Details About the Expert Participants
For this study we included 12 participants living in the United States and Canada. Participants were affiliated with several respected institutions, including Johns Hopkins University, California Institute of Integral Studies, Yale University, and University of Toronto. Ten are also affiliated with clinics, hospitals, or are in private practice. Participant selection was deliberate and was based on having expertise in clinical psychology, psychedelic compounds, psychotic symptoms, and/or medicine. Out of the 12, three participants possessed credentials and experience that demonstrated expertise in all four areas, namely a medical degree combined with substantial clinical experience with individuals with psychotic symptoms and psychedelic compounds. One participant possessed area expertise in all three except psychotic symptoms, three possessed expertise in two areas, and three possessed expertise in one. Two participants had lived experience with psychotic symptoms. The mean number of years participants had worked as a healthcare professional was 23 years, out of which 92% had direct experience with the therapeutic effects of psychedelics. Table 1, below, demonstrates the demographic and relevant experience characteristic of the study experts.
Table 1 List of Experts Interviewed
ID
|
Gender
|
Race / Ethnicity
|
Position
|
Years of Experience as a Healthcare Professional
|
Years of Direct Experience with Psychedelics
|
1
|
Male
|
White
|
Psychiatrist
|
7
|
5
|
2
|
Male
|
White
|
Clinical Psychologist
|
17
|
12
|
3
|
Male
|
White
|
Psychotherapist
|
21
|
7
|
4
|
Male
|
White
|
Psychiatrist
|
62
|
63
|
5
|
Male
|
White
|
Psychiatrist
|
53
|
53
|
6
|
Male
|
Asian
|
Psychiatrist
|
5
|
2
|
7
|
Female
|
White
|
Psychotherapist
|
16
|
5
|
8
|
Male
|
White
|
General Physician
|
9
|
0
|
9
|
Female
|
White
|
Minister, Spiritual counselor
|
0
|
25
|
10
|
Male
|
White
|
Doctor of Nursing
|
24
|
7
|
11
|
Male
|
Hispanic
|
Physician
|
18
|
28
|
12
|
Female
|
White
|
Doctor of Nursing
|
44
|
55
|
Total Years:
|
276
|
263
|
Note. This table demonstrates the number of years spent by 12 participants from varying fields of expertise as Healthcare professionals and Psychedelics investigators.
Themes
Interviews uncovered a broad consensus surrounding six discrete themes as highlighted in Table 2. These included (1) the need for structured guidance that must be established during psychedelic treatments (2) the potential influence of physical and emotional trauma on the development of psychotic symptoms (3) the history of psychiatry and the problematic terminology, pathologization, and stigmatization of psychotic experiences (4) inclusion and exclusion criteria for psychedelic treatment (5) the entropic brain theory as it relates to the effect of psychedelics on people with psychotic symptoms and (6) the differences and similarities between psychotic episodes and experiences of spiritual emergence.
Table 2 Verbal interviewee responses to the questions regarding psychedelic-assisted psychotherapy for psychotic symptoms
Theme and description
|
Exemplar quotes
|
Number of respondents
|
Safety/Guidance
Psychedelic treatment and assessment guidelines for patients with psychotic symptoms
|
“I think a huge thing would be family and peer support and community support. If they don't have a strong support network it's more of a concern”
“You must have a great deal of safeguards in place for the person, including an early trigger for hospitalization and then perhaps the ideal place to treat psychosis, it would be on an inpatient basis”
|
5 (42%)
|
Trauma
Association of experienced trauma and psychotic symptoms
|
“It [psychedelic-assisted psychotherapy] can be helpful for people who have a history of trauma”
“We bring traumatic memories up from the poorly stored locations in the left amygdala. We bring them into an MDMA environment where there are two therapists, who are supporting the person”
|
4 (33%)
|
History of Psychiatry
Systematic reassessment of psychotic diagnoses and treatment protocols
|
“These are terms [psychosis] that are over a century old”
“There should be an ability to build up rapport. Old psychoanalysis would say it is just kind of defined psychosis, as this is somebody that you can't psychoanalyze. They lumped together all of these different conditions”
|
4 (33%)
|
Psychotic Symptoms as an Exclusion Criterion
Need to revise, rethink and nuance protocols, nosology, and phenomenology of psychosis
|
“For these one-shot situations, I think the exclusion criteria are appropriate”
“What would be the effects of psychedelics on people who hear voices, who actually don't meet criteria for psychedelics for psychotic disorders?Versus someone who predominantly has delusions versus someone who's more paranoid?”
|
2 (17%)
|
Entropic Brain Theory
Reassessment of the entropy based descriptions surrounding psychotic states
|
“I have colleagues in the medical field who have been diagnosed with bipolar disorder. They both use psychedelics to positive effect"
“The person who does have a dysfunctional default mode network in the chaotic range, give them a powerful psychedelic substance...break down their default mode network and when it's being reconstructed, direct this person's experience into a more positive mode”
|
2 (17%)
|
Psychedelics and Spiritual Emergencies
Differentiation between psychotic symptoms and spiritual emergence, Delusions determined by cultural context
|
“What makes the difference in our view between spiritual emergence and psychosis is that in spiritual emergence, there remains at some level a sense of center, a sense of self”
“People will meet the textbook criteria for psychosis, but they just happen to have a spiritual emergency and actually the MDMA or psilocybin would be the best solution”
|
3 (25%)
|
*Note: n=12, LSD: Lysergic acid diethylamide, MDMA: 3,4-Methylenedioxymethamphetamine
Psychotic Symptoms as an Exclusion Criterion
Findings indicated that the exclusion criterion barring the participation of people with psychotic symptoms from current psychedelic clinical studies designed for PTSD, anxiety, and depression might be justified since they typically do not provide enough support for this especially vulnerable and high-risk population. Participant 5 noted, “It’s not because we fear that psychosis is necessarily contraindicated...” Several other participants echoed this sentiment saying that in a context where there is substantial support in place, psychedelic-assisted interventions could be both safe and effective for people with symptoms of psychosis. Participant 4 noted that psychotic symptoms are an exclusion criterion in various clinical trials, studies, and treatment programs, which offer psychedelic dosing sessions on an outpatient, short-term basis because the protocols do not offer enough support. For example, a context where such treatment is provided on an inpatient basis and the clinician uses the compound as an adjunctive to long-term supportive psychological work with a person could produce different results from when taken as part of a less supportive program some participants noted. Participant 4 elaborated by saying that the exclusion criteria for less supportive contexts, which provide a “one-shot” or “weekend” experience are justified because “you really don't know what you are going to be dealing with and you don't know how you are going to close or whatever you are going to open.” Participant 7 also mentioned an inpatient context as being effective and that the protocol could be akin to treating substance use disorders.
Participant 1 said that it is probably not true that people with psychotic symptoms cannot receive psychedelics safely and pointed out that part of the reason for the situation at hand may be due to FDA’s criteria requests. On this matter, participant 7 said, “Psychiatrists tend to be quite conservative...” and said, “Why should we deny people the opportunity to have those numinous experiences? That's gatekeeping. That seems like really egregious gatekeeping. I think it would, again, be on an individual basis. And why shouldn't we all have the opportunity to have those mystical experiences?”
When asked about the possibility of data demonstrating safety and efficacy of MDMA for PTSD being relevant to psychedelic-assisted psychotherapy for psychotic symptoms, participant 12 replied, “Why is the field of psychedelic medicine currently lionizing MDMA for PTSD and not for psychosis, another diagnostic category in which many of the defining symptoms are the same and it's forbidden? How did we get there?”
Definitions of Psychosis
One central theme that was raised throughout the interviews was the definition of psychosis. Participants often brought up the heterogeneous nature of psychosis as a category of experience and how the term can mean something different depending on who you ask. Participant 3 discussed how psychosis is on a continuum and that different people draw the line of what is defined as psychosis at different places. Participants 4, 5 and 9 all mentioned that a spiritual emergence must be differentiated from psychosis while participant 3 did not find this distinction useful or helpful.
Participant 6 said that, “There are clusters of psychosis that don't look like each other” while participant 1 talked about how “DSM diagnoses are not single disease entities, so not everyone with a diagnosis of schizophrenia is the same.” For example, several participants mentioned that some individuals may have paranoid delusions and others hallucinations. Participant 4 said, “psychosis doesn't really tell me anything useful as to what's going to be helpful to the person” and that, “These are terms that are over a century old -- before the car, before the light bulb.” Participant 6 also noted the diversity of psychotic experiences, saying that “One person reporting voices may not be at all the same thing. Like somebody that's saying, ‘I hear voices that remind me of the thing that happened’ versus somebody that's mumbling to themselves who keeps looking over to the left of the room. You're talking to them, they keep getting distracted, it literally looks like they're hearing something and they're kind of talking back and they're trying not to show you they're doing that. Those are so different. And so lumping them together as like, ‘hearing voices’ is [not the same].”
Several participants mentioned the importance of whether symptoms are interfering with the patients’ life or are distressing, noting that not everyone who has psychotic symptoms would meet criteria for a DSM-5 psychotic spectrum disorder diagnosis. For example, participant 1 pointed out that, “we know that hearing voices, for instance, is a spectrum.” Other participants discussed how psychotic symptoms may not necessarily be debilitating and how they can actually be beneficial by providing insight and creativity. For example, participant 4 mentioned when referring to relatives of patients with psychosis they interviewed, “in a way, had more hallucinatory experiences than the patient, but they were not interfering with their life. They actually benefited from that because it generated some creative ideas that they could apply in their business, in their writing.”
Participant 12 spoke about how psychosis can be framed as “just receiving channels that other people don't acknowledge.” and that, “It doesn't necessarily mean that they [the channels] don't exist.” They continued to speak about how reality “tends to be socially determined” and how a lot of this [psychosis] is “definitional.” They talked about the example of someone who could see auras of people and what that would be—an experience of psychosis or an extrasensory ability— and mentioned how this person’s “perceptual apparatus would be truncated” if this ability did not exist and how within a psychiatric framework, this would likely be reduced to a hallucination.
Psychedelic-assisted Psychotherapy for Psychotic Symptoms
Participants' responses reflect that psychedelic-assisted psychotherapy may be beneficial for some individuals with psychotic symptoms under the right conditions. Participant 2, a licensed psychedelically-informed clinical psychologist and experience with leading psychedelic clinical trials, said that:
If we're talking about moderate or mild psychotic symptoms, then I certainly think that you could control the setting and provide the type of ongoing support and care for an individual and I think that could be a really interesting line of study. Eventually, down the road, we’re going to need to test whether this is actually true, whether the fear that people have about even severe psychosis or severe risk for psychosis is something that psychedelics bring about when you’re giving psychedelics as part of a therapeutic program. I think that to my knowledge, a lot of the concern comes from evidence in recreational and non-controlled settings where there have been some reports of problems but I don’t know that’s going to be the same when we have it in controlled clinical environments.
Participant 3 mentioned they could see psychedelics being useful in helping to loosen up delusional states saying that “they also might be able to [see] some delusion they've been stuck in….they might open up to a whole bunch of different perspectives and realize there's actually all these different ways of looking at it.” Participant 4 said, “if you had somebody with some hallucinatory experiences, but he is functioning well at work and functioning well in the family, it [the psychotic symptom(s)] is irrelevant and of course you could use psychedelics.” In addition, they mentioned that “there is such a spectrum and people will meet the textbook criteria for psychotic symptoms, but they just happen to have a spiritual emergence and actually the MDMA or psilocybin would be the best solution for that.”
At the same time, while psychedelics may not be contraindicated for psychotic symptoms as participant 5 mentioned, they also said “you must have a great deal of safeguards in place for the person.” Participant 3 likened the psychedelic experience to meditation noting that “when people get into deeper water without guidance, that's when that sometimes, they really, you know [get destabilized]...so it makes me curious that, if, maybe the same thing would work with psychedelics and that you would just need more attention… And only when people are in that fragile state because some of those same people that have had a psychotic episode...but now they are much more grounded… You hear about them going on long meditation retreats and being fine.”
According to the participants’ responses, simply identifying whether there is a history of psychotic symptoms or endorsement of psychotic symptom(s) is not as relevant for determining if the individual will be a good candidate for psychedelic-assisted psychotherapy as whether symptoms are distressing, debilitating, or causing life impairment. Instead, clinicians should remember the heterogeneous nature of psychotic experiences and assess specific symptom endorsement together with levels of functioning. As participant 6 said, “Psychotic depression I could imagine psilocybin being useful for in a way that psychotic mania, I just can’t,” demonstrating how some within this group could be at higher risk than others depending on their specific experience and the need to assess candidacy on a case-by-case basis. It also demonstrates how different compounds could be useful in different situations. In addition, whether symptoms are debilitating must also be taken into account.
While participants mention that psychedelics could certainly be used by individuals with psychotic experiences that are not debilitating, it is also important to note that people on the more severe end of the spectrum may not necessarily be contradicted either. As participant 6 mentioned, “for chronic psychosis, I mean, we have nothing to go on from modern studies about that.” Participant 2 also said that eventually we are going to need to test whether psychedelic-assisted therapy could help people with mild, moderate, and severe psychosis. This is because there is not enough data to dismiss the possibility of psychedelic treatment being beneficial to those with chronic psychosis, only fraught data collected during the First Wave of Psychedelic Research [1].
When asked about the possibility of MDMA being effective for psychotic symptoms in a way similar to PTSD, participant 12 said: “[this] project is the first time that I've ever been brought to consider that, and I can't imagine why no one has, but I've certainly never thought it would before but it seems utterly obvious that that should be the case.” Participant 10 suggested psychedelics facilitating a kind of purge where the psychotic symptoms are released all at once, and participant 12 mentioned something similar where an individual might “move through” the experience and have an outcome that enriches the person.
Potential Effects of Various Psychedelic Compounds on Psychotic Symptoms
Participants were asked about what specific psychedelic compounds might be beneficial to individuals with psychotic symptoms and several suggested MDMA. Table 3, below, demonstrates the themes identified in the study using a thematic analysis approach.
Table 3 Verbal Interviewee Responses to the question arguing for the effectiveness of various psychedelic adjunctives in treating psychotic symptoms
Theme and description
|
Exemplar quotes
|
Number of respondents (percentage of total sample, n=12)
|
MDMA*
Facilitates the processing of traumatic material
|
“MDMA are more likely to have positive emotions, so it's not as likely to activate negative memories”
“MDMA produces this sense of safety that allows people to explore things that otherwise are kind of frightening”
|
5 (42%)
|
Ketamine
Use for psychotic symptoms
|
“Ketamine is something that does seem less likely to push people into scrambled states”
“I recognize for one thing, that Ketamine is an abusable drug and it's difficult to abuse serotonergic psychedelics because the brain just won't let you do it”
|
1 (8%)
|
Psilocybin
Positive outcomes despite being a challenging experience
|
“It was complete torture to this person, and yet they had a complete remission of their depression”
“Memories are restored, they are altered by the experience of the psychedelic work and are not stored in the same way that they were when they were first done”
|
4 (33%)
|
Ayahuasca
Risk of destabilization but may still be therapeutic
|
“Ayahuasca is on the heavy-duty side of triggering such episodes [psychosis], versus MDMA that is maybe a little more mellow. Ayahuasca, is a high risk“
“We had this guy who was hospitalized post-ayahuasca and he still thinks it was the best thing that ever happened to him”
|
2 (17%)
|
Serotonergic Combinations
LSD/Psilocybin/MDMA
|
“Psilocybin, LSD, or the classic psychedelics allow the person back to higher entropic state”
“MDMA is an introductory molecule to modify the psychotic state, then I would use psilocybin or possibly combination of the two”
|
4 (33%)
|
*LSD: Lysergic acid diethylamide, MDMA: 3,4-Methylenedioxymethamphetamine
Participant 5 said that, “If I were to answer your question therefore about which would be the most acceptable, most useful psychedelic, I would say we don't know, but, if you want to produce the possibility of some change, I would think that a drug like MDMA would be the starter molecule.” They also said that “And then if you're looking at trying to modify their psychotic state then I would use psilocybin, or very possibly...a combination of the two (MDMA and psilocybin).” Participant 7 said that MDMA could be useful for its ability to bring about self-compassion, which can be useful for addressing the shame that often comes up with trauma in addition to the stigma of psychotic symptoms.
To further support the possibility of MDMA being effective, participant 2 said, “My bias is that MDMA is a softer first approach to helping people” and that MDMA-assisted psychotherapy is “potentially the only treatment that they need.” Aside from the specific compound, participant 4 stressed that the supportive psychotherapy would also be crucial noting, “I think the best thing, whether it's MDMA or psilocybin, is to offer it as psilocybin- or MDMA- supported psychotherapy where the person would get to know the client well” They mentioned the therapeutic context is important because, the patient “would tell you about their background, their individual development. They would probably tell you about significant things from their family. And then you can decide if it will be helpful to deepen the process by using the MDMA.”
Participant 6 mentioned that MDMA “is almost a perfect drug for trauma in a way that I don't think psilocybin is” and that “MDMA produces this sense of safety that allows people to explore things that otherwise are kind of frightening...” However, when asked about the compatibility of psychedelics and psychotic symptoms, went on to say that “it depends on what we're talking about, but somebody who is acutely psychotic...like they're hallucinating, they have delusions, they’re thought disordered….I don't think I could in good conscience give them MDMA.” When asked if entheogens like psilocybin are less relevant than empathogens, they responded, “Not less relevant. I think just, I would imagine it's easier to go wrong. Maybe it's like a high risk, high reward situation.” Participant 4 echoed this sentiment stating that psilocybin could reactivate traumatic memories, though participants 5 and 6 also mentioned scenarios where psilocybin might be effective. Participant 11 noted that Ayahuasca may be the most likely to cause problems for a person with a history of psychotic symptoms and that in contrast, ketamine may be significantly more safe as a compound that seems “less likely to push people into scrambled states.”
When asked about the clinical profiles of specific compounds, participant 12 mentioned that ketamine is an abusable drug. They did not necessarily say this was a good or bad thing or specific to psychotic symptoms, but simply that there is capacity to abuse, which nuances the clinical profile of the drug, namely safety. They also mentioned that “MDMA is in a kind of middle category between [serotonergics and ketamine]” and that it too has the potential to be abused.
Trauma and Psychotic Symptoms
Considering participant 6’s comment that “MDMA is almost a perfect drug for trauma,” the potential role of trauma in psychotic symptom etiology and symptom maintenance may be extremely relevant to understanding why psychedelic interventions may be effective for individuals with psychotic symptoms. Participant 3 who specializes in psychotic symptom, and has lived experience with psychosis also noted that:
A lot of psychosis is people have a concern, but they're ambivalent about facing it. And so they end up kind of disguising the concern in their mind and turning it into something else, which of course makes them look like they're completely out of touch with reality. And so if they do that successfully enough, then you don't see any connection with the trauma and they don't see any connection with the trauma. And so everybody can say, ‘oh, this is just psychosis.’ But often as you start working on understanding and healing, you start saying, ‘oh, maybe this is connected with the trauma...
They also said that, “Often when they do the research, they say lots of people have PTSD and psychosis, and they talk about it that way, but then they also talk about trauma seems to make psychosis more likely. In fact, having multiple kinds of trauma...the link between multiple kinds of trauma and psychosis is as strong as some of the studies that have found between lung cancer and tobacco” and that, “I think the fact that somebody has lung cancer doesn't mean they smoke. And the fact that somebody has psychosis doesn't mean you're going to find this big prominent history.”
Antipsychotics and Biochemistry
Another recurring theme was that individuals with psychotic symptoms are often highly medicated. Participant 6 said that, “you have this silly thing that happens where people have their report paranoia or they report voices. And then that clicks some flips in somebody's head that's like, ‘oh, they need antipsychotics.” Participant 7 made a similar observation saying that, “I think one of the saddest things having worked in the public system for 15 years in outpatient psychiatry is that we often snow them with these antipsychotics. And it might dull them down because they're highly sedating but it doesn't give them any kind of tools to deal with the things that are still coming up.” Quoting Aaron Beck, participant 3 described CBT for psychotic symptoms as an alternative treatment being able to “suck the juice out of the delusion,” which psychedelic-assisted psychotherapy may be able to help with.
Participant 10 explained that the chemical compounds’ effects may differ depending on drug class and how they interact with the brain. Participant 6 discusses amphetamine-induced psychotic symptoms as a concern, noting that if anyone takes enough amphetamines, it could spark something that at least resembles psychotic symptoms. He noted that this would be important to consider since MDMA is an amphetamine. Participant 5, however, noted it would be unlikely for MDMA in the context of psychedelic-assisted psychotherapy to result in amphetamine-induced psychotic symptoms.
Participant 11 also described an instance of ayahuasca-induced psychotic symptoms occurring in South America and the local psychiatrist saying “It is ayahuasca-induced psychosis” and that “if we shut it off, [through the use of sedatives], they will bounce back,” and that “it's not really as bad as it looks, we just need to reestablish the sleep cycle,” though this person was not a good candidate and should have been identified as such. Participant 10 gave similar recommendations stating how important it is to get sufficient sleep the night after the dosing session, as well as an instance where they needed to prescribe an antipsychotic for a week after ketamine and “she was fine.” They also mentioned that for a psychedelic-assisted psychotherapy program for individuals with psychotic symptoms, one should monitor symptoms over time and be prepared to prescribe antipsychotics. Participant 10 also spoke about how it is possible to administer antipsychotics such as Seroquel to stop the psychedelic effects by hitting a similar range of transmitters, but that this will likely have the negative consequence of hampering memory consolidation and so should ultimately be avoided if possible.
Clinical Recommendations for an Initial Pilot Study
Participants gave a multitude of clinical recommendations for an initial study. For example, participant 1 mentioned that some people who hear voices or just have delusions and technically do not meet criteria for a psychotic disorder diagnosis may be good candidates for an initial trial. At the same time, they stressed the importance of targeting specific symptoms emphasizing the difference in symptom clusters such as between treating someone who primarily hears voices versus someone who has delusions and is paranoid. They also noted that the person should not be in the midst of an episode.
Several participants noted that a strong support system would be particularly important. Participant 6 mentioned that in the psychedelic-guide context, “there should be an ability to build up rapport as so much of it seems to be relational...” and described an instance where poor rapport between the therapists and the client resulted in a difficult situation for the client. This may be especially important in instances where relational or interpersonal trauma may be involved in the client’s clinical picture. Participant 12 spoke about how important a safe and controlled clinical setting would be noting that, “The risk is greater when there's nobody on the ground. Somebody should be ‘ground control’, which sort of implies that there would be a prior agreement” and that someone “takes custody of their body while their consciousness goes elsewhere.” They mentioned that another important element is the preparatory part, which would ideally involve “encouraging the person very strongly to allow [confrontation of fears or traumas].” This would likely be key for someone whose psychotic symptoms are primarily a dissociative reaction to a trauma that is too painful to be accepted as true.
Three participants also recommended inpatient support. Participant 12 said “ You have to be prepared that once someone moves into the realm which we identify as psychosis. You have to be prepared to protect and nourish them in a variety of ways for a couple of months.” They pointed out that ultimately though, there is no data on one specific approach to how this would be carried out, (e.g., inpatient setting, daycare-like setting, etc.), and that ultimately this must be taken seriously so as to mitigate any negative outcomes such as harm to oneself or others, which could have tremendous adverse effects for the field of psychedelic medicine. Participant 10 mentioned that in addition to long-term therapy, the possibility of small groups being helpful. As participant 11 mentioned, it would be important to ask questions like, “What is the support network [for this person]? Where is this? Where is this person going to go afterwards?” and, “Where is this person going directly [afterwards] and who is going to take responsibility for them if they become psychotic?” Further considerations suggested by participant 8, a general physician, include history of drug use, cardiac history, age (over the age of 24 and 30-65 as ideal), family history of sudden cardiac death, assessing for any conditions with an electrolyte panel, signs of infection, current drug usage, presence of tumors, history of homicidal/suicidal ideation, self-harm, presence of weapons at home, social and family support, pharmacodynamics and kinetics of the drugs the potential participant is using, and the metabolism/excretion of the compound in treatment, noting that if the active component of the drug is a metabolite, and the presence of any kidney or liver disease, which may result in the client not being able to excrete the drug as quickly, which may lead to buildup.