), MXiPr (methoxisopropamine), MXPr (methoxpropamine), MXE (methoxetamine), 2-Keto-PCPr, HXM (2-hydroxy-deschloroketamine), meta-Ketamine, MMXE (methoxmetamine), 2-MDCK (methoxyketamine), and TFMDCK (trifluoromethyldeschloroketamine).
Only MXE is directly mentioned as a Schedule I drug in the United States.
PCP Analogs
PCP was invented in the 1950s and was adopted into medical practice as a surgical anesthetic in the 1960s. However, within just a few years, the drug was withdrawn and replaced with ketamine.
PCP worked great as an anesthetic, but it had a major problem…
Roughly 1 in 5 patients treated with PCP would experience post-surgery emergence delirium — a condition in which patients would wake up in a state of panic and confusion, often with hallucinations and intense paranoia. This state would last several hours before wearing off. Even though most patients returned to normal after a few hours, they would be left traumatized for weeks or months after the experience.
Despite being removed from service, PCP quickly found its way onto the streets. Curiously, the drug was only ever popular in the United States — most notably in poor black communities.
Antidrug campaigns throughout the 1970s and 80s aggressively targeted people who used PCP. These campaigns claimed that people who took the drug entered a drug-induced frenzy and became impervious to bullet wounds (which, of course, is not true). Many believe the US government exaggerated these reports and employed anti-PCP drug propaganda to attack black communities.
The draw for PCP was its potency and affordability. Users could pay a dealer as little as $1 to dip a cigarette in some liquid PCP. Smoking PCP-infused cigarettes caused users to blast off into a powerfully dissociative and hallucinogenic state that remained in full force for up to 24 hours.
Even after wearing off, many users report an afterglow akin to LSD or magic mushrooms in which they feel as though they could "see reality more clearly."
PCP has been illegal since 1978 — but new designer analogs of PCP continue to enter the market every year.
A few examples of PCP designer drug analogs include 2-MeO-PCMo, 2'-Cl-PCP, 2'-HO-PCP, 2'-MeO-PCP, 3'-Cl-PCP, 3'-F-PCP, 3'-HO-PCP, 3'-Me-PCP, 3'-Me-PCPy, 3'-MeO-PCP, 3-HO-PCE, 3-Me-PCP, 4'-F-PCP, 4-MeO-PCMo, PCPy (Rolicyclidine), and TCP (Tenocyclidine). Our database contains over 60 unique molecules directly related to PCP.
There are even a few designs that are essentially a mash-up of MDMA and PCP analogs. Examples include 3,4-MD-PCE, 3,4-MD-PCMo, and 3,4-MD-PCP.
Several pharmaceutical analogs of PCP have been explored in the past; however, most have been discontinued.
A few examples include:
Dexodadrol — Discontinued due to causing severe side effects, including hallucinations and nightmares.
Gacyclidine — First explored as a potential treatment for traumatic spinal cord injury but later discontinued after it was found to be ineffective.
Tenocyclidine (TCP) — Developed by Parke-Davis in the 1950s but discontinued and later listed as a Schedule I drug due to having nearly identical effects as PCP.
PCP analogs that have already been officially added to the restricted substances list in the US include TCP (tenocyclidine) and PCPy (Rolicyclidine).
Developing New Arylcyclohexylamines
The arylcyclohexylamine family is a dream for psychedelic chemists. These compounds allow for a nearly infinite combination of functional groups to create new, never-before-seen drugs.
Many (but not all) of the compounds in this family chemists have designed over the past 20 years are in some way psychoactive. A few are overtly toxic — such as PCE (eticyclidine).
Diarylethylamines
This category of dissociative drugs has been on the market since at least 2013. None have reached mainstream popularity yet continue to thrive in the underground dissociative sphere.
These compounds are not well understood, but their effects generally resemble that of the arylcyclohexylamines — they provide a combination of stimulant-like effects similar to the amphetamines as well as a clear dissociative quality.
None of these compounds are explicitly listed on the restricted substances list (in the US, at least).
Examples of designer diarylethylamine analogs include 2-chloro-ephenidine, 2-MeO-diphenidine, 2-MeO-ephenidine, diphenidine, ephenidine, fluorolintane, methoxphenidine, and N-Methylephenidine.
Inhalants
The inhalants are a diverse group of compounds ranging from elemental xenon to amyl-nitrite.
Some of the compounds in this group have clear medical value (like xenon or nitrous oxide), but the majority only serve as drugs of abuse with little medical or mind-expansive value.
In fact, most of the compounds discussed below have been linked with brain damage, lowered IQ, and cognitive impairment.
Xenon Gas
Xenon gas is technically not considered a designer drug — it’s been used in medical practice as an anesthetic for over 70 years. It is, by far, the strongest and most pure dissociative drug in the known universe.
Xenon forms only under the immense force of colliding neutron stars or supernovas. All the xenon on Earth was created billions of years ago and will continue to exist for billions more.
Obtaining pure xenon gas involves pressurizing vast quantities of ambient air until it becomes a liquid, then separating it from the nitrogen, oxygen, carbon dioxide, and other gases.
Xenon is widely considered the perfect anesthetic — it kicks in instantly, is completely non-toxic, doesn’t react with other medications, and is unmatched in its reliability for inducing deeply dissociative and euphoric states of consciousness.
Nitrous Oxide
Nitrous oxide gas (N2O) — also known as “laughing gas” or “hippy crack” — is similar to xenon in terms of its effects but only half as strong.
It’s a popular recreational drug in the form of “whippits” (canisters of N2O used in kitchens for dispensing whipped cream). Canisters can be bought from stores and installed without the cream to inhale the gas directly.
The N2O experience is deeply bizarre. Users remain in a state of pseudo-consciousness — often forgetting where they are who they are and losing touch with their body. This effect only lasts about 60 seconds before wearing off.
N2O was recently banned in several countries, including Australia, The Netherlands, and the UK. It remains unregulated in the United States.
→ Learn More About Nitrous Oxide
Alkyl Nitrites
The alkyl nitrites (AKA “poppers”) are another group of nitrogenous compounds. They're differentiated by varying lengths of alkyl chains connected to a central nitrite group.
There are about a dozen compounds in this family used as recreational drugs, several of which have been explicitly banned around the world.
Amyl nitrites are sold under the guise of “room deodorizer,” “leather polish,” “nail polish remover,” or “videotape cleaner” and marked “not for human consumption” to avoid legal restrictions. They’re most often sold in sex shops because of their alleged aphrodisiac qualities and their strange ability to relax involuntary smooth muscles — such as the anus.
Poppers have been in use since the mid-1970s — especially in the disco scene. Their popularity peaked in the late 80s and early 90s in rave culture and remains popular within the PnP subculture.
These substances are sold in small glass bottles of volatile liquid. The vapors are inhaled by sniffing the top of the container. Doing so induces an instant and short-lived high (lasting between 1–3 minutes). They produce a dissociative and euphoric action often described as “dizzying.”
Amyl nitrite, butyl nitrite, and isobutyl nitrite are officially banned in the United States, but other compounds like cyclohexyl nitrite, isopropyl nitrite, and methyl nitrite have yet to be included.
The potency of these drugs largely comes down to how volatile they are. That is, how readily they evaporate into the air where they can be inhaled to produce their effects:
High potency (high volatility) — methyl-nitrite, ethyl-nitrite, and isopropyl nitrite.
Moderate potency — isobutyl-nitrite and butyl-nitrite.
Low potency — amyl-nitrite, cyclohexyl-nitrite, and hexyl-nitrite.
Hydrocarbons
People have been huffing gasoline, glue, nail polish, and paint thinner for decades.
These compounds produce varying effects, but most have at least some dissociative component to them.
Users feel dizzy and “beside themselves.” Some produce an effect similar to alcohol intoxication (although very short-lived), while others are more euphoric.
Inhaling hydrocarbons and aerosols is not “illegal” per se, but is extremely damaging to the brain, cardiovascular system, kidneys, and liver. Studies show that frequent huffing of these substances leads to cognitive impairment and organ damage.
There are 3 major categories of psychoactive hydrocarbon inhalants:
Aliphatic hydrocarbons — Petroleum products (gasoline and kerosene) and natural gas (propane and butane).
Aromatic hydrocarbons — Toluene (used in paint thinner and model glue), xylene.
Hydrofluorocarbons — 1,1-Difluoroethane and 1,1,1,2-Tetrafluoroethane (found in air dusters and other aerosol products).
Morphinans
Morphinans are a large group of compounds that form the core structure for various opioids, including morphine, levorphanol, and buprenorphine.
Most morphinans target the opioid receptors to produce feelings of euphoria, dissociation, and sedation. They also block the transmission of pain signals traveling to the brain, which makes them useful for treating chronic pain conditions (these compounds will be covered in more depth in Part 8: Opiates and Sedatives).
The main dissociative member of the morphinan group is dextromethorphan (DXM). Codeine falls somewhere in the middle between an opioid analgesic and dissociative. These compounds act like arylcyclohexylamines by targeting the NMDA receptors.
DXM is sold over the counter in cough medications like Robitussin and is currently listed as a Schedule V drug in the United States but is unregulated in the European Union. It is, by far, the most popular dissociative morphinan in existence.
Users take DXM by mixing cough medicine containing DXM with soda or juice in a practice called “robotripping.”
There are four established levels or “plateaus” of the DXM experience, depending on the dose:
Plateau 1 (low dose) — Mild euphoric effects similar to low-dose MDMA or cannabinoids.
Plateau 2 (moderate dose) — Alcohol-like effects, making users feel drunk and lose motor control.
Plateau 3 (high dose) — Dissociative and euphoric effects. Users develop a “robot walk” and often just slump down on a couch or the floor as movement becomes increasingly difficult.
Plateau 4 (very high dose) — Very strong dissociative, even hallucinogenic effects similar to PCP. This dose is also considered deliriant, causing users to see things that aren’t really there.
Designer Drug Series
This has been part 6 in a 10-part series on designer drugs.
Read some of our past series using the links below, or subscribe to receive new posts as they’re released: