Understanding Dissociative Drugs
Dissociative drugs are a class of psychoactive substances that alter perceptions of sight and sound and produce feelings of detachment, or dissociation, from the environment and self [1.2.1]. These effects are distinct from the classic hallucinations produced by substances like LSD or psilocybin [1.2.2]. Users often report feeling disconnected from their own body or that the world around them is unreal [1.2.3]. This class includes well-known substances such as phencyclidine (PCP), ketamine, and dextromethorphan (DXM), as well as the plant Salvia divinorum [1.2.2].
Originally, some of these compounds were developed for medical purposes. For instance, PCP was created in the 1950s as a general anesthetic, but its use in humans was discontinued due to severe adverse psychological effects [1.2.1, 1.2.4]. Ketamine, a chemically similar but less potent drug, is still used as an anesthetic in medical and veterinary settings [1.2.5, 1.5.3].
The Pharmacology: How Dissociatives Affect the Brain
The primary mechanism of action for most classic dissociative drugs—like PCP, ketamine, and DXM—is the disruption of the brain's glutamate system [1.2.3]. Specifically, they act as N-methyl-D-aspartate (NMDA) receptor antagonists [1.3.3]. Glutamate is a crucial excitatory neurotransmitter involved in cognition, memory, emotion, and pain perception [1.2.2]. By binding to and blocking NMDA receptors, these drugs inhibit the normal transmission of electrical signals between neurons, leading to the characteristic dissociative state [1.3.3]. This disruption can cause feelings of detachment, memory impairment, and psychotomimetic effects [1.3.2].
Salvia divinorum is an exception to this rule. While it produces dissociative effects, it works by activating a different target: the kappa opioid receptor on nerve cells [1.2.2]. This makes its pharmacological profile unique among dissociatives.
Common Types of Dissociative Drugs
Several substances fall under the dissociative classification, each with unique properties, methods of use, and associated risks.
Phencyclidine (PCP)
Originally an intravenous anesthetic, PCP is now a Schedule II controlled substance in the U.S., primarily found on the illicit market [1.2.1, 1.9.3]. It often comes as a white crystalline powder that can be snorted, smoked, swallowed, or injected [1.2.1]. Known by street names like "Angel Dust" and "Rocket Fuel," it produces feelings of invulnerability, distorted perceptions, numbness, and slurred speech [1.2.4]. High doses can lead to aggressive or violent behavior, seizures, coma, and death, though fatalities often result from accidents or suicide during intoxication [1.2.1]. Long-term use can cause memory loss, speech difficulties, depression, and social withdrawal for a year or more after cessation [1.8.4].
Ketamine
Developed as a safer alternative to PCP, ketamine is a Schedule III controlled substance used for anesthesia and pain management in medical settings [1.2.5, 1.9.4]. A derivative, esketamine (brand name Spravato®), is FDA-approved as a nasal spray for treatment-resistant depression [1.5.5, 1.9.2]. Illicitly, ketamine is often sold as a white powder and snorted or injected, producing effects similar to PCP but shorter in duration [1.2.5]. At high doses, it can induce a state of extreme detachment known as a "K-hole" [1.5.5]. Chronic use is linked to severe bladder problems (ketamine-induced uropathy), memory issues, and depression [1.2.4, 1.5.5].
Dextromethorphan (DXM)
DXM is a common ingredient in over-the-counter cough and cold medications [1.2.1]. When taken in doses far exceeding the medical recommendation, it acts as an NMDA receptor antagonist and can produce dissociative and euphoric effects [1.2.4]. Misuse, often called "robo-tripping," can cause distorted vision, slurred speech, confusion, and increased heart rate [1.2.1, 1.7.3]. A significant danger comes from the other active ingredients in cough syrups, like antihistamines or acetaminophen, which can be toxic in large quantities [1.2.1].
Salvia Divinorum
This herb from the mint family is native to southern Mexico [1.6.5]. Its active compound, salvinorin A, causes intense but short-lived dissociative experiences and hallucinations when its leaves are chewed or smoked [1.6.2]. Unlike other dissociatives, salvia acts on kappa opioid receptors [1.2.2]. Effects can include uncontrollable laughter, loss of coordination, and feelings of detachment [1.6.5]. While its long-term effects are largely unknown, it is considered a drug of concern by the DEA and is illegal in some states [1.6.5].
Comparison of Common Dissociatives
| Feature | PCP (Phencyclidine) | Ketamine | DXM (Dextromethorphan) | Salvia Divinorum |
|---|---|---|---|---|
| Primary Mechanism | NMDA Receptor Antagonist [1.3.3] | NMDA Receptor Antagonist [1.3.3] | NMDA Receptor Antagonist [1.3.3] | Kappa Opioid Receptor Agonist [1.2.2] |
| Legal Status (US) | Schedule II [1.9.3] | Schedule III [1.9.4] | Legal (in OTC meds) [1.2.1] | Unscheduled federally, illegal in some states [1.6.5] |
| Medical Use | Discontinued for humans [1.2.4] | Anesthetic; depression treatment (esketamine) [1.5.1] | Cough suppressant [1.2.1] | None |
| Duration of Effects | 4-8 hours, but can be longer [1.6.3] | 30-60 minutes [1.2.5] | Up to 6 hours [1.2.1] | Up to 30 minutes [1.6.1] |
| Notable Risks | Severe psychosis, violence, seizures [1.2.1] | "K-hole," bladder damage (uropathy) [1.5.5] | Overdose risk from other medication ingredients [1.2.1] | Intense, unpredictable hallucinations [1.6.5] |
Risks and Long-Term Effects
While the experiences vary, all dissociative drugs carry significant risks.
- Short-Term Risks: Common short-term effects include numbness, disorientation, loss of coordination, and increased blood pressure and heart rate [1.2.5]. Because these drugs distort perception, users are at high risk of accidental injury or behaving in dangerous ways [1.2.3]. Combining them with other depressants like alcohol can lead to respiratory distress and death [1.2.5].
- Long-Term Effects: Chronic use of dissociatives, particularly PCP, is associated with tolerance, dependence, and a withdrawal syndrome that can include headaches, sweating, and drug cravings [1.8.4]. Other potential long-term consequences include memory loss, persistent speech problems, depression, anxiety, and suicidal thoughts [1.8.2].
- Hallucinogen Persisting Perception Disorder (HPPD): A rare but serious risk is HPPD, a condition where individuals re-experience visual disturbances from a previous trip long after the drug has left their system [1.10.3]. These "flashbacks" can be distressing and persist for months or even years [1.10.3]. While classically associated with LSD, HPPD has been linked to dissociatives as well [1.10.2].
Conclusion
Dissociative drugs are a distinct pharmacological class defined by their ability to induce feelings of detachment and distorted reality, primarily by blocking NMDA receptors in the brain [1.2.3, 1.3.3]. From the powerful effects of PCP to the therapeutic potential of ketamine for depression, these substances have a complex profile of effects, uses, and dangers [1.2.1, 1.5.1]. Understanding their mechanisms, risks, and legal status is crucial for both public health and clinical pharmacology. Misuse carries a high potential for adverse psychological and physical outcomes, including addiction and long-term cognitive impairment [1.8.2].
For more information on psychedelic and dissociative drugs, you can visit the National Institute on Drug Abuse (NIDA). [1.2.3]
