Question 1

Is it safe? Are there permanent side effects?

Margaret Ross · Accepted Answer

Psilocybin has a very safe receptor profile and low abuse potential. It is not addictive, and the acute psychedelic effects subside within hours of ingestion.
From a medical point of view, psilocybin can temporarily elevate blood pressure and heart rate after ingestion (although elevations are not clinically significant) so care should be taken to adequately screen cardiac health. Other side effects can include nausea, headache, transient anxiety, and transient paranoia, but these largely resolve within hours of ingestion. Otherwise, from a physiological point of view, psilocybin itself is quite safe.

Safety concerns associated with psilocybin tend to be psychological in nature.  There are risks for people who have a predisposition to developing a psychosis or bipolar disorder, as psychedelic compounds can trigger onset of psychotic symptoms or a relapse. As a result, people with a history of psychosis or bipolar disorder or who have a family history of psychotic disorders or bipolar disorder are usually excluded from psilocybin studies.

While psychedelics are not considered to cause permanent negative mental health outcomes, there have been a small number of case reports of HPPD (Hallucinogen-Persisting Perception Disorder).  However, this is a very rare occurrence, more likely attributed to LSD, and case studies suggests that symptoms tend to resolve with adequate sleep and treatment. Given the rarity of this condition, it is difficult to make accurate estimates of its prevalence.

Question 2

What are the best ways and arguments to help both professionals and those needing help to be more open to the controversial treatments you talk about? I know in the Netherlands psylocybin therapy is allowed but still very few professionals are practicing it

Margaret Ross · Accepted Answer

I usually discuss how politicised psilocybin and psychedelic substances are, which has meant that the medical and therapeutic potential can be overlooked or disregarded by the general population (at least until recently). I usually point out that the rescheduling of psilocybin and its counterparts (LSD, mescaline, etc) occurred as a result of a political backlash and was not based on science. In fact, the science prior to the controlled substances act of 1970 was quite promising but was largely buried. I then discuss evidence from recent studies, which demonstrate not only the safety and tolerability of psychedelic compounds, but its therapeutic efficacy when delivered in combination with psychotherapy. We now have good preliminary evidence to illustrate this.

Occasionally I encounter someone who asks, "Why would you give a dangerous drug to terminally ill patients?!'.  I usually remind them that the toxicity and potential dangerousness of many of the commonly prescribed medications in palliative medicine make psilocybin look pretty tame in comparison. I also like to make the point about how politicised substances can evoke quite emotional viewpoints, which can thwart scientific progress. To make assumptions about the safety of a compound based on our personal/cultural understandings of recreational use of that substance, is unscientific. It is like saying that it’s unethical to offer opiate pain relief to palliative patients based on what we know about street users of heroin.  Many compounds can be helpful or harmful in different contexts.

It’s also worth pointing out the rapid and dramatic amelioration of symptoms in intervention studies.  This is important particularly in the area of palliative medicine, as we don’t have the option of giving patients 12-24 months of weekly psychotherapy if they have a limited prognosis.

Question 3

Therapies with psilocybin consist of sessions where the person is left to himself. Could you imagine it could be more effective if such sessions were (partly) more structured? Anecdotally it has been reported that emotional processing is increased multifold, maybe this could be targeted

Margaret Ross · Accepted Answer

This is a really good question.  The role of therapists during dose day varies between treatments. For example MDMA for PTSD dose sessions see a more directive and active role by the therapists. The therapeutic target is more focused and one is aiming to process specific trauma with the assistance of trained therapists in attendance. 
At this point and given our understanding of the psilocybin and mechanism of drug action, the therapists continue to be largely supportive rather than directive. With psilocybin, the experience is very different to that of MDMA.  
The risk of trying to ‘direct’ that experience means that as therapists, we risk ‘getting in the way’ of surfacing material.  The other issue is that people often find it difficult/distracting to try and find words during peak experiences and doing so can take them out of their experience by observing it rather than being in it.  When people hit a challenging experience, the therapists in attendance can certainly assist with helping the person ‘move into’ the difficult experience, and adopt a more active role in that moment.

Towards the end of the dose session when people are emerging out of the peak psilocybin experience, they may be more verbal and begin making sense of their experience (although this varies - some prefer to maintain an inward focus and not speak). At this point, one can begin helping the person make sense of their experience or begin the process of integrating.

As we develop a more sophisticated understanding of psilocybin and other psychedelics, we may be able to optimise the therapeutic space during the dose session. It may also depend on the condition being treated and the mechanism of action of the compound being used. There are a group of researchers that are re-evaluating the components of the ‘set and setting’ protocol which has remained largely unchanged for decades. It is hoped that we can continue to fine-tune details and optimise the non-pharmacological components of this treatment to further improve psychological outcomes.

Question 4

What is psilocybin?

Margaret Ross · Accepted Answer

Psilocybin is an indole alkaloid tryptamine naturally found in the “psilocybe” species of mushroom (otherwise known as ‘magic mushrooms’).  It can also be produced synthetically in a lab. Being a psychedelic compound, it produces many of the effects that classic psychedelics can produce, including heightened/altered sensory experiences of sound, vision, and bodily sensations, a distorted sense of time, increased sense of empathy and connection to others and the natural world, ego dissolution and mystical/spiritual experiences.  
It can also evoke intense emotional experiences, a sense of unity and being ‘at one with the universe’ (oceanic boundlessness), euphoria and other positive mood states, recollection of life events, but it can also produce disorientation, anxiety and paranoia in some instances. It tends to evoke a state of inward reflection that can be deeply personal and existential (although this is dose and setting dependent too).

Question 5

Why use psilocybin in palliative care? Thank you.

Margaret Ross · Accepted Answer

Thanks for your question! It's a long answer so I’ll break it into two parts - the problem with treating depression and anxiety in people who have a terminal illness, and the potential for psilocybin for distressed terminally ill people.

The current treatment options for depressed or anxious people with a terminal illness roughly fall into two categories - medications (like antidepressants, anti-anxiety medications, anti-psychotics, etc) and talking therapies/creative therapies. These can work very well for some people. However, for those that don’t respond to these treatments, aside from intensive social support, there is little more that we can do to alleviate their distress.
The other problem is that when people are psychologically distressed, this exacerbates their physical symptoms of disease and/or treatment. It can make nausea worse, it can augment their experience of pain, and can increase difficulties with sleep and energy levels.  In addition to their psychological/spiritual distress, it can make their physiological symptoms quite difficult to treat.  
Also, the medications themselves can be problematic - take benzodiazepines for example (commonly prescribed anti-anxiety medication). One can quickly develop problematic tolerance (i.e. one needs increasingly more of the same medication in order to obtain a therapeutic effect), dependence, withdrawal, and anti anxiety medications can increase the risk of developing a delirium. 
Antidepressants can be helpful in reducing the intensity of the depressive mood, but can also ‘mute’ the emotional experience of the consumer. Taken alone (that is, without psychotherapy) it certainly doesn’t address the underlying anguish or concerns of the person.
Talking therapies and creative therapies (art, music, dance) can be very beneficial for many people, but for some, they experience only momentary or modest benefit.

Prior to the rescheduling of psychedelic compounds, there were a number of studies conducted using LSD (another classic psychedelic compound) to treat death anxiety of cancer patients with quite favourable findings (i.e. many reported being able to ‘transcend’ their fear of death, reduced anxiety).  Unfortunately much of that science was buried with the introduction of the Controlled Substances act and rescheduling of psilocybin globally.  Studies in past decade have indicated quite rapid and dramatic reductions in depression and anxiety symptoms of cancer patients, and these improvements were sustained at 6 months in up to 70-80% of participants. (see research by Grob, et al., 2010; Ross, et al., 2016 and Griffiths, et al., 2016).

Psilocybin potentially offers a profound healing experience for someone who is facing terminal illness.
The nature of the psychedelic experience appears to access death anxiety and existential distress in a way that is superior to existing treatments.

Meaning, identity and sense of connectedness can be quite fractured in people with terminal illness. The psilocybin experience appears to allow for new, expanded perspectives (i.e. a new view or relationship with self, others, their illness, the world, death/dying), but can potentially offer experiences of unity, oceanic boundlessness, increased sense of connection, and can occasion mystical or spiritual experiences. 
This can be profoundly therapeutic for someone who has existential distress and particularly for people whose range of experience is very restricted by having a body ravaged with physical disease.

I believe psilocybin assisted therapy for existential anxiety and depression may present a rather ingenious fit of medicine for ailment.

Question 6

Hi Dr. Ross, what level of psychotherapy is involved when psilocybin is administered in palliative care?

Margaret Ross · Accepted Answer

Hi there! 
It’s quite similar in structure to other psilocybin assisted therapy studies. There are essentially 3 phases of treatment - Preparation sessions, dose day and integration sessions.  All phases have 2 therapists present throughout.
Even before the preparatory therapy sessions, there is considerable psychiatric screening involved. This is to ensure that participants are safe enough to tolerate the treatment.  It’s important to emphasise the need to conduct thorough screening, because while psychedelics have quite a safe receptor profile, psychedelics are not safe for everyone. If you are currently experiencing or have history of psychosis or bipolar disorder, OR if you have a first degree relative with psychosis or bipolar, the dose session may trigger an episode or relapse. In addition, people who have experienced complex trauma or dissociation may not safely tolerate the treatment. Additionally, if the therapists are unable to develop adequate rapport with the participant, it may be that additional sessions are required before commencing a dose session, or it may become clear to the therapists that the participant may not safely tolerate the treatment.

In addition to the screening, we obtain a life history and conduct a usual therapy intake session.  There is considerable time dedicated to preparation for the dose session and this includes exploring the intention of the person - what brought them to seek this type of treatment. 
The dose day itself is more hands off for the therapists- the therapists are very much there to support the participants process as necessary but less talking tends to occur on the dose day itself. 
The integration phase is very important. It allows for the participant to explore and make sense of their experiences, unpack any challenging or intense moments and weave insights/learning into their daily life in a way that is meaningful to them.  This way you are more likely to consolidate gains and create lasting change for the person.

Given it is end of life work, much of the therapeutic orientation is ‘meaning centered’/existential in its approach. There are number of issues that someone with a terminal illness may face - having to say goodbye to loved ones left behind, dealing with unfinished business, having complicated/conflicted relationships, unlived potential or missed opportunities, regrets, the betrayal of their physical body and increasing disability as their disease progresses, loss of control, and facing their own death. To the degree with which these concerns occupy one’s mind, these themes can arise within the sessions and therapy focuses on deriving meaning from their psilocybin experiences, in a way that helps them live their remaining precious time more fully and face their mortality with greater acceptance and even peace.

Question 7

As a physician in the United States, what would be a realistic path to be able to provide this invaluable treatment to my patients?

Margaret Ross · Accepted Answer

At the moment, psilocybin remains an illegal schedule 1 substance in the U.S., and as such, the treatment is not able to be provided to your patients outside of an IRB approved clinical trial.  In saying that, it is hoped that phase III clinical trials investigating psilocybin assisted therapy for cancer patients are to commence in the U.S. in the not too distant future.

If you have the skills, team, and the resources, perhaps you could investigate the feasibility of becoming a research site.

Otherwise, keep a close eye on the developments in the research space.  The positive news is that the FDA has granted ‘breakthrough therapy status’ to psilocybin for the treatment of depression.  This means that the drug development and review will be expedited because the research findings are superior to current treatments.  If the research continues to yield promising outcomes, psilocybin assisted therapy may become an approved treatment for depression within the next 3-5 years, perhaps even sooner. 
Thanks for your question!

Question 8

What is the optimal setting/environment for therapeutic psilocybin use?

Margaret Ross · Accepted Answer

Setting tends to go hand in hand with ‘set’, so it’s important that the person is thoroughly screened and carefully prepared to enable an optimal therapeutic encounter.

For the dose setting itself, having a setting that is safe, aesthetically comforting/pleasing, physically safe (so as to keep the person safe while under the influence, particularly if they are disoriented), free from outside interruptions, and in the presence of trusted therapists, the environment is optimised.  It can also be further optimised by having the person bring meaningful objects or photos into the dose space as well.

During the session, a specific music playlist designed to work with the drug phases of the psilocybin is played to facilitate the experience, and eyeshades are worn to help direct an internal focus. The music is intended to enhance and deepen the experience without being intrusive to the individual so careful selection of music is a key factor as well.

Question 9

How long do the treatment effects of a single dose of psilocybin last?

Margaret Ross · Accepted Answer

Studies suggest sustained improvements in depressed mood and anxiety at 6 months of follow-up for 60-80% of participants (see Ross, et al., 2016). A recent follow up of the same study at 3-4 years post their dose experience, found that 60-80% still demonstrated sustained improvement of depressive and anxiety symptomatology.  While it was a small number of participants at followup, the results are quite compelling.
It may be that 2 or more dose sessions offer more therapeutic benefit. Many study designs in psychedelic research are now including more than a single dose session.

It's also worth mentioning that it's not just the psilocybin that produces sustained treatment effects- the therapy before the dose session, and integration therapy after the dose sessions are essential to  consolidate therapeutic insights and help people make sense of their psilocybin experience in a way that promotes meaningful, lasting change.

Question 10

How does psilocybin work?

Margaret Ross · Accepted Answer

While we are still trying to understand the more in depth ways that psilocybin works, there are some key mechanisms that we are beginning to understand (may I suggest you look at studies by David Nutt, Robin Carhart-Harris, & Franz Vollenweider to name a few key researchers in this area).

We know that psilocybin tends to exert influence on the Default Mode Network (DMN) - which is a network of interacting brain regions that are most active while we're at rest, or not focused on external tasks. The DMN also appears to be active when we are thinking about ourselves, the past or worrying about the future, engaging in self referential ideas.  We know that in depression and anxiety, this type of thinking can become quite rigid, negativistic and automatic over time.  Psilocybin seems to relax the DMN so that new and expanded perspectives are possible, and we can attribute new meanings to old problems. The usual rigid pattern is disrupted and in the right conditions, psilocybin appears to promote a state of deep self-reflection and existential focus; a state that is invaluable for therapeutic work. In combination with therapy, we can then leverage these new meanings and perspectives into enduring changes in our mood, thinking and behaviours. 
 
Psilocybin is also a serotonergic agonist (serotonin is a neurotransmitter that is related to emotional processing), meaning that it activates the 5HT2A serotonin receptors,  and has antidepressant effects.  There is even some evidence to suggest that it may promote neurogenesis.

In addition to the DMN downregulation, the experience itself can be quite enriching and transcendent.  Mystical and spiritual experiences can be evoked so the experience can leave one with a sense of awe, increased connectedness to others and the world, and can be profoundly healing.

From a neurobiological point of view, psilocybin exerts a number of potentially beneficial actions, and still the research continues.  We have much to understand about this fascinating compound from a psychological, neurobiological, spiritual and humanistic point of view.

Thanks for your question!

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