Ketamine-Assisted Psychotherapy (KAP)
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Ketamine-Assisted Psychotherapy (KAP) is a promising treatment for mental health disorders. Unlike traditional therapies, KAP does not rely on solely on medication to achieve its therapeutic effects.
Psychedelic Cognitive Behavioral Therapy (On Ketamine, Context and Competencies in "Assisted-Psychotherapy”) (DeMarco, 2024)
Michael DeMarco, PhD
Over 60 years of research on ketamine related to depression, over a hundred so far in 2023. Ketamine was FDA as safe in humans and animals as a medicine in 1970, and has been on the World Health Organization’s (WHO) list of Essential Medicines.
It’s an exciting time in psychedelic mental health as MDMA-Assisted Therapy and Psilocybin assisted psychotherapies await FDA approval in the years ahead, with plant medicines, their ceremonial use and integration also showing promising results in post-experience quality of life from participants around the world, especially when the experience is integrated fully into our lived daily lives as part of psychotherapy (mental health counseling).
While not considered a traditional psychedelic, ketamine, a generic drug with years of study, is known as a dissociative anesthetic, which was found to have positive mental health effects, and that, when paired with psychotherapy, not only acts within hours, but for a number of people, lasts past the initial crisis into the days, weeks and months ahead as subjectively improved mental health. By working closely with a medical provider, and monitoring your experience along the way, working with a psychedelic therapist helps you track measurable improvement in your symptoms throughout your journey, or plot a change in course by changing dose or frequency of sessions.
There is a certain panic on the internet about “cowboy lozenges”, the potential of rampant misuse. However, there is solid research supporting the mental health benefits, as well as how quickly, effectively, and safely ketamine can work for many people. A ketamine “lozenge” is a form of ketamine pressed into something that is too big to swallow as a pill, and is something resembling an Altoid (or a a waxy chew like a Starburst) as a way to let the ketamine absorb into your system and be metabolized to continue doing its thing. Work with your physician and compounding pharmacist on the ideal route of administration for you.
When working regularly with your medical provider and mental health provider/s, you can feel best supported in your medicine work and integration work to safely process what you need to in your personal psychology. Whether dissolving lozenge or liquid, holding or swallowing, iv or im injection, medical grade ketamine will be introduced into your body, dosed in such a way where expecting a range of effects from deep meditation to “ego-dissolving transcendental experiences” (Kolp, 2014).
Many research studies have focused on iv infusion to support what clinicians have recognized in real-world use for decades— that this dissociative anesthetic, regardless of route of administration, also has psychedelic properties when given at low doses and a range of mental health benefits especially when used in conjunction with therapeutic support. “The combination of strong and rapid effects with very small numbers of adverse events suggest that at-home sublingual ketamine therapy is an important avenue for overcoming long-standing barriers to depression and anxiety treatment, safely and conveniently” (Hull et al, 2022).
The Psychedelic Institute model involves a psychotherapist helping you prepare a safe space and monitoring your journey over 2.5 hours, reminding you to check your blood pressure before and after you self administer your physician-prescribed ketamine. We follow up with a 60 minute integration session within 1-4 days of your medicine session to help you process your experience in a way that maximizes the psycho-pharmacological aspects of the medicine. When you feel able to self-administer, we continue our work together with weekly psychotherapy geared towards psychedelic integration to maximize the effects ketamine has on your brain. Psychotherapeutic support nourishes the psychedelic mind.The goal is to hone in on the most effective experience, dose and frequency as supported by weekly monitoring by your mental health team, and self-report generated several times a week.
You’ll need to have a sober sitter with you during your medicine journey for 2.5 hours.
The ketamine therapist works closely with your prescribing clinician to monitor your progress with this medicine, with the goal of minimal dose and frequency needed to elicit the outcome that seems to work best for the individual.
What is Ketamine Integration Therapy?This model of accessing these experiences with the support of a mental health professional is informed by a Western approach to research that suggests the integration part of this work is an essential part of letting this experience have a culturally and personally relevant impact, an extra step that may not make sense in parts of the world where these practices are built into local cultures in other ways. For those of us who lack cultural context or access to what has been called the animistic discourse, or mystical experience, we have western research that seems to suggest that the psychedelic experience that can accompany these various compounds in both organic form or their synthetic alternatives like ketamine, ican be a leading component of relief in a range of mental health issues, with a relatively low risk to health when offered with the care of someone who can help prepare you for the types of experiences you may access with this medicine, and to support you as you let this experience form new meaning. Compounds interact in your brain in a way that supports establishing and maintaining new growth in several domains ranging from the neuronal to the interpersonal, and transcendent. This state of consciousness may be new to you, and you may have experiences that range outside of your own personal ego and day to day identity. Research and historical practice shows us that support and community are important aspects of this work.
…ketamine, can induce an NDE type of experience, which shares features with mystical experience of sacredness, ineffability and general sense of transcendence. The profundity of this experience is often perceived as life-changing. (Ko, 2022)
Your set (mindset, or state of mind), setting, and the senses you have available to you seem to work with the medicine to come together in such a way that you may not have a language for. In the western world, we work with a psychotherapy framework in supporting your developing such a language, in a way that honors and shows reciprocity with the holders of this knowledge from whose wisdom and on whose homelands we continue to benefit.
Non-ordinary states of consciousness, visionary states, journeys- many names for something that goes beyond having this experience be about avoiding a bad trip. The visionary state allows many people to access experiences and emotions in ways that they hadn’t previously. Some of these emotions and experiences may be scary for someone using these medicines without adequate support. If you accessed an emotion or an experience— positive, negative or even if you can’t describe it with words, then the psychedelic compound reacted with you. For psychedelics to be medicine, then we have to use them therapeutically, with support, and towards a therapeutic goal. “Mystical-type phenomena, long considered to have therapeutic potential, may work to impact decision-making and behavior in a sustained manner” (Dakwar, 2018).
Using a pre-existing medical model seems to be a way for people to access this therapeutic and be best supported with any negative outcomes. Clinical trials are not service providers, and underground use adds a layer of trauma of fearing legal consequences as part of your healing. Call your lawmakers and support the legalization of psychedelics and their continued funding for research and psychotherapeutic uses around the world. Until that happens, we have ketamine and its record for eliciting a psychedelic, “mind manifesting” experience as well as improvement in mental health symptoms that for some, lasts indefinitely.
For others, regular access to a psychedelic experience and the possible visionary state and mystical experiences that accompany these medicines may be of benefit, as supported by your doctor and a psychedelic therapist, chaplain, or other psychedelic specialist.
- Benefits of Ketamine-Assisted Psychotherapy
As with any treatment, there is no guarantee that you will gain benefit from this treatment, but about 70% of people in clinical trials have reported improvements in psychiatric symptoms, including, but not limited to: reduction of feelings of depression, anxiety and obsessive-compulsive symptoms
reduced suicidal thoughts
increased reward value of an action, and an increased motivation to seek out that action and reward
increased feelings of connection
balanced sense of meaning, and a sense that the future can be different than the past
increased cognitive flexibility, that is, a more flexible way of looking at things
increased sense of aliveness and a decrease in anxiety about death
sense of being more emotionally connected
pleasure in movement
felling better connected to your body
Ketamine-Assisted Psychotherapy goes beyond the drip!
Ketamine-assisted psychotherapy is a process that begins with referral from your mental health and/or medical provider
- ketamine assisted psychotherapy
- neural plasticity
- psychedelic assisted psychotherapy
- psychedelic cognitive behavioral therapy
- psychedelics
How does it work?
Research has shown that ketamine acts as a neuroplastogen- a catalyst for the rapid regrowth of connections between neurons following treatment. Paired with cognitive behavioral therapy, we can work on supporting that neuroplasticity to maximize the effects over time.
Significant progress has been made toward understanding how psychedelics affect neuroplasticity. Data thus far supports the theory that psychedelics stimulate dendritogenesis, synaptogenesis, and the upregulation of plasticity-related genes in a 5-HT2A receptor-dependent manner, affecting the cortex in particular. The window of neuroplasticity appears to open within a few hours and may last a few days, although neuroplastic changes occurring during this time may survive for at least a month. Because neuroplastic changes occur in an experience-dependent manner, experiences people have during this time may have a greater psychological impact than they otherwise would. Future research should attempt to confirm preclinical findings in humans, clarify optimal doses and specific neuroplastic effects for different psychedelic compounds, and further explore the consequences of psychedelic-enhanced neuroplasticity for both patient groups and healthy people.(Calder & Hasler, 2022)
See also: Ketamine, Psychedelic Drugs Change Structure of Neurons
“… ketamine-assisted psychedelic therapy of alcoholic patients induces… a positive transformation of nonverbalized (mostly unconscious) self-concept and emotional attitudes to various aspects of self and other people, positive changes in life values and purposes, important insights into the meaning of life and an increase in the level of spiritual development. Most importantly, these psychological changes were shown to favor a sober lifestyle.” (Kolp 2011)
“As a specialty clinic, we Require ongoing medical and mental health support and a referral to the Institute for cases where prior therapy or other medicine hasn’t shown Improvement for your specific Mental Health COncerns. Combination Therapy, using medicine and psychotherapy, is common, despite the Unique profiles of ketamine and serotonergic psychedelics.” Psychedelic Institute of Mental Health & Family Therapy
Alternatives
Your ongoing medical provider and mental health provider may offer alternatives with you that may include different medicines, counseling, behavioral changes, and coaching. We also offer psychedelic-alternatives which have been shown to help people relax into a true psyche-delic, soul-opening, mind-manifesting state.
If your team suggests in-person support, we can provide resources to find ketamine therapy in your area or by telehealth
Ketamine-Assisted Psychotherapy is “bubble work” to support what therapeutic ketamine may bring up for individuals who have been prescribed this medicine by their ongoing medical and mental health providers as an off-label medicine, for which there is consistent research supporting its use for your specific situation. Your prescriber and pharmacist has gone over with you how to minimize any adverse affects from this medicine.
What are the side effects
Ketamine at sub-anesthetic doses has been used and studied for pain management and off-label for various psychiatric conditions ranging from Anxiety, Depression, OCD and PTSD* to Eating Disorders and Substance Dependence issues.
In a meta-analysis of 60 studies of the standard ketamine model for the treatment of TRD, the most common side effects were headache, dizziness, anxiety, dissociation, elevated blood pressure, and blurred vision, with most effects resolving shortly after the procedure (Short, et al 2018).
Ketamine is generally considered safe, including for those who are experiencing suicidal ideation (thoughts or plans for suicide). The main side effects are dissociation, intoxication, sedation, high blood pressure, dizziness, headache, blurred vision, anxiety, nausea, and vomiting. Ketamine is avoided or used with extreme caution in the following groups:
people with a history of psychosis or schizophrenia, as there is concern that the dissociation ketamine produces can make psychotic disorders worse
people with a history of substance use disorder, or are on certain medications
people who are pregnant or breastfeeding
-from Ketamine for treatment-resistant depression: When and where is it safe? (Grinspoon, 2022)
In long term high dose use, there have been reports of effects on the liver and the bladder, but these were considered unlikely in the studies over 6-12 sessions at the doses used with ketamine-assisted psychotherapy. Reports of patients becoming dependent or addicted to ketamine when used as an adjunct to psychotherapy are very rare. It is possible for some people to develop tolerance and a need to increase their dosage and/or space apart their medicine journeys to get the most out of the least dose effective for treatment.
A sober sitter is required when working with this or any other medicine that may have visionary effects
Before and after your ketamine treatment, it may be helpful to rest and take some time for some quiet contemplation, as opposed to going straight from a high-energy, high-stimulus environment into the medicine, then back into that same environment. Regardless of your journey experience, ketamine is having an effect on your brain, and you will want to give it every opportunity to do its work. You may feel emotionally fragile/vulnerable at points during this process. Working with your psychotherapist to establish resources for yourself before, during, and after your session is essential.
Although medical providers who prescribe off-label medicines as well as the patients who take them do so at their own risk, generally the risk is not great when measured against the possible benefits. You and your medical provider in collaboration with an experienced compounding pharmacist will make a considered judgement as to whether it is reasonable to use this treatment in your particular case, and refer to the appropriate mental health support before, during and after your use of this compound to reduce harm and maximize mental health benefits.
As there is a potential for ketamine to be misused, it must be carefully stored securely out of reach from children, animals, etc. and you self-administer your medication during your session with your therapist and as directed by your prescribing clinician.
“…there is no clear evidence that addiction potential of ketamine is more serious than other drugs we prescribe with due caution in psychiatry such as stimulants or sedatives. Serious risk may exist in certain sub-populations, just as it does with other medications, but this warrants a similar approach in cautious prescribing where appropriate, rather than preclude prescribing altogether.
The authors of this paper have several years of experience in the use of PO, SL, and IN ketamine for mood disorders [31, 32]. Patients have been highly treatment resistant, and these ketamine formulations have been well tolerated and life saving for many patients who have not responded to other treatments.”
- from Non-parenteral Ketamine for Depression: A Practical Discussion on Addiction Potential and Recommendations for Judicious Prescribing (Swainson, et al, 2022)
Further information will be provided by your medical provider and compounding pharmacist. The Psychedelic Practitioner’s role is to prepare you for the vivid experiences you may have at different doses and frequencies, help you set intentions for areas you’d like to explore, and help you integrate your experiences afterwards to maximize the neural plasticity gained as a response to the medicine, regardless of experience— the same neural plasticity we are working towards in cognitive behavioral therapy, using a rational emotive approach without ketamine. Ketamine helps us work with that neuroplastic state more effectively, while supporting you in making meaning from your experiences.
All members of your Institute Psychedelic Practitioner Support Team have been trained experientially in this medicine, and provide care and support within their own clear scopes of practice.
See also: PsychiatryAdvisor- Ketamine: Usage in the Home
Combining ketamine and psychotherapy for the treatment of PTSD
“For decades, identification of baseline variables that predict the effects of psychedelic drugs has proven illusory. Although the findings presented here are not definitive, they can serve as an important synthesis of the evidence scientists have compiled to date. This information will become increasingly valuable as psychedelic substances continue to be decriminalized and incorporated into medical contexts. Those high in the traits of absorption, openness, and acceptance as well as a state of surrender may represent ideal candidates for psychedelic therapy. In contrast, individuals low in those traits or that are in preoccupied, apprehensive, or confused states are more likely to experience adverse reactions. ”— Predicting Reactions to Psychedelic Drugs: A Systematic Review of States and Traits Related to Acute Drug Effects, 2021
What are the risks compared to traditional AntiDepressants?
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A retrospective study of oral ketamine for depression included “Twenty-two studies, including 4 randomized clinical trials (RCTs), 1 case series, 6 case reports, 5 open-label trials and 6 retrospective chart reviews studies involving 1667 patients with depression... All included studies reported significant improvement following ketamine administration. Ketamine was well tolerated without serious adverse events.
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A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings reports that around 8% of people who underwent iv ketamine treatment for depression had their symptoms worsen, and that around 6% had an increase in suicidal ideation.
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A 2022 retrospective analysis of ketamine by IM injection - “Reported AEs during IM ketamine treatment included nausea, vomiting, abnormal vital signs, panic attacks, hallucinations, confusion, potentially unsafe movement, and bladder pain. There were no severe AEs observed. Out of 2532 treatments, an AE occurred during 59 (2.3%) treatments, and all AEs resolved prior to patients leaving the clinic. Patients experienced an abnormally large change in vital signs, as noted by the clinician, at 4 (0.16%) out of 2532 treatments.”
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Evidence suggests that traditional antidepressant treatment may in some cases result in worsening depression and increased risk of suicidality in pediatric and adolescent patients. The United States Food and Drug Administration requires that traditional antidepressants carry a black box warning regarding such a risk in patients up to age 24. Many studies of antidepressant‐induced suicidality among adults have also reported an increased risk, while several other investigations involving that population have not supported such a finding.
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Only a third of patients respond to first-line antidepressant treatment, while another third has a partial response and a final third does not respond at all.
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A 2022 review of studies published in Molecular Psychiatry suggests that the huge research effort based on the serotonin hypothesis has not produced convincing evidence of a biochemical basis to depression. This is consistent with research on many other biological markers.
More than 10,000 published reports describe ketamine’s high level of effectiveness and its confirmed biological safety in most cases, although like all drugs there is the possibility of some adverse effects in some people (Bauman, Kish, Baumann, & Politis, 1999; Dachs & Innes, 1997; Ersek, 2004; Reich & Silvay, 1989; Ross & Fochtman, 1995; Shapiro, Wyte, & Harris, 1972). Clinical studies have generally detected no long-term impairment of behavior or personality functioning as a result of repeated ketamine use (Siegal, 1978), but some individual case studies of ketamine dependence have raised questions at times (e.g., Jansen 1990, 2000, summary in Jansen 2001) and there have been some recent concerns about, for example, toxicity to the urinary system (e.g., Selby et al., 2008; Wood, 2013.)
A 2007 study suggests ketamine to have some addiction potential, including pleasure and psychological dependence, which may be confounding variables. Another way to define “pleasure” is psychological relief from pain. This graph from the study shows ketamine scoring as slightly more addictive potential than cannabis, but not nearly as much addictive potential as alcohol or tobacco. Ketamine was scored as having a low incidence of physical dependence.
A study from July 2022 suggests ketamine has very little addiction potential. An analysis of ketamine and cocaine use in mice reveals that the drugs trigger release of the neurotransmitter dopamine through different mechanisms, and indicates that the risk of addiction to ketamine is low.
Expert opinion: Based on available data, the most common side effects of ketamine/esketamine are generally transient, mild, and self-limited. These include dissociation, nausea, headache, elevated heart rate, and blood pressure. Treatment with esketamine may lead to an increased risk of lower urinary tract symptoms, such as dysuria or urgency. However, severe bladder pathology has not been reported among patients receiving doses of esketamine/ketamine in line with prescribing guidelines for depression. There is considerable data that ketamine at high doses can lead to long-term impairments in cognition. However, the esketamine clinical trials found that cognition generally remains stable or improves over time, suggesting that when used appropriately, there is no increased risk of cognitive impairment. Nikayin, S., Murphy, E., Krystal, J. H., & Wilkinson, S. T. (2022). Long-term safety of ketamine and esketamine in treatment of depression. Expert opinion on drug safety, 21(6), 777–787. https://doi.org/10.1080/14740338.2022.2066651
See also: Antidepressant Discontinuation Syndrome (2006), and Do antidepressants have any potential to cause addiction? (1999), and Can antidepressants be addictive? (2022) for context and comparison
Adverse Effects of Psychedelic-Assisted Psychotherapy
Is ketamine found in nature?
- Will therapeutic ketamine harm my bladder?
https://link.springer.com/article/10.1007/s00213-020-05611-y
"The results indicate that the use of single or repeated doses of esketamine at 0.25–0.5 mg/kg is unlikely to cause urothelial toxicity."
https://www.psychiatrist.com/jcp/depression/oral-ketamine-for-depression-practical-considerations/"There were no cases of bladder toxicity."
https://link.springer.com/article/10.1007/s00213-020-05611-y#Sec11
"However, severe bladder pathology has not been reported among patients receiving doses of esketamine/ketamine in line with prescribing guidelines for depression.""It should be noted that recreational ketamine consumption tends to be several orders of magnitude higher (one survey reported 34% of users reported use of 1 g or more in a typical session(Winstock et al., 2012)) than the doses prescribed in the clinical setting for depression. Although adverse effects of long-term ketamine use on the bladder would not necessarily be expected with the therapeutic dosing and frequency used in the treatment of depression, the lack of assessment of urinary symptoms has been another limitation in RCTs of ketamine (Short et al., 2018)."
https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.1022.6283&rep=rep1&type=pdf
"Additionally, concerns have been raised about the possible incidence of bladder toxicity with repeated ketamine use (Middela, 2011). Only future clinical research can establish whether maintenance ketamine infusions represent a safe and effective option for initial ketamine responders."
https://www.tandfonline.com/doi/pdf/10.1080/00952990.2020.1769118
"Scientific data show that, in a clinical setting, the applied doses of ketamine are well-tolerated by humans and its negative effects are manageable. These effects seem to be dose and frequency-related, which is strongly supported by the scientific literature and by the analyzed threads, where the adverse effects of ketamine were mentioned as mild and manageable."
"The most serious of these side effects is ketamine-induced ulcerative cystitis or ‘ketamine bladder’. This is a recently identified condition characterised by extremely painful and frequent urination that seems to have severe and potentially long lasting impacts on the patient. However, drug users who take ketamine less than daily have not reported, and show no evidence of ‘ketamine bladder’.xt goes here
Role / Scope of the Psychedelic Practitioner
Your provider is not a medical clinician, and does not have the authority to work outside of the scope of practice for a licensed marriage and family therapist and the clinicians LMFT’s may supervise and/or refer to for additional support.
Your ketamine prescription comes from an independently licensed medical clinician who has assessed your needs and administers the medicine in office, or teaches you how to take it on your own (self-administer).
Your medical provider may or may not be a psychedelic practitioner with a broad basis in psychotherapy and support.
Collaboration defines ketamine-assisted psychotherapy in particular and psychedelic-assisted psychotherapy in general.
The mental health clinician and support team offer harm-reduction / support for the mental health effects of this medicine as well as the psychotherapeutic issues that can result from poor medication management. Integration of your experiences with this medicine (or any medicine) involves standard psychotherapy with the aim of reduction of negative mental health symptoms, and does not constitute a recommendation to use/abuse any particular medication or psychoactive compound, prescribed or otherwise.
As these compounds are decriminalized and become legal in some municipalities, the role of the mental health provider is to ensure people who explore these medicines have trained mental health support to help minimize negative symptoms and maximize mental health improvements. Best practices involve screenings before starting ketamine-assisted psychotherapy and throughout treatment as well as periodically once you have finished your initial treatment as well as active engagement in logging thoughts, feelings and behaviors throughout working with the mental health clinician. We are able to share your progress with your primary mental health and medical team as you find most helpful.
The psychedelic practitioner does not store, dispense, prescribe or direct the medical aspects of your prescription medication, but offers support during the most beneficial time after its onset and the days/weeks/months following, and offers support in tending to your set and setting when working with a medicine that has visionary side-effects.
Ketamine integration with a psychedelic therapist and support team helps you apply any shift in thinking to your body, mind and spirit using an existentially-based, cognitive behavioral therapy lens. A quality ketamine therapist understands the types of experiences that clients may report on a range of dosing typically used in psychedelic-assisted psychotherapy. Integration of these experiences is ongoing in your life, and can be augmented by psychotherapeutic, peer, group, and community support. The emerging field of psychedelics collaborates with many types of care and support, and can fine-tune your sessions according to your specific needs, in collaboration with someone of another license or specialty area.
Sublingual ketamine is more bioavailable (30%) than oral ketamine (20%).2 A recent study3 described safety and efficacy of IV ketamine at doses of 0.5 mg/kg and 1.0 mg/kg and no benefit to lower doses. This translates to 1.5 or 3.0 mg/kg if dosed sublingually, and 2.5 or 5.0 mg/kg if dosed orally. With this in mind, only 24,5 of 7 retrospective studies from the systematic review included patients with appropriately dosed ketamine. All others were below the equivalent expected SL and oral doses. Two prospective studies also underdosed ketamine at 25 mg bid6 or or 0.5 mg/kg daily,7 and 1 prospective study used a potentially adequate total daily dose of 50 mg tid,8 but divided doses may have contributed to a reduced or slower ketamine response. (Swainson, 2019)
A harm reduction model supports the least amount of medicine for the most amount of observed benefit paired with psychotherapy to maximize any positive effects. Your dosing may depend on the route of administration. We will collaborate with your medical team and compounding pharmacy to find the route that you find works best.
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June 2022 study shows that ketamine assisted psychotherapy is more effective than ketamine alone.
Provider Referral for Ketamine-Assisted Psychotherapy
Rule changes for at-home psychotherapy once the public health emergency (PHE ends)
Permanent rule changes regarding telehealth services for behavioral/mental health
Ketamine Multi-media
Click the play button above to watch a short clip about ketamine therapy
Oral ketamine augmentation for anxiety and depression
Clinical Efficacy of Ketamine
Dr. Cusin from Mass General presents on real world ketamine research and results from 2021
Amazing presentation. Now that you know, you know. Donate some money.
Ketamine therapy research by year listed on Pubmed.gov- Over 500 papers in 2022 alone
Ketamine Therapy Research & Selected Bibliography:
Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability (Apeldoorn, et al, 2022)
Depression and antidepressant effects of ketamine and its metabolites: The pivotal role of gut microbiota (Hua, 2022)
Ketamine and its metabolites: Potential as novel treatments for depression (Zhang, 2022)
The effect of IV ketamine in patients with major depressive disorder and elevated features of borderline personality disorder (Chen, et al, 2022)
Gender differences in the antianhedonic effects of repeated ketamine infusions in patients with depression (Zheng, 2022)
An Expert-Informed Introduction to the Elements of Psychedelic-Assisted Therapy (Brainfutures, 2022)
Ketamine may exert rapid antidepressant effects through modulation of neuroplasticity, autophagy, and ferroptosis in the habenular nucleus (Zhang, et al, 2022)
Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression (BottemanN, et al, 2022)
Safety, effectiveness and tolerability of sublingual ketamine in depression and anxiety: A retrospective study of off-label, at-home use (Hassan, et al, 2022)
Real-world depression, anxiety and safety outcomes of intramuscular ketamine treatment: a retrospective descriptive cohort study (Ahuja, et al, 2022)
Towards an understanding of psychedelic-induced neuroplasticity (Calder & Hasler, 2022)
Neurobiological, behavioral, and cognitive effects of ketamine in adolescents: A review of human and pre-clinical research (Acevedo, et al, 2022)
Ketamine for suicidality: An umbrella review (Shamabadhi, et al, 2022)
Ketamine induces rapid antidepressant effects via the autophagy-NLRP3 inflammasome pathway (Lyu, et al, 2022)
Active mechanisms of ketamine-assisted psychotherapy: A systematic review (Joneborg, 2022)
Psychedelic integration: An analysis of the concept and its practice (Bathje, et al, 2022)
Comparison of psychedelic and near-death or other non-ordinary experiences in changing attitudes about death and dying (Sweeney, et al, 2022)
Magnetoencephalography biomarkers of suicide attempt history and antidepressant response to ketamine in treatment-resistant major depression (Gilbert, 2022)
Ketamine Augmented Psychotherapy (KAP) in mood disorder: User guide (Bottemanne et al, 2022)
Low addiction risk with medical use of ketamine: Animal study (2022)
A short burst of reward curbs the addictiveness of ketamine (2022)
The abuse liability of ketamine: A scoping review of preclinical and clinical studies (Le, et al, 2022)
Ketamine Assisted Psychotherapy: A Systematic Narrative Review of the Literature (Drozdz et al, 2022)
Ketamine for Bipolar Depression: Biochemical, Psychotherapeutic, and Psychedelic Approaches (Bennett et al, 2022)
Psychedelic assisted therapy for major depressive disorder: Recent work and clinical directions (McCartney, et al, 2022)
Sustained effects of single doses of classical psychedelics in humans (2022)
A Systematic Review of Neurocognitive Effects of Subanesthetic Doses of Intravenous Ketamine in Major Depressive Disorder, Post-Traumatic Stress Disorder, and Healthy Population (Shiroma, et al 2022)
Ethnoracial Inclusion in Clinical Trials of Ketamine in the Treatment of Mental Health Disorders (Michaels, et al, 2022)
A case series of group-based ketamine-assisted psychotherapy for patients in residential treatment for eating disorders with comorbid depression and anxiety disorders (Robison & LaFrance, 2022)
Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis (Alnefeesi, et al, 2022)
Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review (2022)
Buddhist-like opposite diminishing and non-judging during ketamine infusion are associated with antidepressant response: an open-label personalized-dosing study (Stocker et al, 2022)
Psychedelics and Psychotherapy: Cognitive-Behavioral Approaches as Default (2022)
Toward Synergies of Ketamine and Psychotherapy (2022)
Long-term safety of ketamine and esketamine in treatment of depression (2022)
Oral ketamine reduces the experience of stress in people with chronic suicidality (2022)
Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review (Strous, et al 2022)
A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings (2022)
Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder (Grabski, et al, 2022)
Mechanisms of ketamine and its metabolites as antidepressants (Hess,et al, 2022)
Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review (Walsh, et al, 2022)
Gut microbiota is involved in the antidepressant-like effect of (S)-norketamine in an inflammation model of depression (Wang, et al, 2021)
Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study (Can, et al, 2021)
Ketamine Treatment for Depression in Patients With a History of Psychosis or Current Psychotic Symptoms: A Systematic Review (Veraart, et al, 2021)
The effectiveness, safety and tolerability of ketamine for depression in adolescents and older adults: A systematic review (Di Vincinzo, et al, 2021)
Six-week oral ketamine treatment for chronic suicidality is associated with increased grey matter volume (Gallay, 2021)
Ketamine-Assisted Psychotherapy for PTSD Related to Racial Discrimination (Halstead, et al, 2021)
Ketamine-assisted psychotherapy for trauma-exposed patients in an outpatient setting: A clinical chart review study (Davis, et al, 2021)
Cognitive Behavioral Therapy to Sustain the Antidepressant Effects of Ketamine in Treatment-Resistant Depression: A Randomized Clinical Trial (Wilkinson et aL, 2021)
A Potential Case of Acute Ketamine Withdrawal: Clinical Implications for the Treatment of Refractory Depression (Roxas, et al 2021)
Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics (2021)
Ancient Roots of Today's Emerging Renaissance in Psychedelic Medicine (2021)
Can Ketamine be taken orally? (2021)
Ketamine’s Role in Spirituality: How One Synthetic Drug Catalyzes a Natural Experience (Woods, 2021)
Ketamine specifically reduces cognitive symptoms in depressed patients: An investigation of associated neural activation patterns (Stippl et al, 2021)
Long-term safety and efficacy of sublingual ketamine troches/lozenges in chronic non-malignant pain management (Maudlin et al, 2021)
Predicting Reactions to Psychedelic Drugs: A Systematic Review of States and Traits Related to Acute Drug Effects (Adal, et al, 2021)
Same But Different: Antidepressant Mechanisms of Psilocybin and Ketamine (Gallenstein, 2021)
Intranasal Ketamine for Depression in Adults: A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials (An, et al, 2021)
Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants (Kadriu, et al, 2021)
Pharmacokinetics of ketamine and its major metabolites norketamine, hydroxynorketamine, and dehydronorketamine: a model-based analysis (Kamp, et al, 2020)
Ketamine can be produced by Pochonia chlamydosporia: an old molecule and a new anthelmintic? (Ferreira et al, 2020)
GABA interneurons are the cellular trigger for ketamine's rapid antidepressant actions (Gerhard, et al, 2020)
Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials (Kryst et al, 2020)
An Update on the Efficacy and Tolerability of Oral Ketamine for Major Depression: A Systematic Review and Meta-Analysis (Nuñez et al, 2020)
Effects of Serial Ketamine Infusions on Corticolimbic Functional Connectivity in Major Depression (Vasavada, et al, 2020)
Oral Ketamine for Depression, 2: Practical Considerations (2019)
Efficacy of ketamine therapy in the treatment of depression (Mandal, et al, 2019)
Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports (Martial, 2019)
The Efficacy of Ketamine in the Palliative Care Setting: A Comprehensive Review of the Literature (2019)
Oral Ketamine for Depression: A Systematic Review (Rosenblat et al, 2019)
Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites (Yang, 2019)
The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects (Abdallah, et al, 2018)
Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy (Dore, et al, 2018)
Ketamine for Depression (Hyde, 2018)
Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial (Arabzadeh 2018)
Impact of oral ketamine augmentation on hospital admissions in treatment-resistant depression and PTSD: a retrospective study (Hartberg, et al, 2018)
Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine (Fattore, et al, 2018)
Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms (Zanos, et al, 2018)
Side-effects associated with ketamine use in depression: a systematic review (Short et al, 2017)
Antidepressant drug action--From rapid changes on network function to network rewiring (2016)
Ketamine: 50 Years of Modulating the Mind (2016)
Ketamine safety and tolerability in clinical trials for treatment-resistant depression (Wan, et al, 2015)
A Rare Urachal Cyst in a Case of Ketamine-induced Cystitis Provides Mechanistic Insights (2015)
Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish (Opler, et al, 2015)
Ketamine Psychedelic Psychotherapy: Focus on its Pharmacology, Phenomenology, and Clinical Applications (Kolp 2014)
What is hydroxynorketamine and what can it bring to neurotherapeutics? (Singh,et al, 2014)
A randomized controlled trial of intranasal ketamine in major depressive disorder (Lapidus, 2014)
Ketamine: Use in Anesthesia (Marland, et al, 2013)
Ketamine Psychedelic Therapy (KPT): A Review of the Results of Ten Years of Research (Kolp 2011)
What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression (Gaynes, et Al, 2009)
Development of a rational scale to assess the harm of drugs of potential misuse (Nutt & King, 2007)
Ketamine psychedelic therapy (KPT): a review of the results of ten years of research (Krupitsky 1997)
Ketamine and norketamine plasma concentrations after i.v., nasal and rectal administration in children (Malinovsky, et al, 1996)
Ketamine Psychotherapy: Results and Mechanisms (Krupitsky 1996)
Evaluation of ketamine HCl for anti-depressant activity (Sofia, 1975)
The Use of Ketamine in Psychiatry (Khorramzadeh, et al, 1973)
CLINICAL TRIAL OF KETAMINE (CI-581): A PRELIMINARY REPORT (Oduntan, et al,1970)
Featured
Jun 7, 2024
Jun 7, 2024
Jun 4, 2024
Preliminary evidence demonstrates that Ketamine-Assisted Psychotherapy (KAP) can significantly improve depression, demoralization and existential distress in seriously ill people. We will discuss: 1. the history and science of psychedelics; 2. ketamine pharmacology, and KAP indications and delivery models; 3. putative KAP mechanisms of action; and 4. examples of KAP program development, including making the case, potential obstacles, and creative solutions.
Jun 4, 2024
Apr 24, 2024Ketamine in Bipolar Disorder: A Review (Wilkowska, et al, 2020)
Apr 24, 2024
Apr 24, 2024
Apr 20, 2024
Relatively few pharmacologic agents are proven safe and effective in adults with TRD. NNT estimates for investigational psilocybin and esketamine in TRD indicate clinical meaningfulness. The NNH profile for both aforementioned agents is clinically acceptable. Our results underscore the clinical relevance of these treatment options in adults with TRD.
Apr 20, 2024
Apr 20, 2024
A low number to treat and a high number to harm suggests efficacy and safety of racemic ketamine and esketamine across thousands of clients. It takes not very many ketamine treatments to help, and a large number of treatments to statiscally help and harm, also indicating a range of safe repeated dosing.
Apr 20, 2024
Mar 26, 2024
Mar 26, 2024
Sep 28, 2023Deep posteromedial cortical rhythm in dissociation (2020)
Sep 28, 2023
Dissociation in human beings is a self-reported state of mind, and no experimental technique in rodents or in humans can currently define this subjective experience in full. However, the clinically guided paradigm reported here could provide a framework of behavioural, optical and physiological tools to enable exploration of the neural activity that underlies dissociative states (Vesuna, et al, 2019).
Sep 28, 2023
Sep 19, 2023Ketamine in neuropsychiatric disorders: an update (Johnston, et al, 2023)
Sep 19, 2023
Considerable clinical research supports the use of—or further research with—subanesthetic-dose ketamine and its (S)-enantiomer esketamine in multiple neuropsychiatric disorders including depression, bipolar disorder, anxiety spectrum disorders, substance use disorders, and eating disorders, as well as for the management of chronic pain.
Sep 19, 2023
Sep 17, 2023Development and psychometric validation of a novel scale for measuring ‘psychedelic preparedness’
Sep 17, 2023
Significant differences between those scoring high and low (on psychedelic preparedness) before the psychedelic experience were found on measures of mental health/wellbeing outcomes assessed after the experience, suggesting that the scale has predictive utility.
Sep 17, 2023
Mar 21, 2023
While the neural underpinnings remain to be clarified, the psychedelic-induced state seems to allow one to recollect and process deep autobiographical information, achieve new understandings of one's self and relationships with others, and gain greater appreciation of one's place within the cosmos.5,61,62 This state is closely linked to the concept of “mystical experience” which in multiple studies with classic psychedelics predicts therapeutic efficacy.9,11,45,47,55 “Ego dissolution” is another term used to describe a loss of the usual sense of self as separate entity.13 The quality and degree of psychedelic-induced ego dissolution and mystical experience are typically measured in clinical trials with validated psychometric instruments such as the 5-Dimensional Altered States of Consciousness Questionnaire and the Mystical Experience Questionnaire.9,11,45,47,49,55,61
Mar 21, 2023
Mar 6, 2023The NMDA receptor antagonists memantine and ketamine as anti-migraine agents (Podkawa, et al, 2023)
Mar 6, 2023
Migraine is a debilitating disorder affecting females more frequently than males. There is some evidence that drugs targeting glutamate receptors: memantine and ketamine might be beneficial in the therapy of this entity. Therefore, the purpose of this work is to present NMDA receptor antagonists, memantine and ketamine, as potential anti-migraine agents.
Mar 6, 2023
Mar 4, 2023Ketamine and the conscious mind (1972)
Mar 4, 2023
It is a matter of opinion whether or not a chemically induced transcendental experience should be available to anyone who desires it, but to induce such a state when it is not requested by the patient is a different ethical problem.
Mar 4, 2023
Feb 17, 2023A pilot randomized controlled trial of ketamine in Borderline Personality Disorder (2023)
Feb 17, 2023
Infusions were well tolerated in both groups. Dissociative symptoms during infusion were more intense with ketamine than midazolam (t(12.3) = 3.61, p = 0.01), but they resolved by 40 min after infusion in both groups. Post-infusion adverse events were at the expected low levels in both groups.
Feb 17, 2023
Feb 11, 2023
Pharmacologically enhanced psychotherapy is one potential means of prolonging ketamine’s effects, with the class of psychedelic medications (in which ketamine is included) yielding encouraging results
Feb 11, 2023
Jan 30, 2023
stress and chronic pain appear to drive alterations in Tiam1-Rac1 signaling and synapse connectivity and function that are rescued by ketamine treatment, but the manner of change and the brain regions/neural circuits involved may differ.
Jan 30, 2023
Jan 28, 2023Toward Synergies of Ketamine and Psychotherapy (Mathai, et al, 2022)
Jan 28, 2023
Finally, it is valuable to recognize the similarities between ketamine and classic (serotonergic) psychedelics such as psilocybin and lysergic acid diethylamide (LSD), which produce overlapping subjective phenomena in spite of diverging pharmacological mechanisms of action (Bowdle et al., 1998; Studerus et al., 2010). For classic psychedelics, it is well-established that a subset of psychoactive effects, often referred to as mystical-type effects and characterized by a sense of unity, predict greater therapeutic response across a variety of conditions such as depression, existential distress, and substance use disorders (Garcia-Romeu et al., 2014; Griffiths et al., 2016; Roseman et al., 2018). Interestingly, it has been hypothesized that the same mechanisms that drive the efficacy of these treatments may also be responsible for dose-dependent psychiatric risks, like that of psychosis (Haarsma et al., 2021). However, the relevant psychoactive effects of classic psychedelics appear to be optimized in careful experimental conditions that consider the benefit, safety, and tolerability of such (Johnson et al., 2008; dos Santos et al., 2018). While similar optimization has not been pursued for ketamine, increasing research suggests that mystical- and peak-type experiences, such as measured by the Hood Mysticism Scale (HMS) and 11D-ASC questionnaire, increase the likelihood of various therapeutic benefits (Dakwar et al., 2014, 2018; Mollaahmetoglu et al., 2021; Rothberg et al., 2021; Sumner et al., 2021).
Jan 28, 2023
Jan 22, 2023Ketamine’s Role in Spirituality: How One Synthetic Drug Catalyzes a Natural Experience (Woods, 2021)
Jan 22, 2023
The psychedelic effects associated with ketamine encourages a detachment from these thoughts processes— bringing forth a sense of intense and often overwhelming spiritual vulnerability for the patient. Therefore, an individual’s perception of pain may be significantly altered by ketamine because he or she is not experiencing typical, waking-reality thought processes but is instead experiencing unfamiliar, subconscious levels of thought. That is to say, these spiritual experiences are ordinarily invisible to us and are inaccessible using our normal states of consciousness (Strassman 54). Consequently, these spiritual-in-nature, ketamine variables may alter the patients’ response to various pain experiences, thus affecting their recovery options (Dedeli).
Jan 22, 2023
Jan 22, 2023
“…we isolated and characterized molecules from the nematophagous fungus Pochonia chlamydosporia and tested these compounds on three nematodes: Caenorhabditis elegans; Ancylostoma ceylanicum; and Ascaris suum.”
Jan 22, 2023
Jan 21, 2023
“…we found a clear increase in signal diversity for all three psychedelic agents at the group level, with effects being strongest for KET. These increases went beyond those expected from the changes to the frequency spectrum.”
Jan 21, 2023
Jan 21, 2023Neural Mechanisms and Psychology of Psychedelic Ego Dissolution (Stoliker et al, 2022)
Jan 21, 2023
Surmising that the experience of ego dissolution exists at the center of the psychedelic experience and that its neural mechanisms may be close to the roots of the subject-object dichotomy may explain why phenomenological encounters with this experience can be intimate and fundamentally change self-identification and interactions with the world. Continued investigation of the neural mechanisms of ego dissolution and the dichotomy of separation between the self and the world may advance scientific understanding of sentience. The value of psychedelics may then, under appropriate conditions, be their power to catalyze meaningful philosophical and scientific understanding of the “u” (i.e., self) in the universe.
Jan 21, 2023
A resource on direct-to-consumer marketing of medicines
The media swings between hype of psychedelic medicines including ketamine, and ketamine panic pieces about making these treatments too accessible. Learn more about how medicines are marketed in the US, and know that most things in life come with some sort of personal risk, including working with any medicine or compound that has psychological effects.
If you’re concerned about the level of support you are receiving through telemedicine or telehealth, please visit your in-person medical provider and mental health provider to coordinate your ongoing mental health plan. This goes beyond slick advertising campaigns, without which, people may not know such treatments exist.
This old advertisement for an anti-depressant contains all sorts of inaccuracies, including “only your doctor can diagnose depression”, and is literally a cartoon marketing a brand of medicine every 5 minutes on television, along with all the other prescription drug ads with the lines “Ask your doctor about X”, which general practitioners prescribe, mostly without mental health therapy support. These medicines come with discontinuation / withdrawal sydnromes, and for adolescents, may even increase likelihood of suicide.
Adverse Effects of Psychedelic-Assisted Psychotherapy
