Phencyclidine: From medical innovation to a declining hallucinogen

Phencyclidine, once developed as an intravenous anaesthetic, quickly fell out of medical use due to its unpredictable and often severe psychological effects. While originally intended to provide pain relief and induce unconsciousness, its impact on brain function led to symptoms such as hallucinations, confusion, and dissociation. As a result, it was replaced by safer alternatives such as ketamine, which shares a similar mechanism but with a more controlled pharmacological profile. Despite its removal from medical practice, phencyclidine became a widely abused hallucinogen, known on the streets as “angel dust.” However, its popularity has waned in recent years, overshadowed by other substances that provide similar dissociative effects with a lower risk of prolonged psychosis.

How Phencyclidine Affects the Brain

Phencyclidine’s primary action is on the NMDA receptor channel, a crucial component of the brain’s glutamate system that regulates memory, learning, and perception. By blocking this receptor, the drug disrupts normal neurotransmission, leading to profound alterations in consciousness. This mechanism is responsible for its hallucinogenic effects, often compared to those of lysergic acid diethylamide (LSD), though with a greater tendency to induce agitation and erratic behaviour.

In addition to targeting NMDA receptors, phencyclidine also interacts with sigma receptors, which are involved in the modulation of pain perception and mood regulation. This dual action contributes to its ability to cause dissociation, a state in which users feel detached from their surroundings and even their own bodies. However, these effects come at a cost, as prolonged use can lead to cognitive impairment, paranoia, and psychotic episodes resembling schizophrenia.

Why Phencyclidine Was Abandoned as an Anaesthetic

When phencyclidine was first introduced for medical use, its ability to produce analgesia made it a promising candidate for surgical anaesthesia. However, early clinical observations revealed that patients who received the drug often experienced extreme disorientation and hallucinations upon waking. This post-operative delirium made it unsuitable for human use, leading researchers to explore alternative compounds. Ketamine, a closely related drug with a similar mechanism, emerged as a safer substitute. Unlike phencyclidine, ketamine has remained in use, particularly in emergency and veterinary medicine, due to its milder dissociative effects and more predictable recovery profile.

The Rise and Fall of Phencyclidine as a Recreational Drug

Despite its rejection in medical settings, phencyclidine gained traction as a recreational drug due to its potent hallucinogenic properties. In the 1970s and 1980s, it was commonly used in powdered or liquid form, often mixed with other substances and smoked or ingested. Users sought its dissociative effects, which could range from euphoria and altered perception to complete detachment from reality. However, its unpredictability soon became evident, as some individuals experienced extreme paranoia, violent behaviour, or prolonged psychotic episodes.

Over time, the risks associated with habitual phencyclidine use became more widely recognised. Reports of users exhibiting erratic and aggressive behaviour led to stricter legal controls, and the emergence of alternative hallucinogens, including LSD and ketamine, contributed to its decline. Today, phencyclidine is rarely encountered in mainstream drug culture, with its reputation tarnished by its association with severe psychiatric disturbances.

Can Phencyclidine Induce Long-Term Mental Health Issues?

One of the most controversial aspects of phencyclidine use is its potential link to schizophrenia-like symptoms. Studies have shown that the drug can trigger psychotic effects in both first-time and chronic users, with symptoms including paranoia, auditory hallucinations, and cognitive disorganisation. In individuals predisposed to mental illness, these effects can be prolonged, raising concerns about whether the drug can contribute to the onset of schizophrenia. While definitive evidence linking phencyclidine to the development of schizophrenia is lacking, its ability to exacerbate symptoms in stabilised patients suggests that it poses a significant risk to those with underlying vulnerabilities.

Why Phencyclidine Is No Longer a Major Drug of Abuse

The decline in phencyclidine’s popularity can be attributed to several factors. Increased awareness of its psychotic effects, the development of more refined dissociative substances, and stricter drug enforcement measures have all played a role in reducing its availability. Ketamine, in particular, has largely replaced phencyclidine in both medical and recreational contexts due to its more controlled effects and lower risk of long-term psychosis. Additionally, the unpredictability of habitual phencyclidine use has made it a less desirable option for those seeking hallucinogenic experiences.

Phencyclidine’s journey from a medical anaesthetic to a notorious hallucinogen and its subsequent decline in popularity underscores the complexities of drug development and misuse. While its ability to block the NMDA receptor channel made it a powerful anaesthetic, the associated psychotic effects rendered it unfit for medical use. As a recreational drug, its ability to induce schizophrenia-like symptoms and violent behaviour led to widespread concern and eventual legal control. Today, phencyclidine is largely viewed as an outdated and dangerous substance, with ketamine emerging as the preferred alternative in both medical and illicit settings. While the long-term consequences of habitual phencyclidine use remain debated, its role in exacerbating psychiatric symptoms serves as a cautionary tale about the risks of unregulated hallucinogen consumption.