The Chemical That Rewrote the Rules of Consciousness
Phencyclidine, more commonly known as PCP or angel dust, is one of the most controversial and misunderstood substances in the history of psychopharmacology. Initially developed in the 1950s as a promising surgical anesthetic, PCP was quickly abandoned for human medical use due to its profound psychological side effects. Yet, despite its notoriety as a dangerous street drug, PCP remains a compound of intense interest in neuroscience due to its unique pharmacology, profound dissociative effects, and complex impact on brain function.
PCP belongs to the class of arylcyclohexylamines, a family that includes other dissociatives such as ketamine and MXE. Unlike most recreational drugs that target dopamine or serotonin, PCP is primarily a non-competitive NMDA receptor antagonist, disrupting glutamate signaling in the brain. This results in sensory distortion, altered body perception, and extreme detachment from reality—a mental state unlike that induced by any other psychoactive compound.
Despite its high abuse potential and association with erratic behavior, PCP has also contributed significantly to our understanding of psychosis, consciousness, and neurochemical regulation. In laboratory settings, PCP has been used to induce schizophrenia-like symptoms in animal models, helping researchers unravel the mechanisms behind hallucinations and cognitive disintegration.
In this blog post, we’ll explore the history, pharmacology, effects, risks, and cultural myths surrounding PCP, all backed by decades of scientific research. You’ll also discover lesser-known facts about this infamous drug, including its role in neuroscience research and its influence on how we understand the architecture of the human mind.
The Origins of PCP: From Operating Rooms to Urban Streets
PCP was first synthesized in 1926 but gained attention in the 1950s when the pharmaceutical company Parke-Davis introduced it as a surgical anesthetic under the trade name Sernyl. Early trials found that PCP offered powerful analgesic effects with minimal respiratory depression, a valuable feature in anesthesia. However, as reports of post-operative delirium, hallucinations, and agitation emerged, its use in human patients was swiftly discontinued by 1965.
Veterinary use of PCP continued briefly, particularly for large animals, but this too was phased out due to behavioral abnormalities following administration. Around the same time, PCP began to leak into the recreational drug scene, initially among college students and later spreading into urban areas during the 1970s. The drug’s relatively easy synthesis and potent effects made it popular but unpredictable.
By the late 1970s and 1980s, PCP had become notorious for its association with violent or erratic behavior, earning it a place in sensationalist media headlines. Reports of individuals displaying superhuman strength, resistance to pain, and self-mutilation while under the influence of PCP created a mythos that persists to this day. However, many of these extreme cases were complicated by polysubstance use, poor psychiatric screening, or exaggerated reporting.
Interestingly, PCP was the first dissociative anesthetic to be used on humans, preceding ketamine. Its replacement, ketamine, shares a similar mechanism of action but produces a shorter duration of action and fewer psychiatric side effects, which made it preferable in clinical settings. Nevertheless, PCP paved the way for our understanding of dissociative pharmacology and led directly to the development of safer alternatives.
Lesser-known fact: In the 1960s, PCP was briefly studied for its potential to treat depression—a direction that modern science is revisiting today with more controlled compounds like ketamine and its derivatives.
How PCP Works: NMDA Receptors, Dopamine, and Cognitive Chaos
At the molecular level, PCP’s primary mechanism of action is as a non-competitive antagonist of the NMDA receptor, a subtype of glutamate receptor. NMDA receptors are critical for synaptic plasticity, memory, and conscious awareness, and blocking them leads to the profound cognitive and perceptual disruptions associated with dissociative states.
By binding inside the NMDA channel, PCP prevents calcium influx, effectively shutting down communication between neurons that rely on excitatory glutamate signaling. This creates a form of functional disconnection within the brain, leading to a breakdown in reality processing. Users may experience time dilation, body distortion, hallucinations, or the sensation of floating outside their bodies.
But PCP’s action doesn’t stop at NMDA. It also influences dopamine, norepinephrine, and serotonin levels, contributing to its stimulating and mood-altering effects. The increased dopamine activity is partially responsible for the euphoric or manic states some users experience, while elevated norepinephrine can fuel anxiety and hyperarousal.
Interestingly, PCP is one of the few substances that can reliably produce a full psychotic episode in healthy individuals, making it a valuable model for studying schizophrenia. In animal models, PCP administration produces behavioral and cognitive deficits that closely mimic those seen in human schizophrenia patients, such as social withdrawal, working memory deficits, and thought disorganization.
Fascinating fact: PCP-induced psychosis can persist for days—even weeks—after the drug has left the bloodstream. This delayed onset of psychotic symptoms has made PCP an important research tool in uncovering how glutamatergic dysfunction contributes to mental illness.
The PCP Experience: Dissociation, Hallucinations, and Euphoria
The effects of PCP vary dramatically depending on dose, route of administration, setting, and individual neurobiology. Low doses (5–10 mg) may produce mild euphoria, numbness, and light dissociation, while moderate doses can cause hallucinations, confusion, and profound detachment from reality. At higher doses, users can enter a state known as the “blank stare”, where motor control, speech, and cognition break down entirely.
The hallmark of PCP intoxication is its intense dissociative quality—users often feel disconnected from their bodies, as if they are observing themselves from outside. This is sometimes accompanied by auditory hallucinations, delusions of grandeur, or feelings of invincibility. These experiences can be euphoric or terrifying, depending on the user’s mental state and environment.
Unlike classic psychedelics, which amplify sensory input, PCP tends to suppress external stimuli, creating a “tunnel-vision” consciousness. This makes it highly unpredictable; users may feel impervious to pain, exhibit robotic or erratic movements, and even black out entire portions of the trip.
The physical side effects of PCP include increased heart rate, elevated blood pressure, muscle rigidity, and at higher doses, seizures or coma. One reason PCP is so dangerous is that it blunts pain perception while increasing aggression in some individuals, which can result in unintended self-injury or violence, particularly in chaotic settings.
Little-known insight: PCP’s effects are longer-lasting than most street drugs. While ketamine wears off in under an hour, PCP’s peak can last 4–6 hours, with lingering effects for 12–24 hours or more, making acute medical interventions more complex.
Myths, Dangers, and Public Perception
PCP is one of the few drugs that has entered the realm of urban legend. Stories of users ripping off their own limbs, exhibiting superhuman strength, or becoming entirely immune to pain have circulated for decades. While some of these stories are based in truth, many are exaggerated or conflated with other substances like synthetic cannabinoids or methamphetamines.
One of the reasons PCP earned such a dangerous reputation is its broad dose-response curve—the difference between a euphoric dose and a psychotic one is often razor-thin. Inexperienced users may take more thinking the drug hasn’t kicked in yet, leading to unpredictable and severe effects. Additionally, PCP is often laced into cannabis or other powders unknowingly, exposing users to its effects without informed consent.
Unlike opioids or alcohol, PCP does not cause respiratory depression, but death can occur from trauma, seizures, or hyperthermia, especially when used in physically demanding or high-temperature environments. Chronic use can lead to persistent cognitive impairment, depression, and social isolation. Tolerance builds quickly, and withdrawal—though not typically life-threatening—can involve cravings, depression, and agitation.
Perhaps one of the most dangerous myths about PCP is that it cannot be detected in standard drug tests. In reality, PCP is included in most 5-panel drug screens and can be detected for up to 7–10 days in urine, depending on the dose and frequency of use.
Interesting note: PCP analogues like 3-MeO-PCP and 4-MeO-PCP are emerging in online drug markets. These compounds share many of PCP’s effects but have subtle differences in duration, intensity, and risk, making them a new frontier in designer dissociatives.
5. PCP in Research and Medicine: From Psychosis to Consciousness Studies
Despite its notorious street reputation, PCP has had a significant impact on neuroscience research. Because it reliably induces schizophrenia-like symptoms, it has been used in both animal and human models to study the glutamate hypothesis of psychosis—the theory that NMDA receptor dysfunction is central to disorders like schizophrenia and schizoaffective disorder.
Researchers have used PCP to understand how cortical circuits break down during psychosis, allowing for better-targeted antipsychotic medications. It has also contributed to the development of novel therapies for negative symptoms of schizophrenia, which are typically harder to treat than hallucinations or delusions.
Interestingly, PCP’s dissociative profile is now being re-examined through the lens of altered states of consciousness. Alongside ketamine and other NMDA antagonists, it has helped map out the neural architecture of self-awareness, body perception, and internal-external boundaries. This research is critical not only for psychiatric disorders but also for understanding anesthesia, meditation, and near-death experiences.
In the future, studying PCP analogues may lead to the development of dissociative-based therapies that provide the therapeutic benefits of ego disruption and neuroplasticity without the chaotic side effects. Compounds that tweak PCP’s chemical scaffold while reducing dopaminergic activity may hold promise as non-hallucinogenic antidepressants.
Surprising fact: A variant of PCP known as CI-395 was studied in the 1990s for its neuroprotective effects in stroke models, though it was abandoned due to behavioral side effects. The idea of a “therapeutic dissociative” remains an active area of exploration.
Effects
The effects of PCP can vary depending on the dose. For instance, low doses can cause a numbness in the extremities and slurred speech. On the other hand, moderate and large doses can cause users to experience a variety of effects, such as a loss of balance and bloodshot eyes. Due to the illegal production of PCP, users might not know the exact amount they’re taking.
The effects of PCP can cause users to lose their body image, develop paranoia, and depersonalize themselves. It can also cause individuals to become agitated and disoriented. Like other drugs, it can alter mood states in unpredictable ways. For instance, some people may become animated or detached after using PCP. It can also induce feelings of power, strength, and invulnerability.
Studies conducted during the 1970s revealed that the media’s portrayal of violent incidents involving people using PCP was greatly exaggerated. They also stated that these types of incidents were usually limited to individuals with a reputation for being aggressive. Although these types of incidents are rare, they have been publicized.
Some of the most common types of violent incidents that were reported during the 1970s were property damage and self-mutilation. Although these were not noted in the medical use of PCP during the 1950s and 1960s, they have been widely dismissed as unsubstantiated.
PCP users who use recreational doses often experience a psychotic state, which can involve feelings of detachment and paranoia. Symptoms of this condition can resemble those experienced during a schizophrenic episode.
The symptoms of this disorder are summarized in a mnemonic device known as the red dot. These include amnesia, delusions, and dilated pupils.
Phencyclidines and Children
The use of phencyclidines in children has been linked to a variety of adverse reactions, including behavioral and psychological problems. These include aggression, unpredictability, and belligerence. They can also impair judgment and lead to cravings and persistent desires. Children who use phencyclidines often experience problems at school.
Phencyclidines are synthesized drugs from cyclohexane and are members of the arylcyclohexylamine class. They are composed of a cyclohexane ring bonded to two additional rings at R1, the piperidine ring and the phenyl ring. The first letter of PCP (phenyl cyclohexane) is pronounced “piper”, and the second letter, phenyl, stands for aromatic phenyl.
Methods of administration
Although PCP can be obtained in different liquid and powder forms, it is typically sprayed onto leafy substances such as marijuana, tobacco, and herbs.
Inhalation of PCP can be done through smoking. Fry or sputter refers to street terms for tobacco cigarettes or marijuana that have been infused with PCP.
Depending on the purity, PCP can be insufflated. Its free base can be absorbed through the mucus membranes of some individuals.
Managing Intoxication
Intoxicated individuals who use PCP are usually treated with supportive care. This includes controlling their breathing, body temperature, and circulation. They are also given drugs such as lorazepam to treat seizures and agitation.
Although some antipsychotics are commonly used to treat psychotic symptoms, they can also cause side effects such as dystonia. These drugs are known to be very risky, and phenothiazines can lower the threshold for seizures. If an individual is given an antipsychotic, intramuscular haloperidol is usually recommended.
In the past, forced acid diuresis was often used as a decontamination method to increase the clearance of PCP from the body. However, it is now widely known that only around 10% of the dose of PCP is taken out by the kidneys. This means that this method would not result in increased urinary clearance. Also, urinary acidification can cause muscle breakdown, which is not an unusual side effect of PCP toxicity.
Pharmacology
PCP is known for its ability to block the activity of the ionotropic glutamate receptor known as the NMDA receptor. This receptor is also involved in the development of schizophrenia and other mental disorders. In the 1980s, David Lodge and colleagues noted that the effects of various dissociative agents, such as ketamine and dextromethorphan, on the development of schizophrenia were due to their interactions with the receptor.
Studies also suggest that PCP can block the activity of the nAChRs. These findings show that the interactions between the two receptor systems can affect the development of synaptic plasticity and the function of the brain’s glutamatergic synapses. In addition, prolonged use of PCP can lead to memory loss. This is because the effects of the drug can prevent the excitatory activity of the glutamate in certain regions of the brain. Some of the acute effects of PCP on the cerebellum include decreased breathing rate, blood pressure, and muscle coordination loss.
The effects of prolonged use of PCP can block the excitatory activity of the glutamate in certain regions of the brain, such as the hippocampus and the cerebellum. These effects can lead to memory loss as one of the consequences of prolonged use. The effects on the cerebellum can manifest in various acute symptoms, such as decreased breathing rate, blood pressure, and pulse rate.
Like ketamine, PCP can also be used as a partial agonist of the D2 High receptor in the rat brain. This activity can be associated with the development of psychotic features. This drug’s affinity for the human cloned D2 High receptor could be used as a treatment for PCP psychosis.
Aside from its interactions with the NMDA receptor, PCP can also be used as a partial agonist of the D2 High receptor. This drug’s ability to increase the extracellular levels of dopamine has been known to lead to increased neurotransmission. Unfortunately, it does not have an affinity for the human dopamine transporter.
Inhibition of monoamine reuptake by PCP can be mediated by the interactions between the drug’s various allosteric sites. One of these is the PCP site 2, which is a not-well-characterized site that is associated with this activity.
Studies have shown that the interactions between PCP and opioid receptors can lead to the production of analgesia.
Analogues
Around 30 different types of analogs of PCP were reported to be used on the street during and the 1980s, mainly in the US. A few of these were widely used, such as tenocyclidine, eticyclidine, and PCPy. Less common variants of these drugs are 3-HO-PCP, 3MeO-PCMo, or 3-MeO-PC.
The structural motifs required for PCP-like activity can be derived from the relationship between the structure of the different derivatives and their psychoactive effects. Although the effects of these drugs are similar to those of PCP, different potencies, mixtures of dissociative, stimulant, and anesthetic, and different substituents are known.
In some countries, such as Australia, New Zealand, and the US, these compounds are considered analogues of PCP and are therefore illegal drugs.
PCP—A Powerful Compound with a Complex Legacy
Phencyclidine is one of the most potent and perplexing compounds in the world of psychoactive substances. From surgical anesthetic to street drug, from model of psychosis to tool for consciousness research, PCP has left an indelible mark on both neuroscience and popular culture.
Understanding PCP requires nuance. While it poses serious risks, it also offers valuable insights into brain function, dissociation, and mental illness. As science continues to explore the safe boundaries of consciousness-altering compounds, PCP’s legacy—however turbulent—remains a critical chapter in the ongoing story of mind, medicine, and meaning.
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