Ketamine: Catalyst for Paradigm Change in Mental Health
Scott Shannon, M.D. FAACAP
We see signs of a failing mental health care system everywhere we look. Depression is now endemic in the US. Rates of suicide have risen by about 30% in the last twenty years, despite the escalating use of anti-depressants [1] Less than half of patients respond to their first prescribed anti-depressant [2] and over time, treatment-resistant major depression affects 30 to 40% of those prescribed [3]. Ac- cording to the CDC, deaths of despair—those caused by drugs, alcohol, and suicide—more than doubled from 1999 to 2017 [4]. Furthermore, it is no better for teens: 42% of high schoolers have recently reported feelings of sadness or hopelessness [5], and only half of suffering children find the care they need [6].
The COVID-19 pandemic has made things even worse. The rates of depression had already increased to over 20% prior to COVID [7], and new research from a 2021 Boston University study found that only 12 months into the pandemic, bed past 30% [8]. The pandemic accelerated a pernicious trend of overwhelm and compassion fatigue among nurses and physicians, with 40 to 60% now experiencing burnout and depression [9]. Caregivers have been particularly affected. As canaries in the coal mine for the mental health of our culture, teen visits to the emergency room for suspected suicide attempts escalated by 51% between 2019 and 2021 for girls [10]. These numbers carry jaw-dropping power.
This data points to an ineffective model of mental healthcare, and the pandemic dramatically exposed and worsened the preexisting flaws of the already broken system. Despite the labors of caring, dedicated, and intelligent providers, we are not making progress. Clearly, we need a new model of care with new treatment options to tackle this growing crisis. Luckily, there are new options for care that may help address it including ketamine. Ketamine offers both the potential to more effectively treat those suffering and a catalyst for a profound and much-needed shift in our paradigm of mental health care.
With ketamine as a tool, providers can focus on holistic patient care. The problem of the ineffective model of care does not lie with the providers but in fact, with the very foundations of the care they provide. Modern psychiatry is built upon the premise that the symptomatic brain is broken, chemically im- balanced, and the only hope for relief comes from medications to rebalance neurotransmitters. This chemical imbalance theory posits that the typical psychiatrist must deeply understand the nuances of the neurochemical environment of the human brain, the most complex system in the known universe. However, after a brief interview, the psychiatrist selects a pharmaceutical agent to improve the delicately nuanced neurotransmitter soup found within the central nervous system, thereby (or ideally) relieving suffering. Not only does a psychiatrist select this without any biological assessment of the brain or neurochemicals, but they are also making this selection without any psychiatric access to a solid understanding of how anti-depressants actually work. So, while this process is sometimes effective at muffling psychic distress and misery, more often than not, they are merely dulling the inner turmoil and simply enabling individuals to care less about it. As a result, their apathy might even extend past their suffering. Studies have found that individuals treated with anti-depressants often care less about everything else, including their spouse, other relationships, sexual passion, and more. Regardless of these
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Ketamine: Catalyst for Paradigm Change in Mental Health
challenges, the vast majority of people are not cured by these agents [11].
Perhaps, then, building the edifice of modern psychiatry on an unclear, untestable model for treating those suffering is creating the real imbalance in our field. The use of psychiatric medications came on empirically without a proper foundation in science while simultaneously serving as a boon for the pharmaceutical industry. The first antipsychotic (chlorpromazine) and first antidepressant (iproniazid) were both discovered through serendipity [12] and soon after, in 1988, Prozac was introduced. Since then, the use of anti-depressant medications has steadily risen to almost 14% of the US population [13], reaching 24% in some demographics such as women over 60 [14]. This consistent increase in use provides pharmaceutical companies with $5.6 billion in US sales alone for these medications [15]. Still, the chemical im- balance of serotonin in depression has never been proven [16], and there is now considerably more evidence disproving its connection to depression [17]. This rebalancing of neuro- transmitters stands at the very core of what modern psychiatry does, yet it is never presented as the evidenced-based foundation for how and why we practice. As the evidence for the serious limitations of the existing model grows, so too does the number of dis- satisfied psychiatrists and suffering individuals, all in search of a new path. They all share a sense of impotence with our current options and an increasing impatience for something more effective.
Nevertheless, it is not all doom and gloom. The last decade has seen exciting developments in psychedelic medicine (PM). This renewed model of care utilizes a psychedelic framework to create a therapeutic container, encouraging a patient’s inner exploration via a range of medicines that act as catalysts for altering consciousness and opening new doorways of awareness, insight, and experience. Medicines such as psilocybin or
MDMA—and, of course, ketamine—are given to augment psychotherapy delivered with preparation, integration, and focused attention to set and setting (the container). They open new experiential territory in the psyche and function as catalysts for cognitive shifts—something we have not yet seen with psychopharmacology. We now have research that documents how psilocybin can alter an individual’s metaphysical belief system and their existential world [18, 19], which has benefits like decreased fear of death [20] and durable relief of depression [21]. This spiritual belief system frees our motivation, establishes hope, and secures a sense of connection, or it can lock us into despair, isolation, and apathy. PM seems to open our spiritual perspective to inquiry and revision and it may be spiritual medicine.
The research supporting the enduring value of PM has come on forcefully in the last few years. The FDA has awarded three versions of PM Breakthrough Therapy Status [22, 23]. The published effect sizes of MDMA, for example, humble those found in the suppressive tools of conventional psychopharmacology by a factor of 2x to 3x in effect size [24]. While we wait for the definitive results from the large Phase III studies, expected in May of 2023 [25], a range of other neuroimaging and smaller clinical results support the promise found in this research. However, we cannot and should not make the same mistake we have made with medications like Prozac. Psychedelic medicine, while powerful and much needed, is not a complete mental health care system. Psychedelics are merely a tool, and their efficacy does not eliminate the need for a comprehensive system of care that educates, prevents, and offers other avenues for support.
We must acknowledge that a broad range of presenting complaints in mental health are not appropriate for PM. These include child psychiatry, adjustment issues, self-limiting concerns, family conflict, and all of the
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presentations driven by epigenetic and lifestyle issues, For example, we now appreciate that diet and nutrition play a significant role in the risk for depression, bipolar disorder and anxiety. We know that our inherited genes as expressed by single nucleotide polymorphisms (SNPs) are a factor in less than 30% of major mental illnesses. The balance of the risk is driven by environmental factors such as abuse history (adverse childhood experiences-ACEs), relational support and lifestyle choices that alter the expression of our genes by epigenetic modification. Lifestyle choices include diet, exercise and self-care. These appear to alter our genetic expression by methylation of the histones found on the genes. A focus on PM alone that misses the opportunity to address our risk factors is an incomplete system.
Quite simply, psychedelic medicine should not be mistaken for comprehensive mental health care, and any overly enthusiastic attempt to make it so will ultimately harm patients. Integrative medicine (also known as natural medicine or holistic medicine) can supply this broad foundation for psychedelic medicine, partly because it and PM share the same roots. Integrative medicine builds upon a foundation of body-mind-spirit unity, and both posit that all healing—and health it- self—is built upon the innate ability of our being to move towards wholeness when barriers, such as excessive self-referential thinking, are removed. These models are built on the concept that each person we meet has the innate capacity to self-heal. This stands in stark contrast to the chemical imbalance model of conventional psychiatry that does not embrace the concept of healing, just medication maintenance. Integrative psychiatry and psychedelic medicine can represent a complete mental health care system.
This concept of body-mind-spirit unity brings us quickly to spiritual medicine. Spiritual medicine embodies a different perspective and requires a different type of caregiver.
relationship—one that’s built more on per- sonal journeys and emotional insight rather than one centered around enduring and im- personal neurotransmitter manipulation. PM validates this new perspective of wholeness by moving the seat of power from the therapist to the person immersed in the psychedelic experience. The therapist takes on the role of sitter, container, and facilitator. At the same time, the individual immersed in the close encounter with the depths of the psyche plays the role of expert and explorer. Thus, the classic polarity of wise expert and suffering patient or client so central to the psycho- therapeutic paradigm becomes reorganized to reflect this new perspective about the primacy of the psyche and its innate spiritual wisdom.
Spiritual medicine is our most potent medicine, and is always personal: it is not scalable, cannot be commodified as a proto- col, does not embrace a postmark, and always holds irreconcilable mystery. PM and its spiritual incisiveness carry the power of a surgeon’s knife to the psyche not the blunt and often damaging instruments we have grown so frustrated with. It is no surprise that the excitement about psychedelic medicine is palpable. We see it in the professional interest in drastically oversubscribed training programs and the explosion of political action across the country. There is no mistake: our healthcare professionals, our society, and the boundless suffering populace cry out for a spiritual and grounded approach to care.
This shift from the status quo reveals that introducing a new paradigm—one that pre scribes medication to speed psychotherapy, not fuel apathy—can deepen our potential to heal and help repair the rift between therapists and prescribers. MDMA and psilocybin have been the main actors, but it is time to introduce a new character: ketamine. Keta mine offers a portal to effective mental health care that engages our spiritual self, lubricates psychotherapy, and relieves depression.
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Ketamine: Catalyst for Paradigm Change in Mental Health
Ketamine is fueling this profound shift in the paradigm of mental health care. It supports the industry in moving away from a suppressive model of care that fears the psyche to an evocative model that honors the psyche.
Ketamine plays this pivotal role in this transition from the old models of mental health (daily mediated suppression of the psyche and the therapist as an external ex- pert) to a new evocative model in a few different ways. First, ketamine typically works better for severe depression than conventional medications. Dr. C. Andrade, a well- known psychiatric researcher, described it in a 2017 review article, “the marked acute antidepressant efficacy of ketamine, even in medication-refractory patients, now seems beyond doubt” [26]. This potency has gathered the attention of modern conventional psychiatry and pharmaceutical companies, as witnessed with the release of Spravato (found as one-half of generic ketamine) by Janssen in 2019 [27]. Second, ketamine works when given in an episodic manner and does not re- quire daily doses to suppress symptoms [28]. Third, ketamine is an agent that decreases the activity of the default mode network just as classic psychedelics do [29]. So, it can trigger profound psychedelic-like insights that can alter someone's life trajectory with just a single dose. Finally, many are finding that keta- mine, like MDMA or other classic psychedelics, can enhance psychotherapy by accelerating and deepening the process.
These facets become quite apparent when you work with ketamine in a clinical setting, as they foster exploration and allow the practitioner to go beyond an infusion routine. As more and more practitioners are drawn to ketamine by one of these angles, more and more begin to embrace the paradigm of PM. It is a slippery ride on an effective slope. Many professionals were drawn to mental health by the promise of working with the human mind, and, finally, after years of ineffective medicines and faulty systems, there is a tool that
opens up this realm for exploration: keta- mine.
Ketamine can create psychedelic effects while simultaneously being an accepted part of the conventional toolbox, ultimately bridging the old and new models of care. Ketamine is a gentle, safe, and more accessible entry point for explorations of the psyche, providing flexibility and provider confidence. Whether you are a novice psychonaut (explorer of the psyche), an unseasoned practitioner, or a veteran of many decades working in the trenches, ketamine might help all practitioners understand what is available to them and become comfortable in this realm prior to full legalization of psychedelics.
To begin with, let us explore the items that reflect ketamine’s ease, comfort, and safety:
Ketamine reduces anxiety. It quiets that part of our central nervous system that worries and frets. Many classical psychedelic medicines can have a significant element of anxiety as part of the journey (found in 20% of participants in one LSD study [30]. If you are new to psychedelics, this tension can be intimidating and overwhelming. Research indicates that ketamine is euphoric and mood boosting for most people [31]. Unpleasant or frightening trips are possible but much less likely than with psilocybin or LSD as ketamine is well tolerated in a range of ages and indications [32-36]. Ketamine opens the floodgates slowly. Both ketamine and the classical psychedelics decrease the activity of the default mode network [29], which may be our closest brain equivalent to the ego [37]. The classical psychedelics can and will release a tsunami of unconscious material that can be very powerful (and overwhelming).
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when these self-created filters are decreased. Ketamine does decrease the filter of the self. However, it simultaneously decreases the power of cortical functioning [38] and thus reduces the unpredictable wave of the unconscious material brought to awareness. Traumatic experiences may be accessed, but the weight of the new in- sights is typically more limited. Ketamine can work as a gentler introduction to these inner experiences.
It is brief. The half-life of ketamine is short, about 45 minutes [39]. This means that the entire experience lasts less than one hour. Good or bad, the journey is short and manageable. The total time from check-in at the office to walking out the front door is typically about two to three hours. People clear from the effects of ketamine fully in a few hours, and the practitioner can treat multiple people in a workday.
It is safe. Over the last 50 years or so, ketamine has become a well-known and well-utilized medication in operating rooms, emergency departments, and pain centers. The track record is one of safety and predictability at the doses being employed in psychiatry (0.5 to 1.5 mg/kg) [33-36]. A few years ago, at a Kriya conference Steve Levine, then of the Ketamine Treatment Centers, noted that they had delivered over 10,000 psychiatric doses of ketamine without one serious adverse event [40]. With modest caution, keta- mine has proven to be a safe medication for psychiatric applications.
It is pharmacologically clean. Unlike MDMA and the classic psychedelics, ketamine has little in the way of
contraindications with psychiatric medications. The Phase II and Phase III protocols for MDMA, psilocybin, and LSD include a contraindication for concurrent dosing with most psychiatric medications, especially anti- depressants. This means most psychiatric patients must endure a medication taper and washout period that can take weeks to months. This is not trivial. Many patients have been on these medications for years, if not decades. After years of medication management, the body’s ability to find neuro- transmitter balance begins to weaken and fail. This is the primary unspoken liability of psychiatric prescribing, but ketamine does not challenge levels of the monoamines commonly targeted with psychiatric medications (dopamine, serotonin, and norepinephrine). As such, it does not require a taper of psychiatric medications or a washout. Plainly put: ketamine is more straightforward for the patient and the psychiatrist.
It is cheap. While it may be crass to talk about cost, it is a genuine concern. Over half of Americans limit health care simply due to the cost [41]. As deductibles and co-pays grow, so does treatment avoidance. The cost of ketamine is not a limitation. The cost of the medicine needed for a typical intramuscular injection is less than $5. The vast majority of the price for ketamine-assisted work lies in the cost of the provider’s time. Group therapy and trainee involvement offer some potential solutions to this challenge. In a very real way, ketamine frees us from the exorbitant business model of pharmaceutical companies.
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Ketamine: Catalyst for Paradigm Change in Mental Health
Ketamine can also create powerful and psychedelic-like effects, aiding the caregiver in supporting healing. Like classic psychedelics, it diminishes the effects of the default mode network. It also dramatically enhances neuroplasticity [42]. This shift may explain some of the power of ketamine to lift mood, alter insight and enhance motivation; this is a big part of the inherent attractiveness of ketamine. Overall, it possesses a number of other observable effects that make it attractive to providers working in this space:
Ketamine is powerful. Never mind that ketamine is not a true psychedelic. This experience may be one of the most profound alterations of consciousness that anyone will ever experience with any agent. As a dissociative agent, ketamine disconnects most of our cortical awareness and creates an experience that will astound patients. Patients and practitioners should not underestimate the power of this experience. This dramatic and abrupt departure from our normal state of consciousness often triggers curiosity and profound respect.
Ketamine alters our thinking. Keta- mine modifies the default mode net- work, disrupts slower thalamocortical relays, and significantly enhances neuroplasticity [29, 43, 42]. It offers a new way of thinking, particularly about one’s life and the big picture of our existence. A different vantage point offers a new perspective. People come away with a refreshed look at their life journey and options for change. After a ketamine experience, the brain is more open to change. This enhanced plasticity lasts most acutely for 24 plus hours [43], but with proper integration, the changes could last a lifetime.
Ketamine has a clear and varied dose-response curve. Individuals can dial in the intensity of experience they would like to have low dose: verbal, yet quite altered (somewhat like pe- yote); moderate dose: some verbal capacity, but without most of the personal narrative (more like psilocybin); high dose: nonverbal and disconnected from our body and earthly plane (similar to 5-MeO-DMT). This dose response curve reflects how our consciousness functions. Different doses open up unique elements of consciousness and thus unique pathways for healing awareness. We must learn this terrain well and enhance our ability to direct specific mental health and psychotherapeutic challenges in a specific direction. We have yet to map this needed but uncharted territory. Ketamine offers guidance on this needed task.
Ketamine offers therapists a pathway to process trauma and can also be applied to the therapeutic encounter in a number of other ways as well. The dissociative mechanism inherent with ketamine reduces the intensity of all emotions, including fear and anxiety, making it a valuable tool for psychotherapy. It helps to limit the excessive emotional pain linked to trauma and interpersonal conflict. Once partially dissociated, someone with a trauma history can access distressing emotions without disorganizing terror or panic. MDMA does this as well, but it maintains complete cognitive clarity. Given this difference, MDMA is a superior tool for processing trauma, but it is not yet available for therapists legally.
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Ketamine enhances immediate psychotherapy. The options for keta- mine-assisted psychotherapy are two- fold: immediate and delayed: The im- mediate psychotherapeutic benefits are part of the low-dose lozenge method in which the practitioner sits with someone under the influence of low-dose sublingual lozenges (most common) or a slowed IV drip or sub- cutaneous injection (less common). Low-dose lozenges provide a twilight experience that enhances access to painful material and speeds psycho- therapy (called the psycholytic model) [44]. We tolerate the difficult insights better and can process our wounding at a much deeper level. Ego controls are reduced but not gone. This catalyzes psychotherapeutic exploration. Ketamine is an anesthetic agent, but when used in this manner, it opens our access to trauma and re- pressed pain. Some direct processing is possible after the traveler emerges from a deeper (psychedelic) IV or IM session. The challenge here is that, especially with the IM injection, this time frame between first engagement and full sobriety can be quite brief. However, it allows for some existential processing and anchoring of the major experiential qualities. Immediate psychotherapy can take many forms, and therapists will find that ketamine offers manifold options to guide another toward healing.
Ketamine enhances delayed psycho- therapy. The alterations found with dissociation in these brain regions and in these specific brain locations (de- fault mode network, amygdala, and hippocampus) [29, 45, 46], while maxi- mal for the hour’s journey, linger for beyond 24 hours. This offers a
practical window for enhancing conventional psychotherapy. Our experience indicates that the results are enhanced and synergistic if conventional psychotherapy occurs within 36 hours of the dosing. Psychotherapists unfamiliar with Ketamine Assisted Psychotherapy (KAP) will comment that the gains made in one of these penumbral sessions will often surpass all of the conventional therapy done in the prior months or even years in terms of cognitive flexibility and insight gained. Delayed psycho- therapy can simply look like effectively catalyzed conventional care.
Ketamine enhances group psycho- therapy. While inherently powerful, group psychotherapy can be challenging to orchestrate well. Participants may come from a wide range of perspectives and vary in comfort with the process. Ketamine facilitates a pro- found experience that supports a more consistent shared foundation for group exploration. It also reduces the anxiety that may block open sharing and genuine honesty. Providing a normative experience of processing with peers also reduces stigma and shame. The powerful psychedelic experience drives a deeply enhanced sense of connection and bonding that often takes months of regular group sessions to nurture. Ketamine often provides a quality of heartopening and unconditional positive regard. While this is not as consistent or deep as that found with MDMA, ketamine can foster a sense of group caring and comradery that feels priceless. In toto, ketamine can unleash the power of group work and facilitate gains that may exceed those found in individual work, as humans often feel a sense of
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Ketamine: Catalyst for Paradigm Change in Mental Health
safety in numbers. Group work may be the future of PM.
Ketamine enhances psychotherapeutic training. Ketamine provides psychotherapists an invaluable tool for learning the basics of psychedelic- assisted psychotherapy. Given these dosing and delivery options, a vast range of journey experiences can be arranged for the apprenticing therapist to witness and support. The short time frame of a ketamine journey makes it more practical for psycho- therapeutic training. Ketamine is more predictable than the classic psychedelics. This makes it an ideal tool to deliver safe and effective training experiences that do not overwhelm the student seeking to learn from another’s powerful inner experience. The fact that these powerful inner and outer experiences can be linked in time also builds empathy and therapeutic wisdom. For therapists in training for work in PM, it is very important to have a personal experience of a powerful state of non-ordinary consciousness. Ketamine provides this and more in a safe and manageable manner. It will allow the emerging profession to train the providers needed to usher in this new paradigm.
Ketamine can also enhance the study of consciousness, perhaps opening opportunities to recalibrate the mental health field in other ways. For those deeply interested in the power of psychedelics to alter and improve our mental health, ketamine offers some very advanced capabilities that deserve consideration. The dissociative mechanisms of keta- mine bring some unique characteristics not shared by classic psychedelics. Much of our cortical self-referential loops are taken offline by the interruptions of these relays [47-
50]. This, in turn, creates a much different experience of consciousness. These relays are also progressively altered by the dose of ketamine involved. Classic psychedelics leave these relays less impacted, but instead they create massive shifts in the default mode net- work with more specificity [51, 52]. Ketamine drives a less specific and more generic separation of awareness from the cortex (and thus the body) [53]. This dose-dependent effect provides psychedelic explorers with useful options for experience and training.
Ketamine offers a sense of pure consciousness. This journey introduces the inner traveler to a noncognitive open field of awareness that is unique and awe inspiring. In other words, ketamine decreases our thinking brain enough for us to realize that our awareness exists even without thought. This profound experience of- ten takes years of meditation practice to encounter reliably. This experience of being freed from the limits of severe anxiety or depression can help a client to find hope, let go of outmoded perspectives and open up to more significant change and flexibility. More than that, ketamine often catalyzes profound spiritual insights that alter our worldview.
Gamma power relates to the nature of consciousness. Electroencephalographic (EEG) research documents that gamma wave (30-80 cycles per second) power may be one of the best measures of human consciousness [54- 57]. For example, it is dramatically reduced or eliminated by conventional anesthetic agents [58]. Richard Davidson’s work at UW with Tibetan monks showed that gamma power is increased by meditative practice in a dose-dependent manner: a monk with
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30,000 hours of practice on the mat demonstrates more gamma power than one with 10,000 hours [59]. Very few agents have been documented to increase gamma power. Ketamine is one of them [60, 61]. Interestingly, ketamine increases gamma power through the typical psychiatric dose range of 0.5 to 1.2 mg/kg and then begins to deteriorate, coincident with the loss of recall and awareness in the ketamine session [62, 63]. Gamma power and ketamine may prove to be a portal to a complete understanding of the neural correlates of conscious- ness.
Dissociation is different. While many will say that ketamine is not a classic psychedelic medicine and thus should play no role in the training of professionals, the opposite is true: a fully dissociated experience is unique and not approximated by classic psychedelics. Ketamine provides a unique experience that teaches us about the underlying nature of consciousness. Psychedelics provide profound disruption of our cortical functions, while ketamine disconnects us from these limitations. Both are useful. There is no priority in these two different road maps. It is merely terrain to be explored and appreciated. Like- wise, they also have unique strengths for working with a stuck psyche.
Ketamine can mimic the near-death experience. Near-death experiences (NDE) have been studied for decades. We now know that these close encounters with death provide some individuals with an amazing refresh of their worldview and a spiritual perspective that creates a durable shift in the survivor’s perspective on life.
This shift results in a movement towards more openness, enhanced love for others, and greater personal optimism, among other positives [64]. In contrast, a small percentage (10 to 20%) of revived people share this specific experience, the essence of it is remarkably consistent and powerful [65]. Recently published research compared the central themes of 15,000 psychedelic journey narratives with 625 NDE reports [66]. The researchers found that the ketamine experience most consistently aligned with the NDE journey compared to other psychedelic agents. Unfortunately, a significant percentage of those facing an NDE do indeed perish. The same is not true of ketamine. As mentioned, ketamine is quite safe, and the death of the physical body is unheard of when employing psychiatric doses. However, the death of the ego and self can be quite common. This may be part of the enormous transformation possible with a keta- mine experience. Ironically, death of the ego may be life-giving.
Ketamine, and the larger PM system, are not without challenges. Like most psychoactive tools, it can build dependence and elicit addictive behavior [67]. Frontal lobe disconnection syndrome [68] and erosive cystitis [69] can occur in populations with excessive daily use, even if prescribed. The pandemic forced the federal government in the US to relax re- strictions on remote prescribing, allowing for more prescriptions with less oversight. This has unleashed a wave of dangerous profiteering that seems to be an unfortunate echo of the oxycontin disaster that is still unfolding in our society [70]. Daily (and often escalating) use of controlled substances such as ketamine is not part of the psychedelic framework. The psychedelic framework is built upon episodic
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Ketamine: Catalyst for Paradigm Change in Mental Health
transformative excursions into the psyche, not the numbing and avoidance that can be found with the daily use of ketamine. This destructive use of ketamine might ultimately, and counterintuitively, keep us stuck in the old model of managing misery rather than respecting the transformative power of the psyche. If ketamine use is punitively restricted or diminished due to these missteps, it will darken our promising path to a new paradigm in mental health.
What is more, access to this kind of PM treatment is paramount. Since many psychedelic medicines are currently illegal, they are out of reach for many individuals and practitioners. For most practitioners, this legal barrier stands even more foreboding given the career and financial cornerstone their licensure represents. While the barrier on psychedelics does appear to be softening in some places—Oregon and Colorado have now legalized a regulatory pathway for treatment with psilocybin [71]—the emerging paradigm may take a decade or more to reach most patients and caregivers. Nevertheless, Ketamine is legal. Furthermore, ketamine can be a gateway medicine to the new paradigm by opening up both therapeutic access and clinical training.
Years from now, we will likely have MDMA, psilocybin, and many other legal options to provide the much-needed care in the new paradigm of psychedelic medicine. Unfortunately, these agents are years away from approval and ready access. Given the massive load of suffering that we all face, we must speed up the transition to psychedelic medicine and medication-assisted psycho- therapy. Ketamine can help us achieve that goal immediately.
Ketamine is a non-specific agent that supports many different functions, all of which can lead to better health and root-cause healing. It can be a chameleon that is cognitively loosening or psychedelically inspiring, pre- dominantly verbal or non-verbal, and it can
even simulate a near-death experience. Keta- mine can treat severe treatment-resistant de- pression, provide deep access to conscious- ness, facilitate psychotherapy, and train psychedelic psychotherapists. Ketamine can also be a path for enhanced self-care and prevention. Dissociation is a powerful tool for therapeutically manipulating consciousness that can be applied in many ways. Ketamine offers a comprehensive and unique range of possible clinical interventions, which we are just beginning to comprehend.
Our society is experiencing pain and dis- tress on epic levels. The mental health care crisis we are currently experiencing is all the more damning as providers and patients alike have lost confidence in conventional tools. Finally, after decades of working at odds with each other, psychotherapy and medication can start to work together towards the same laudable goal: accessing and aiding the psyche. With new, powerful tools at our disposal, like ketamine, we are now moving into a paradigm of care that genuinely respects consciousness and the inner realms of the psyche. This, too, helps mental health professionals in not only embracing the coming psychedelic paradigm but in rejuvenating their passion for caregiving. Ketamine, accessible now, allows us to explore and honor the psyche, not fear it. Ketamine is a much-needed catalyst to open the psyche, transform mental health care, and address this crisis directly.
AUTHOR INFORMATION
Scott Shannon M.D. FAACAP
(scott.shannon@wholeness.com) Shannon, S
REFERENCES:
1. https://www.cdc.gov/nchs/products/data- briefs/db433.htm
The(2023, June). Ketamine: Catalyst
for Paradigm Change in Mental Health.
Journal of Psychedelic Psychiatry, 5(2).
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1. Alemi F, Min H, Yousefi M, Becker LK, Hane CA, Nori VS, Wojtusiak J. Effectiveness of com- mon antidepressants: a post market release study. EClinicalMedicine. 2021 Oct 25;41:101171. doi: 10.1016/j.eclinm.2021.101171. PMID: 34877511; PMCID: PMC8633963.
2. Zhdanava M, Pilon D, Ghelerter I, Chow W, Joshi K, Lefebvre P, Sheehan JJ. The Prevalence and National Burden of Treatment-Resistant De- pression and Major Depressive Disorder in the United States. J Clin Psychiatry. 2021 Mar 16;82(2):20m13699. doi: 10.4088/JCP .20m13699. PMID: 33989464.
3. https://www.cdc.gov/nchs/images/data- briefs/351-400/db362-fig1.png
4. https://www.cdc.gov/healthyyouth/data/yrbs/pdf/ YRBS_Data-Summary-Trends_Re- port2023_508.pdf
5. Whitney DG, Peterson MD. US National and State-Level Prevalence of Mental Health Disor- ders and Disparities of Mental Health Care Use in Children. JAMA Pediatr. 2019 Apr 1;173(4):389-391. doi: 10.1001/jamapediat- rics.2018.5399. PMID: 30742204; PMCID: PMC6450272.
6. Arias D, Saxena S, Verguet S. Quantifying the global burden of mental disorders and their eco- nomic value. EClinicalMedicine. 2022 Sep 28;54:101675. doi: 10.1016/j.eclinm.2022.101675. PMID: 36193171; PMCID: PMC9526145.
7. Ettman CK, Cohen GH, Abdalla SM, Sampson L, Trinquart L, Castrucci BC, Bork RH, Clark MA, Wilson I, Vivier PM, Galea S. Persistent depressive symptoms during COVID-19: a na- tional, population-representative, longitudinal study of U.S. adults. Lancet Reg Health Am. 2022 Jan;5:100091. doi: 10.1016/j.lana.2021.100091. Epub 2021 Oct 4. PMID: 34635882; PMCID: PMC8488314.
8. Burrowes SAB, Casey SM, Pierre-Joseph N, Talbot SG, Hall T, Christian-Brathwaite N, Del- Carmen M, Garofalo C, Lundberg B, Mehta PK, Mottl-Santiago J, Schechter-Perkins EM, Weber A, Yarrington CD, Perkins RB. COVID-19 pan- demic impacts on mental health, burnout, and longevity in the workplace among healthcare workers: A mixed methods study. J Interprof Educ Pract. 2023 Sep;32:100661. doi: 10.1016/j.xjep.2023.100661. Epub 2023 Jun 8. PMID: 37305404; PMCID: PMC10248469.
9. https://www.cdc.gov/mmwr/vol- umes/70/wr/mm7024e1.htm
10. vanov I, Schwartz JM. Why Psychotropic Drugs Don't Cure Mental Illness-But Should They? Front Psychiatry. 2021 Apr 6;12:579566. doi:
11. 10.3389/fpsyt.2021.579566. PMID: 33889091;
PMCID: PMC8057300. 12. Ban TA. The role of serendipity in drug discovery. Dialogues Clin Neurosci. 2006;8(3):335-44. doi: 10.31887/DCNS.2006.8.3/tban. PMID: 17117615; PMCID: PMC3181823.
13. Pratt L.A., Brody D.J., & Gu Q. Antidepressant use among persons aged 12 and over: United States, 2011–14. NCHS Data Brief, No. 283. Hyattsville, MD: National Center for Health Statis- tics. 2017.
14. https://www.cdc.gov/nchs/products/data- briefs/db377.htm
15. https://psychcentral.com/blog/top-25-psychiat- ric-medications-for-2020#top-25-list
16. Patten SB. Medical models and metaphors for depression. Epidemiol Psychiatr Sci. 2015 Aug;24(4):303-8. doi: 10.1017/S2045796015000153. Epub 2015 Feb 16. PMID: 25682806; PMCID: PMC7192190.
17. https://www.sciencenews.org/article/chemical- imbalance-explain-depres- sion#:~:text=The%20phrase%20%E2%80%9Cc hemical%20imbal- ance%E2%80%9D%20is,goes%20for%20other %20brain%20chemicals.
18. Nayak SM, Singh M, Yaden DB, Griffiths RR. Belief changes associated with psychedelic use. J Psychopharmacol. 2023 Jan;37(1):80-92. doi: 10.1177/02698811221131989. Epub 2022 Nov 1. PMID: 36317643.
19. Timmermann C, Kettner H, Letheby C, Roseman L, Rosas FE, Carhart-Harris RL. Psychedelics al- ter metaphysical beliefs. Sci Rep. 2021 Nov 23;11(1):22166. doi: 10.1038/s41598-021- 01209-2. PMID: 34815421; PMCID: PMC8611059.
20. Sweeney MM, Nayak S, Hurwitz ES, Mitchell LN, Swift TC, Griffiths RR. Comparison of psy- chedelic and near-death or other non-ordinary experiences in changing attitudes about death and dying. PLoS One. 2022 Aug 24;17(8):e0271926. doi: 10.1371/jour- nal.pone.0271926. PMID: 36001643; PMCID: PMC9401141.
21. Sloshower J, Skosnik PD, Safi-Aghdam H, Pathania S, Syed S, Pittman B, D'Souza DC. Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial. J Psychopharmacol. 2023 Mar 20:2698811231154852. doi: 10.1177/02698811231154852. Epub ahead of print. PMID: 36938991.
22. https://www.medscape.com/viewarticle/921789 10
Ketamine: Catalyst for Paradigm Change in Mental Health
https://www.prnewswire.com/news-releases/psy- chedelics-are-gaining-traction-as-therapies-and- medicines-301226599.html
Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora G M, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamil- ton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted therapy for severe PTSD: a ran- domized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021 Jun;27(6):1025-1033. doi: 10.1038/s41591-021-01336-3. Epub 2021 May 10. PMID: 33972795; PMCID: PMC8205851.
https://www.empr.com/home/news/drugs-in-the- pipeline/phase-3-trial-evaluating-mdma-assisted- therapy-for-ptsd-meets-endpoints/
Andrade C. Ketamine for Depression, 1: Clinical Summary of Issues Related to Efficacy, Adverse Effects, and Mechanism of Action. J Clin Psy- chiatry. 2017 Apr;78(4):e415-e419. doi: 10.4088/JCP.17f11567. PMID: 28448702.
https://www.fda.gov/news-events/press-an- nouncements/fda-approves-new-nasal-spray- medication-treatment-resistant-depression-avail- able-only-certified
Hietamies TM, McInnes LA, Klise AJ, Worley MJ, Qian JJ, Williams LM, Heifets BD, Levine SP. The effects of ketamine on symptoms of de- pression and anxiety in real-world care settings: A retrospective controlled analysis. J Affect Dis- ord. 2023 Aug 15;335:484-492. doi: 10.1016/j.jad.2023.04.141. Epub 2023 May 16. PMID: 37201900.
Li M, Woelfer M, Colic L, Safron A, Chang C, Heinze HJ, Speck O, Mayberg HS, Biswal BB, Salvadore G, Fejtova A, Walter M. Default mode network connectivity change corresponds to ket- amine's delayed glutamatergic effects. Eur Arch Psychiatry Clin Neurosci. 2020 Mar;270(2):207- 216. doi: 10.1007/s00406-018-0942-y. Epub 2018 Oct 23. PMID: 30353262.
Hirschfeld T, Prugger J, Majić T, Schmidt TT. Dose-response relationships of LSD-induced subjective experiences in humans. Neuropsycho- pharmacology. 2023 May 9. doi: 10.1038/s41386-023-01588-2. Epub ahead of print. PMID: 37161078.
Tsang VWL, Tao B, Dames S, Walsh Z, Kryskow P. Safety and tolerability of intramus- cular and sublingual ketamine for psychiatric
treatment in the Roots To Thrive ketamine-assisted therapy program: a retrospective chart re- view. Ther Adv Psychopharmacol. 2023 May 25;13:20451253231171512. doi: 10.1177/20451253231171512. PMID: 37256163; PMCID: PMC10225955.
Oughli HA, Gebara MA, Ciarleglio A, Lavretsky H, Brown PJ, Flint AJ, Farber NB, Karp JF, Mulsant BH, Reynolds CF 3rd, Roose SP, Yang L, Butters MA, Lenze EJ. Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Ben- efits, and Effect on Cognition. Am J Geriatr Psy- chiatry. 2023 Mar;31(3):210-221. doi: 10.1016/j.jagp.2022.11.013. Epub 2022 Dec 5. PMID: 36529623.
Smith-Apeldoorn SY, Veraart JK, Spijker J, Kamphuis J, Schoevers RA. Maintenance keta- mine treatment for depression: a systematic re- view of efficacy, safety, and tolerability. Lancet Psychiatry. 2022 Nov;9(11):907-921. doi: 10.1016/S2215-0366(22)00317-0. PMID: 36244360.
Abdallah CG, Roache JD, Gueorguieva R, Aver- ill LA, Young-McCaughan S, Shiroma PR, Puro- hit P, Brundige A, Murff W, Ahn KH, Sherif MA, Baltutis EJ, Ranganathan M, D'Souza D, Martini B, Southwick SM, Petrakis IL, Burson RR, Guthmiller KB, López-Roca AL, Lauten- schlager KA, McCallin JP 3rd, Hoch MB, Tim- chenko A, Souza SE, Bryant CE, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH. Dose-related effects of ketamine for antidepressant-resistant symptoms of posttrau- matic stress disorder in veterans and active duty military: a double-blind, randomized, placebo- controlled multi-center clinical trial. Neuropsy- chopharmacology. 2022 Jul;47(8):1574-1581. doi: 10.1038/s41386-022-01266-9. Epub 2022 Jan 19. Erratum in: Neuropsychopharmacology. 2022 May 11;: PMID: 35046508; PMCID: PMC8767037.
Tamman A, Anand A, Mathew SJ. A comparison of the safety, feasibility, and tolerability of ECT and ketamine for treatment-resistant depression. Expert Opin Drug Saf. 2022 Jun;21(6):745-759. doi: 10.1080/14740338.2022.2049754. Epub 2022 Mar 14. PMID: 35253555.
Di Vincenzo JD, Siegel A, Lipsitz O, Ho R, Teo- pizKM,NgJ,LuiLMW,LinK,CaoB,Ro- drigues NB, Gill H, McIntyre RS, Rosenblat JD. The effectiveness, safety and tolerability of keta- mine for depression in adolescents and older adults: A systematic review. J Psychiatr Res. 2021 May;137:232-241. doi:
Shannon
10.1016/j.jpsychires.2021.02.058. Epub 2021
Mar 1. PMID: 33706168.
Carhart-Harris RL, Friston KJ. The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas. Brain. 2010 Apr;133(Pt 4):1265-83. doi:10.1093/brain/awq010. Epub 2010 Feb 28.
PMID: 20194141; PMCID: PMC2850580.
Abdallah CG, Ahn KH, Averill LA, Nemati S, Averill CL, Fouda S, Ranganathan M, Morgan PT, D'Souza DC, Mathalon DH, Krystal JH, Driesen NR. A robust and reproducible connectome fingerprint of ketamine is highly associated with the connectomic signature of antidepressants. Neuropsychopharmacology. 2021 Jan;46(2):478-485. doi: 10.1038/s41386-020-00864-9. Epub 2020 Sep 23. PMID: 32967000; PMCID: PMC7852889.
https://www.ncbi.nlm.nih.gov/books/NBK47035
CanAT,HermensDF,MohamedAZ,ShanZY, Dutton M, Gallay C, Forsyth G, Jamieson D, Lagopoulos J. Treatment response with ketamine in chronic suicidality: An open label functional connectivity study. J Affect Disord. 2023 Jun 15;331:92-100. doi: 10.1016/j.jad.2023.03.064. Epub 2023 Mar 22. PMID: 36963514. LamannaJ,IsottiF,FerroM,SpadiniS,Rac- chetti G, Musazzi L, Malgaroli A. Occlusion of dopamine-dependent synaptic plasticity in the prefrontal cortex mediates the expression of de- pressive-like behavior and is modulated by keta- mine. Sci Rep. 2022 Jun 30;12(1):11055. doi: 10.1038/s41598-022-14694-w. PMID: 35773275; PMCID: PMC9246912. WadeBSC,LoureiroJ,SahibA,KubickiA, Joshi SH, Hellemann G, Espinoza RT, Woods RP, Congdon E, Narr KL. Anterior default mode network and posterior insular connectivity is pre- dictive of depressive symptom reduction follow- ing serial ketamine infusion. Psychol Med. 2022 Sep;52(12):2376-2386. doi: 10.1017/S0033291722001313. Epub 2022 May 17. Erratum in: Psychol Med. 2022 Sep;52(12):2399. PMID: 35578581; PMCID: PMC9527672. HoracekJ,BrunovskyM,NovakT,TislerovaB, Palenicek T, Bubenikova-Valesova V, Spaniel F, Koprivova J, Mohr P, Balikova M, Hoschl C. Subanesthetic dose of ketamine decreases pre- frontal theta cordance in healthy volunteers: im- plications for antidepressant effect. Psychol Med. 2010 Sep;40(9):1443-51. doi: 10.1017/S0033291709991619. Epub 2009 Dec 9. PMID: 19995475. DossMK,MaddenMB,GaddisA,NebelMB, Griffiths RR, Mathur BN, Barrett FS. Models of psychedelic drug action: modulation of cortical- subcortical circuits. Brain. 2022 Apr 18;145(2):441-456. doi: 10.1093/brain/awab406. PMID: 34897383; PMCID: PMC9014750. GattusoJJ,PerkinsD,RuffellS,LawrenceAJ, Hoyer D, Jacobson LH, Timmermann C, Castle D, Rossell SL, Downey LA, Pagni BA, Galvão- Coelho NL, Nutt D, Sarris J. Default Mode Net- work Modulation by Psychedelics: A Systematic Review. Int J Neuropsychopharmacol. 2023 Mar 22;26(3):155-188. doi: 10.1093/ijnp/pyac074. PMID: 36272145; PMCID: PMC10032309. Carhart-arrisRL,RosemanL,BolstridgeM, Demetriou L, Pannekoek JN, Wall MB, Tanner M, Kaelen M, McGonigle J, Murphy K, Leech R, Curran HV, Nutt DJ. Psilocybin for treatment- resistant depression: fMRI-measured brain mechanisms. Sci Rep. 2017 Oct 13;7(1):13187.
Levine, S; 2017, “Reflections on 10,000 admin-
istrations of ketamine.” 11/4/2017, Kriya Ketamine Conference-Burlingame, California.
https://www.kff.org/health-costs/poll-finding/kff-health-tracking-poll-march-2022/
Kopelman J, Keller TA, Panny B, Griffo A,Degutis M, Spotts C, Cruz N, Bell E, Do-Nguyen K, Wallace ML, Mathew SJ, Howland RH, Price RB. Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression.
Transl Psychiatry. 2023 May 9;13(1):159. doi: 10.1038/s41398-023-02451-0. PMID: 37160885; PMCID: PMC10170140.
Shaw AD, Muthukumaraswamy SD, Saxena N, Sumner RL, Adams NE, Moran RJ, Singh KD.
Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine. Neuroimage. 2020 Nov 1;221:117189. doi: 10.1016/j.neuroimage.2020.117189. Epub 2020 Jul 23. PMID:
32711064; PMCID: PMC7762824.
Garcia-Romeu A, Richards WA. Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions.
Int Rev Psychiatry. 2018 Aug;30(4):291-316.
doi: 10.1080/09540261.2018.1486289. Epub2018 Nov 13. PMID: 30422079.
Yuan S, Luo X, Chen X, Wang M, Hu Y, Zhou Y, Ning Y, Zhang B. Functional connectivity
differences in the amygdala are related to the antidepressant efficacy of ketamine in patients with
anxious depression. J Affect Disord. 2023 Jan 1;320:29-36. doi: 10.1016/j.jad.2022.09.125.
Epub 2022 Sep 28. Erratum in: J Affect Disord. 2023 Jun 15;331:461. PMID: 36181911.
12
Ketamine: Catalyst for Paradigm Change in Mental Health
doi: 10.1038/s41598-017-13282-7. PMID:
29030624; PMCID: PMC5640601.
Ait Bentaleb K, Boisvert M, Tourjman V, Potvin S. A Meta-Analysis of Functional Neuroimaging Studies of Ketamine Administration in Healthy V olunteers. J Psychoactive Drugs. 2023 Mar 15:1-14. doi: 10.1080/02791072.2023.2190758. Epub ahead of print. PMID: 36921026.
Uhlhaas PJ, Singer W. Abnormal neural oscilla- tions and synchrony in schizophrenia. Nat Rev Neurosci. 2010 Feb;11(2):100-13. doi: 10.1038/nrn2774. PMID: 20087360.
Hunt T, Schooler JW. The Easy Part of the Hard Problem: A Resonance Theory of Conscious- ness. Front Hum Neurosci. 2019 Oct 31;13:378. doi: 10.3389/fnhum.2019.00378. Erratum in: Front Hum Neurosci. 2020 Sep 04;14:596409. PMID: 31736728; PMCID: PMC6834646.
Tonello L, Cocchi M, Gabrielli F, Tuszynski JA. Stream of consciousness: Quantum and bio- chemical assumptions regarding psychopathol- ogy. Med Hypotheses. 2017 Apr;101:78-84. doi: 10.1016/j.mehy.2017.02.013. Epub 2017 Feb 28. PMID: 28351500.
Cavinato M, Genna C, Manganotti P, Formaggio E, Storti SF, Campostrini S, Arcaro C, Casanova E, Petrone V, Piperno R, Piccione F. Coherence and Consciousness: Study of Fronto-Parietal Gamma Synchrony in Patients with Disorders of Consciousness. Brain Topogr. 2015 Jul;28(4):570-9. doi: 10.1007/s10548-014-0383- 5. Epub 2014 Jul 29. PMID: 25070585.
Nicolaou N, Georgiou J. Global field synchrony during general anaesthesia. Br J Anaesth. 2014 Mar;112(3):529-39. doi: 10.1093/bja/aet350. Epub 2013 Oct 29. PMID: 24169819.
Lutz A, Greischar LL, Rawlings NB, Ricard M, Davidson RJ. Long-term meditators self-induce high-amplitude gamma synchrony during mental practice. Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16369-73. doi: 10.1073/pnas.0407401101. Epub 2004 Nov 8. PMID: 15534199; PMCID: PMC526201.
Nagy D, Stoiljkovic M, Menniti FS, Hajós M. Differential Effects of an NR2B NAM and Keta- mine on Synaptic Potentiation and Gamma Syn- chrony: Relevance to Rapid-Onset Antidepres- sant Efficacy. Neuropsychopharmacology. 2016 May;41(6):1486-94. doi: 10.1038/npp.2015.298. Epub 2015 Sep 25. PMID: 26404843; PMCID: PMC4832008.
Nugent AC, Ballard ED, Gould TD, Park LT, Moaddel R, Brutsche NE, Zarate CA Jr. Keta- mine has distinct electrophysiological and behav- ioral effects in depressed and healthy subjects. Mol Psychiatry. 2019 Jul;24(7):1040-1052. doi:
10.1038/s41380-018-0028-2. Epub 2018 Feb 27.
PMID: 29487402; PMCID: PMC6111001. 62. Purdon PL, Sampson A, Pavone KJ, Brown EN.
Clinical Electroencephalography for Anesthesi- ologists: Part I: Background and Basic Signa- tures. Anesthesiology. 2015 Oct;123(4):937-60. doi: 10.1097/ALN.0000000000000841. PMID: 26275092; PMCID: PMC4573341.
63. Zacharias N, Musso F, Müller F, Lammers F, Saleh A, London M, de Boer P, Winterer G. Ket- amine effects on default mode network activity and vigilance: A randomized, placebo-controlled crossover simultaneous fMRI/EEG study. Hum Brain Mapp. 2020 Jan;41(1):107-119. doi: 10.1002/hbm.24791. Epub 2019 Sep 18. PMID: 31532029; PMCID: PMC7268043.
64. Greyson B. Persistence of Attitude Changes After Near-Death Experiences: Do They Fade Over Time? J Nerv Ment Dis. 2022 Sep 1;210(9):692- 696. doi: 10.1097/NMD.0000000000001521. Epub 2022 Mar 29. PMID: 35350036.
65. Kopel J. Near-death experiences in medicine. Proc (Bayl Univ Med Cent). 2019 Jan 11;32(1):163-164. doi: 10.1080/08998280.2018.1542478. PMID: 30956619; PMCID: PMC6442886.
66. Martial C, Cassol H, Charland-Verville V, Palavicini C, Sanz C, Zamberlan F, Vivot RM, Erowid F, Erowid E, Laureys S, Greyson B, Tagliazucchi E. Neurochemical models of near- death experiences: A large-scale study based on the semantic similarity of written reports. Con- scious Cogn. 2019 Mar;69:52-69. doi: 10.1016/j.concog.2019.01.011. Epub 2019 Feb 1. PMID: 30711788.
67. Le TT, Cordero IP, Jawad MY, Swainson J, Di Vincenzo JD, Jaberi S, Phan L, Lui LMW, Ho R, Rosenblat JD, McIntyre RS. The abuse liability of ketamine: A scoping review of preclinical and clinical studies. J Psychiatr Res. 2022 Jul;151:476-496. doi: 10.1016/j.jpsychires.2022.04.035. Epub 2022 May 10. PMID: 35623124.
68. Orhurhu VJ, Vashisht R, Claus LE, Cohen SP. Ketamine Toxicity. 2023 Jan 30. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Pub- lishing; 2023 Jan–. PMID: 31082131.
69. Chan EOT, Chan VWS, Tang TST, Cheung V, Wong MCS, Yee CH, Ng CF, Teoh JYC. Sys- tematic review and meta-analysis of ketamine- associated uropathy. Hong Kong Med J. 2022 Dec;28(6):466-474. doi: 10.12809/hkmj209194. Epub 2022 Dec 5. PMID: 36464318.
70. https://www.nytimes.com/2023/02/20/us/keta- mine-telemedicine.html
13
Shannon
71. https://healingmaps.com/psilocybin-laws-colo- rado-oregon-differences/
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