Phencyclidine (PCP) & LSD
Phencyclidine (PCP), originally developed as an anesthetic in the 1950s, exerts its psychoactive effects through a multifaceted mechanism of action centered primarily around antagonism of the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptor critical for synaptic plasticity, learning, and memory.
PCP binds within the ion channel of the NMDA receptor complex in a non-competitive manner, thereby preventing calcium influx and disrupting normal excitatory neurotransmission. This blockade leads to a cascade of downstream effects including cortical disinhibition, which can manifest as hallucinations, delusions, and cognitive fragmentation.
In addition to its NMDA antagonism, PCP interacts with a variety of other neurotransmitter systems: it inhibits dopamine reuptake, leading to increased dopaminergic transmission in mesolimbic and mesocortical pathways; it binds with moderate affinity to sigma-1 receptors, which are implicated in neuroplasticity and psychotomimetic effects; and it exhibits weak agonist activity at nicotinic acetylcholine receptors.
These diverse interactions contribute to the compound’s unique dissociative profile characterized by analgesia, altered body perception, and profound detachment from the environment.
Lysergic acid diethylamide (LSD), a semi-synthetic ergoline derivative, acts predominantly as a partial agonist at several serotonin (5-HT) receptor subtypes, with its psychoactive effects most strongly linked to 5-HT2A receptor activation.
LSD binds with high affinity to 5-HT2A receptors, particularly in the prefrontal cortex, where it modulates glutamatergic transmission by increasing excitatory post-synaptic potentials via cortical pyramidal neurons. This activation enhances signal propagation and disrupts normal thalamocortical gating, effectively flooding the cortex with sensory information.
LSD’s affinity is not limited to 5-HT2A; it also interacts with 5-HT1A, 5-HT2C, dopamine D2 receptors, and various adrenergic receptors, contributing to its complex and prolonged psychoactive profile. The resulting experience includes vivid visual hallucinations, altered sense of time, ego dissolution, and profound shifts in cognition and mood.
Notably, LSD’s binding kinetics at the 5-HT2A receptor involve a unique "lid" formed by extracellular loops that may account for its long duration of action, as the molecule remains bound for extended periods, continuously modulating receptor activity.
The combination of PCP and LSD represents a convergence of dissociative and serotonergic hallucinogenic mechanisms, resulting in a complex and potentially unpredictable pharmacodynamic interaction.
The NMDA receptor antagonism by PCP, which typically leads to sensory deprivation and cognitive disintegration, may be synergistically intensified or rendered more chaotic by the hyper-associative, cortical excitation induced by LSD’s 5-HT2A agonism.
At the neurochemical level, PCP's disinhibitory effect on dopaminergic and glutamatergic signaling could amplify the psychedelic effects of LSD, potentially leading to heightened perceptual distortions, increased risk of psychosis, and profound detachment from reality.
Moreover, the overlapping dopaminergic activity may result in heightened euphoria, mania, or paranoia, particularly in individuals predisposed to mood or psychotic disorders.
While LSD alone can provoke anxiety and transient psychosis, its combination with PCP may increase the likelihood of long-lasting delusional states or violent behavior due to PCP’s notorious effect on aggression and impulse control.
Cognitive disorganization induced by PCP could reduce the user's ability to navigate the introspective and symbolic content often brought on by LSD, increasing the risk of disorientation, panic, or dissociative fugue states.
Physiologically, both substances can independently elevate heart rate and blood pressure; their combination could synergize these sympathomimetic effects, posing cardiovascular risks, especially in vulnerable individuals.
Reliable scientific data on the specific interaction between PCP and LSD in controlled settings is limited, primarily due to ethical and legal constraints.
This combination is not like mixing cannabis with a psychedelic or taking MDMA and LSD together (the so-called "candyflip"), which has a more established history of recreational synergy. LSD and PCP both have strong, often conflicting effects on perception, emotion, and motor control. The result can just as easily be a terrifying, disjointed, paranoid, or completely delusional state that even experienced users can't ground or integrate. PCP also uniquely carries risks of aggression, self-harm, blackouts, and disinhibition, and when layered onto the suggestibility and intensity of an LSD trip, that can become truly dangerous.
All things considered, we recommend avoiding this combination.
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