Phencyclidine (PCP) & Dextromethorphan (DXM)
PCP or Phencyclidine is a dissociative drug that acts primarily by antagonizing the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptor. Glutamate is the most abundant excitatory neurotransmitter in the central nervous system (CNS). By inhibiting these receptors, PCP disrupts the normal function of glutamatergic systems, leading to its characteristic dissociative effects. Besides, PCP has actions at other receptor sites, including dopaminergic, opioid, and nicotinic receptors, which contribute to its complex pharmacological profile.
DXM or Dextromethorphan is an antitussive (cough suppressant) found in many over-the-counter cold and cough medications. Similar to PCP, DXM is also an NMDA receptor antagonist, though it is less potent in this regard. DXM's psychoactive effects, observed at doses higher than those recommended for cough suppression, are primarily due to its action on the NMDA receptors, leading to dissociative effects. Additionally, DXM is metabolized into dextrorphan, which contributes to its effects and also acts on sigma-1 receptors, further enhancing its psychoactive properties. DXM affects serotonin levels as well, which can lead to alterations in mood and perception.
When combined, PCP and DXM can potentiate each other's effects on the NMDA receptor, possibly leading to an enhanced dissociative state. However, this combination increases the risk of adverse effects and toxicities due to the overlapping mechanism of action, particularly concerning the CNS and cardiovascular system. The combined inhibition of NMDA receptors can lead to an unpredictable increase in the intensity of both drugs' psychological and physiological effects.
Side Effects and Dangers:
- Psychological Distress: The combination can increase the likelihood of experiencing severe anxiety, paranoia, and psychotic episodes.
- Physical Harm: The synergistic effects may lead to increased heart rate, blood pressure, and body temperature, escalating the risk of cardiac events, hypertension, and hyperthermia.
- Cognitive Impairment: Both substances can induce significant cognitive dysfunctions, such as memory loss, impaired judgment, and dissociation from reality, which may be exacerbated when used together.
- Increased Risk of Neurotoxicity: Excessive inhibition of NMDA receptors can lead to excitotoxicity, a process that can damage or kill neurons.
We have not come across confirmed data on acute and fatal conditions associated with this combination. While specific data on the combination of PCP and DXM is scarce, the overlapping NMDA receptor antagonism suggests that combining these substances could significantly increase the risk of adverse psychological and physical effects. The dissociative effects may be enhanced, but so too are the risks of severe side effects, including heightened potential for psychosis, neurotoxicity, cardiovascular complications, and acute behavioral changes leading to harm.
Considering the above, we recommend treating this combination with great caution.
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