Investigation of “out-of-body experiences” has implications for understanding both normal bodily-self integration and its vulnerabilities. Beyond reported associations between OBEs and specific brain regions, however, there have been few investigations of neurochemical systems relevant to OBEs. Ketamine, a drug used recreationally to achieve dissociative experiences, provides a real-world paradigm for investigating neurochemical effects. We investigate the strength of the association of OBEs and ketamine use relative to other common drugs of abuse. Self-report data from an online survey indicate that both (...) lifetime frequency of ketamine use and OBEs during ketamine intoxication were more strongly related to the frequency of OBEs and related phenomena than other drugs. Moreover, the apparent effects of other drugs could largely be explained by associated ketamine use. The present results, consistent with the role of NMDA receptors in OBEs, should encourage future studies of the role of neurochemical systems in OBEs. (shrink)

Ketamine, a dissociative anesthetic commonly used by US physicians, has recently been shown to be a powerful anti-depressant and is also capable of eliciting transpersonal experiences that can be transformative. Although currently approved in the US only for use as an anesthetic, physicians there can legally prescribe it off-label to treat various psychological/ psychiatric problems and it has been used for these non-anesthetic purposes in Argentina, Iran, Mexico, Russia, and the UK, as well as in the US. The literature on (...) using ketamine psychotherapeutically is reviewed and two case studies using ketamine-enhanced psychotherapy for treating death anxiety in terminally-ill people are reported. The potential importance of beginning formal research on using KEP during end-of-life for those suffering death anxiety is emphasized. (shrink)

This commentary compares clinical aspects of ketamine with the amphetamine model of schizophrenia. Hallucinations and loss of insight, associated with amphetamine, seem more schizophrenia-like. Flat affect encountered with ketamine is closer to the clinical presentation in schizophrenia. We argue that flat affect is not a sign of schizophrenia, but rather, a risk factor for chronic schizophrenia.

Ketamine is a dissociative drug that has been used medically since the 1970s primarily as an anesthetic agent but also for various psychiatric applications. Anecdotal reports and clinical research suggest substantial potential for ketamine as a treatment in conjunction with psychological interventions. Here, we review historical and modern approaches to the use of ketamine with psychotherapy, discuss the clinical relevance of ketamine’s acute psychoactive effects, propose a unique model for using esketamine with Acceptance and Commitment Therapy, and suggest considerations for (...) moving medication-assisted psychotherapy forward as a field. (shrink)

Within the context of the so-called psychedelic renaissance, ketamine (C13H16CINO) has been increasingly used for therapeutic purposes. While ketamine clearly has healing powers, what interests me here is less ketamine for healing than what I will call the possibility of knowledge by ketamine. Drawing upon Deleuze and Guattari's arguments for the centrality of metal and metallurgy as a perspective on matter, I speculate that knowledge by ketamine is not identical with, yet verges on, a kind of becoming-metal of consciousness, and (...) an intuition of what Deleuze and Guattari call a ‘nonorganic life’ proper to matter. Ketamine trips provide vantage, and in some sense experience of that metallic dimension Deleuze and Guattari claim is inherent in all matter, a fluidity and transformability which for them is the basis of a hydraulic as opposed to solid model of matter, and clue to a vitality that supersedes the distinction of life and death. Intuition of the fundamentally hydraulic or metallic nature of matter is essential to what Deleuze and Guattari call a nomadic or ‘minor’ science, one that, because it centres continuous variation rather than discrete form, is capable of challenging the conservative tendencies of ‘major’ or State science. Without making claims for ketamine as in any sense sufficient for a becoming-metal of consciousness, ketamine may be constructively conjugated with other knowledges – knowledge by meditation, by dance, by music, or by martial arts, to name only a few. Such minor sciences of transformation and transmutation remain capable of a negative or corrosive relation to the State, despite the ever-present reality of recapture. (shrink)

BackgroundDepressive disorders are a common form of psychiatric illness and cause significant disability. Regulation authorities, the medical profession and the public require high safety standards for antidepressants to protect vulnerable psychiatric patients. Ketamine is a dissociative anaesthetic and a derivative of a hallucinogen. Its abuse is a major worldwide public health problem. Ketamine is a scheduled drug and its usage is restricted due to its abuse liability. Recent clinical trials have reported that ketamine use led to rapid antidepressant effects in (...) patients suffering from treatment-resistant depression. However, various flaws in study designs, and possible biased reporting of results, may have influenced those findings. Further analyses of ketamine use are needed to ensure patient safety.DiscussionThe use of ketamine in research and treatment of depressive disorders is controversial. Recently, mental health professionals raised ethical concerns about an ongoing ketamine trial in the UK. Also, a Canadian agency reviewed the existing evidence and did not recommend prescribing ketamine to treat depressive disorders. Findings obtained from tightly controlled research settings cannot be easily translated to clinical practice as substance abuse is commonly comorbid with depressive disorders. An effective antidepressant should reduce severity of depressive symptoms without liability problems. Although the US FDA has not approved the use of ketamine to treat depressive disorders, some psychiatrists offer off-label repeat prescription of ketamine. Prescribing ketamine for treating depressive disorders requires substantial empirical evidence. Clinicians should also consider research findings on ketamine abuse. Depressive disorders can be chronic conditions and the current evidence does not rule out the risk of substance abuse after repeat prescription of ketamine. Off-label ketamine use in treating depressive disorders may breach ethical and moral standards, especially in countries seriously affected by ketamine abuse. This article presents two real-world clinical vignettes which highlight ethical principles and theories, including autonomy, nonmaleficience, fidelity and consequentialism, as related to off-label ketamine use.ConclusionWe urge clinicians to minimise the risk of harming patients by considering the empirical evidence on ketamine properties and attempting all standard antidepressant therapies before considering the off-label use of ketamine. (shrink)

Previous research conducted in 1999 highlighted ethical concerns behind challenge studies inducing psychosis with ketamine and made recommendations to enhance ethical standards. Recently, a plethora of clinical trials have evaluated the efficacy of ketamine to treat mood disorders, which lead to complex ethical issues. Pharmaceutical companies and researchers hope to profit by developing patentable variations on ketamine for treating depression. Media have labeled ketamine as a “miracle” antidepressant. Some clinics offer expensive off-label use of ketamine to treat mood disorders. This (...) article examines the ecological validity of ketamine trials, measures to protect patients, informed consent procedures, financial inducements to participants and conflict of interest of researchers, therapeutic misconception, concealment, and deception. Further recommendations are purposed to improve ethical standard of clinical research involving ketamine. (shrink)

We wish to point out an additional consequence of the Catch-22 described by Andreae and colleagues (Andreae et al. 2016). The decades-long research gridlock of controlled drugs has unintentionally...

Psychotherapy with the use of psychedelic substances, including psilocybin, lysergic acid diethylamide (LSD), ketamine, and 3,4-methylenedioxymethamphetamine (MDMA), has demonstrated promise in treatment of post-traumatic stress disorder (PTSD), anxiety, addiction, and treatment-resistant depression. Psychedelic-assisted psychotherapy (PP) represents a unique psychopharmacological model that leverages the profound effects of the psychedelic experience. That experience is characterized by strong dependency on two key factors: participant mindset and the therapeutic environment. As such, therapeutic models that utilize psychedelics reflect the need for careful design that promotes (...) an open, flexible, trusting mindset and a supportive setting. To meet this need, the PP model is increasingly supplemented by auxiliary methods, including meditation, relaxation, visualization or spiritual practices. We suggest virtual reality (VR) as a full-spectrum tool able to capitalize on and catalyze the innately therapeutic aspects of the psychedelic experience, such as detachment from familiar reality, alteration of self-experience, augmentation of sensory perception and induction of mystical-type experiences. This is facilitated by VR’s evidenced capacity to: aid relaxation and reduce anxiety; buffer from external stimuli; promote a mindful presence; train the mind to achieve altered states of consciousness (ASC); evoke mystical states; enhance therapeutic alliance and encourage self-efficacy. While these unique VR features appear promising, VR’s potential role in PP remains speculative due to lack of empirical evidence on the combined use of VR and PP. Given the increased commercial interest in this synergy there is an urgent need to evaluate this approach. We suggest specific VR models and their role within PP protocols to inspire future direction in scientific research, and provide a list of potential disadvantages, side effects and limitations that need to be carefully considered. These include sensory overstimulation, cyber-sickness, triggering memories of past traumatic events as well as distracting from the inner experience or strongly influencing its contents. A balanced, evidence-based approach may provide continuity across all phases of treatment, support transition into and out of an ASC, deepen acute ASC experiences including mystical states and enrich the psychotherapeutic process of integration. We conclude that the potential application of VR in modulating psychedelic-assisted psychotherapy demands further exploration and an evidence-based approach to both design and implementation. (shrink)

In Ian Brassington’s article in a previous issue of this journal, he argues that suicide for the purpose of avoiding suffering is not, as Kant has contended, contrary to the moral law. Brassington’s objections are not cogent because they rely upon the exegetically incorrect premise that according to Kant the priceless value of personhood is in the noumenal world that we have no perception of. On the basis of Kant’s normative, metaphysical and epistemological theory, I argue, contrary to Brassington, that (...) according to Kant personhood’s moral value is explicitly in the sensible, phenomenal realm. While I argue that suicide solely to avoid suffering is immoral, I show that Kant’s normative system allows some acts of suicide to be morally permissible. In the course of the discussion of the value of humanity’s rationality and the immorality of suicide, I will discuss the broader modern medical ethical implications of Kant’s arguments, such as the moral impermissibility of using rationality depriving drugs, such as ketamine, solely to avoid pain. (shrink)

Current research on the neural basis of consciousness is based mainly on neuroimaging, physiology and psychophysics. This target article reviews what is known about biochemical factors that may contribute to the development of consciousness, based on loss of consciousness (i.e., coma). There are two theories of the biochemical mode of action of general anaesthetics. One is that anaesthesia is a direct (i.e., not receptor-mediated) effect of the anaesthetic on cellular neurophysiological function; the other is that some alteration of receptor function (...) occurs. General anaesthetics are mainly GABA agonists but some (such as ketamine) are glutamate antagonists. They also affect other systems, particularly cholinergic ones. There are various comas of metabolic origin. For example, a combination of small doses of the iron chelators desferrioxamine and prochlorperazine induce a profound and long lasting coma in humans. The mechanisms that might mediate this include redox mechanisms at the glutamate synapse, post-synaptic endocytosis of dopamine and iron, and intracellular iron-dopamine complexes, which are powerful dismuters of the superoxide anion. New findings in cell biology relating to endocytosis and recycling of receptors are discussed in a wider context. These biochemical events may induce coma by two mechanisms: (i) Consciousness may depend on widespread cortical (or cortico-thalamic) activation. (ii) Whereas these biochemical changes are widespread, only the changes in a subset of consciousness' neurons may count. An experimental program to distinguish between these two alternatives is proposed. (shrink)

We examine the ethical, social, and regulatory barriers that may hinder research on therapeutic potential of certain controversial controlled substances like marijuana, heroin, or ketamine. Hazards for individuals and society and potential adverse effects on communities may be good reasons for limiting access and justify careful monitoring of these substances. Overly strict regulations, fear of legal consequences, stigma associated with abuse and populations using illicit drugs, and lack of funding may, however, limit research on their considerable therapeutic potential. We review (...) the surprisingly sparse literature and address the particular ethical concerns pertinent to research with illicit and addictive substances, such as undue inducement, informed consent, therapeutic misconception, and risk to participants, researchers, and institutions. We consider the perspectives of key research stakeholders and explore whether they may be infected with bias. We conclude by proposing an empirical research agenda to provide an evidentiary basis for ethical reasoning. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Excited DeliriumWhat’s Psychiatry Got to do With It?Paul B. Lieberman, MDIf in life we are surrounded by death, so too in the health of our intellect by madness.—WittgensteinDelirium is a medical syndrome defined as “a relatively acute decline in cognition that fluctuates over hours or days” whose primary manifestation is a deficit of attention. It is common, estimated to occur in 10% to more than 50% of hospitalized patients, (...) with higher prevalence rates among people in nursing homes and at the end of life. It is often fatal, with a mortality rate in the hospital estimated to be 25% to 33%. Caused by a wide variety of conditions and frequently difficult to diagnose, it lacks characteristic postmortem pathology (Josephson & Miller 2018)‘Excited delirium,’ as Byju and Friesen forcefully argue (Byju & Friesen, 2023), is, if nothing else, an excuse. The ‘diagnosis’ has not been empirically validated and remains controversial (American Psychiatric Association, 2020). And while delirium is usually treated by internists and emergency medicine physicians, psychiatrists should also be concerned about the misuse of a putative medical diagnosis and join actively in discussion about it. For one thing, patients mis-diagnosed with this condition, as Byju and Friesen’s examples suggest, may actually have another psychiatric condition and, so, be people for whose safety we should advocate. Moreover, the kinds of police interventions which Byju and Friesen document as involving excited delirium also befall patients with other psychiatric problems in whom the issue of delirium does not arise.There are at least two broad ways in which psychiatrists are qualified and obligated to engage with this issue. As physicians, we should join our medical colleagues in carefully but persistently telling the scientific, medical truth. As psychiatrists, we should bring psychiatric knowledge into the discussion, for example, by explaining what can happen when people who do not, apparently, have a diagnosable mental disorder interact under stress with other people who, apparently, do.Delirium is a clinical diagnosis, made when characteristic signs and symptoms are present which should not be made ‘by exclusion’ when, as may happen, other causes are not found. There is no evidence of delirium in any of the three clinical descriptions Byju and Friesen provide. Perhaps such evidence exists which is not in their brief reports, but these three people appear to have had, either, another psychiatric condition, such as psychosis or drug intoxication, or perhaps no [End Page 353] diagnosis at all. Psychiatrists are particularly wellpositioned to make this point since patients with mental health problems are often misdiagnosed when they seek medical attention and are told, and treated as if, “it’s all (“just”!) psychological.”Excited delirium, if it exists, is fatal in 10% of cases (Gonin, Beysard, Hersin, & Carron, 2018) and, although this is lower than the rate for delirium in general, it is still high. Medical personnel must be available to evaluate and ensure the safety of patients in custody.The potential conflict between protecting the patient and protecting the public should not be overstated. Although physical trauma and excessive administration of medications, including ketamine 500 mg IV (Orhurhu, Vashicht, Claus, & Cohen, 2023) can be lethal, mechanical restraint by itself is not (Chieze et al., 2019; Gleerup et al., 2019): something else is necessary, such as asphyxiation (Evans, Wood, & Lambert, 2003). Nor is restraint necessary in many cases in which ‘de-escalation’ techniques can be equally effective (Garriga et al., 2016; Fernández-Costa, 2020). Perhaps these points are best made by law enforcement leaders—and they have been—but psychiatrists can add that safe management of potential violence can be provided for agitated people with psychiatric conditions.Although it is not clear what kind of strength ‘superhuman’ strength might be (certainly not medical), relative imperviousness to pain is clinically described. Its locus classicus is Beecher’s observation, during World War II, that injured soldiers awaiting return home from the front, required lower than usual doses of analgesics (Beecher, 1946). And it’s a common experience, scientifically confirmed, that physical trauma may not become painful until sometime after the injury (Melzack, Wall, & Ty, 1982). But pain is a warning. Its absence is not a license, but a caution... (shrink)

Recent research offers good reason to think that various psychedelic drugs—including psilocybin, ayahuasca, ketamine, MDMA, and LSD—may have significant therapeutic potential in the treatment of various mental health conditions, including post-traumatic stress disorder, depression, existential distress, and addiction. Although the use of psychoactive drugs, such as Diazepam or Ritalin, is well established, psychedelics arguably represent a therapeutic step change. As experiential therapies, their value would seem to lie in the subjective experiences they induce. As it is the only way for (...) trainee psychedelic therapists to fully understand their subjective effects, some have suggested that firsthand experience of psychedelics should form part of training programs. We question this notion. First, we consider whether the epistemic benefits offered by drug-induced psychedelic experience are as unique as is supposed. We then reflect on the value it might have in regard to the training of psychedelic therapists. We conclude that, absent stronger evidence of the contribution drug-induced experiences make to the training of psychedelic therapists, requiring trainees to take psychedelic drugs does not seem ethically legitimate. However, given the potential for epistemic benefit cannot be entirely ruled out, permitting trainees who wish to gain first-hand experience of psychedelics may be permissible. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Excited DeliriumWhat’s Psychiatry Got to do With It?Paul B. Lieberman, MDIf in life we are surrounded by death, so too in the health of our intellect by madness.—WittgensteinDelirium is a medical syndrome defined as “a relatively acute decline in cognition that fluctuates over hours or days” whose primary manifestation is a deficit of attention. It is common, estimated to occur in 10% to more than 50% of hospitalized patients, (...) with higher prevalence rates among people in nursing homes and at the end of life. It is often fatal, with a mortality rate in the hospital estimated to be 25% to 33%. Caused by a wide variety of conditions and frequently difficult to diagnose, it lacks characteristic postmortem pathology (Josephson & Miller 2018)‘Excited delirium,’ as Byju and Friesen forcefully argue (Byju & Friesen, 2023), is, if nothing else, an excuse. The ‘diagnosis’ has not been empirically validated and remains controversial (American Psychiatric Association, 2020). And while delirium is usually treated by internists and emergency medicine physicians, psychiatrists should also be concerned about the misuse of a putative medical diagnosis and join actively in discussion about it. For one thing, patients mis-diagnosed with this condition, as Byju and Friesen’s examples suggest, may actually have another psychiatric condition and, so, be people for whose safety we should advocate. Moreover, the kinds of police interventions which Byju and Friesen document as involving excited delirium also befall patients with other psychiatric problems in whom the issue of delirium does not arise.There are at least two broad ways in which psychiatrists are qualified and obligated to engage with this issue. As physicians, we should join our medical colleagues in carefully but persistently telling the scientific, medical truth. As psychiatrists, we should bring psychiatric knowledge into the discussion, for example, by explaining what can happen when people who do not, apparently, have a diagnosable mental disorder interact under stress with other people who, apparently, do.Delirium is a clinical diagnosis, made when characteristic signs and symptoms are present which should not be made ‘by exclusion’ when, as may happen, other causes are not found. There is no evidence of delirium in any of the three clinical descriptions Byju and Friesen provide. Perhaps such evidence exists which is not in their brief reports, but these three people appear to have had, either, another psychiatric condition, such as psychosis or drug intoxication, or perhaps no [End Page 353] diagnosis at all. Psychiatrists are particularly wellpositioned to make this point since patients with mental health problems are often misdiagnosed when they seek medical attention and are told, and treated as if, “it’s all (“just”!) psychological.”Excited delirium, if it exists, is fatal in 10% of cases (Gonin, Beysard, Hersin, & Carron, 2018) and, although this is lower than the rate for delirium in general, it is still high. Medical personnel must be available to evaluate and ensure the safety of patients in custody.The potential conflict between protecting the patient and protecting the public should not be overstated. Although physical trauma and excessive administration of medications, including ketamine 500 mg IV (Orhurhu, Vashicht, Claus, & Cohen, 2023) can be lethal, mechanical restraint by itself is not (Chieze et al., 2019; Gleerup et al., 2019): something else is necessary, such as asphyxiation (Evans, Wood, & Lambert, 2003). Nor is restraint necessary in many cases in which ‘de-escalation’ techniques can be equally effective (Garriga et al., 2016; Fernández-Costa, 2020). Perhaps these points are best made by law enforcement leaders—and they have been—but psychiatrists can add that safe management of potential violence can be provided for agitated people with psychiatric conditions.Although it is not clear what kind of strength ‘superhuman’ strength might be (certainly not medical), relative imperviousness to pain is clinically described. Its locus classicus is Beecher’s observation, during World War II, that injured soldiers awaiting return home from the front, required lower than usual doses of analgesics (Beecher, 1946). And it’s a common experience, scientifically confirmed, that physical trauma may not become painful until sometime after the injury (Melzack, Wall, & Ty, 1982). But pain is a warning. Its absence is not a license, but a caution... (shrink)

Little is known about how individuals with and without mood disorders perceive the inherent risks and helpfulness of participating in innovative psychiatric research, or about the factors that influence their willingness to participate. We conducted an online survey with 80 individuals (self-reported mood disorder [n = 25], self-reported good health [n = 55]) recruited via MTurk. We assessed respondents’ perceptions of risk and helpfulness in study vignettes associated with two innovative research projects (intravenous ketamine therapy and wearable devices), as well (...) as their willingness to participate in these projects. Respondents with and without mood disorders perceived risk similarly across projects. Respondents with no mood disorders viewed both projects as more helpful to society than to research volunteers, while respondents with mood disorders viewed the projects as equally helpful to volunteers and society. Individuals with mood disorders perceived ketamine research, and the two projects on average, as more helpful to research volunteers than did individuals without mood disorders. Our findings add to a limited empirical literature on the perspectives of volunteers in innovative psychiatric research. (shrink)

The field of consciousness studies has long benefitted from the investigation of non- ordinary states of consciousness, both spontaneous and facilitated by mind-altering agents. In the present study, I look at the implications of spontaneous near-death experiences and experiences facilitated by the dissociative anaesthetic ketamine. These experiences reputedly have similar phenomenologies, such as a feeling of dying, motion through darkness, entering another realm, visions of light, and a sense of separation from the physical body. To assess whether ketamine and near-death (...) experiences really are similar, I undertake a systematic comparison of 36 accounts of NDE-like experiences under ketamine with 36 accounts of NDE that resulted from cardiac arrest or other life-threatening circumstances in which wakefulness was maintained . The results suggest that ketamine and near- death experiences are indeed similar, which might be taken to imply that NDEs have a purely chemical or psychophysiological basis. However, this conclusion is not inevitable, and I draw upon the intriguing 'spatial' or 'situated' characteristic of ketamine and near-death experiences to suggest an alternative to both neuropsychological reductionism and a straightforward post-mortem survival theory. To develop the idea of a dynamic interrelation of consciousness and 'place', I draw on contemporary Japanese philosophies of body-mind. (shrink)