Dissociative substances have long occupied a distinct category in the realm of psychoactive compounds. However, emerging research and evolving perspectives suggest that these substances share essential characteristics with classic psychedelics. This paper explores the case for considering dissociatives as a subset of psychedelics, highlighting their shared mechanisms of action, perceptual alterations, therapeutic potential, and implications for the broader understanding of altered states of consciousness.

Dissociative substances and classic psychedelics have traditionally been separated into distinct categories due to differences in their subjective effects and historical use. Dissociatives, such as ketamine, PCP, and DXM, are often associated with a sense of disconnection from one’s body and environment, while classic psychedelics, including LSD and psilocybin, are known for their vivid visual hallucinations and altered perceptions. However, recent research has illuminated the overlap between these categories, leading to the recognition of dissociatives as a subset of psychedelics.


Examples of Dissociatives

Traditional dissociative psychedelics are substances that induce dissociation, altering perception, cognition, and producing a sense of detachment from one’s surroundings. Here is a list of examples of traditional dissociative psychedelics:

  1. Ketamine: Used medically as an anesthetic, ketamine can induce dissociative and hallucinogenic effects. It interacts with NMDA receptors and has been studied for its potential therapeutic applications in treating depression and other mental health conditions.
  2. PCP (Phencyclidine): Initially developed as an anesthetic, PCP is a powerful dissociative psychedelic. It acts on NMDA receptors and is known for its hallucinogenic properties. PCP has a high potential for misuse and is classified as a Schedule II controlled substance.
  3. DXM (Dextromethorphan): Found in some over-the-counter cough medications, DXM can induce dissociative effects at higher doses. It acts on NMDA receptors and serotonin transporters. Abuse of DXM for recreational purposes can lead to adverse effects.
  4. Nitrous Oxide (Laughing Gas): While primarily used as an anesthetic in medical settings, nitrous oxide can induce dissociative effects when inhaled recreationally. It works by antagonizing NMDA receptors.
  5. Salvinorin A (Salvia divinorum): Salvinorin A is the active compound in the plant Salvia divinorum. It produces potent dissociative and hallucinogenic effects and works on kappa opioid receptors rather than the more common serotonin or NMDA pathways.

It’s important to note that the recreational use of dissociative psychedelics can pose risks, and their legal status varies in different regions. Additionally, their potential for misuse and adverse effects underscores the importance of responsible and informed use, as well as ongoing research into their therapeutic applications.


Are These Really Psychedelic?

Dissociative psychedelics and traditional psychedelics, both impact the brain’s serotonin system, albeit through different mechanisms. Serotonin, a neurotransmitter, plays a crucial role in regulating mood, emotions, and cognition. Traditional psychedelics primarily interact with the serotonin 2A receptor (5-HT2A), leading to profound alterations in perception and consciousness. Dissociative psychedelics, although distinct in their effects, also influence the serotonin system, particularly through their actions on N-methyl-D-aspartate (NMDA) receptors.

In the case of traditional psychedelics, such as LSD and psilocybin, the serotonin 2A receptor activation induces a cascade of neural changes, resulting in altered sensory perception and a heightened sense of interconnectedness. These substances are partial agonists at the 5-HT2A receptor, leading to increased serotonin release and altered signal transmission in the brain. Dissociative psychedelics, on the other hand, like ketamine, primarily interact with NMDA receptors, which are involved in glutamate neurotransmission. Despite this difference, both traditional and dissociative psychedelics can indirectly affect serotonin levels by modulating glutamatergic signaling, impacting mood and cognitive processes.

The commonality in the impact on serotonin systems suggests a shared neural pathway, albeit through distinct receptor systems. Understanding these interactions sheds light on the complex interplay between neurotransmitter systems and provides insights into the therapeutic potential of psychedelics for conditions like depression and anxiety. Ongoing research in this field aims to unravel the intricate mechanisms by which these substances influence serotonin and other neurotransmitter systems, paving the way for potential therapeutic applications in mental health treatment.


NMDA Receptors

The N-methyl-D-aspartate (NMDA) receptor is a type of ionotropic glutamate receptor found in the central nervous system, playing a crucial role in synaptic transmission and plasticity. These receptors are essential for normal cognitive function, learning, and memory. When glutamate, the primary excitatory neurotransmitter, binds to the NMDA receptor, it opens a channel that allows the flow of positively charged ions such as calcium and sodium into the neuron. This activation is vital for synaptic plasticity, a process that underlies learning and memory by strengthening or weakening synaptic connections between neurons.

Dissociative psychedelics act as agonists at the NMDA receptors, meaning they bind to and activate these receptors. By doing so, they modulate the normal functioning of glutamatergic neurotransmission. The increased activity at NMDA receptors leads to a disruption of the usual balance of excitatory and inhibitory signaling in the brain, resulting in dissociative effects. These effects include altered perceptions of reality, a sense of detachment from one’s body or surroundings, and changes in cognition. The specific impact may vary depending on factors like dosage, individual sensitivity, and the unique pharmacological profile of each dissociative psychedelic. Understanding these interactions provides insights into both the potential therapeutic effects and the risks associated with the use of dissociative psychedelics.


Difference in Effects

Psychedelics that agonize the serotonin 5-HT2A receptor, such as LSD and mescaline, induce profound alterations in perception and consciousness. The 5-HT2A receptor is a subtype of the serotonin receptor, and when activated by these psychedelics, it leads to a cascade of neural changes. This activation primarily occurs in the prefrontal cortex, disrupting the typical filtering of sensory information and leading to intensified and altered perceptions. Users may experience vivid visual hallucinations, synesthesia (blending of senses), and a heightened sense of interconnectedness. The subjective effects often involve a sense of unity with the environment, altered time perception, and a deepening of introspective thoughts. The serotonin system’s involvement suggests a link between these psychedelics and mood regulation, contributing to their potential therapeutic applications for conditions like depression and anxiety.

On the other hand, dissociative psychedelics like ketamine exert their effects by agonizing NMDA receptors. These receptors are crucial for glutamatergic neurotransmission and synaptic plasticity. When NMDA receptors are activated by dissociative psychedelics the typical balance of excitatory and inhibitory signaling in the brain is disrupted. This results in dissociative effects, including a sense of detachment from reality, out-of-body experiences, and alterations in perception of time and space. Salvia divinorum, another dissociative psychedelic, acts on kappa opioid receptors rather than the more common serotonin or NMDA pathways, leading to intense but often short-lived dissociative experiences. The differences in receptor targets contribute to the contrasting subjective effects between psychedelics agonizing 5-HT2A receptors and those targeting NMDA receptors.

While classic psychedelics often evoke visionary experiences and sensory synesthesia, dissociatives bring about experiences of depersonalization, derealization, and out-of-body sensations. Both categories challenge the conventional boundaries of perception and self-identity, inviting individuals to explore their internal landscapes and confront deep-seated emotions.


Therapeutic Potential

Dissociative psychedelics have shown promising therapeutic potential in the treatment of various mental health conditions. One notable application is in the management of treatment-resistant depression. Ketamine, when administered at sub-anesthetic doses, has demonstrated rapid and robust antidepressant effects. The mechanisms behind this are complex, involving the modulation of glutamatergic neurotransmission and the induction of synaptic plasticity. Ketamine’s ability to provide relief from depressive symptoms in a relatively short timeframe, compared to traditional antidepressants, offers a novel approach for individuals who do not respond well to conventional treatments.

In addition to depression, dissociative psychedelics have shown efficacy in addressing conditions like anxiety disorders and post-traumatic stress disorder (PTSD). The dissociative effects induced by substances like ketamine may contribute to a temporary disruption of maladaptive thought patterns and emotional responses. This can create a therapeutic window during which individuals can more effectively engage in psychotherapy and process traumatic experiences. Ongoing research is exploring the optimal dosages, treatment protocols, and long-term outcomes associated with the use of dissociative psychedelics in mental health settings.  As the field of psychedelic-assisted therapy continues to evolve, further research and clinical trials will provide a clearer understanding of the full scope of therapeutic potential offered by dissociative psychedelics.


Expanding the Understanding of Altered States

Considering dissociatives as a subset of psychedelics encourages a broader and more inclusive perspective on altered states of consciousness. It emphasizes the shared features of these substances, such as ego dissolution, emotional processing, and enhanced introspection, while acknowledging their unique characteristics. This expanded view enhances our understanding of the complex relationship between psychoactive compounds and the human mind.

The boundaries between dissociatives and classic psychedelics are gradually dissolving, and a more holistic perspective on altered states of consciousness is emerging. By recognizing the shared mechanisms of action, perceptual alterations, therapeutic potential, and their impact on our understanding of consciousness, we pave the way for a deeper exploration of the diverse experiences that these compounds can offer. As research continues to unfold, the conversation surrounding dissociatives and psychedelics promises to be both dynamic and transformative in the field of psychoactive substances and mental health therapy.

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