These findings suggest that psychological mechanisms may be involved in some of the anti-addiction benefits resulting from ketamine. Future research can evaluate whether the psychoactive effects of ketamine influence improvements in larger samples.

The most common adverse drug reactions associated with ketamine are nausea, vomiting, dizziness, diplopia, drowsiness, dysphoria, and confusion. Reports of the emergence phenomenon exist for approximately 6% to 12% of patients.

The dominant factor spanned a continuum of experiential facets whose opposite extreme flagged words that appear to describe mental expansion, including the terms universe, space, world, consciousness, breakthrough, existence, earth, dimension, reality, flame, and tunnel—all of which would be consistent with the phenomenology of the mystical experience (3). References to liminal conscious beings, also characteristic of the mystical experience, were described by the terms entity, sitter, alien, beings, and spirit. A theme of immediate time horizon was indicated by the term seconds and also suggested by references to bodily systems such as eyes and lungs, along with physiological functions inhale(d), exhaled, and breath. At the level of neurotransmitter receptors, this constellation of induced conscious alterations was linked most strongly with drugs that preferentially bind to D1, 5-HT7, KOR, 5-HT5A, as well as Sigma-1 and NMDA. The codependencies embedded in this profile of receptor bindings and subjective terms were most closely associated with the hallucinogenic drugs DMT, salvinorin A, 5-MeO-DMT, and ketamine. The anatomical brain regions that coexpress these sets of receptor density proxies included some of the highest regions of the association cortex, especially the rostral and dorsal anterior cingulate cortex, temporoparietal junction, and also prominently in the primary motor and sensory cortices.

This case study adds to the scant literature regarding ketamine treatment for individuals with bipolar disorder and ASD. We did not find ASD to be a contraindication for IV ketamine and ketamine assisted psychotherapy. Reductions in anger outbursts, anxiety, suicidality, and depression suggest ketamine treatment might be tailored to individuals with bipolar disorder and ASD, and additional systematized research is warranted. Although potential mechanisms of action are not clear, these data add to the discussion regarding clinical practice considerations and the potential for ketamine to improve quality of life and associated metrics.

Psychiatry is in a growth phase in which several psychedelic medicines have entered its arena with great promise. Of these, presently, ketamine is the only medicine that may be legally prescribed. We hypothesize that at subanesthetic doses, ketamine produces a unique spectrum of altered states, ranging from psychoactive to deep ego-dissolving experiences, that are intrinsic to ketamine’s therapeutic effects. When these experiences are embedded in a therapeutic relationship—a setting—that fosters an amplification of the recipient’s subjective consciousness, personal growth, inner healing, greater clarity, and better relationships may well ensue. While much of the literature on ketamine labels its dissociative effects as ‘side effects’, alteration of consciousness is a component and unavoidable ‘effect’ of its therapeutic impact. From its inception in the clinical trials of the 1960s, ketamine was recognized for producing dissociative, psychedelic effects on consciousness in subjects as they emerged from ketamine-induced anesthesia. Unanticipated and unintegrated, these experiences of ‘emergence phenomena’ were felt to be disturbing. Accordingly, such experiences have been typically labeled as dissociative side effects. However, in a conducive set and settings, these experiences have been demonstrated to be of positive use in psychiatry and psychotherapy, providing a time-out from usual states of mind to facilitate a reshaping of self-experience along with symptomatic relief. In this way, ketamine-assisted psychotherapy (KAP) offers a new potential in psychiatry and psychotherapy that is powerfully valanced toward recognizing experience, individuality, and imagination. Essential to a successful therapeutic experience and outcome with KAP is close attention to the subjective experience, its expression by the recipient and integration of the ketamine experience as a healing opportunity.

Ketamine is an N-methyl-d-aspartate antagonist which is increasingly being researched and used as a treatment for depression. In low doses, it can cause a transitory modification in consciousness which was classically labelled as 'dissociation'. However, ketamine is also commonly classified as an atypical psychedelic and it has been recently reported that ego dissolution experiences during ketamine administration are associated with greater antidepressant response. Neuroimaging studies have highlighted several similarities between the effects of ketamine and those of serotonergic psychedelics in the brain; however, no unified account has been proposed for ketamine's multi-level effects - from molecular to network and psychological levels. Here, we propose that the fast, albeit transient, antidepressant effects observed after ketamine infusions are mainly driven by its acute modulation of reward circuits and sub-acute increase in neuroplasticity, while its dissociative and psychedelic properties are driven by dose- and context-dependent disruption of large-scale functional networks. Computationally, as nodes of the salience network (SN) represent high-level priors about the body ('minimal' self) and nodes of the default-mode network (DMN) represent the highest-level priors about narrative self-experience ('biographical' self), we propose that transitory SN desegregation and disintegration accounts for ketamine's 'dissociative' state, while transitory DMN desegregation and disintegration accounts for ketamine's 'psychedelic' state. In psychedelic-assisted psychotherapy, a relaxation of the highest-level beliefs with psychotherapeutic support may allow a revision of pathological self-representation models, for which neuroplasticity plays a permissive role. Our account provides a multi-level rationale for using the psychedelic properties of ketamine to increase its long-term benefits

Greater antidepressant response (reduction in Montgomery-Asberg Depression Rating Scale at 24 h) correlated with the 11-dimension altered states of consciousness dimensions: spirituality, experience of unity, and insight. The first qualitative interview revealed that all participants experienced perceptual changes. Additional themes emerged including loss of control and emotional and mood changes. The final interview showed evidence of a psychedelic afterglow, and changes to perspective on life, people, and problems, as well as changes to how participants felt about their depression and treatments.Conclusions:
The current study provides preliminary evidence for a role of the psychedelic experience and afterglow in ketamine’s antidepressant properties. Reflexive thematic analysis provided a wealth of information on participants’ experience of the study and demonstrated the psychedelic properties of ketamine are not fully captured by commonly used questionnaires.

The discovery of ketamine as a rapid-acting antidepressant spurred significant research to understand its underlying mechanisms of action and to identify other novel compounds that may act similarly. Serotonergic psychedelics (SPs) have shown initial promise in treating depression, though the challenge of conducting randomized controlled trials with SPs and the necessity of long-term clinical observation are important limitations. This review summarizes the similarities and differences between the psychoactive effects associated with both ketamine and SPs and the mechanisms of action of these compounds, with a focus on the monoaminergic, glutamatergic, gamma-aminobutyric acid (GABA)-ergic, opioid, and inflammatory systems. Both molecular and neuroimaging aspects are considered. While their main mechanisms of action differ-SPs increase serotonergic signaling while ketamine is a glutamatergic modulator-evidence suggests that the downstream mechanisms of action of both ketamine and SPs include mechanistic target of rapamycin complex 1 (mTORC1) signaling and downstream GABAA receptor activity. The similarities in downstream mechanisms may explain why ketamine, and potentially SPs, exert rapid-acting antidepressant effects. However, research on SPs is still in its infancy compared to the ongoing research that has been conducted with ketamine. For both therapeutics, issues with regulation and proper controls should be addressed before more widespread implementation.

All participants’ symptoms declined throughout treatment. Psychedelic treatment participants saw a larger, more consistent decrease. Researchers conclude that KAPT may be effective for treating chronic pain/MDD comorbidity, anxiety and Post-Traumatic Stress Disorder (PTSD). Findings imply that the psychedelic approach may be more effective. This pilot study serves as a basis for more extensive research that will inform how clinicians administer treatment to optimize outcomes.