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Is Ketamine a Psychedelic? Does it Matter?

Is Ketamine a Psychedelic? Does it Matter?

October 21, 2022

Over the past few years, psychedelics such as LSD and psilocybin mushrooms have garnered much attention as researchers explore their potential use in treating mental health conditions.   


Ketamine and its close cousin Spravato (esketamine) are often included in this motley crew of psychedelics due in part to their “mind-altering” effects.  


Though many are eager to label ketamine a psychedelic, others are less certain, feeling it would be most appropriate to avoid associating ketamine with psychedelics.  Let’s explore these different viewpoints to get a clearer sense of whether ketamine is genuinely a psychedelic and why the label matters if it does at all.  


What is a Psychedelic? 

One obvious way of determining whether ketamine is a psychedelic is by comparing its features to those listed in its definition. Unfortunately, there are no agreed-upon criteria for what makes something a psychedelic drug. Experts waver on the importance of three conditions.


#1: Psychedelics Cause Altered States of Consciousness

Though there is much disagreement about what counts as a psychedelic, it’s generally accepted that they must induce specific mind-altering effects. Some argue this is all that is required. In other words, they claim that as long as the substance causes a “psychedelic experience,” then it’s a psychedelic.  


But what are psychedelic experiences? While the list is potentially endless, psychedelic experiences are generally thought to impact one’s perception of themselves and the world around them, alter the way they think and reason, and provide insights into how their mind works and the nature of reality. They include experiences like the sense of being at one with the world, distortions of space and time, profound inner peace, ego dissolution, and many more.  


#2: Their Conscious Effects Must Have Therapeutic Benefits

While many agree that psychedelics must cause certain altered states of consciousness, some argue that this isn’t enough. They claim that these changes in thought and perception must have a therapeutic effect on the mind or promote psychological growth. As Dr. Yehuda, director of the Center for Psychedelic Psychotherapy and Trauma Research at Mount Sinai Hospital in New York, notes when discussing ketamine’s status as a psychedelic:


The unanswered question in all of this is whether the transpersonal state is what heals you or whether it’s something about the molecule. […] The dissociation or psychoactive effects of ketamine might be incidental. They occur. But that’s not necessarily why the healing is happening.


For these experts, if ketamine’s mind-altering effects have nothing to do with its mental health benefits, then it’s not a psychedelic. 


#3: Psychedelics Must Act on Specific Areas in the Brain

In the world of psychedelics, some have been around for longer than others and are more well-studied. For example, mescaline and psilocybin mushrooms have been used since ancient times and were researched heavily in the 1950s and ‘60s. These compounds all appear to affect serotonin (a chemical messenger in the brain) at the “2A” receptor. 


Some researchers feel these “classical psychedelics” are the only true ones and that what really matters when deciding whether to categorize a new agent as a psychedelic is how it works in the brain. As Dr. Yehuda notes:


When we talk about chemistry and drug development, we should mostly be defining a psychedelic drug on the basis of the chemistry of the molecule, its pharmacokinetics, and its mechanism of action


Does Ketamine Meet These Conditions?

How does ketamine stack up against these criteria? As far as its effects on the brain go, ketamine does not act as the classical psychedelics do. It works on N-methyl-D-aspartate (NMDA) receptors, causing an increase of glutamate and brain-derived neurotrophic factor (BDNF) instead of serotonin.  Under this condition, then, ketamine is not a psychedelic. 

Credit: Yang H. Ku/C&EN

However, acting on a specific set of serotonin receptors is not the only way to produce psychedelic experiences. As Dr. Steve Levine, co-founder of Heading Health, states:


It does appear that subjective psychedelic effects may be induced by a number of stimuli or conditions that also include sensory deprivation, virtual reality, meditation, and suggestibility, among others, and not necessarily mediated through a particular brain receptor.


Importantly, many of these psychedelic experiences can be produced by ketamine. It is most commonly associated with dissociative experiences (i.e., the sense that one is separate from their thoughts and body). It can also cause distortions in one’s perception of space and time. Patients have also reported gaining new perspectives and an enhanced ability to make sense of their thoughts. Rarely, ketamine can cause delusions and delirium, otherwise known as psychotomimetic effects. In many ways, then, ketamine seems to have the right sorts of effects on the mind to be considered a psychedelic. 


However, it’s worth highlighting that the experiences won’t be identical to “classical psychedelics.” For example, psilocybin appears more likely to cause what’s known as ego dissolution, where one loses their subjective sense of self. Classical psychedelics may also have a greater tendency to induce visual distortions. In general, because they have different effects on the brain, their conscious effects will differ. As Dr. Arif Noorbaksh, Psychiatrist at Heading, states:


Ketamine is distinct because it works on a completely different neurotransmitter system (glutamate), exerts an effect in different areas of the brain, and as a result, the perceived effects are different.  They both result in non-ordinary states of consciousness, but the experience a particular person has when exposed to conventional psychedelics versus ketamine will be different.


When it comes to the therapeutic effects of the altered states of mind that ketamine puts subjects in, the evidence is mixed. A 2020 review concluded that overall, the evidence does not suggest that ketamine’s dissociative effects are responsible for its antidepressant properties. Others argue that ketamine’s ability to cause a shift in perspective and increase cognitive flexibility and open-mindedness are directly responsible for its therapeutic effects. For example, Celia Morgan, professor of psychopharmacology at the University of Exeter, found in a recent experiment that individuals who underwent ketamine and talk therapy experienced longer-lasting antidepressant effects. Professor Morgan notes that talk therapy “requires that individuals think differently about things and learn new ways of thinking about old problems.” As a result, ketamine’s ability to induce shifts in perspective and open-mindedness may explain why it appears to enhance the effects of therapy alone. 


Where does this leave us? According to some criteria, ketamine seems to be a psychedelic, while on others, it does not. The answer as to whether ketamine is a psychedelic, then, depends on who you ask and which criteria they feel are most essential.


Does it Matter What We Call It?

Some might think this is all just semantics and that there’s no real principle we can use to determine what to call ketamine. 


While the dispute may be verbal, how we talk about ketamine matters. As Dr. Noorbaksh notes:


I think it matters insofar as the term “psychedelic” comes with preconceived notions for many people, and it also places the emphasis on the acute effects of the agent rather than the potentially longer-term effects these agents can have on neuroplasticity, relation to self and others, and other important contributors to mental health.


As a result, it’s important to be mindful of the language we use to describe and categorize ketamine and to avoid clinging to one label or another without regard for how this impacts patients. As Dr. Levine suggests:


Ultimately, whether a molecule is “truly” a psychedelic is likely beside the point. […] Let’s not let feeling precious about terminology distract from the real goal, which is improving well-being in a safe and responsible way.  




Talk with your doctor to determine whether this treatment is right for you, or you can schedule an appointment with someone from our team of psychiatrists or therapists to advise you on this or any other potential treatments for depression, including ketamine, Spravato, and TMS. Call us at 805-204-2502 or request an appointment here.

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Ketamine Vs. Esketamine (Spravato) – What’s the Difference?

Ketamine Vs. Esketamine (Spravato) - What’s the Difference?

October 18, 2022
Source: NeuroMend

In 2019, 19 years after researchers first demonstrated ketamine’s therapeutic effects on depression, the Food and Drug Administration (FDA) approved Janssen Pharmaceuticals’ esketamine nasal spray (Spravato) for treatment-resistant depression. In 2020, it was also approved by the FDA for major depressive disorder (MDD) with co-occurring suicidal ideation. With similar names, ingredients, and research-backed mental health benefits, many are likely to wonder whether there are any important differences between the two and if there are any reasons for preferring one over the other. 


Let’s explore how they compare. 

What are They Made Of? 

Ketamine, or more specifically racemic ketamine, is made up of two enantiomers (i.e. pairs of molecules that are mirror images of each other), known as r- and s- ketamine (arketamine and esketamine). Esketamine contains only the S enantiomer.

How Do They Work?

Both ketamine and esketamine are thought to work by blocking N-methyl-D-aspartate (NMDA) receptors, which causes a release of glutamate (a chemical messenger in the brain) and, ultimately, brain-derived neurotrophic factor (BDNF), which helps neurons regrow and form new connections. 


Though they share this mechanism of action, esketamine has a four-fold higher affinity for the NMDA receptor, which means it is more potent. 

Which is More Effective?

For some drugs, one enantiomer is more “effective” than the other, which raises the question, are ketamine and esketamine equally beneficial?


In the past few years, several randomized controlled trials have directly compared the antidepressant effects of ketamine and esketamine. However, synthesizing their findings can be difficult as the studies utilize different methods of administration, treatment durations, depression-related outcomes, and more. 


Despite these obstacles, a team of researchers set out to comb through the data. They analyzed 36 randomized controlled trials comparing the efficacy of ketamine and esketamine on depression in a 2022 meta-analysis. They found that while the racemic mixture was more effective overall, the evidence suggests this is not the case when the same method of administration is used alongside doses that account for differences in potency. For example, one study found that when administered intravenously and in equally potent doses, both formulations had similar remission rates after 24 hours. 

Do They Feel the Same?

Both ketamine and esketamine are psychoactive substances, meaning they can alter one’s normal state of consciousness, affecting one’s thoughts, feelings, and perceptions. For example, ketamine is known for causing feelings of relaxation, dissociation, alterations in the perception of space and time, and more. A natural question, then, is whether the esketamine experience differs from the ketamine one. 


Answering this question exhaustively and definitively is challenging for several reasons. To start, ketamine and esketamine can cause a wide range of experiences, so much research needs to be done to demonstrate how likely each drug is to produce each one. Second, because esketamine is more potent, it’s not always clear that researchers have used equivalent doses. 


By and large, the experiences appear to be pretty similar. With that said, a few interesting preliminary findings reveal how they might differ. For example, some studies have found that ketamine is more likely to cause feelings of dissociation (i.e, a feeling of being disconnected or separate from one’s thoughts and body). 


Another important result has to do with how pleasurable the experiences are. Some studies indicate that the combination of ar- and esketamine is less likely to produce unpleasant reactions like stress and anxiety. For example, one researcher found that:


The (R)-enantiomer was able to balance the (S)-enantiomer’s adverse parts of the altered state of consciousness and promote positive psychedelic experiences so that a more coherent state of consciousness is experienced. 


It’s important to note that much future research will need to confirm these results and compare the drugs across all their potential subjective effects. It’s also worth pointing out that the therapeutic significance of ketamine and esketamine’s psychoactive effects is currently unclear, so any differences in how they feel may not impact how well they work.

What is the Treatment Like?

Treatments differ by how the drug is administered, the number of sessions needed, and appointment length. 


Esketamine is only available as a nasal spray called Spravato. For this treatment, patients visit their physician’s office twice a week for the first four weeks, once a week for the next four weeks, and then bi-weekly if needed for maintenance. Each appointment lasts two and a half hours.


Ketamine is available in several different forms, each with a slightly different protocol. At Heading, we offer intramuscular ketamine. This treatment takes place over three weeks, with three sessions in the first week, two in the second, and one in the third. Patients may continue to receive additional treatments for maintenance if needed. Each appointment lasts around an hour and a half. 

Does Insurance Cover Them?

Several insurance companies cover Spravato for treatment-resistant depression and MDD with suicidal ideation. While ketamine can be more difficult to find coverage for, our team has worked closely with insurance companies to ensure we can secure coverage for most patients.  Click here for a complete list of participating providers.

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The Surprising Connections Between Caffeine and Mental Health

The Surprising Connections Between Caffeine and Mental Health

October 13, 2022

Between coffee, tea, soft drinks, and energy drinks, caffeine is one of the most commonly consumed psychoactive drugs. According to the Centers for Disease Control and Prevention (CDC), around 80 percent of U.S. adults consume caffeine daily. 


Despite its widespread popularity or perhaps because of it, caffeine often goes under the radar as something with no significant effects other than a short boost in attention and alertness. However, caffeine can have important effects on one’s mood and overall mental health that are worth considering when deciding whether to include it in your diet.


It’s well known that caffeine can provide a short-term elevation in one’s mood. However, it may also have a beneficial effect on depression. A recent meta-analysis of seven studies found that the risk of depression decreased by eight percent per cup of coffee when consumed in moderate amounts.


The data only shows that caffeine use is correlated with lower rates of depression, not that it causes it. However, we know that caffeine promotes the release of dopamine and that dopamine deficiencies may contribute to depression. This is why some antidepressants, such as bupropion and phenelzine, modulate dopamine signaling. Additionally, when consumed from natural sources like coffee, caffeine also comes with other ingredients which can reduce inflammation and oxidative stress in the brain (more on this below).


Caffeine stimulates the release of cortisol, epinephrine, and norepinephrine, which are associated with feelings of stress and anxiety. This is likely why some feel anxious and jittery after a cup of coffee. Some individuals may even experience anxiety that is severe enough to warrant the diagnosis of a caffeine-induced anxiety disorder, according to the current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V).


Several factors may explain why some are more prone to experience anxiety from caffeine. One obvious factor is how anxious they are in general. Studies have found that patients with panic disorder, generalized anxiety disorder, and social anxiety disorder tend to experience stronger anxiety-promoting effects from caffeine. 


The source of one’s anxious tendencies may play an important role in determining whether coffee makes them feel more or less nervous. For example, individuals with attention deficit hyperactivity disorder (ADHD) sometimes experience anxiety that stems from difficulties in concentration and executive control. Because caffeine can enhance attention and concentration, it can alleviate stress in individuals with ADHD. 


Aside from baseline anxiety symptoms, there may also be a genetic component that explains why some individuals are more likely to experience anxiety from caffeine. Studies have found that specific gene variants for the receptor that caffeine binds to can make one more susceptible to its anxiety-inducing effects. 

Interactions With Antidepressants

Caffeine can alter how our bodies process and respond to certain drugs, including some antidepressants. One way it can do this is by slowing down or speeding up the rate at which our livers break down antidepressants, impacting how much of the drugs build up in our systems. 


Some antidepressants can have an activating or energizing effect. When combined with caffeine, some patients might find that the compounds work together to produce feelings of tension and anxiety. Patients should be mindful of how their body reacts to caffeine while on antidepressants and discuss any adverse reactions with their physician. 


Caffeine looks similar to a neurotransmitter called adenosine, which is partially responsible for regulating our sleep-wake cycles. When adenosine binds to its receptor, it tells the brain it’s time to sleep. Because of its resemblance to adenosine, caffeine can bind to the same receptor and block adenosine in the process. This prevents adenosine from triggering sleepiness. 


Caffeine can interfere with sleep for much longer than one might initially think. This is because several of caffeine’s metabolites (i.e., the chemicals produced as the body breaks down caffeine) can also cause wakefulness. While individual factors affect how long this process takes, caffeine and its metabolites can negatively impact sleep for up to 12 hours.  


A poor night’s sleep can lower one’s mood and exacerbate a range of symptoms associated with mental health conditions, so it’s important to be mindful of how caffeine affects your ability to sleep and to avoid consuming it within 12 hours of your bedtime. 

Naturally Occurring Sources of Caffeine Are Better

It’s best to get caffeine from natural sources like coffee and tea instead of synthetic sources like caffeine pills or energy drinks. The reason is that natural sources of caffeine come with other healthy ingredients. For example, tea contains antioxidants that can decrease oxidative stress in the brain, a change associated with improvements in depression. Similarly, caffeine contains chlorogenic acid, an antioxidant and anti-inflammatory. Naturally occurring sources of caffeine may also include a class of compounds known as phenols, which studies have found can work synergistically with caffeine to heal our bodies and minds. 


If you feel you need to see a mental health professional or could use help deciding which service is right for you, please give us a call at 805-204-2502 or fill out an appointment request here. We have a wide variety of providers, including therapists, psychiatrists, nurse practitioners, and nutritional therapists, who can see you in as little as one day via teletherapy. 

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October 11, 2022

Obsessive-compulsive disorder (OCD) is a condition characterized by recurrent, unpleasant intrusive thoughts and repetitive behaviors aimed at reducing anxiety or preventing some undesirable event. It currently afflicts between two to three million U.S. adults.


The condition is typically treated with some combination of cognitive-behavioral therapy (CBT) and a type of oral antidepressant called selective serotonin reuptake inhibitors. However, studies indicate that around half of OCD patients fail to respond adequately to the standard treatments. Moreover, many that respond to SSRIs discontinue due to undesirable side effects (e.g., weight gain, sexual dysfunction, emotional numbness, etc.). 


Because of this, researchers began to search for novel treatments. Many focused on finding new applications for a non-invasive procedure called transcranial magnetic stimulation (TMS), initially approved by the FDA for treatment-resistant depression in 2008. In 2018, TMS became FDA-approved for OCD. 


Here are answers to common questions about this new intervention.  

What is TMS?

TMS is a drug-free and noninvasive procedure used to treat various brain disorders, including several mental health conditions. It uses magnetic coils placed just above the scalp to send magnetic pulses into specific regions of the brain associated with symptoms of the conditions it is being used to treat. For example, in the case of treatment-resistant depression, the pulses are sent toward regions of the brain associated with mood regulation.

By sending repeated pulses to these specific areas of the brain, TMS “trains” neurons in those areas to fire differently and create new, healthier connections.

How Does TMS for OCD Work?

TMS for OCD works in much the same way as TMS for treat-resistant depression, except for two key differences. First, the magnetic pulses are directed at deeper structures in the brain, which are more closely associated with OCD. For example, one of the primary targets is the right orbitofrontal cortex, which studies have found is hyperactive in adults with OCD. It is also thought to be partially responsible for the unending urge to repeat compulsive behaviors that individuals with OCD experience. Other targeted areas include the supplementary motor cortex, medial prefrontal cortex, and anterior cingulate cortex.


Unlike treatment-resistant depression, which is associated with underactive neurons in parts of the brain related to mood regulation, OCD is connected with brain regions firing too much. As a result, in addition to targeting different areas of the brain, technicians utilize another type of stimulation called low wave stimulation, which inhibits, rather than activates, regional brain activity.  


What are the Advantages of TMS for OCD

TMS has several advantages compared to the first-line oral medications used to treat OCD. 


One of the problems with oral medications is that they are often imprecise, spreading throughout the brain and targeting many more areas than are directly implicated in the conditions they are meant to treat. This causes many unwanted side effects, such as weight gain, sexual dysfunction, emotional numbing, and more. TMS can deliver incredibly localized treatments, targeting the very source of the symptoms and avoiding unwanted side effects. 


Aside from lacking precision, first-line oral medications often must be taken continuously to cause and maintain their therapeutic effects. After a round of TMS treatments, the benefits can last for a substantial period of time. On average, results last between four to fourteen weeks and can easily be sustained with quick maintenance sessions.  

How Heading Does TMS for OCD Differently

In many cases, TMS is offered as a standalone treatment. While it can be very effective on its own, studies have found its effects can be amplified when combined with other interventions. For example, one experiment found that patients who underwent TMS and CBT experienced nearly a 60 percent drop in their OCD symptoms and that for 80 percent of the subjects, their symptoms decreased by at least 40 percent. 


At Heading, patients have access to our integrated team of mental health specialists with wide-ranging expertise to complement their TMS and enhance its therapeutic effects. By combing TMS with other therapies, our patients benefit from the synergistic effects of a holistic approach to mental health.


Talk with your doctor to determine whether this treatment is right for you or schedule an appointment with one of our psychiatrists or therapists to advise you on this or any other potential treatments, including ketamine, Spravato, and TMS. Call us at 805-204-2502 or request an appointment here

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The Problem of Delayed Treatment for Mental Health Conditions

The Problem of Delayed Treatment for Mental Health Conditions

October 9, 2022

From recognizing one needs treatment to finding an in-network provider to scheduling an appointment, getting help for one’s mental health can be a time-consuming and disheartening process. One study found that since 2000, individuals with schizophrenia, mood, and anxiety disorders have taken nearly 32 months on average to receive their first treatment. 

Aside from the immediate harm of suffering from the symptoms of a mental illness, a delay in treatment is associated with a range of negative outcomes, highlighting the importance of prompt access to rapidly effective interventions. 


Here are some key findings: 

Rates of Treatment Response and Remission

When examining the impact of the duration of untreated illness (DUI) on mental health outcomes, much research has focused on rates of response (i.e., at least a 50 percent reduction in symptoms) and remission (i.e., a full recovery). A meta-analysis, which compiled data from several studies on the topic found some striking results. In particular, they found that:


  • Patients with a DUI shorter than eight weeks after their first episode of depression have a 70 percent greater probability of achieving a response
  • Patients with a DUI shorter than eight weeks after their first episode of depression have a 65 percent greater probability of achieving remission


Response to Antidepressants

Researchers looked specifically at the response to antidepressants and found similar results. For example, studies have found that:


  • Patients with obsessive-compulsive disorder who did not receive treatment within the first 24 months were 28 percent less likely to respond to SSRIs (selective-serotonin-reuptake inhibitors)
  • Subjects with major depressive disorder who did not receive a first-line antidepressant until  six months or more after their depression started were 13 percent less likely to experience remission
  • Longer DUI was associated with a lower response to antipsychotics and a higher rate of relapse in individuals with schizophrenia



Mental illness can bring about feelings of hopelessness and despair which can cause patients to think about or attempt to commit suicide. Several studies have found that a longer DUI is associated with more suicidal thoughts and attempts for a range of conditions. For example, studies have found that:


  • Bipolar patients with a longer DUI showed a higher number of suicide attempts during a five-year follow-up
  • In patients with schizophrenia, suicidal plans or attempts were significantly higher in subjects from communities without an early detection program relative to those from early detection communities
  • Depressed patients with a longer DUI also showed an increase in the number of hospitalizations and suicide attempts


Cognitive Performance

Deficits in cognitive performance (e.g., in tasks involving memory, attention, verbal abilities, etc.) have become one of the core features of mood disorders and are significantly associated with DUI. A 2020 study found that:


  • Over half of the subjects diagnosed with major depressive or bipolar disorder showed mild cognitive impairment.
  • Those with major depressive disorder who showed cognitive impairment had a six month longer DUI on average
  • Remission was associated with improvements in memory, executive function, and attention, but not in visuospatial abilities or verbal fluency


Physiological Changes in the Brain

Researchers have found that as mental health conditions go untreated, they can produce a range of physiological changes in the brain. For example, one meta-analysis found that:


  • Long durations of untreated illness are associated with brain changes in individuals who have schizophrenia, bipolar disorder, major depressive disorder, panic disorder, and obsessive-compulsive disorder 
  • In schizophrenia, significant changes can occur within the first year
  • Some brain changes may be associated with poor treatment response


Associations with other Chronic Conditions

Mental illness is associated with various other chronic health conditions, such as heart disease and diabetes. Again, a longer DUI is associated with worse outcomes regarding many of these conditions. A 2022 study found that:


  • Subjects with depressive and bipolar disorders with DUIs longer than one and two years, respectively, were nearly 30 percent more likely to have physical comorbidities
  • Longer DUIs were significantly associated with higher BMIs, which can cause or exacerbate other physical conditions

These findings highlight two general takeaways. First, there is an obvious need to shorten the time it takes for patients to receive treatment. Given the wide range of adverse outcomes that become more prevalent as DUI increases across several mental health conditions, individuals dealing with mental illness must receive treatment as soon as possible. 


Second, there is a need for novel treatments. Even when patients can see a physician, first-line treatments can take several weeks to months to work. For a sizable subset of these individuals, these solutions may not be effective, even when their illness is recent. Additionally, longer DUIs are associated with physiological changes in the brain, which may be why standard treatments tend to be less effective over time. As a result, solutions working in different ways targeting different parts of the brain, like ketamine, TMS, or other emerging interventions, may prove critical for treating individuals who do not respond to first-line treatments.


At Heading Health, we utilize a multi-pronged approach to combat these issues. First, we offer an integrated team of specialists who work together to provide prompt care tailored to each patient’s individual needs. In most cases, we can see patients within 24-48 hours. To support this approach, we use cutting-edge treatments with rapid and sustained responses, meaning patients get in and get better quickly.


Talk with your doctor to determine whether these treatments are right for you, or schedule an appointment with one of our psychiatrists or therapists to advise you on any other potential treatments for depression, including ketamine, Spravato, and TMS. Call us at 805-204-2502 or request an appointment here.

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Interview with an Expert: Should Ketamine Be Combined with Psychotherapy?

Interview with an Expert: Should Ketamine Be Combined with Psychotherapy?

October 7, 2022

With evidence mounting in support of ketamine’s therapeutic effect on depression and other mental health conditions, clinics and physicians are increasingly prescribing it as a standalone solution. While ketamine has clear benefits on its own, experts are beginning to explore the role psychotherapy plays in enhancing or extending its effects.


In a recent edition of The Peter Attia Drive, Professor of Psychopharmacology and leading ketamine scholar Celia Morgan addresses this topic, among several others related to ketamine’s use in treating depression and other mental health conditions. 


Her take? Psychotherapy is critical to obtaining a lasting effect from ketamine. Here’s why.


Ketamine Increases Neural Plasticity

One of the key reasons Professor Morgan believes ketamine is most effective when combined with psychotherapy is its mechanism of action (i.e., how it changes the brain to produce its therapeutic effects).


When ketamine enters the brain, it attaches to N-methyl-D-aspartate (NMDA) receptors, causing a release of glutamate (a chemical messenger in the brain) and brain-derived neurotrophic factor (BDNF). The result is that neurons (tiny cells in the brain that send and receive information from each other) have an increased ability to grow, reorganize, and rewire themselves in response to new experiences, a phenomenon known as neural plasticity.


Among other things, neural plasticity enables us to learn and acquire new habits, including our cognitive and emotional tendencies. Professor Morgan argues that because many psychological therapies target these mental habits, they may be more effective when used after ketamine treatments. She states:


We know that what we’re asking people to do in psychological therapy is to think differently about things and learn new ways of thinking about old problems. [Neural plasticity] seems to me like an intuitively appealing mechanism.


Professor Morgan goes on to suggest that not only might therapy be beneficial but that its precise timing after a ketamine treatment may be especially critical, stating:


I think the idea you know for me as a psychologist is that you could time your psychological therapy when your brain is most plastic. […] We know from animal studies this might be starting four hours following the ketamine days peaking about 24 hours.


Ultimately, more research needs to be done to determine when ketamine causes the greatest increase in neural plasticity in humans. Professor Morgan notes that:


We want to be doing some work at the moment to sort of chart the time course of that in humans by looking at EEGs […] and trying to target the window of this synaptic plasticity


Experimental Participants Receiving Therapy Maintain Therapeutic Benefits for Longer

Ketamine’s impact on neural plasticity suggests that ketamine should enhance the effects of psychotherapy in theory, but how does this pan out in practice?


In a recent study on the effectiveness of ketamine in the treatment of alcohol use disorder, Professor Morgan compared the effects of ketamine used on its own and when combined with psychotherapy. They found the greatest reductions in drinking and abstinence in the group that received ketamine alongside psychological therapy. 


What’s particularly shocking is that 86 percent of the ketamine therapy subjects remained abstinent for six months after three ketamine infusions. Given the small number of treatments, the six-month benefit patients experienced further suggests therapy had a positive impact. As professor Morgan highlights, studies show the antidepressant effects of a single IV ketamine infusion typically last from three days to a week, though repeated administrations can extend this effect.



While more research is needed to confirm and clarify therapy’s role in enhancing and extending the effects of ketamine on depression and other mental health conditions, these early results suggest the two therapeutic solutions work synergistically to deliver an optimal outcome.


Talk with your doctor to determine whether this treatment is right for you or schedule an appointment with one of our psychiatrists or therapists to advise you on this or any other potential treatments for depression, including ketamine, Spravato, and TMS. Call us at 805-204-2502 or request an appointment here.

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What Does Spravato Feel Like? A Patient’s Perspective 

What's Does Spravato Feel Like? A Patient's Perspective

October 3, 2022

This post was written by a member of our team currently receiving treatment, using Spravato, in Michigan where he resides. He wanted to share his story with us in hopes that it might help patients seeking care with Heading. While he is not a patient of Heading (as Heading provides care to patients in Texas) his treatment program, environment, and experiences detailed in his share are very similar to those at Heading. We are grateful he chose to share his story with us.




I have suffered from anxiety and depression for most of my life. Treatment began at age 12 when I was diagnosed with generalized anxiety and obsessive-compulsive disorder (OCD). While the initial treatments helped to some degree, many symptoms remained, and the side effects of the drugs I took became intolerable. 


Over the next 17 years, I switched from one oral antidepressant to the next, desperately trying to find something that addressed my symptoms without causing side effects that were worse than what I was trying to treat. Eventually, my psychiatrist recommended a drug called Spravato (esketamine nasal spray), a rapid-acting drug used for treatment-resistant depression. He told me that Spravato works differently than traditional antidepressants by increasing levels of glutamate and brain-derived neurotrophic factor (BDNF). These two changes have been associated with improvements in depression and anxiety. Knowing this, I felt hopeful that I might get the benefits I was looking for without the drawbacks I was trying to avoid.


Though I was excited about trying out the new intervention, I grew increasingly anxious as I awaited my first treatment session. Both esketamine (the active ingredient in Spravato) and its more famous cousin, ketamine, are psychoactive, meaning they can alter one’s normal state of consciousness, affecting one’s thoughts, feelings, and perceptions. 


Before trying Spravato, I had very little experience with psychoactive drugs and none with anything that might be considered a psychedelic. As a result, I had no idea what to expect. To make matters worse, I felt that I wouldn’t react well to the experiences that Spravato might bring about because I suffered from severe anxiety. I went into my appointment blind to what I was about to experience. Though my fears were unwarranted, I would have benefited greatly from a clear and honest description of what was to come.  


My Experience with Spravato

Below I describe to the best of my ability what I typically feel during a Spravato treatment session. Though some of these experiences may generalize, it’s important to remember that everyone’s brain is unique and may react differently to Spravato.



One of the more talked about effects of Spravato is its ability to cause dissociation. Though it is described differently by different people, the effect is generally characterized as a temporary feeling of disconnection from one’s thoughts and feelings.


I like to describe my personal experiences with dissociation as akin to the sensation one gets when looking at their avatar through a virtual reality headset. Everything is in the location it’s supposed to be and moves when it should, but you don’t identify with your avatar. Its movements don’t feel like your movements. Its body doesn’t feel like your body.


The feeling of separation from my thoughts is harder to describe. The best I can say is that it feels like I am “viewing” my thoughts rather than “thinking” them. They simply pass by, unauthored by me.


Feeling of Relaxation

Despite having unusual sensations like the feeling of dissociation, I often experience a wave of relaxation as my concerns and worries drift away. My thoughts quiet down, and former troubles begin to feel like they don’t matter as much.


Feelings of Stress and Anxiety

Though Spravato can be pleasurable, it can also be unpleasant and stressful. I believe this is at least partially the result of the following two factors.


First, while under the effects of Spravato, my mind tends to focus on unpleasant thoughts at the core of many of my worries (more on this below). Though these thoughts are easier to entertain at the time, they can still be challenging to confront.


Second, aside from its psychological or psychoactive effects, Spravato causes physical sensations that tend to be more unpleasant. For example, I often get dizzy and feel like I am slowly spinning in my chair. As a result, I feel nauseous. When these sensations become too intense, the overall experience can become quite stressful. Fortunately, my doctor prescribed an antiemetic (i.e., an anti-nausea drug), so these sensations have become less frequent and more tolerable.


Increased Empathy

The state that Spravato puts me in makes it easier for me to put myself in other peoples’ shoes. Often, I will spend time thinking about past arguments or disagreements. While doing so, I have an easier time understanding where the other person was coming from and why their reactions and feelings were appropriate. More generally, I tend to have a stronger concern for the well-being of others.  


Enhanced Ability to Confront Unpleasant Thoughts

Through my Spravato experiences, I have realized that at the heart of many of my daily fears are more general worries that I have trouble recognizing or confronting. While under the effects of Spravato, my attention is almost unavoidably directed toward these fundamental concerns


Here’s a personal example to shed light on how this works. Among the many things I worry about, work is often at the top of the list. I worry while working on assignments, submitting them, waiting for feedback, etc. Though I had spent so much energy feeling anxious about this, I never looked at the underlying concern or belief that connected all these more specific worries. During one Spravato treatment, I realized that I had deep concerns about my intellectual abilities and that I viewed each work assignment as a potential instance where my real lack of capability would be revealed.


Though the fear remains, knowing it exists and is responsible for so many other specific worries has made it easier to deal with.


Visual Distortions

Around 10 minutes into each treatment, I start to notice some visual effects. First, my vision becomes fuzzy, and I have trouble refocusing each time I move my eyes. Over the next few minutes, this effect increases in intensity until everything looks as though it is shaking for a few seconds after I shift from looking at one spot to another.


Aside from becoming fuzzier and shakier, my vision tends to change in a different way. Specifically, objects appear to be slowly expanding and contracting as if they are breathing. Often, I’ll try to match my breath to the rate at which the things are “breathing.” It’s pretty relaxing.


When I close my eyes, I notice a further visual effect. As I keep them shut, I see faint geometric patterns. This is especially noticeable when my eyes are almost but not completely closed, which happens to me somewhat frequently when dozing off under Spravato. My guess is that my brain is doing its best to interpret the unusual visual stimuli it is getting, and the result is that I have some minor closed-eye visuals.


Post-Treatment Effects

Though many of the effects subside by the end of the two-hour treatment, some remain for several hours. I tend to feel tired, off-balance, and a bit groggy. These effects slowly dissipate as the day goes on but do not linger into the next day.


Concluding Thoughts

From enhanced empathy to feelings of dissociation, Spravato experiences can feel intense or overwhelming when you don’t know what to expect. After I learned first-hand what the experience feels like, my Spravato sessions became much more relaxing and pleasant. Hopefully, my descriptions will help other anxious patients get there more quickly.


Stay tuned for part two of this blog, where I describe the long-term effects of Spravato on my depression and anxiety.

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FDA Approves Fast Acting Antidepressant – Auvelity

FDA Approves Fast-Acting Antidepressant: Auvelity

September 23, 2022

On August 19, the U.S. Food and Drug Administration (FDA) approved Axsome Therapeutics’ Auvelity for the treatment of major depressive disorder (MDD) in adults. This new drug has several significant benefits over traditional antidepressants, making it an exciting advancement that offers new hope for individuals struggling with depression.

Here are six key takeaways.

#1: It’s Rapid Acting

One of the main drawbacks of many oral antidepressants is that they can take a long time to work. For example, selective serotonin reuptake inhibitors (SSRIs), like Zoloft, Prozac, and Lexapro, can take four to six weeks before they even begin to take effect.


Given how debilitating depression and anxiety can be, rapid symptom relief is critical. Initial studies indicate that patients taking Auvelity showed improvements in depression severity scores in as little as one week.

#2: It Works Through a Novel Mechanism of Action

The standard array of antidepressants works primarily on one or more of three of the brain’s chemical messengers: serotonin, norepinephrine, and dopamine. More specifically, they increase the amount of these neurotransmitters in the space between neurons (nerve cells in the brain that receive and relay information to each other).


Auvelity contains two compounds, bupropion, and dextromethorphan. This treatment combination works by inhibiting N-Methyl-D-aspartate (NMDA) receptors, which increases the intracellular levels of glutamate, an excitatory neurotransmitter found throughout the central nervous system (CNS). This increase in glutamate causes the release of another chemical called brain-derived neurotrophic (BDNF) factor, which may help symptoms of depression by allowing neurons to form new connections more easily.


#3: It Can Be Taken Orally

Auvelity is the first FDA-approved NMDA antagonist for depression that can be taken orally as opposed to intravenously (through an IV), intramuscularly (injected into the muscle), or intranasally (sprayed into the nose). While these alternative routes of administration have their advantages, some may feel they lack the convenience of a pill that can be taken in the comfort of one’s home.


#4: It is Not Associated with Weight Gain or Sexual Dysfunction

Even when the standard antidepressants are effective, they can come with side effects that lead patients to discontinue them despite their therapeutic effects.


Likely due to its novel mechanism of action, dextromethorphan-bupropion was not found to be associated with weight gain or sexual dysfunction, two of the more commonly experienced side effects. Additionally, the clinical trials found that, unlike ketamine or Spravato (intranasal esketamine), dextromethorphan-bupropion did not cause transient psychotomimetic effects (i.e., delusions, delirium, perceived distortions of space and time, etc.). 


#5: It Can Be Used as a First-Line Treatment

Though there are other treatments for depression that work through novel mechanisms, such as Spravato and TMS, they are approved by the FDA for treatment-resistant depression (i.e., depression that has not responded to multiple oral antidepressants).


A lack of FDA approval often results in a lack of insurance coverage. This means patients who would prefer to try one of these novel treatments but have yet to undergo a series of trials with standard oral antidepressants must first wait through weeks or months of potentially unsuccessful treatments.


Auvelity changes this. Because it is FDA approved for major depressive disorder full stop, doctors can use it as a first-line treatment for depression before a patient has tried other antidepressants.


#6: It is Not the Same as Ketamine or Spravato

While ketamine, Spravato, and Auvelity are all NMDA antagonists, Auvelity is unique in ways that makes them difficult to compare. For example, Auvelity exerts its NMDA antagonism continuously but at a lower level of intensity. In contrast, ketamine and Spravato cause a flood of glutamate in a relatively short period of time. The differential effect of this on treatment outcomes is not yet known, as no studies have compared these medications directly. 


Talk with your doctor to determine whether this treatment is right for you, or you can schedule an appointment with one of our team of psychiatrists or therapists to advise you on this or any other potential treatments for depression, including ketamine, Spravato, and TMS. Call us at 805-204-2502 or request an appointment here.

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Study Finds Ketamine Provides Rapid Relief from Severe Suicidal Ideation​

Study Finds Ketamine Provides Rapid Relief from Severe Suicidal Ideation

September 20, 2022

Each year, around 800,000 people die from suicide, and nearly 20 times that number attempt it. 


Though the causes of suicide and suicide attempts are varied, it is often preceded by suicidal ideation (i.e., contemplations, wishes, and preoccupations with death and suicide). As a result, researchers have increasingly been searching for compounds that treat these thoughts and feelings. 


Ketamine has stood out as a promising candidate, with several studies indicating that it is highly effective against suicidal ideation. While these results are encouraging, they generally have not focused on patients experiencing more severe suicidal ideation (SI) or in the middle of a suicidal crisis. Additionally, as far as outcomes go, many studies have measured the number of “treatment responders” (i.e., individuals who experience at least a 50 percent reduction in symptom severity) as opposed to the amount who experience remission (i.e., a complete absence of suicidal ideas).  


To fill in these gaps, a team of researchers led by Dr. Mocrane Abbar conducted a double-blind placebo study to assess the effects of ketamine on cases of severe SI. Due to its double-blind placebo-controlled structure, half of the subjects were given an inactive ingredient not known to improve SI. Additionally, neither the subjects nor the experimenters knew whether ketamine or the placebo was given. 

Key Findings

Below are some of the key findings from this study.



The Majority of Patients Achieved Full Remission

Sixty-three percent of the severely depressed subjects achieved complete remission of their suicidal ideation after just three days and two ketamine infusions.


It Worked Rapidly

SI is an urgent condition warranting an immediate and swift response. As such, it’s vital that ketamine not only works for many patients but also exerts its effects quickly and robustly.


As the graph above shows, many patients achieved remission almost immediately. Specifically, 43.8 percent of participants suffering from severe suicidal ideation achieved remission of their symptoms only two hours after their first infusion.



The Effect was Persistent

Immediate and robust relief of SI is a significant result on its own. However, this finding may have a limited impact if SI promptly returns. Fortunately, the researchers found that the effect lasted six weeks for nearly 70 percent of the patients.

While far from permanent, the six-week reprieve many patients experienced is promising for several reasons. For one thing, given that suicidal ideation is strongly associated with suicide attempts, these subjects may be far less likely to attempt suicide within those six weeks. Second, repeated infusions may lengthen this period of relief even further. Additionally, patients who have yet to create a holistic system of support to supplement their pharmacological treatments with other forms of therapy may find they have more energy to do this while the ketamine is lifting the heavy mental burden of severe SI.



The Effect was Strongest for Those Suffering from Bipolar Disorder

The research team found that ketamine’s therapeutic effect on SI generally depended on the mental condition the patient was suffering from.  More specifically, they found that ketamine infusions had the strongest impact on SI in patients who have bipolar disorder.


Among individuals suffering from depression, the effect was more moderate, with 42 percent of subjects experiencing a remission of their SI.  To shed light on the result, the researchers note that “one study of treatment-resistant depression suggests that repeated doses of ketamine might be necessary for some patients to achieve remission of severe suicidal ideas.” In other words, it may be that this group would have experienced a more significant improvement in their SI symptoms had they undergone more ketamine infusions.  Future studies will need to verify whether this is true.



It Alleviated “Mental Pain”

In addition to compiling more robust, reliable evidence that ketamine is a good treatment for severe SI, the research team collected data that may shed light on why it is so effective. In particular, they measured patients’ levels of “mental pain” and looked for correlations with remission levels.


They found that patients’ self-reported mental or psychological pain was strongly correlated with the severity of their SI and that the ketamine infusions had the most substantial positive effect on their SI when they alleviated psychological pain. This suggests that ketamine’s impact on SI is, at least partly, the result of its ability to relieve psychological pain.


Research continues to verify ketamine’s therapeutic effect on SI. This study provides some of the strongest evidence to date, suggesting that ketamine can provide rapid relief in cases of suicidal crises. It also sheds light on why ketamine has this effect and indicates that the degree to which it is helpful may depend on the individual’s particular mental health condition. 


If you are experiencing symptoms of SI, please contact the Suicide Crisis and Prevention Lifeline at 988


If you feel you need to see a mental health professional or could use help deciding which service is right for you, please give us a call at 805-204-2502 or fill out an appointment request here. We have a wide variety of providers, including therapists, psychiatrists, nurse practitioners, and nutritional therapists who can see you in as little as one day via teletherapy.  

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Ketamine and Alcohol Use Disorder​

Ketamine and Alcohol Use Disorder

September 13, 2022

Alcohol Use Disorder (AUD), a condition characterized by a problematic pattern of alcohol consumption despite physical, mental, and social consequences, is among one of the most common and costly psychiatric conditions. According to National Center for Drug Abuse Statistics, the condition affects around 10 percent of Americans aged 12 and older and is responsible for three million deaths every year.


Because AUD remains a difficult condition to treat, researchers are actively seeking novel therapeutic solutions. Due largely to its well-documented effects on depression, many experts are investigating whether ketamine may prove helpful against AUD. As Professors Celia Morgan and Amy McAndrew note:


Depressive symptoms are common in individuals entering treatment for AUD, and the likelihood of alcohol relapse is elevated in patients with such symptoms.


Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification.


Early experiments have produced promising results, with several studies finding ketamine improved abstinence and lowered relapse rates. For example, one study found that 66 percent of patients with AUD who received ketamine infusions alongside psychotherapy were abstinent one year later compared to 24 percent of patients who did not receive ketamine.


Recent Study Suggests Therapy Makes Ketamine a More Effective Treatment For AUD

While some experts feel that ketamine can be highly impactful when delivered on its own in the absence of any therapy, others feel patients must be supervised and receive guidance from experts during and after treatment for it to be consistently effective. As Rosaline Watts, a leading scholar in the field of psychedelic research, explains when discussing one of her recent experiments, “the drug was a catalyst to the therapeutic process, not the therapeutic process itself.”


With the importance of therapy in mind, a team of researchers led by Morgan and McAndrew set out to directly assess the role of therapy in ketamine-based treatments with a focus on mindfulness. In their study, they reason that:


The subjective experiences that accompany ketamine infusions may provide a new perspective that may be helpful in psychological therapy. Ketamine induces a dose-dependent sense of dissociation and disembodiment that has been described as facilitating an “observer state” similar to that described in mindfulness, which may be helpful for allowing patients to consider thoughts and emotions from a more removed perspective.




The researchers conducted a double-blind-placebo controlled study to assess the importance of therapy in ketamine-assisted treatments for AUD. This means special precautions were taken so that neither the subjects nor the experimenters knew what treatment they received, which helps ensure the results are more objective, reliable, and free from bias.


Because the researchers wanted to examine the effects of both ketamine and therapy on AUD, they needed two placebos (i.e., “inactive” treatments), resulting in four possible treatment combinations.


  1. Ketamine infusions with psychological therapy/mindfulness-based relapse prevention
  2. Saline (drug placebo) infusions with psychological therapy/mindfulness-based relapse prevention
  3. Ketamine infusions with alcohol education (“therapy placebo” where subjects were taught general facts about addiction and alcohol use disorder)
  4. Saline infusions with alcohol education


Findings – Efficacy and Safety

After three treatment sessions the researchers noticed several important outcomes. They found the number of days abstinent at three and six months after treatment was higher in the groups that received ketamine either with or without therapy, corroborating findings from earlier experiments.

                                                                                               Photo Credit to Professors Morgan and McAndrew


The team found some promising results when it comes to whether mindfulness makes ketamine a more effective tool against AUD. In particular, they found that relative to the subjects that received saline with alcohol education (i.e., both placebos), the group that received ketamine alongside mindfulness-based relapse prevention showed the largest percentage increase in the number of days they remained abstinent. However, the latter finding was not statistically significant, meaning future studies will need to verify that the combination of ketamine infusions with mindfulness-based relapse prevention is more effective than ketamine alone.


Because ketamine has the potential for abuse when used in recreational settings, Morgan and McAndrew sought to assess whether this might make it a less viable option for individuals with AUD. To do so, they tracked whether subjects used ketamine during the follow-up portion of the experiment after the supervised ketamine infusions had been administered.


They found that around six percent of the subjects reported using ketamine on one occasion during this period. Importantly, these individuals stated they had used ketamine recreationally before the experiment. Future studies will be needed to further determine whether AUD puts one at a greater risk of using ketamine outside supervised settings.



Though the research is in its early stages, evidence suggests that ketamine, whether used alone or in conjunction with therapy, may help individuals recovering from AUD maintain sobriety.


As researchers continue to explore and identify new psychiatric uses for ketamine, it is becoming increasingly clear that psychological therapy is required to unlock the full benefits of this treatment. Patients and practitioners alike should bear this in mind as they consider ketamine as a therapeutic alternative.

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