OPEN Foundation

Bill (William A.) Richards is a clinical psychologist in the Psychiatry Department at the Johns Hopkins School of Medicine, where he has pursued research with psychedelics during the past sixteen years, including his current studies on psilocybin-assisted psychotherapy with cancer patients coping with end-of-life issues. Richards’ psychedelic research stems back to 1963; he worked with colleagues such as Walter Pahnke and Stanislav Grof in the late 1960’s and early 1970s. More recently, he details his decades of scientific scholarship on psychedelics and human consciousness in his book, “Sacred Knowledge: Psychedelics and Religious Experiences.” OPEN Foundation talked to Richards, who is immediately affable and speaks about his work with both serious and tangible enthusiasm. [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][Bill Richards will be among the speakers at our ICPR 2016 conference on psychedelics research.]

You’re a clinical psychologist with formal training in theology and comparative religion and have spent your entire career investigating the promise of psychedelics in clinical treatment. How did all these disparate strains of interest come together?

When I first arrived in college, I thought I would be a minister and majored in Philosophy and minored in Psychology and Sociology. Then I went to Yale Divinity School, where I studied courses such as contemporary Hindu systems and language analysis, and my vision of religion grew increasingly rich and broad. But at the end of the first year, I wasn’t sure it was right for me.

Then I studied in Germany (at the University of Göttingen) where I accidentally stumbled on psychedelics in 1963. While I found some of the theological courses there rather pedantic—sometimes arguing over the meaning of certain Hebrew words—to my surprise, I discovered the experiential dimension of religion in the School of Medicine, where different alternative states of consciousness were taken seriously, including experiences of a religious nature often viewed as revelatory.

After Yale, I went to Andover Newton Theological School and studied the Psychology of Religion, followed by courses at Brandeis University with the Humanistic/Transpersonal psychologist, Abraham Maslow. Then I was offered a job working with psychedelics and moved from Boston to Baltimore (where I pursued psychotherapy research with LSD, DPT, MDA and psilocybin at the Maryland Psychiatric Research Center). But I felt I didn’t have the right letters after my name to qualify as a researcher so I continued my studies at Catholic University, got a PhD and became a licensed clinical psychologist.

When I went through graduate school some people seemed to look at me as if I was aimless—I studied music, philosophy, psychology and religion—but looking back, I see it was the perfect training for the work I do. I became a psychedelic therapist long before the name was even invented and somehow, I intuitively seemed to know what I was doing!

What did you initially work on in the early days?

When I arrived in Baltimore we had two federal grants from the National Institute of Mental Health to pursue research with LSD-assisted psychotherapy: one for treating alcoholics and the other for treating what we labelled “neurotics” at the time, hospitalised people who were depressed, anxious or suffering with personality disorders. I also began working with cancer patients struggling with anxiety and depression (which had minimal funding). One of the reasons I was hired was my theological background.

From working with such disparate groups, I’ve learned that people are people no matter what their diagnosis. Everyone experiences grief, guilt and anger, high points and low ones, and yearns for a philosophy or understanding that helps life make sense.

Could you please guide me through how you work with someone in a clinical setting?

The basic format for a session with a psychedelic substance is that there are two therapists present; one is the primary and the other is the co-therapist. We treat one person at a time, which allows each volunteer to have an interior focus. The subject lies on a couch; we use eyeshades and headphones to help them relax but also, to help them dive deeply into the mind. This produces a safe and productive way to work, as the subject doesn’t get distracted by sensory perceptions of what’s in the room, or any pressures to be social and interact. Typically, people experience more profound content when an initial psychedelic session is structured in this manner than they might otherwise in a different setting. In terms of measuring the variables, it’s also easier to work with one person at a time. If several subjects were in the room, simultaneously having psychedelic experiences, it would complicate the research design.

I read an article in the New Yorker mentioning how you created a set of “flight instructions” for those undergoing psychedelic therapy. At what point did you create this and why?

It’s not something I ever wrote down as a formal document; it’s more like an informal checklist shared with the subject in person. It helps to cement the relationship and promotes a sense of security. It covers practicalities from how we handle someone going to bathroom or what to do if they feel the need to vomit, to how to navigate within their field of consciousness. For example, if something threatening appears, we encourage subjects to reach out for support if they need it, and to look the threatening image in the eye. In other words, to go towards it because when people seek control by trying to avoid what’s there, that’s when they become paranoid and confused. Resistance usually comes from fighting what’s happening. Telling them to “Trust, Let go, and Be open” is our basic mantra. We also encourage them to send their intellects outside to play in the yard during the period of drug action, rather than trying to cognitively categorise the experience when it is occurring.

Many researchers posit that the power of suggestion may play a role when medical professionals administer psilocybin. Is it true that under such conditions, the patient will be more likely to fulfil the therapist’s expectations (including avoiding a bad trip)?

It’s critical that people feel safe. We suggest that people declare “Open House” in their minds, affirming that everyone and everything is welcome. I’d say the content of an interior journey is rarely influenced by suggestion, though, because people have radically different experiences in identical settings. In very low doses, psychological suggestion may play a stronger role in terms of imagery but in medium and high doses, the content seems independent of what one might expect and often quite surprising.

It’s often a struggle for people to coordinate their language and ideas with their actual experiences on psychedelics. For example, I recently worked with an atheist who had a profound spiritual experience and subsequently claimed to have “seen God”. Then there are those who yearn to experience a beatific vision of Christ, like some priests, but instead find themselves dealing with childhood issues, such as being molested. Psychedelics reliably seem to take you right to where the work needs to be done.

This unpredictability is why some people fear psychedelics, labelling them as dangerous. But for the individual undergoing the unfolding process, there’s an incredible wisdom and choreography to all of it that makes sense. In other words, what happens isn’t chaotic or by chance—it all has meaning.

You refer to psychedelics as ‘entheogens,’ which literally means a compound that “generates the divine within,” and your work is focused on mystical/religious experience and its benefits. Many religious scholars have wondered if chemically induced mystical experiences are the same as naturally occurring ones. What do you think?

There may well be a chemical substrate to everything we experience. For example, we know that DMT is naturally produced in humans. One hypothesis is that when someone deep in meditation experiences a spiritual moment, more DMT is generated, or perhaps the balance of CO₂ to O₂ in the blood changes, or whatever. But there’s probably always a chemical substrate that correlates with whatever we experience, with and without psychedelic substances.

I have no idea if saints throughout history ate psychogenic mushrooms in their stew or if they had mystical experiences simply due to the makeup of their natural biochemistry.

What is a gift of grace and what is induced by what we eat? Who knows? But there is no doubt that incredibly profound mystical experiences sometimes happen when one ingests psychedelics in adequate dosage in a supportive environment with serious intentions. They are wonderful tools because they are so reliably potent in helping people actually experience deep, transformative states of human consciousness. Phenomenologically, the content of transcendental psychedelic sessions (retrospectively described) appears indistinguishable from the content reported in the historical literature of mysticism, so it is probable that they indeed reflect the same quality and depth of experiencing.

You employ scientific methods to explore psychedelic experiences, or states of consciousness that often are highly individual and ineffable. Is it really possible for science to explore mystical experiences?

The science is the design of the research project. Let’s say one person gets Ritalin and the other psilocybin with the same expectation in a “double-blind” design; the only thing different is the content of the capsule, which no one knows except for the pharmacist. Science thereby establishes that, yes, it really is psilocybin that triggers profound experiences, not just suggestion because those who were administered Ritalin did not report the same experiences.[1]

I am now conducting a psychedelic study with leaders from different world religions. There’s a waiting list control group, so following screening and acceptance some are randomly assigned to immediate preparation for psilocybin while others have to wait 6 months before they enter the active phase of the study. We’re comparing what happens to those who haven’t taken psilocybin with those who have and collecting this information through questionnaires, and formal interviews with family and colleagues. We’re especially interested in studying changes in attitudes and behaviour that tend to be reported after transcendental states of consciousness have been experienced. The state of consciousness we call “mystical”, characterised by reports of unity, transcendence of time and space, intuitive knowledge, sacredness, deeply-felt positive mood and ineffability, appears not only to be awesomely meaningful for those who experience and remember it, but it also appears to facilitate what William James called “fruits for life.”

Why it is important to explore such states?

Some people just live their lives, never worrying about where we came from, where we’re going and why we’re on this little planet spinning through space. Others do. Maybe it’s a gene. Some of us have a religious or philosophical gene that wants to understand what life means. I think most people ask these questions when life gets difficult, when they’re forced to approach death (their own or a loved one’s) or even when they see the birth of a child. It’s that sense of mystery.

I like to think that, as part of our current evolution within consciousness, we are beginning to understand that we are still being created and waking up. I think the current focus on meditation, spiritual development, yoga and beyond in our culture reflects a yearning to awaken to broader consciousness. I believe mystical consciousness is simply intrinsic to our being.

Research has proven that psychedelics facilitate the occurrence of mystical forms of consciousness in healthy volunteers with a high degree of reliability. Would you then say that mystical experience is a key factor in the benefits subjects derive from psychedelic treatment?

Yes. If there could be only one key factor that would be it. Experiencing a sense of unified consciousness is life-transforming for many people. In that sense, we are not really studying the effect of psilocybin as a simple drug effect so much as we’re studying the effects of discrete alternative states of human consciousness.

The most dramatic shifts in attitudes and behaviour seem to happen in the aftermath of a mystical experience. We see changes in a person’s concept of what the nature of reality is, who they are, their connection to others; it gives them a sense of confidence that there is nothing within that cannot be forgiven and resolved; there’s an increase in self worth; an appreciation of beauty and treasuring others, even those one disagrees with. The ideal treatment appears to be one that includes both experiences of psychodynamic resolution and some kind of mystical transcendence.

Does having a psychedelic experience challenge the prevailing materialistic paradigm?

I would rather say it enriches or deepens it. Philosophically, I think the question that arises is “What is the ultimate nature of matter?” When we look at matter from the viewpoint of quantum physics, we’re just beginning to understand there are deeper substrates to the so-called “material world”.

It has been reported consistently in psychedelic research that mystical experiences, when they occur, have a powerful effect in removing the fear of death; there’s something about these states that feels more real than everyday reality. This brings up the classic mind/body problem: what is the relationship of the brain to consciousness? If, as some theorise, the brain receives and processes consciousness like a radio would a radio signal, where does consciousness actually originate? Another example: if you dissect a television set, you cannot find a trace of the blonde newscaster who just delivered the news inside of it. But the broadcast did happen—it came from somewhere. We’re at the edge of a fascinating frontier, in psychiatry, in religious studies and in physics. Ultimately, we honestly still do not know what we are.

Many first-wave studies have been criticised as being flawed in more than one way, and sometimes even unethical. Was this simply how science was done at the time, or did the ‘wild enthusiasm’ for this novel range of substances play a part in the sometimes reckless way in which experiments were conducted? Historically, it led to popular hysteria and ultimately restrictive legislation, which have taken decades to recover from.

There was a lot of early enthusiasm. When psychedelics first appeared in modern Western culture, they were just sent through the mail to therapists. Timothy Leary wasn’t the only one working with these substances. A lot of people were using them clinically at universities or in private practices, both in Europe and North America to experiment with their usefulness. While some clinicians weren’t trained as researchers and there were no control groups, many carried out studies with great responsibility and care. Psychedelics actually have a remarkable safety record. Indigenous groups have used these chemicals in their plant-based forms (ayahuasca, psilocybin-containing mushrooms, peyote, etc.) in group formats for thousands of years without anyone ever checking their blood pressure.

In the 1960’s we weren’t prepared to deal with psychedelics and many people clumsily misused them. The media reaction was alarmist and psychedelics were quickly devalued. The press is much saner now, approaching psychedelics from a much more sober, grounded perspective.

Why is that? Our research designs are much tighter today. We have gathered decades more of testimonials and statistics about how extraordinary these drugs are. The entire field has matured—we know more. We’re smarter. We’ve learned that psychedelics are not for everyone. There are a multitude of ways to explore personal and spiritual growth, so even if they one day become legally available, I don’t think everyone will be interested in using them. In fact, some people should be wisely counselled not to, such as those with some severe forms of mental illness.

Suppose that you had all means of scientific investigation ready to use, which question would you like to have answered?

In my book there are three chapters that address such questions—one on medical, one on educational and one on religious frontiers—and I could go down any of those paths. Medically, the promise of psychedelics in treating addictions appears to be very hopeful. Outside medical treatment, they may well hold great promise in facilitating creativity and perhaps that’s what I’d explore.

 One problem is that people who generally shouldn’t be taking psychedelics—such as young people, who do it recreationally—are taking them whereas responsible, established scholars aren’t. So what we frequently see in the press are stories on how young people are ending up in emergency rooms, rather than hearing about how scientists are discovering new insights through the use of psilocybin, DMT, mescaline or LSD. Steve Jobs once claimed that psychedelics gave him critical intuitive insights that enhanced his creativity in life. I would love to give well-trained physicists on the frontier of their discipline a structured psychedelic experience. There could be really valuable new insights and perspectives from such a study.

I also have a wild fantasy that some day it will be an option (for those in religious studies) to have a psychedelic experience with academic credit. Whether they are studying to become a Christian minister, Jewish rabbi, Hindu or Buddhist priest or Islamic imam, I propose that having a profound religious experience could be a part of their training, rather than relying on scriptures and traditions alone.

Do you have any plans for future psychedelic studies you would like to carry out?

I would love to see work done exploring the value of psychedelics with sociopathic personalities. The way we fill prisons today is not enlightened. There are ways of helping those with traumatised childhoods to gain a sense of personal value and respect for other people, and to develop a sense of ethics that is genuine and not imposed, but instead rises from within. It wouldn’t be cheap and it would require intensive therapy, but compared to locking someone up for life, it would still make good sense economically, as well as altruistically. Especially for young people just beginning to tumble into the prison system, such treatment just might change the course of their lives.

[1] see csp.org/psilocybin for published research studies and commentaries

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Much like the Holy Grail symbolised well-being, infinite wealth, and abundance of food in Arthurian literature, today the infamous neurotransmitter, serotonin, is linked with mood, attention, hunger and more (Young & Leyton, 2002; Wingen, et al., 2008; Feijó, et al., 2011). However, today serotonin may be accredited with too much. Just as Harmon (2009) described the effect of serotonin on the swarm process of locusts, serotonin seemingly has had the same effect on our neuroscientists (Harmon, 2009).

Serotonin is one of three reptilian monoamine neurotransmitters, alongside dopamine and norepinephrine (Kolb & I.Q., 2003). The serotonin receptor has seven main subfamilies, more than the other two monoamines, and has even more subtypes. Although serotonin is indeed a crucial neurotransmitter, it is important to note that it is merely a modulator of other neurotransmitters. Serotonin fine-tunes the action of glutamate and GABA, the principal neurotransmitters, mediating the excitatory and inhibitory signals in the brain. The exception is 5HT₃, which mediates the flow of ions (Ciranna, 2006). As a multifunctional neuromodulatory transmitter, to truly understand its function, there is a need to better understand the second-messenger pathways downstream to reveal the successive key biochemical steps. Serotonin is not the magic bullet for mental health, as penicillin was for gram-negative bacteria. It may only be one of several fingers on the trigger.

Much of serotonin’s claim to fame in the world of mental health is related to LSD findings. Only four years after Hofmann’s famous discovery, LSD was used to model psychosis (Miller, 2014). Almost a decade later, the remarkable similarity between the structures of LSD and serotonin led to the discovery of serotonin in the brain. From this, the scientific community began to infer the relationship between the brain’s chemistry and behavioural outcomes (Miller, 2014). More than 70 years later, there are over one million papers that contain ‘serotonin’ in their titles.

It is reminiscent of the days leading up to the first full sequencing of the human genome, when the scientific community was excited about finding the faulty gene that led to each and every illness. Currently, the neuroscience community has become infatuated with a simple molecule’s role in a variety of complex mental disorders. However, today we understand that disorders are polygenic, and the outcome is dependent on several variables, such as protein production, compensatory mechanisms and environmental influences (Bethesda, 1998). Serotonin may play a significant role in mental illness, but several other factors likely also influence the outcome of disease presentation. The modelling of schizophrenic-like psychosis induced by phencyclidine (PCP) and ketamine demonstrates that glutamate receptors and dopamine can also play a pivotal role in mental health (Javitt, 2007). As much as the driver plays a key role in manoeuvring an automobile, some researchers have not yet acknowledged the importance of the fuel, engine, road taken and other seemingly mundane variables.

Thomas Ray expands extensively on the variegated mannerism of psychedelics. In his paper on “Psychedelics and the Human Receptorome”, he illustrates the multifaceted interaction that psychedelics have with various receptors (Ray, 2010). In conjunction with the National Institute of Mental Health-Psychoactive Drug Screening Program (NIMH-PDSP), he has presented the receptor affinity and promiscuity for 35 psychedelic drugs. The results demonstrate that these 35 drugs do not selectively interact with a single receptor, but rather with a wide range of different classes simultaneously. Even compounds with very similar molecular structures have very different mechanisms (See figure 1 for a comparison between DOB and DOI).

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For example, DOB’s highest affinity is for 5HT_2B, 5HT_2A and 5HT_C, and it interacts to a lesser extent with 21 other receptors. As for DOI, its highest affinity is for 5HT_2C and two other non-serotonergic receptors, with 23 other receptors affected (Ray, 2010). What is more surprising is that for many popular hallucinogens and empathogens, their highest affinity was not necessarily for serotonin. The highest affinity of mescaline, MDMA and ibogaine was for Alpha-2C, Imidazoline 1 and Sigma-2 receptors, respectively. In addition, only one of the 35 drugs displayed a selective receptor affinity, which was the atypical psychedelic Salvinorin A, which solely affects the κ-opioid receptor (KOR) (Ray, 2010). All other 34 tested substances were more promiscuous with their range of receptors.

From Ray’s 2010 paper, we can tell that psychedelics in fact interact with a diverse range of receptors. Although phenylalkylamines are more selective than ergolines and tryptamines, only DOB and MEM can fit today’s framework of radically selective psychedelics, as they are highly selective and the least promiscuous. Furthermore, this study truly highlights the molecular pharmacology community’s vague understanding of the complexity of psychedelics. In the 1990s, DOI was the hallucinogen of choice when illustrating the molecular mechanisms of hallucinogens, as it was widely assumed to be a 5HT₂ selective agonist (Glennon, et al., 1991; Darmani, et al., 1994). However, Ray’s study revealed that DOI is the most promiscuous of all psychedelic substances. Hence, when reviewing papers that solely focus on the relationship between psychedelics and serotonin prior to 2010, it’s important to verify whether the authors presumed the psychedelic at hand was selective or not.

The emphasis should not be on the relationship between a psychedelic and its receptor of choice, but on its mechanism as a whole. It is not enough to state that the alteration of consciousness lies within the agonistic effects on the 5HT_2A receptor. Lisuride, a drug typically used for Parkinson’s disease, is also a 5HT_2A agonist and regulates the same cortical neurons as these classic hallucinogens, but leads to no psychoactive effects (Gonzalez-Maeso, et al., 2007). The difference between the hallucinogenic and non-hallucinogenic properties lies within the regulation of protein subunits and cytoplasmic enzymes. It is crucial to bear in mind that the essence of the mechanism is not how the receptor is manipulated, but how the whole neuronal pathway is influenced.

This article does not mean to simply dismiss the importance of serotonin in the understanding of psychedelic mechanisms or the neurobiology of the mind. Indeed, the use of the 5HT_2A antagonist ketanserin alone can inhibit the psychedelic actions of hallucinogenic 5HT_2A agonists, such as LSD and DOI (Sadzot, et al., 1989; Borroto-Escuela, et al., 2014). When subjects were treated with ketanserin prior to psilocybin ingestion, the hallucinogenic effects also did not ensue. However, the other effects of psilocybin, such as multiple-object tracking impairment and reduction of arousal and vigilance, were not affected by the ketanserin. This demonstrates how non-5-HT₂ receptor sites mediate some of the perceptible mental effects of psilocybin (Carter, et al., 2005). More importantly, it indicates that the hallucinations induced by 5HT_2A receptors are moderated by the drug’s interactions with non-5HT receptor subtypes as well. It is time for neuroscientists to look at the pathways downstream of 5-HT_2A receptors to not only understand how LSD and psilocybin induce hallucinations, but how they are modulated as well.

In sum, Ray’s 2010 paper illustrates that not all serotonergic agonists lead to psychedelic effects, and not all hallucinogens are serotonergic agonists. The principle of the drunkard’s search, in which the drunk will only look for his keys under the streetlight although his keys are across the street in the dark, describes the current state of the neuroscience community. The questions in the field of neuroscience are too often linked only to the neurotransmitters we understand, but not the lesser known receptors such as imidazole and sigma. Much like the complex correlation between genes and disorders, one must be cautious not to draw an all too simple connection between the psychedelic experience and its neurotransmitters. Although we do have serotonin to praise for demonstrating that behaviour is largely determined by neurochemistry, its partner biochemical processes must be acknowledged as well. In order to fully understand the complexity of the mechanisms of psychedelic tools, the complete tapestry of the brain needs to be unravelled. Serotonin is not the “Holy Grail” of neurotransmitters, but one of the many specific components.

References:

Bethesda, 1998. Genes and Diseases. National Center for Biotechnology Information : s.n.
Borroto-Escuela, D. et al., 2014. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signalling of D2-5-HT2A heteroreceptor complexes.. Biochem Biophys Res Commun, 443(1), pp. 278-284.
Ciranna, L., 2006. Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology. Current Neuropharmacology, 4(2), pp. 101-114.
Darmani, N., Mock, O., Towns, L. & Gerdes, C., 1994. The head-twitch response in the least shrew (Cryptotis Parva) is a 5-HT2- and not a 5-HT1C-mediated phenomenon. Pharmacol Biochem Behav, Volume 48, pp. 383-96.
Feijó, F. de M., Bertoluci, M. & Reis, C., 2011. Serotonin and hypothalamic control of hunger: a review. Rev Assoc Med Bras., 57(1), pp. 74-7.
Glennon, R., Darmani, N. & Martin, B., 1991. Multiple populations of serotonin receptors may modulate the behavioral effects of serotonergic agents. Life Science, Volume 45, pp. 2493-8.
Gonzalez-Maeso, J. et al., 2007. Hallucinogens Recruit Specific Cortical 5-HT2A Receptor Mediated Signalling Pathways to Affect Behavior. Neuron, 53(3), pp. 439-452.
Halberstadt, A. L. & Geyer, M. A., 2011. Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology, 61(3), pp. 364-381.
Harmon, K., 2009. When Grasshoppers Go Biblical: Serotonin Causes Locusts to Swarm. Scientific American, 30 January.
Kolb, B. & Whishaw, I., 2003. Fundamentals of Human Neuropsychology. 5th Edition ed. New York: Worth Publishers.
Miller, R. J., 2014. Drugged: The Science and Culture Behind Psychotropic Drugs. 1st edition ed. Oxford University: s.n.
Ray, T. S., 2010. Psychedelics and the Human Receptorome. PLOS, p. 10.1371.
Sadzot, B. et al., 1989. Hallucinogenic drug interactions at human brain 5-HT2 receptors: implications for treating LSD-induced hallucinogenesis.. Psychopharmacology (Berl), 98(4), pp. 495-9.
Wingen, M. et al., 2008. Sustained attention and serotonin: a pharmaco-fMRI study. Human Psychopharmacology, 23(3), pp. 221-230.
Young, S. & Leyton, M., 2002. The role of serotonin in human mood and social interaction. Insight from altered tryptophan levels. Pharmacol Biochem Behav, 71(4), pp. 857-865.
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